Intervenciones psicológicas para la psicosis en adolescentes
Resumen
Antecedentes
La psicosis es una enfermedad caracterizada por alteraciones del pensamiento y las percepciones que resultan en delirios y alucinaciones. La psicosis es muy poco frecuente en adolescentes pero puede tener graves consecuencias. Los fármacos antipsicóticos son el tratamiento principal y han mostrado su efectividad. Sin embargo,existe nueva evidencia que sugiere que ciertas intervenciones psicológicas, como la terapia de rehabilitación cognitiva, la psicoeducación, la terapia familiar y la psicoterapia de grupo, podrían ser útiles para adolescentes con psicosis.
Objetivos
Evaluar los efectos de varias intervenciones psicológicas para los adolescentes con psicosis.
Métodos de búsqueda
Se realizaron búsquedas en el Registro de Ensayos basado en estudios del Grupo Cochrane de Esquizofrenia (Cochrane Schizophrenia) que incluye registros de ensayos clínicos (última búsqueda el 8 de marzo de 2019).
Criterios de selección
Todos los ensayos controlados con asignación aleatoria que compararan varias intervenciones psicológicas con el tratamiento habitual u otras terapias psicológicas para adolescentes con psicosis. Para los análisis, se incluyeron los ensayos que cumplían con los criterios de inclusión e informaban datos utilizables.
Obtención y análisis de los datos
Se examinaron los estudios para su inclusión y se evaluó el riesgo de sesgo de los estudios incluidos, de manera independiente y fiable. Para los datos dicotómicos se calcularon los riesgos relativos (RR) e intervalos de confianza (IC) del 95% sobre la base de un análisis por intención de tratar. Para los datos continuos, se usaron las diferencias de medias (DM) y los IC del 95%. Se utilizó un modelo de efectos aleatorios en los análisis. Con el uso de GRADE se creó una tabla "Resumen de los hallazgos".
Resultados principales
La presente revisión incluye 7 estudios (n = 319) que evalúan un grupo heterogéneo de intervenciones psicológicas con riesgo de sesgo variable. Ninguno de los estudios informó acerca de eventos adversos. Ninguno de los estudios fue patrocinado por la industria. A continuación, se resumen los principales resultados de cuatro de las seis comparaciones, y la certeza de estos (basados en el sistema GRADE). Todas las puntuaciones de las escalas son puntuaciones medias finales.
Terapia de rehabilitación cognitiva (TRC) + tratamiento habitual (TH) versus TH
Dos estudios compararon el añadir TRC al TH de los participantes con TH solo. Un estudio informó el estado global (CGAS, puntuación alta= bueno). No hubo diferencias claras entre los grupos de tratamiento (DM ‐4,90; IC del 95%: ‐11,05 a 1,25; participante = 50; estudios = 1; certeza muy baja). Un estudio informó el estados mental (PANSS, puntuación alta= malo). Las puntuaciones fueron claramente más bajas en el grupo de TH (DM 8,30; IC del 95%: 0,46 a 16,14; participante = 50; estudios = 1; certeza muy baja). Claramente, más participantes del grupo de TRC mostraron una mejoría en el funcionamiento cognitivo (prueba de memoria inmediata de números) en comparación con las cifras que mostraron una mejoría en el grupo de TH (1 estudio, n = 31, RR 0,58, IC del 95%: 0,37 a 0,89; certeza muy baja). Para el funcionamiento global (VABS, puntuación alta = bueno), los análisis de las puntuaciones informadas no mostraron diferencias claras entre los grupos de tratamiento (DM 5,90; IC del 95%: ‐3,03 a 14,83; participante = 50; estudios = 1; certeza muy baja). El número de participantes que abandonaron el estudio de forma temprana fue similar en cada grupo (RR 0,93; IC del 95%: 0,32 a 2,71; participantes = 91; estudios = 2; certeza baja).
Terapia psicosocial en grupo (TPG) + TH versus TH
Un estudio evaluó los efectos de añadir TPG a la medicación habitual del participante. Las puntuaciones del estado global (CGAS, alto = bueno) fueron claramente más altas en el grupo de TPG (MD 5,10, IC del 95% 1,35 a 8,85; participantes = 56; estudios = 1; certeza muy baja), pero hubo poca o ninguna diferencia clara entre los grupos en cuanto a las puntuaciones del estado mental (PANSS, alta = malo, DM ‐4,10, IC del 95%: ‐8,28 a 0,08; participantes = 56; estudios = 1; certeza muy baja) y no hubo diferencias claras entre los grupos en cuanto al número de participantes que abandonaron el estudio antes de tiempo (RR 0,43, IC del 95%: 0,15 a 1,28; participantes = 56; estudios = 1; certeza muy baja).
Programa de rehabilitación cognitiva (PRC) + Programa de tratamiento psicoeducativo (PTP) versus PTP
Un estudio evaluó los efectos de combinar dos intervenciones psicológicas (PRC + PTP) con solo PTP. Las puntuaciones del estado global (CGAS, puntuación alta = bueno) no fueron claramente diferentes (DM 1,60, IC del 95% ‐6,48 a 9,68; participantes = 25; estudios = 1; certeza muy baja), al igual que las puntuaciones del estado mental (BPRS total, puntuación alta = malo, DM ‐5,40, IC del 95%: ‐16,42 a 5,62; participantes = 24; estudios = 1; certeza muy baja) y las del funcionamiento cognitivo (SPAN‐12, puntuación alta = bueno, DM 2,40 IC del 95%: ‐2,67 a 7,47; participantes = 25, estudios = 1; certeza muy baja).
Terapia psicoeducativa (PE) + terapia multifamiliar (TMF) versus terapia grupal no estructurada (TGNE, todos a largo plazo)
Un estudio comparó PE + TMF con TGNE. El análisis de las puntuaciones informadas del estado global (CGAS, puntuación alta = bueno, DM 3,38, IC del 95% ‐4,87 a 11,63; participantes = 49; estudios = 1; certeza muy baja)y de las puntuaciones del estado mental (PANSS total, puntuación alta = malo, DM ‐8,23, IC del 95%: ‐17,51 a 1,05; participantes = 49; estudios = 1; certeza muy baja) no mostraron diferencias claras. El número de participantes que requirieron ingreso hospitalario ((RR 0,84; IC del 95%: 0,36 a 1,96; participantes = 49; estudios = 1) y el número de participantes que abandonaron el estudio antes de tiempo en cada grupo también fueron similares (RR 0,52, IC del 95%: 0,10 a 2,60; participantes = 55; estudios = 1; certeza baja).
Conclusiones de los autores
La mayoría de las estimaciones del efecto de los principales desenlaces son ambiguas. Solo se sugiere un efecto para cuatro resultados en las tablas del Resumen de hallazgos presentadas. Comparada con el TH, el TRC puede tener un efecto positivo en el funcionamiento cognitivo, sin embargo el mismo estudio informa datos que indican que el TH puede tener un efecto positivo en el estado mental. Otro estudio que comparó la TPG con el TH informa datos que sugieren que la TPG puede tener un efecto positivo en el estado global. Sin embargo, la estimación de los efectos para todos los criterios de valoración principales de esta revisión deben considerarse con importante cautela, ya que se basan en datos de un pequeño número de estudios con riesgo de sesgo variable. Nuevos datos podrían alterar estos resultados y se necesitan estudios más amplios y de mejor calidad antes de poder llegar a conclusiones firmes sobre los efectos de las intervenciones psicológicas en los adolescentes con psicosis.
PICO
Resumen en términos sencillos
Intervenciones psicológicas para la psicosis en adolescentes
Preguntas de la revisión
¿Las intervenciones psicológicas son efectivas y seguras para los adolescentes con psicosis? ¿Existen diferencias en el efecto entre las distintas intervenciones psicológicas?
Antecedentes
La psicosis es una enfermedad mental caracterizada por alteraciones en los pensamientos y percepciones como delirios (falsas creencias), alucinaciones (ver u oír cosas que otros no ven ni oyen) y puede darse durante la adolescencia. Cuando esto sucede, el joven debe acudir a un profesional de la salud mental que a menudo le prescribirá medicamentos. Sin embargo, junto con los medicamentos, es probable que los adolescentes con psicosis se beneficien de terapias psicológicas apropiados para su edad como la terapia de rehabilitación cognitiva, la psicoeducación, la terapia familiar y la psicoterapia de grupo. Estas intervenciones pueden abordar las necesidades sociales y psicológicas, como la integración con los compañeros y hacer frente al estigma y la exclusión. Esta revisión examina los efectos de dichas intervenciones para jóvenes con psicosis usando datos de ensayos controlados aleatorizados.
Búsqueda
El documentalista del Grupo Cochrane de Esquizofrenia (Cochrane Schizophrenia) buscó en su registro de ensayos en marzo de 2016 y en marzo de 2019 ensayos que hubieran asignado al azar a adolescentes con psicosis a diferentes grupos terapéuticos. Los grupos terapéuticos podían incluir intervenciones psicológicas (con o sin su tratamiento habitual), solo medicamentos, tratamiento habitual y otras intervenciones psicológicas (con o sin tratamiento habitual).
Ensayos encontrados
Esta revisión solo incluye siete ensayos realizados en diversas partes del mundo. Los ensayos compararon varias intervenciones psicológicas diferentes con el tratamiento habitual o con otros tipos de intervenciones psicológicas, e informaron sobre diferentes criterios de valoración, lo que dificulta la comparación de estudios. Los autores de la revisión estaban interesados en el efecto de estas terapias sobre siete criterios de valoración principales: estado global, estado mental, efectos adversos, funcionamiento cognitivo, funcionamiento global, uso del servicio y abandono temprano del estudio. Ninguno de los estudios incluidos informó sobre datos de efectos adversos.
Resultados
El efecto absoluto de las intervenciones psicológicas (IP, comparación de las IP con el tratamiento habitual [TH])
Los análisis de los datos informados sugieren que la terapia de rehabilitación cognitiva podría ayudar a mejorar la memoria a corto plazo (una función cognitiva), pero el tratamiento habitual podría ser mejor que la terapia de rehabilitación cognitiva para mejorar el estado mental. La terapia de grupo también puede ser útil para mejorar el estado global. Todos los demás análisis de los criterios de valoración principales mostraron que las IP tenían poco o ningún efecto en comparación con el TH.
Efectos relativos de las IP (comparación de una IP con otro tipo de IP)
Los análisis no mostraron diferencias reales entre los distintos tipos de IP.
Conclusiones
Algunas intervenciones psicológicas podrían tener efectos beneficiosos para los criterios de valoración seleccionados, pero, en general, la mayoría de los resultados indican poco o ningún efecto. Sin embargo, todos los resultados se basaron en datos de un reducido número de estudios con pocos participantes. También preocupan los métodos empleados en estos estudios. Por ello, existe una considerable incertidumbre acerca de la fiabilidad de los hallazgos. No es posible establecer conclusiones firmes basadas en esta evidencia. Se necesitan ensayos controlados aleatorizados pertinentes y bien realizados.
Authors' conclusions
Summary of findings
| COGNITIVE REMEDIATION THERAPY + TREATMENT‐AS‐USUAL compared to TREATMENT‐AS‐USUAL (all short‐term) for psychosis in adolescents | ||||||
| Patient or population: Adolescents with psychosis Intervention: COGNITIVE REMEDIATION THERAPY + TREATMENT‐AS USUAL (CRT + TAU) | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with TREATMENT‐AS‐USUAL (TAU) | Risk with COGNITIVE REMEDIATION THERAPY + TREATMENT‐AS‐USUAL (CRT + TAU) | |||||
| Global state: Average endpoint score CGAS (high score = good) | The mean endpoint global state score (CGAS) in the control group was 55.4 + 12.1 | The mean endpoint global state score (CGAS) in the intervention group was 4.9 lower | ‐ | 50 | ⊕⊝⊝⊝ | * data for prespecified outcome of importance: clinically important change (as categorical data) was not reported. |
| Mental state: Average endpoint score PANNS (high score = poor) | The mean endpoint mental state score (PANSS) in the control group was 54.2 + 12.0 | The mean endpoint mental state score (PANSS) in the intervention group was 8.30 higher (0.46 higher to 16.14 higher) | ‐ | 50 | ⊕⊝⊝⊝ | * data for prespecified outcome of importance: clinically important change (as categorical data) was not reported. |
| Cognitive functioning: clinically important change Not attaining normal cognitive function (Memory Digit Span) | Study population | RR 0.58 | 31 | ⊕⊝⊝⊝ | ||
| 1,000 per 1,000 | 580 per 1,000 | |||||
| Global functioning: Average endpoint VABS Score (high score = good) | The mean endpoint VABS score for the control arm was 73.5 + 19.5 | The mean endpoint VABS score for the intervention arm was 5.90 higher (3.03 lower to 14.83 higher) | 50 | ⊕⊝⊝⊝ Very Low 2,3,4,5,6 | * data for prespecified outcome of importance: clinically important change (as categorical data) was not reported. | |
| Adverse events: Clinically important effect | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data for this important outcome. |
| Service use: Hospital admission for any reason | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data for this important outcome. |
| Leaving the study early: For any reason | Study population | RR 0.93 | 91 | ⊕⊝⊝⊝ | ||
| 111 per 1,000 | 103 per 1,000 | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded by one level (the results were imprecise with the estimated change in mean CGAS score and the mean PANSS score had a wide confidence interval). 2 Downgraded by one level (the author reported that the study was a single‐blind study and likely the participants were not blind to the allocation status as the comparator arm was treatment‐as‐usual. This increased the risk of bias of the study findings). 3 Downgraded by one level (binary outcome was unavailable. We therefore employed the mean endpoint CGAS score, PANSS score and Composite Cognitive score as alternative indicators). 4 Downgraded by one level (majority of participants in one of the studies were recruited while they were inpatients. The comparator group was treatment‐as‐usual and the intervention arm was CRT. Therapists, patients and relatives were likely aware of the allocated arm. This design could pose a high risk of bias due to compromise in allocation concealment). 5 Downgraded by one level (data used are from one trial with small sample size). 6 Downgraded by one level (in one of the studies, there were fewer than 50% left the study early following randomisation. The study did not report the details of the intention‐to‐treat analysis). | ||||||
| GROUP PSYCHOSOCIAL THERAPY + TREATMENT‐AS‐USUAL compared to TREATMENT‐AS‐USUAL (all short‐term) for psychosis in adolescents | ||||||
| Patient or population: Adolescents with psychosis | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with TREATMENT‐AS‐USUAL (TAU) | Risk with GROUP PSYCHOSOCIAL THERAPY + TREATMENT‐AS‐USUAL (GPT + TAU) | |||||
| Global state: Mean endpoint score (CGAS, high score = good) | The mean endpoint global state score (CGAS) in the control group was 49.7 + 6.8 | The mean endpoint global state score (CGAS) in the intervention group was 5.1 higher | ‐ | 56 | ⊕⊝⊝⊝ | |
| Mental State: Mean endpoint total score on PANSS (high score = poor) | The mean endpoint score PANSS total score in the control group was 64.3 + 6.7 | The mean endpoint score PANSS total score in the intervention group was 4.1 lower | ‐ | 56 | ⊕⊝⊝⊝ | |
| Cognitive functioning: Attaining normal cognitive functioning ‐ Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on mental state. |
| Global functioning: Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on global functioning. |
| Adverse events: Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on adverse events |
| Service Use: Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on service utilisation. |
| Leaving the study early: For any reason | Study population | RR 0.43 | 56 | ⊕⊝⊝⊝ | ||
| 308 per 1,000 | 132 per 1,000 | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded by one level (the study did not report any details regarding random sequence generation and allocation concealment). 2 Downgraded by one level (the study did not report any details regarding blinding of participants and assessors). 3 Downgraded by one level (the authors have reported attrition in the intervention and control group and the number of participants who left the study early was fewer than 50%. However they have not been clear if the final analysis was done with intention‐to‐treat analysis where the outcome of all young people who were originally randomised were taken into account). 4 Downgraded by one level (binary outcome was unavailable. We therefore used continuous scores on CGAS (Global state) and PANSS (mental state) as an alternative indicator). | ||||||
| STRUCTURAL GROUP THERAPY + TREATMENT‐AS‐USUAL compared to HANDICRAFT GROUP + TREATMENT‐AS‐USUAL (all short‐term) for psychosis in adolescents | ||||||
| Patient or population: Adolescents with psychosis | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with HANDICRAFT GROUP + TREATMENT‐AS‐USUAL (TAU) | Risk with STRUCTURAL GROUP THERAPY + TRAETMENT‐AS‐USUAL (SGT + TAU) | |||||
| Global State: Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on global state. |
| Mental State: Mean endpoint total score on PANSS (high score = poor) | The mean endpoint PANSS score in the control group was 55.61 + 3.5 | The mean endpoint PANSS score in the intervention group was 2.57 lower | ‐ | 48 | ⊕⊝⊝⊝ | |
| Cognitive functioning: Attaining normal cognitive functioning ‐ Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on mental state. |
| Global functioning: Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on global functioning. |
| Adverse events: Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on adverse events. |
| Service Utilisation: Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on service utilisation. |
| Leaving the study early: For any reason | Study population | RR 0.71 | 60 | ⊕⊕⊝⊝ | ||
| 233 per 1,000 | 166 per 1,000 | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded by one level (significant number but fewer than 50% of participants were lost to follow‐up over the course of the trial. No mention of intention‐to‐treat analysis was found in the paper). 2 Downgraded by one level (binary outcome was unavailable. We therefore used continuous scores on PANSS (mental state) as an alternative indicator). 3 Downgraded by one level (data obtained from only one trial that had a small sample size). | ||||||
| COGNITIVE REMEDIATION PROGRAMME + PSYCHOEDUCATIONAL TREATMENT PROGRAMME compared to PSYCHOEDUCATIONAL TREATMENT PROGRAMME (all medium‐term) for psychosis in adolescents | ||||||
| Patient or population: Adolescents with psychosis | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with PSYCHOEDUCATIONALTREATMENT PROGRAMME (PTP) | Risk with COGNITIVE REMEDIATION PROGRAMME + PSYCHOEDUCATIONAL TREATMENT PROGRAMME (CRP + PTP) | |||||
| Global state: Average endpoint score GAS (high score = good) | The mean endpoint global state score (GAS) in the control group was 47.3 + 9.3 | The mean endpoint global state score (GAS) in the intervention group was 1.60 higher (6.48 lower to 9.68 higher) | ‐ | 25 | ⊕⊝⊝⊝ 1, 2, 3, 4 | * Data for prespecified outcome of importance: clinically important change (as categorical data) was not reported. |
| Mental state: Average endpoint score BPRS (high score = poor) | The mean endpoint BPRS scores in the control group was 43.3 + 14.6 | The mean endpoint BPRS scores in the intervention group was 5.40 lower (16.42 lower to 5.62 higher) | ‐ | 25 | ⊕⊝⊝⊝ | * Data for prespecified outcome of importance: clinically important change (as categorical data) was not reported. |
| Cognitive functioning: Mean endpoint score SPAN‐12 (high score = good) | The mean endpoint score on SPAN scores in the control group was 49.7 + 6.1 | The mean endpoint score on SPAN scores in the intervention group was 2.40 higher (2.67 lower to 7.47 higher) | ‐ | 25 | ⊕⊝⊝⊝ | * Data for prespecified outcome of importance: clinically important change (as categorical data) was not reported. |
| Global functioning: Clinically important change ‐ as defined by each of the studies | See comment | See comment | Not estimable | ‐ | See comment | For this comparison: no studies reported useable data on global functioning. |
| Adverse effects: Clinically important adverse effect ‐ as defined by each of the studies | See comment | See comment | Not estimable | ‐ | See comment | For this comparison: no studies reported useable data on adverse events. |
| Service use: Hospital admission for any reason | See comment | See comment | Not estimable | ‐ | See comment | For this comparison: no studies reported useable data for hospital admission. |
| Leaving the study early: For any reason | See comment | See comment | Not estimable | ‐ | See comment | For this comparison: no studies reported data for leaving the study early. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded by one level (allocation concealment and blinding of participants and raters not well explained). 2 Downgraded by one level (the authors analysed various outcome data for variable numbers of participants. Multiple outcome measures were reported but not all measures were completed by all participants. No intention‐to‐treat analysis was conducted and this posed a high risk of bias). 3 Downgraded by one level (the sample size for the studies were small. The estimate of effect was not significant with a relatively wide confidence interval that crossed the line of no effect). 4 Downgraded by one level (binary outcome was unavailable. We, therefore, employed BPRS score and Global State score as an alternative indicator). | ||||||
| COMPUTER‐ASSISTED COGNITIVE REMEDIATION PROGRAMME compared to COMPUTER GAMES (all short‐term) for psychosis in adolescents | ||||||
| Patient or population: Adolescents with psychosis | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with COMPUTER GAMES (CG) | Risk with COMPUTER‐ASSISTED COGNITIVE REMEDIATION PROGRAMME (CACR) | |||||
| Global state: Average endpoint score HoNOSCA (high score = good) | The mean endpoint global state score (HoNOSCA, 8 weeks) in the control group was 16.2 + 6.0 | The mean endpoint global state score (HoNOSCA, 8 weeks) in the intervention group was 2.0higher | ‐ | 32 | ⊕⊕⊝⊝ | * data for prespecified outcome of importance: clinically important change (as categorical data) was not reported. |
| Mental state: Average endpoint score PANNS (high score = poor) | The mean endpoint Mental state score (PANNS, 8 weeks) in the control group was 60.9 + 22.7 | The mean endpoint Mental state score (PANNS, 8 weeks) in the intervention group was 3.7higher | ‐ | 32 | ⊕⊕⊝⊝ | * data for prespecified outcome of importance: clinically important change (as categorical data) was not reported. |
| Cognitive functioning: Average endpoint score RBANS (high score = good) | The mean endpoint score RBANS score (8 weeks) in the control group was 92.3 + 14.4 | The mean endpoint score RBANS score (8 weeks) in the intervention group was 8.7 lower | ‐ | 32 | ⊕⊕⊝⊝ | * data for prespecified outcome of importance: clinically important change (as categorical data) was not reported. |
| Global functioning: Average endpoint score SOFAS (high score = good) | The mean endpoint global functioning score (SOFAS, 8 weeks) in the control group was 52.8 + 10.7 | The mean endpoint global functioning score (SOFAS, 8 weeks) in the intervention group was 0.7 lower | ‐ | 32 | ⊕⊕⊝⊝ | * data for prespecified outcome of importance: clinically important change (as categorical data) was not reported. |
| Adverse events: Clinically important change | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data for this important outcome. |
| Service use: Hospital admission | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data for this important outcome. |
| Leaving the study early: For any reason | Study population | RR 2.33 | 32 | ⊕⊕⊝⊝ | ||
| 71 per 1,000 | 166 per 1,000 | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded by one level (the participants for the intervention and control arm were trained by the same trainer. The sessions for both the groups were conducted in the same setting with the same frequency and duration. So the trainers and the adolescents were not blind to the group status. This confers high risk of bias, as allocation concealment may have been compromised, as the trainer and the adolescents were aware of the allocation status, although the outcome assessors were blind to the allocation status). 2 Downgraded by one level (the sample size of participants randomised was only 24. The magnitude of changes in the mean score of PANSS and HoNOSCA at the endpoint were both small and the confidence intervals were very wide for the mean endpoint scores for both HoNOSCA and BPRS making the results imprecise). 3 Downgraded by one level (the study did not report binary outcomes for mental state or cognitive functions. We therefore used continuous scores on HoNOSCA for global state, RBANS ‐ L (language) scores for cognitive functioning and SOFAS for global functioning as an alternative indicator). 4 Downgraded by one level (significant number but fewer than 50% of participants were lost to follow‐up over the course of the trial). | ||||||
| PSYCHOEDUCATIONAL + MULTIFAMILY TREATMENT compared to NONSTRUCTURED INTERVENTION (all long‐term) for psychosis in adolescents | ||||||
| Patient or population: Adolescents with psychosis | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with NONSTRUCTURED GROUP THERAPY (NSGT) | Risk with PSYCHOEDUCATIONAL + MULTIFAMILY TREATMENT (PE + MFT) | |||||
| Global state: Mean endpoint score CGAS (high score = good) | The mean endpoint global state score on CGAS (104 weeks) in the control group was 70.67 + 13.6 | The mean endpoint global state score on CGAS (104 weeks) in the intervention group was 3.38 higher | ‐ | 49 | ⊕⊝⊝⊝ | |
| Mental State: Mean end point score PANSS ‐ (high score = good) | The mean endpoint mental state score on PANSS (104 weeks) in the control group was 53.58 + 18.23 | The mean endpoint mental state score on PANSS (104 weeks) in the intervention group was 8.23 lower | ‐ | 49 | ⊕⊝⊝⊝ | |
| Cognitive functioning: Attaining normal cognitive functioning ‐ Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on mental state. |
| Global functioning: Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on global functioning. |
| Adverse events: Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on adverse events. |
| Service use: Number of participants needing admission | Study population | RR 0.84 | 49 | ⊕⊕⊝⊝ | ||
| 333 per 1,000 | 280 per 1,000 | |||||
| Leaving the study early: For any reason | Study population | RR 0.52 | 55 | ⊕⊕⊝⊝ | ||
| 143 per 1,000 | 74 per 1,000 | |||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded by one level (therapists were the same for intervention and control groups for each type of clients and were thus not blind to status of the participants increasing the risk of bias). 2 Downgraded by one level (although the study stated that the data were analysed using intention‐to‐treat analysis, it was strictly not the case at the end of two years, increasing the risk of bias). 3 Downgraded by one level (the magnitude of change in the mean score of CGAS at the endpoint was small and the confidence intervals were very wide for the mean endpoint scores for CGAS, making the results imprecise). 4 Downgraded by one level (binary outcome was unavailable. We therefore used continuous scores on CGAS (global state) and PANSS (mental state) as an alternative indicator). | ||||||
Background
Description of the condition
Psychosis is an illness characterised by patients having alterations in thoughts and perceptions as delusions (false beliefs) and hallucinations (seeing or hearing things that others do not see or hear, Griswold 2015). Psychosis in adolescence is a rare but serious illness (Pencer 2005). Patients with psychosis may have positive psychotic symptoms, especially delusions and hallucinations, and typically feature one or many comorbidities, including negative symptoms, mood symptoms, substance use disorders, medical diseases and PTSD (Post Traumatic Stress Disorder) (McGorry 2008). Adolescents with psychosis have difficulties in connecting with reality, may have hallucinations and delusions and deficits in cognitive capacities (Vila 2015). Young people with psychosis may have impairments across several cognitive domains such as processing speed, attention span and verbal memory (Ang 2004, McCarthy 2016). These deficits impact on social and occupational functioning. A large population‐based study from Sweden (Gillberg 1986) on young people aged 13 to 18 years of age has shown that the prevalence of psychosis in adolescents aged 13 years was 0.9 per 10,000 population and was 17.6 per 10,000 population at 18 years of age. However, a later study (Poulton 2000) had suggested a much higher rate of up to 14% population prevalence of psychotic symptoms in 11 year‐old children.
Currently, the concept of psychosis, as recognised by DSM‐V, emphasises that the boundaries between many of the psychotic disorder categories are fluid over the life course (APA 2013). Likewise, in ICD‐11, it has been proposed that various psychotic disorders be classified under sections titled "schizophrenia spectrum and other primary psychotic disorders", "disorders due to substance use or addictive behaviours" and "secondary mental or behavioural syndromes associated with disorders or diseases classified elsewhere" (Gaebel 2012). Although not always clear at the outset, these psychotic symptoms in adolescents may be part of a serious illness like schizophrenia, psychotic affective disorders, or be more transient in nature such as substance‐induced psychosis (McGorry 2008; Werry 1991).
Schizophrenia is a neurodevelopmental disorder (Owen 2011) which often has its onset during adolescence (Ballageer 2005). The DSM‐V criterion FOR schizophrenia includes the presence of two or more of the symptoms of delusions, hallucinations, disorganised speech, grossly disorganised behaviour and negative symptoms for a minimum period of one month, associated with impairment in one of the major areas of functioning and some signs of the disorder lasting for a continuous period of at least six months (APA 2013). Onset OF schizophrenia between the ages of 13 to 17 years is known as adolescent‐onset schizophrenia (Hollis 2000a; Werry 1992). The criteria for diagnosing schizophrenia in the adolescent age group are similar to the criteria used for adults with schizophrenia using ICD‐10 (International Classification of Diseases, 10th Revision) (WHO 1992) and DSM‐V (APA 2013). People with adolescent‐onset schizophrenia OFTEN have more affective symptoms and increased behaviour problems (Werry 1991), and may have a more severe and unremitting course with poorer outcome than adult‐onset schizophrenia (Hollis 2000b). However, at times, there may be difficulties in differentiating juvenile‐onset bipolar disorder from non‐affective psychosis (Singh 2014). Understandably, there is reticence among clinicians to make a formal diagnosis of schizophrenia in many cases, despite the reduced likelihood of a full or prolonged remission following first‐episode psychosis (Hollis 2000b).
Juvenile‐onset affective disorder may be associated with mood‐congruent psychotic symptoms. Psychotic symptoms are common in adolescents with mood disorders (Algon 2012). As many as 16 to 87.5% of young people with bipolar disorder and 4% of young people with major depressive disorder have reported coexisting psychotic symptoms (Pavuluri 2004; Ulloa 2000). It is important to recognise psychotic symptoms in affective disorders in adolescents, as they may have poorer prognoses than those who have an affective disorder without psychotic symptoms (McCarthy 2014).
Use of alcohol and Illicit drugs is not uncommon in adolescents and young people (Miller 1996). Psychosis in adolescents is often associated with cannabis and other illicit drug use (Schubart 2010; Zammit 2010). Rates of substance misuse among young people with first‐episode psychosis range from 25 to 60% (Compton 2011; Tucker 2009). A typical drug‐induced psychosis often remits following abstinence from the illicit drug (Caton 2005). Because of the severity of the psychotic symptoms, treatment for these young people often requires additional antipsychotic medications as well as psychological therapies (Driver 2013; Imran 2011). However, cannabis use by the age of 15 years can be associated with increased risk of psychosis in adult life as well (Arseneault 2004).
It must be noted that 'childhood‐onset' (APA 2013) or 'very early onset' schizophrenia, that is, schizophrenia occurring below the age of 13, is extremely rare and will not be considered directly here. Childhood‐onset schizophrenia has been reviewed separately by some of the authors of the current review (Kennedy 2007; Kennedy 2007a).
Late adolescence is a critical period in brain development and this may make this age group particularly vulnerable to onset of schizophrenia (Gogtay 2011; Rapoport 2011). There needs to be well developed evidence‐based treatment protocols for the adolescents with psychosis (Kline 2015). Psychiatric assessment of adolescents requires the clinician to obtain a longitudinal clinical history from the caregivers as well as the young person and also conduct a detailed mental state examination (King 1997).The point of intervening appropriately for adolescents with psychosis is to delay or prevent the onset of schizophrenia and other chronic severe mental illnesses, reduce psychological distress, provide symptom relief and reduce the incidence of high risk behaviours as completed suicide, self harm, posing harm to others and, by all this, foster a good therapeutic relationship with clinical teams early on in life (Marshall 2011). Possible treatment options for adolescents with psychosis include medications, psychological treatments and social rehabilitation.
Description of the intervention
Psychological interventions include a wide range of treatment which can be administered on an individual or group basis that aim to modify behaviour, emotions or feelings (Ballou 1995). The National Institute of Health and Clinical Excellence (NICE) Guidelines recommends the use of psychological interventions in routine care of young people with psychosis and schizophrenia (NICE 2013). The recommendations include guidelines for managing transient or attenuated psychotic symptoms, first‐episode psychosis, subsequent acute episodes of psychosis or schizophrenia, managing crisis situations, early post‐acute period and facilitating recovery of a young person with psychosis. The importanceof psychological interventions has been mentioned several times in the NICE guidelines which discuss the role of CBT (cognitive behaviour therapy) and family‐based interventions in young people with psychosis, taking into consideration preferences of the patients and their families. A recent audit of mental health teams for adults in the UK showed that there was a positive attitude towards using psychological therapies (Prytys 2011).
In a review on early psychosis, Haddock 2005 mentions the focus of psychological interventions could be: a) interventions focussing on the prodromal or 'high‐risk' phase of early psychosis, where the individual does not have 'full‐blown' psychotic symptoms and the person does not meet the criteria for a psychotic illness; b) interventions focussing on the period of first‐episode psychosis when the individual has definite psychotic symptoms; c) interventions focussing on recovery from first‐episode psychosis; d) interventions addressing comorbid symptoms and issues associated with first‐episode psychosis as substance misuse, affective symptoms, etc. The current review will cover the latter three groups relevant to adolescents with established psychosis.
i. Cognitive Remediation Therapy (CRT), individual or computer‐assisted
Studies on Cognitive Remediation Therapy (CRT) or Cognitive Remediation Therapy Programme (CRP) have focussed on improving cognitive symptoms and functioning (Frazier 2012a; Kline 2015). The goal of this treatment is to improve cognitive functioning in specific domains such as processing speed, verbal memory and other cognitive domains and, in doing so, also improve the person's social and occupational functioning. In keeping with the increasing use of technology, computer‐assisted cognitive remediation therapy through the use of mobile devices has been tested in the delivery of CRT (Baum 2006).
ii. Cognitive Behaviour therapy (CBT), individual or group
Cognitive Behaviour Therapy (CBT) incorporates principles of behaviour modification and cognitive techniques to challenge maladaptive thinking. CBT has been used for a variety of psychiatric diagnoses in adolescents (Stallard 2005) and adults (Hawton 1989; Kuipers 1997).Cognitive Behaviour Therapy (CBT) for psychosis addresses positive psychotic symptoms such as hallucinations or delusions, negative symptoms such as apathy, avolition or amotivation and re‐training executive functions (Morrison 2010). CBT may also address comorbid affective symptoms and substance misuse problems. CBT can be offered to individuals or groups.
iii. Family‐based interventions
Family‐based interventions focus on reducing expressed emotions and improving acceptance of the illness by the family members of the patient. In family therapy, the therapist addresses the family as a unit. During systemic family therapy, relationships between family members are assessed and reducing expressed emotions of close family members towards the patient was shown to reduce the possibility of relapse of psychosis (Leff 1989). Understanding the systems and subsystems of the family helps the family to change for the better (Barker 2013). Family therapy aims to encourage open communication, partnership and collaboration among family members. Family therapy has been undertaken in outpatients and inpatients (Glick 1993). It has been used for adults with schizophrenia (Kuipers 2002) and adolescents with psychosis (Kline 2015). It is usually delivered over five to six weekly sessions (Barker 2013).
iv. Adherence‐improvement therapy
Treatment‐adherence therapies mainly try to improve insight and, in addition, may use behavioural approaches to improve adherence to medications and engagement with services. Adherence to medications, regular clinical reviews, monitoring and reporting of side effects of treatments and psychological interventions are all likely to impact the overall outcome of young people with psychosis (Gearing 2005). Nonadherence to treatment is a major clinical problem for young people on long‐term medications (Salema 2011). Adherence‐improvement therapy usually has an educational component that may be delivered in face‐to‐face therapy sessions, through printed educational material, showing videos or any other medium of communication (Gearing 2005). Some therapists have tried to improve adherence by empowering young people to participate more actively in their disease management, increasing social support through peers, providing incentives for behaviour change, and improving the acceptability of treatment (Salema 2011).
v. Psychoeducation
Psychoeducation involves didactic skilful communication of key information about a disorder with the patient and their family in order to empower patients to be knowledgeable and engaged with the larger treatment programme. The process of psychoeducation involves educating patients and their family members and answering questions that they may have about the illness. The patient and family is given information on treatment adherence and other topics such as aetiology of the illness, that are crucial in engagement and recovery of a young person with psychosis (Gearing 2008). Timely and well balanced psychoeducation reduces the possibility of relapse of psychosis and is likely to improve coping of the adult patients with schizophrenia and their family (Pitschel‐Walz 2001). Psychoeducation can be delivered as part of an office‐based family therapy or in a multi‐group family setting for adolescents and be part of a therapy following a cognitive behavioural therapy paradigm (Baum 2006; Ruffolo 2005).
vi. Group therapy
In group psychotherapy, one or more therapists treat a group of patients together following the principles of CBT, behaviour therapy (such as relaxation training and social skills training), psychoeducation in groups or any other acceptable psychological technique that has been used successfully in a group setting. Group therapy involves one or more therapists seeing a small number of patients in a group. Literature has highlighted the therapeutic value of group processes over and above client‐therapist interactions in a group therapy setting (Yalom 2005). Groups can be run by trained therapists in line with CBT, psychodynamic or other paradigms. They could be open or closed groups where new membership is restricted once the group work has begun. Groups often meet in the presence of a therapist at scheduled intervals over the course of a few months. Group therapy has been used for a variety of problems in adults with psychosis (Gumley 2016).
Delivery of psychological therapy need to standardised in terms of: a) therapy quality (the extent to which the therapy was delivered well enough) and b) therapist competence (capacity of the therapist to deliver treatment in terms of knowledge and skills, Fairburn 2011). The above therapies were compared with each other or with standard care.
How the intervention might work
There is robust evidence to show that psychosis has a bio‐psycho‐social basis (Henquet 2008; Thewissen 2011). Psychological therapies, in the form of supportive counselling make the treatment programme patient‐centred (Gondek 2017). Psychological interventions for psychosis almost always have a component of psychoeducation, that empowers the patient and their caregivers to understand the illness better, help the young person engage with the treating team more meaningfully, ensure safety and likely improve medication adherence (Kline 2015).
It has been hypothesised that CBT in adults with depression produces new learning through synaptogenesis (formation of connections between various neurons) (Goldapple 2004, Yang 2014). There may be a similar mechanism of action resulting in possible brain changes following psychological therapy in adolescents with psychosis. The underlying premise of CBT is that thoughts and behaviours are related and can be rationally challenged. It may be acceptable to certain young people who are in a stage of life where they are trying to explain their worldly experiences logically. Cognitive remediation therapy and cognitive behavioural therapy aim to improve cognitive and adaptive functioning and maybe particularly suitable in adolescents who may have more neuronal plasticity and are earlier in the course of illness progression.
Family is the most important source of support for the young person and it is crucial that the family members understand the nature of the illness. Family therapy helps in aiming to improve the functioning of the family as a whole including that of the young person (Leff 1989).
In group therapy, the 11 therapeutic factors emphasised by Yalom (Yalom 2005) that influence change and healing include, amongst others, universality (group members realising they are not alone in their problems), altruism (gaining a sense of value by helping other group members), corrective recapitulation (resolution of family and childhood conflicts within the safety of the group family), socialising techniques (learning tolerance, empathy and interpersonal skills), group cohesiveness (developing a sense of acceptance and belonging) and catharsis (releasing suppressed emotions by disclosing information to group members). We have thus classified group therapy separately from individual therapy.
Psychological therapies, as part of a broader programme, that focus on vocational training are likely to reduce stigma and help the person to training or employment. Thus psychological interventions for adolescents may act through a number of different mechanisms.
Why it is important to do this review
In the last 20 years, there has been considerable research on psychological interventions for adults with psychosis. As a large proportion of adults with psychotic illnesses have their onset in adolescence, it is crucial to review the evidence of psychological interventions in adolescents. Intervening during adolescence may help to prevent the onset of more serious enduring mental disorders that persist life‐long, reduce acute psychological distress, reduce stigma, reduce high risk behaviours and foster a better therapeutic alliance with mental health services.
Schizophrenia is a neurodevelopmental disorder and it is important that any psychological treatments delivered are effective for the target age group, be they children or adults. What works with adults may not do so with children or adolescents. This review aims to evaluate available evidence and gaps in current research on psychological interventions for adolescents with psychosis.
Objectives
To assess the effects of various psychological interventions for adolescents with psychosis. See Differences between protocol and review.
Methods
Criteria for considering studies for this review
Types of studies
All relevant randomised controlled trials related to psychological interventions for adolescents with psychosis. If a trial was described as a 'double‐blind' trial but implied randomisation, we included such trials in the sensitivity analysis (see Sensitivity analysis). If the inclusion of such trials did not result in a substantive difference, they remained in the analyses. However, If including such trials did not result in statistically significant differences, we did not add the data from these lower quality studies to the results of the better trials, but presented such data within a subcategory. Quasi‐randomised studies were excluded, such as those allocating by alternate days of the week. In trials where people are given additional treatments within a psychological intervention trial, data were included only if the adjunct treatment was evenly distributed between groups and only the psychological intervention was randomised.
Types of participants
Studies with adolescent participants, aged 13 years to 17 years, with a diagnosis of any form of psychosis including acute psychosis, schizophrenia or related disorders, including schizophreniform disorder, schizoaffective disorder, delusional disorder and affective psychosis were included if they met the criteria set by the review group. In trials that recruited adolescents as well as adults, data for adolescents only were included if found to be available. Complete trial data were used only if 75% or more of the participants were within the age group of 13 to 17 years. The review has excluded studies that were only on prodromal psychosis. However, it included studies that had a mixed group of young people with a variety of psychosis such as affective psychosis, schizophrenia and others. The review was restricted to young people older than 13 years as it is extremely rare for children younger than 13 years of age to develop psychosis and this is covered in a separate review (Kennedy 2007; Kennedy 2007a).
Types of interventions
1. Psychological interventions for adolescents with psychosis
Psychological interventions are defined as any psychological intervention, whether group or individual, aimed at either reducing symptoms or enhancing social and individual functioning. The psychological interventions needed to be standardised and replicable and delivered by trained therapists in a well‐structured care programme. The psychological interventions were categorised as follows:
i. Cognitive Remediation Therapy (individual CRT or computer‐assisted CRT)
ii. Cognitive Behaviour Therapy (CBT)
iii. Family‐based interventions
iv. Adherence‐improvement therapy
v. Psychoeducation
vi. Group therapy of any modality
2. The control treatment
(a) Absolute effect of psychological interventions: control treatment was defined as standard care without a dedicated programme of type described above.
(b) Relative effect of psychological interventions: some studies used the comparator arm of one of the above modalities of psychological treatments. In other words, they compared one form of psychological treatment with another.
Types of outcome measures
We divided outcomes into short‐term (less than six months), medium‐term (seven to 12 months) and long‐term (more than one year).
Primary outcomes
1. Global state
1.1 Clinically important change ‐ as defined by each of the studies
1.2 Relapse
2. Mental state
2.1 Clinically important change in psychotic symptoms ‐ as defined by each of the studies
2.2 Clinically important change in mood symptoms ‐ as defined by each of the studies
3. Cognitive functioning
3.1 Clinically important change ‐ as defined by each of the studies
3. Global functioning
3.1 Clinically important change ‐ as defined by each of the studies
4. Adverse effects
4.1 Clinically important adverse effects ‐ as defined by each of the studies
5. Service use
5.1 Hospital admission ‐ as defined by each of the studies
Secondary outcomes
1. Global state
1.1 Any change in global state ‐ as defined by each of the studies
1.2 Average endpoint/change score on global state scale
2. Mental state
2.1 Any change in mental state ‐ as defined by each of the studies
2.2 Average endpoint/change score on mental state scale
3. Cognitive functioning
2.2 Any change in cognitive symptoms ‐ as defined by each of the studies
2.3 Average endpoint/change score on cognitive function scale
4. Global functioning
4.1 Any change in global functioning ‐ as defined by each of the studies
4.2 Average endpoint/change score on global functioning scale
5. Social functioning
5.1 Average endpoint/change score on social skills scale
5.2 Educational status/occupational status
5.3 Compliance with (a) drug treatment and (b) other non‐drug treatments
6. Adverse effects/events
6.1 Death, suicide or natural causes
6.2 Attempted suicide, suicidality or self harm
6.4 Incidence of clinically important depression/anxiety
6.5 Change in drug/alcohol use
6.6 General adverse effects
6.7 Specific adverse effects
6.8 Average endpoint or change score on adverse effects scale
7. Service use
7.1 Days in hospital
8. Economic outcomes
9. Quality of life/satisfaction with care for either recipients of care or carers
9.1 Clinically important change in quality of life/satisfaction ‐ as defined by each of the studies
9.2 General impression of carer/other
9.3 Average endpoint/change score in quality of life/satisfaction
10. Leaving the study early
10.1 For any reason
10.2 For specific reason
'Summary of findings' table
The GRADE approach was used to interpret findings (Schünemann 2008) and we exported data from our review using GRADEpro to create a 'Summary of findings' table for each comparison. These tables provided outcome‐specific information concerning the overall quality of evidence from each of the included studies in the comparison and the magnitude of effect of the interventions examined. We considered the sum of available data on all outcomes were important to patient‐care and decision‐making. We aimed to include the following main outcomes in the 'Summary of findings' table (see Differences between protocol and review):
-
Global state: clinically important change ‐ as defined by each of the studies
-
Mental state: clinically important change ‐ as defined by each of the studies
-
Cognitive functioning: clinically important change ‐ as defined by each of the studies
-
Global functioning: clinically important change ‐ as defined by each of the studies
-
Adverse effects: clinically important adverse effect ‐ as defined by each of the studies
-
Service use: hospital admission
-
Leaving the study early ‐ for any reason
If data were not available for our preferred outcomes but available for ones that were similar, we presented the closest outcome to the prespecified one in the table but took this into account when grading the finding.
Search methods for identification of studies
Electronic searches
Cochrane Schizophrenia Group’s Study‐Based Register of Trials
On 31 May 2016 and 8 March 2019, the information specialist searched the register using the following search strategy:
((*Child* OR *Adolescent*) in Participants) AND (*Psychological Intervention* in Intervention) of STUDY
In such a study‐based register, searching the major concept retrieves all the synonyms and relevant studies because all the studies have already been organised based on their interventions and linked to the relevant topics (Shokraneh 2017).
This register is compiled by systematic searches of major resources (AMED, BIOSIS, CENTRAL, CINAHL, ClinicalTrials.Gov, Embase, ISRCTN, MEDLINE, PsycINFO, PubMed, WHO ICTRP) and their monthly updates, ProQuest Dissertations and Theses A&I and its quarterly update, Chinese databases (CBM, CNKI, and Wanfang) and their annual updates, handsearches, grey literature, and conference proceedings (see Group's website). There is no language, date, document type, or publication status limitations for inclusion of records into the register.
For previous searches, please see Appendix 1.
Searching other resources
1. Reference searching
References of all identified included studies were inspected for further relevant studies.
2. Personal contact
The first author of each included study was contacted for further information regarding unpublished trials.
Data collection and analysis
Selection of studies
SD and RD independently inspected citations from the searches and identified relevant abstracts. AK also independently reinspected a random 20% sample to ensure reliability. Full reports of the abstracts meeting the review criteria were obtained. References/abstracts that the review authors disagreed on were further inspected by AK. Again, AK reinspected a random 20% of reports in order to ensure a reliable selection was made. Where it was not possible to resolve disagreements by discussion, reviewers attempted to contact the authors of the study for further clarifications.
Data extraction and management
1. Extraction
SD and RD extracted data from all included studies. In addition, to ensure reliability, AK independently extracted data from a random sample of these studies, comprising 10% of the total. Again, any disagreements that arose were discussed, decisions were documented and, if necessary, authors of studies were contacted for clarifications. With remaining problems, AK helped to clarify issues and final decisions were recorded. Wherever possible, data extracted from the trials were presented only in graphs and figures, and were included only if two authors independently reached the same result. Attempts were made to contact authors through open‐ended requests in order to obtain missing information or for clarification, whenever necessary. If studies were multi‐centre trials, where possible, data extraction was carried out relevant to each component centre separately.
2. Management
2.1 Forms
Data extraction was done onto standard simple forms.
2.2 Scale‐derived data
Continuous data from rating scales were included only if:
a. the psychometric properties of the measuring instrument were described in a peer‐reviewed journal (Marshall 2000); and
b. the measuring instrument was not written or modified by one of the trialists for that particular trial. Ideally, the measuring instrument was: i. a self‐report or ii. completed by an independent rater or relative (not the therapist). Since this was not often reported clearly, it has been mentioned in the Description of Studies if this was the case or not.
2.3 Endpoint versus change data
There are advantages of both endpoint and change data. Change data is known to remove a component of between‐person variability from the analysis. On the other hand, calculation of change needed two assessments (baseline and endpoint), which can be difficult in unstable and difficult to measure conditions such as schizophrenia. Primarily in this review, endpoint data have been used, and change data have only been used if the former was unavailable. Endpoint and change data were combined in the analysis as mean differences (MDs) were used rather than standardised mean differences throughout (Higgins 2011).
2.4 Skewed data
Continuous data on clinical and social outcomes were often not normally distributed. To avoid the pitfall of applying parametric tests to nonparametric data, reviewers aimed at applying the following standards to all data before inclusion: a) standard deviations and means were reported in the paper or obtained from the authors; b) when the scale started from the finite number zero, the standard deviation, when multiplied by two, was less than the mean (as otherwise the mean is unlikely to be an appropriate measure of the centre of the distribution (Altman 1996)); c) if a scale started from a positive value (such as PANSS (Positive and Negative Syndrome Scale) which can have values from 30 to 210), the calculation described above was modified to take the scale starting point into account. In these cases, skew was considered to be present if 2SD > (S ‐ S min), where S is the mean score and S min is the minimum score. Endpoint scores on scales often had a finite start and endpoint and these rules could be applied. When continuous data were presented on a scale that included a possibility of negative values (such as change data), it is difficult to tell whether data are skewed or not. Skewed data from studies were entered for fewer than 200 participants in additional tables rather than into an analysis. Skewed data posed less of a problem for looking at means if the sample size was large, and these we entered these into the syntheses.
2.5 Common measure
To facilitate comparison between trials, reviewers converted variables that were reported in different metrics, such as days in hospital (mean days per year, per week or per month) to a common metric (e.g. mean days per month).
2.6 Conversion of continuous to binary
Wherever possible, outcome measures were converted to dichotomous data. This was done by identifying cut‐off points on rating scales and dividing participants accordingly into 'clinically improved' or 'not clinically improved'. It was assumed that if there was a 50% reduction in a scale‐derived score such as in the Brief Psychiatric Rating Scale (BPRS, Overall 1962) or the Positive and Negative Syndrome Scale (PANSS, Kay 1986), this could be considered as a clinically significant response (Leucht 2005; Leucht 2005a). If data based on these thresholds were not available, the primary cut‐off presented by the original authors was used.
2.7 Direction of graphs
Where possible, data were entered in such a way that the area to the left of the line of no effect indicated a favourable outcome for psychological interventions for psychosis in adolescents. Where keeping to this made it impossible to avoid outcome titles with clumsy double‐negatives (e.g. 'Not improved'), data where the left of the line indicated an unfavourable outcome were reported. This was noted in the relevant graphs.
Assessment of risk of bias in included studies
Again SD and RD worked independently to assess risk of bias by using the criteria described in the Cochrane Handbook of Systematic Reviews of Interventions (Higgins 2011) to assess quality of the trials. This set of criteria is based on evidence of associations between an overestimate of effect and high risk of bias of the article such as sequence generation, allocation concealment, blinding, incomplete outcome data and selective reporting.
If raters disagreed, the final rating was made by consensus, with the involvement of another member of the review group (AK). Where inadequate details of randomisation and other characteristics of trials were found, authors of the studies were contacted in order to obtain further information. Nonconcurrence in quality assessment was reported, and if disputes arose as to which category a trial was to be allocated, again, resolution was sought by discussion.
The level of risk of bias was noted in both the text of the review and in the 'Summary of findings' table 1.
Measures of treatment effect
1. Binary data
For binary outcomes, a standard estimation of the risk ratio (RR) and its 95% confidence interval (CI) was calculated. It has been shown that RR is more intuitive (Boissel 1999) than odds ratios and that odds ratios tend to be interpreted as RRs by clinicians (Deeks 2000).
2. Continuous data
For continuous outcomes, mean difference (MD) between groups was estimated. Reviewers preferred not to calculate the effect size measures of standardised mean difference (SMD). However, if scales of very considerable similarity were found to be used, it was presumed that there was a small difference in measurement, and effect size was calculated and transformed back to the units of one or more of the specific instruments.
Unit of analysis issues
1. Cluster trials
Studies increasingly employ 'cluster randomisation' (such as randomisation by clinician or practice) but analysis and pooling of clustered data pose problems. Firstly, authors often fail to account for intra‐class correlation in clustered studies, leading to a 'unit of analysis' error (Divine 1992) whereby P values are spuriously low and CIs with unduly narrow and statistical significance are overestimated. This causes type I errors (Bland 1997; Gulliford 1999).
Where clustering is not accounted for in primary studies, we planned to present data in a table, with a (*) symbol to indicate the presence of a probable unit of analysis error. In subsequent versions of this review, we will seek to contact first authors of studies to obtain intra‐class correlation coefficients for their clustered data and to adjust for this by using accepted methods (Gulliford 1999). Where clustering has been incorporated into the analysis of primary studies, we planned to present these data as if from a non‐cluster‐randomised study, but adjust for the clustering effect.
Reviewers sought statistical advice and were advised that the binary data as presented in a report was to be divided by a 'design effect'. This was calculated using the mean number of participants per cluster (m) and the intra‐class correlation coefficient (ICC) [Design effect = 1 + (m ‐ 1) * ICC] (Donner 2002). If the ICC was not reported, it was assumed to be 0.1 (Ukoumunne 1999). If cluster studies were appropriately analysed, taking into account intra‐class correlation coefficients and relevant data documented in the report, synthesis with other studies was possible using the generic inverse variance technique.
2. Cross‐over trials
A major concern of cross‐over trials was the carry‐over effect. It occurs if an effect (e.g. pharmacological, physiological or psychological) of the treatment in the first phase of a trail is carried over to the second phase of the trial. As a consequence, on entry into the second phase, the participants may differ systematically from their initial state despite a wash‐out phase. For the same reason, cross‐over trials are not appropriate if the condition of interest is unstable (Elbourne 2002). As both effects are very likely in severe mental illness, only data of the first phase of cross‐over studies was used in this review.
3. Studies with multiple treatment groups
Where a study involved more than two treatment arms, if relevant, additional treatment arms in comparisons were presented. If data were binary, they were simply added and combined within a two‐by‐two table. If data were continuous data, they were combined following the formula in section 7.7.3.8 (Combining groups) of the Handbook. Where the additional treatment arms were found to be not relevant, these data were not reproduced.
Dealing with missing data
1. Overall loss of credibility
At some degree of loss of follow‐up, data must lose credibility (Xia 2009). Reviewers chose that, for any particular outcome, should more than 50% of data be unaccounted for, these data were not reproduced or used within the analyses, except for the outcome of leaving the study early. If, however, more than 50% of those in one arm of a study were lost, but the total loss was less than 50%, such data were marked with (*) to indicate that such a result may well be prone to bias.
2. Binary
In the case where attrition for a binary outcome was between 0 and 50% and where these data were not clearly described, data were presented on a 'once‐randomised‐always‐analysed' basis (an intention‐to‐treat analysis). Those who left the study early were all assumed to have the same rates of negative outcome as those who completed, with the exception of the outcome of death and other adverse effects. For those outcomes, the rate of those who stayed in the study ‐ in that particular arm of the trial ‐ was used for those who did not. We undertook a sensitivity analysis to test how prone the primary outcomes were to change when 'completer' data only were compared to the intention‐to‐treat analysis using the above assumptions.
3. Continuous
3.1 Attrition
In the case where attrition for a continuous outcome was between 0 and 50% and completer‐only data were reported, data were reproduced.
3.2 Standard deviations
If the standard deviations were not reported, reviewers first tried to obtain the missing values from the authors. If not available, where there were missing measures of variance for continuous data, but an exact standard error and confidence intervals were available for group means, and either the P value or T value was available for differences in the mean, it was calculated according to the rules described in the Handbook (Higgins 2011). When only the standard error (SE) was reported, standard deviations (SDs) were calculated by the formula SD = SE * square root (n). Chapters 7.7.3 and 16.1.3 of the Handbook (Higgins 2011) present detailed formula for estimating SDs from P values, T or F values, confidence intervals, ranges or other statistics. If these formulas did not apply, we calculated the SDs according to a validated imputation method which was based on the SDs of the other included studies (Furukawa 2006). Although some of these imputation strategies can introduce error, the alternative was to exclude a given study’s outcome and thus to lose information. Nevertheless, the validity of the imputations was examined in a sensitivity analysis excluding imputed values.
3.3 Last observation carried forward
Reviewers anticipated that, in some studies, the method of last‐observation‐carried‐forward (LOCF) would be employed within the study report. As with all methods of imputation to deal with missing data, LOCF introduces uncertainty about the reliability of the results (Leucht 2007). Therefore, where LOCF data were used in the trial, if fewer than 50% of the data were assumed, these data were reproduced and it was indicated that they were the product of LOCF assumptions.
Assessment of heterogeneity
1. Clinical heterogeneity
All included studies were initially taken into consideration, without seeing comparison data, to judge clinical heterogeneity. All studies were simply inspected for clearly outlying people or situations which were not predicted would arise. When such situations or participant groups arose, these were fully discussed.
2. Methodological heterogeneity
All included studies were initially taken into consideration, without seeing comparison data, to judge methodological heterogeneity. All studies were simply inspected for clearly outlying people or situations which were not predicted would arise. When such methodological outliers arose, these were fully discussed.
3. Statistical heterogeneity
3.1 Visual inspection
Graphs were visually inspected to investigate the possibility of statistical heterogeneity.
3.2 Employing the I2 statistic
Heterogeneity between studies was investigated by considering the I2 method alongside the Chi2 P value. The I2 provided an estimate of the percentage of inconsistency thought to be due to chance (Higgins 2003). The importance of the observed value of I2 depends on: i. magnitude and direction of effects and ii. strength of evidence for heterogeneity (e.g. P value from Chi2 test, or a confidence interval for I2). An I2 estimate which was greater than or equal to around 50% accompanied by a statistically significant Chi2 statistic, was interpreted as evidence of substantial levels of heterogeneity (Section 9.5.2 ‐ Higgins 2011). When substantial levels of heterogeneity were found for the primary outcome, reasons for heterogeneity were explored (Subgroup analysis and investigation of heterogeneity).
Assessment of reporting biases
1. Protocol versus full study
Reporting biases arise when the dissemination of research findings is influenced by the nature and direction of results. These are described in section 10.1 of the Handbook (Higgins 2011). Reviewers attempted to locate protocols of included randomised trials. If the protocol was available, outcomes in the protocol and in the published report were compared. If the protocol was not available, outcomes listed in the methods section of the trial report were compared with actually reported outcome results.
2. Funnel plot
Reporting biases arise when the dissemination of research findings is influenced by the nature and direction of results (Egger 1997). These are described in Section 10 of the Handbook (Higgins 2011). Reviewers were aware that funnel plots may be useful in investigating reporting biases but they are of limited power to detect small‐study effects. Funnel plots for outcomes where there were ten or fewer studies, or where all studies were of similar sizes were therefore not used. In other cases, where funnel plots were possible, statistical advice in their interpretation was sought.
Data synthesis
We understand that there is no closed argument for preference for use of fixed‐effect or random‐effects models. The random‐effects method incorporates an assumption that the different studies were estimating different, yet related, intervention effects. This often seemed to be true to us and the random‐effects model took into account differences between studies even if there was no statistically significant heterogeneity. There was, however, a disadvantage to the random‐effects model: it put added weight onto small studies which often were the most biased ones. Depending on the direction of effect, these studies could either inflate or deflate the effect size. Reviewers chose random‐effects model for all analyses. The reader is, however, able to choose to inspect the data using the fixed‐effects model.
Subgroup analysis and investigation of heterogeneity
1. Subgroup analyses ‐ only primary outcomes
1.1 Cognitive remediation therapy versus standard care
Subgroup analyses investigating 'cognitive remediation therapy' and standard care were anticipated. We had undertaken to analyse the data for this comparison and have presented it in the Results section.
1.2 Clinical state, stage or problem
We had proposed to undertake this review and provide an overview of the effects of psychological interventions for adolescents with psychosis. In addition, however, if there were data on subgroups of people in the same clinical state, stage and with similar problems, we would have reported this separately. Only one study (Koren 2015) had provided some information on the stage of illness but the data were too sparse to be used meaningfully.
2. Investigation of heterogeneity
If inconsistency was found to be high, it was reported. First, reviewers investigated whether data were correctly reported. Second, if data were correct, the graphs were visually inspected and studies were successively removed outside of the company of the rest to see if heterogeneity was restored. For this review, it was decided that should this occur with data contributing to the summary finding of no more than around 10% of the total weighting, data would be presented. If not, data were not pooled and issues were discussed. We know of no supporting research for this 10% cut‐off but are investigating use of prediction intervals as an alternative to this unsatisfactory state. When unanticipated clinical or methodological heterogeneity was obvious, the hypotheses regarding this for future reviews or versions of this review were simply stated. Reviewers did not anticipate undertaking analyses relating to these.
Sensitivity analysis
1. Implication of randomisation
Reviewers aimed to include trials in a sensitivity analysis if they were described in some way as to imply randomisation. For the primary outcomes, these studies were included and if there was no substantive difference when the implied randomised studies were added to those with better description of randomisation, then all data from these studies were employed.
2. Assumptions for lost binary data
Where assumptions had to be made regarding people lost to follow‐up (see Dealing with missing data), the findings of the primary outcomes were compared when we used our assumption compared with completer data only. If there was a substantial difference, it was reported and discussed, but reviewers continued to employ the assumption.
Where assumptions had to be made regarding missing SD data (see Dealing with missing data), findings on primary outcomes were compared when reviewers used the assumption compared with complete data only. A sensitivity analysis was undertaken testing how prone results were to change when 'completer' data only were compared to the imputed data using the above assumption. If there was a substantial difference, it was reported and discussed, but reviewers continued to employ the assumption.
3. Risk of bias
Reviewers analysed the effects of excluding trials that were judged to be at high risk of bias across one or more of the domains of randomisation (implied as randomised with no further details available), allocation concealment, blinding and outcome reporting for the meta‐analysis of the primary outcome. If the exclusion of trials at high risk of bias did not substantially alter the direction of effect or the precision of the effect estimates, data from these trials were included in the analysis.
4. Imputed values
A sensitivity analysis was undertaken to assess the effects of including data from trials where imputed values for ICC were used in calculating the design effect in cluster‐randomised trials.
If substantial differences were noted in the direction or precision of effect estimates in any of the sensitivity analyses listed above, the data were not pooled from the excluded trials with the other trials contributing to the outcome, but were presented separately.
5. Fixed‐effect and random‐effects
All data were synthesised using a random‐effects model; however, reviewers also synthesised data for the primary outcome using a fixed‐effect model to evaluate whether the greater weights assigned to larger trials with greater event rates altered the significance of the results compared to the more evenly distributed weights in the random‐effects model.
Results
Description of studies
For detailed description of included studies, excluded studies and those that are ongoing studies please see: Characteristics of included studies; Characteristics of excluded studies; Characteristics of ongoing studies.
Results of the search
The systematic search identified 3573 references. Duplicates were scrutinised and removed. There were 3483 unique reports. The 3483 reports were screened for inclusion by reviewing the titles and abstracts, and 3279 records were excluded. Two hundred and four full‐text articles were reviewed for eligibility. There were 13 ongoing studies that will be considered for future versions of this review. Seven studies, with 27 references, fulfilled our predetermined inclusion criteria and were included in the quantitative meta‐analysis. The results of the search are shown in the PRISMA table (Figure 1).
Study flow diagram.
Included studies
Seven studies met the inclusion criteria (Calvo 2014; Holzer 2014; Koren 2015; Puig 2014; She 2016; Ueland 2004; Wykes 2007). Ueland 2004 published medium‐term data of a follow‐up duration of one year that were included in the analysis. Calvo 2014 had longer term follow‐up data published separately. The data from the longer term two‐year follow‐up Calvo 2014 were included in the analysis.
1. Length of trials
1.1. Short‐term (up to six months)
Five of the seven studies reported short‐term outcomes (up to six months). She 2016 reported data for up to six weeks, Holzer 2014 reported data up to eight weeks. Koren 2015; Puig 2014 reported data up to three months.
1.2 Medium‐term (six months to one year)
Medium‐term follow‐up (six months to one year) data were reported by Wykes 2007 (26 weeks) and Ueland 2004 (one year).
1.3 Long‐term (more than one year)
The study conducted by Calvo 2014 published data for a two‐year follow‐up and data from this publication were included in this review.
2. Participants
Five studies (Holzer 2014; Koren 2015; Puig 2014; She 2016; Wykes 2007) included young people with psyhosis or schizophrenia as defined by clear operational criteria. One of the studies (Calvo 2014) included adolescents with schizophrenia and affective psychosis. Holzer 2014 included young people with diagnosed psychotic illnesses such as schizophrenia, schizoaffective disorder, schizotypal disorder as well as those who were at high risk of psychosis.
There were 319 adolescent participants in total for the seven included studies. All studies clearly reported the gender of the trial participants. Most participants were aged between 13 and 17 years. All the studies randomised fewer than 100 participants each.
3. Setting
Three of the studies were conducted in inpatient settings (She 2016; Ueland 2004; Wykes 2007). Four of the studies were conducted exclusively in the outpatient setting (Calvo 2014; Holzer 2014; Koren 2015, Puig 2014). The studies were conducted in China (She 2016), Norway (Ueland 2004), the United Kingdom (Wykes 2007), Spain (Calvo 2014; Puig 2014), Switzerland (Holzer 2014), and Russia (Koren 2015). All the studies were conduted in a single centre. All seven studies were published in the period between 2004 (Ueland 2004) and 2016 (She 2016).
5. Interventions
5.1 Psychological Interventions
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Cognitive Remediation therapy: individual (CRT) or computer‐assisted (CACRT)
Ueland 2004 compared a cognitive remediation programme (CRP) and psychoeducational treatment programme (PTP) compared to the PTP only. Central elements of the PTP were parent seminars, problem‐solving sessions, milieu therapy and network groups. The CRP group received 30 hours of individual training consisting of four modules: cognitive differentiation, attention, memory and social perception. Wykes 2007 compared cognitive remediation therapy (CRT) given thrice a week in 40 one hourly sessions and treatment‐as‐usual, compared with treatment‐as‐usual. In each session of CRT, a variety of tasks were presented to practice the component processes in remembering, complex planning and problem solving. Puig 2014 compared cognitive remediation with treatment‐as‐usual (TAU). Computer‐assisted cognitive remediation were compared to non‐therapeutic computer games in the study by Holzer 2014.
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Group psychosocial therapy (GPT)
Basal training of communication skills based on a psychoeducational approach with elements of motivational training, training to cope with residual symptoms of illness, along with the use during treatment of art therapy methods directed to developing communication skills was used in Ueland 2004
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Nonstructured group therapy (NSGT)
This included problem‐solving and crisis management; the facilitators did not follow a pre‐set model but used a supportive group approach that connected persons facing similar challenges, thus enabling members to share experiences and advice (for example, on medication and side effects). During nonstructured intervention, no written material was provided to parents or adolescents.
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Psychoeducation + multi‐family treatment
Adolescents and parents received group psychoeducational interventions separately. Adolescent participants received 12 sessions of group psychoeducational interventions of 90 minutes each session, conducted every 15 days. One or both parents of the adolescents also received a group psychoeducational intervention for parents lasting 90 minutes, every 15 days. Both contents and group structure were the same in the adolescents and parents’ version of the group treatment. Groups specifically focussed on problem‐solving strategies to manage daily life situations associated with the disease to manage crises and to prevent relapses of psychosis. At the end of each group session, participants were encouraged to put the skills learnt in actual practice.
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Structural group therapy (SGT)
The intervention consisted of a 12‐session group therapy activity intervention programme. This was used by She 2016. Each session lasted 1 hour, with different themes and types of activities and was held twice a week for six weeks. The content of the group activity was varied e.g. centred around engaging with the group, improving self awareness, expressing and accepting likes and dislikes of others, helping one to express emotions effectively, becoming aware of one's strengths and self concepts, rebuilding self cognitions, addressing stigma of the disease and becoming aware of changes one has undergone over time.
5.2 Control interventions
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Computer Games
A set of video games that require attention and visuomotor skills was used as a control intervention by Holzer 2014. The participants of the computer games group received once a week a 2.5 hours of session of video games over eight weeks.
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Handicraft Activities
The control group that was part of She 2016 included a handicraft group, twice a week over six weeks. The details of the activities have not been described in detail by the authors.
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Treatment‐as‐usual: where participants continued their normal care. Treatment‐as‐usual was the comparator for Koren 2015, Puig 2014, and She 2016.
6. Outcomes
Listed below are scales used in the trials where usable data could be obtained:
6.1 Global state scales
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Global Assessment Scale (GAS, Endicott 1976)
The Global Assessment Scale (GAS) was reported by Ueland 2004. This scale rates psychological or psychiatric health on a scale ranging from 0 to 100.
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Children's Global Assessment Scale (CGAS, Shaffer 1983)
The Children's Global Assessment Scale (C‐GAS) was used in three studies (Calvo 2014; Puig 2014; Wykes 2007). No usable data from this scale was reported by Wykes 2007. The C‐GAS is used to rate the global mental state of children and adolescents on a single point rating from 1 (very poor) to 100 (no problem) based on the child's emotional and behavioural difficulties, usually over a period of the preceding three months.
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Health of Nation Outcome Scale for Children and Adolescents (HoNOSCA) (Gowers 1999)
The HoNOSCA was reported by Holzer 2014. This scale was developed to rate the outcome of children and adolescents with mental health difficulties who were aged three to 18 years. The scale has 13 clinical items and each item is rated on a 5‐point severity scale, with higher scores indicating more problems. On repeat administration, a change score can also be calculated, with two additional items.
6.2 Mental state scales
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Brief Psychiatric Rating Scale (BPRS) (Overall 1962)
This is a clinician‐rated 16‐item scale that assesses major psychiatric symptoms. Each item is scored on a 7‐point scale ranging from 1 (not present) to 7 (extremely severe). The range of scores possible for the 18‐item standard scale is between 18 and 126, high scores indicating more severe symptoms. There is an expanded version of the BPRS scale which has 24 items and the maximum score possible is 168. The BPRS was used by Ueland 2004.
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Positive And Negative Symdrome Scale (PANSS) (Kay 1986)
The PANSS assesses psychotic symptomatology and has three subscales; positive symptoms (7 items), negative symptoms (7 items) and general psychopathology (16 items). Each item is rated on a 7‐point scale ranging from 1 (absent) to 7 (extreme). There is also a total score generated by the scale. Since the lowest score for each item is 1, the minimum total score for anyone rated on PANSS is 30. The PANSS was used by Calvo 2014, Holzer 2014, Koren 2015, Puig 2014, and She 2016.
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Child Behaviour Checklist (CBCL, Achenbach 1991)
CBCL is a 118‐item parent‐ or teacher‐rated instrument to quantify psychopathology in children aged six to 18 years. The CBCL generates an internalising, externalising and total psychopathology score, in addition to several subscale scores. This scale was reported by Ueland 2004.
6.3 Cognitive functioning scales
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Backward Masking Test (BMT) (Rund 1996)
The BMT is a cognitive task which is used to assess pre‐attentional processing and the earliest phases of visual information processing. The task consists of 30 stimulus presentations where 10 are presented with no mask, 10 with a 33.0 ms stimulus onset mask, and the last 10 with a 49.5 ms stimulus onset mask. The maximum possible score in each condition is 20, as identification of each digit in the pair is scored separately. The BMT was used by Ueland 2004.
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Span of Apprehension Task (SPAN‐12, Asarnow 1992)
The SPAN measures early visual information processing. Subjects are presented with sets of three to 12 letters that are flashed for 83 ms. They are then asked to identify target letters from a sequence of letters shown to them. One hundred and twenty‐eight trials are presented with 64 in each array size. This instrument was used by Ueland 2004.
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Wisconson Card Sorting Test (WCST, Heaton 1993)
The WCST is a neuropsychological test to assess the ability to display flexibility in changing schedules of reinforcement also known as 'set shifting'. Patients are required to match cards but are not given information on how to do so. The test warrants the use of several cognitive functions such as attention, working memory and visuospatial processing. The WCST was used by Puig 2014, Ueland 2004, and Wykes 2007.
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Kimura recurring figures test (Kimura 1963).
The Kimura recurring figures test is used to assess sustained visual attention. First, the subject is shown 20 stimulus cards with geometric or 'nonsense' figures presented in succession. Then 100 cards are shown for three seconds each. Among the 60 distracter cards, eight of the original cards are randomly interspersed five times and the subject is instructed to indicate whether the card has been seen previously. A perfect performance yields a score of 40 on the test. This instrument was used by Ueland 2004.
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Trail Making Test (TMT) (Tombaugh 2004)
The TMT is a neuropsychological test of visual attention and task switching. It consists of two parts. Part A includes 25 targets which are numbered, while part B is shorter and consists of 15 targets which are arranged using alternative numbers and letters (A, 1, B, 2 etc). Individuals are required to connect numbered dots as quickly as possible while maintaining accuracy. The test thus provides information about cognitive abilities such as visual search speed, scanning, processing speed with mental flexibility assessed by part A and executive functions assessed by part B. This instrument was used by Ueland 2004.
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Digit Span Test part of WAIS III (Weschler 1997)
The Digit Span Test is used to measure attention and concentration. Progressively increasing number of digits (starting from one) are told to the patient by the interviewer with specific instructions to remember and relay them back. The greater the number of digits the person is able to remember, the better the score is. The digit span test was reported by Puig 2014 and Wykes 2007.
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Modified 6 elements test (Shallice 1991)
In the modified six elements test, participants perform three tasks, each of which have two sections. This test was reported by Wykes 2007.
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Weschler Memory Scale III (WMS III, Weschler 1997)
The WMS III is a neuropsychological test that uses both visual and auditory stimuli to measure various memory and attention functions in individuals aged 16 to 89 years. The WMS has eight primary indexes, auditory Immediate, visual Immediate, immediate memory, auditory delayed, visual delayed, auditory reception delayed, general memory, and working memory. It also consists of four supplemental auditory process composites. The WMS III was used by Puig 2014.
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Rey Auditory Verbal Learning Test (RAVLT, Schmidt 1996)
The RAVLT was used by Puig 2014 to assess verbal memory in patients. The test can be used for people aged 16 years and older.
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Weschler Intelligence Scale for Children IV (WISC IV, Weschler 2003)
The WISC IV is a paper and pencil or web‐based tool used to measure a child's intellectual ability. It can be administered to children between the ages of six and 16 years.The tool generates a full scale IQ which is representative of the child's general intellectual ability along with five primary index scores. The five primary index scores represent various abilities in discrete cognitive domains and are verbal comprehension index, visual spatial index, fluid reasoning index, working memory index, and processing speed index. The WISC IV was used by Puig 2014.
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Weschler Adult Intelligence Scale III (WAIS III) Weschler 2001
The WAIS III is an IQ test used to assess intelligence and cognitive ability in individuals aged 16 to 89 years. The test consists of 14 subtests, each of which increases in complexity and difficulty. The tool provides scores for verbal IQ, performance IQ, and full scale IQ, along with four secondary indices, namely, verbal comprehension, working memory, perceptual organisation, and processing speed. The WAIS III was used by Puig 2014 and Wykes 2007.
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Controlled Oral Word Association Test (COWAT) (Benton 1978)
The COWAT tests verbal fluency and is a subtest of the Multilingual Aphasia Examination (MAE; Benton, Hamsher, & Sivan, 1994). The COWAT is also part of the Halstead Reitan Neuropsychological Battery. The COWAT was used by Puig 2014.
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Repeatable Battery for Assessment of Neuropsychological States (RBANS) (Randolph 1998)
The RBANS tests immediate memory and consists of ten subtests for visuospatial/constructional, language, attention, delayed memory, amongst other cognitive constructs. The RBANS was used by Holzer 2014.
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Degraded Stimulus Continuous Performance Test (CPT, Nuechterlein 2006)
The CPT is a measure of sustained visual attention. wherein participants are required to press a button every time they saw the 'target' number. Along with the 'target' number, several other single digit numbers were presented to serve as noise trials while all stimulus presentations were degraded. The CPT was used by Ueland 2004.
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Landro Verbal Learning Paradigm (Landro 2008)
The Verbal Learning Paradigm is a tool used to assess verbal learning and long‐term verbal memory. The test consists of a 12‐word list and the key variable for verbal learning is the total number of correct responses across eight trials (maximum possible score is 96). For the items that are not retrieved, selective reminders are provided. To assess long‐term verbal memory, the key measure is the number of items recalled after one hour of presentation (maximum possible score 12). Ueland 2004 used the Verbal Learning Paradigm.
6.4 Global functioning scales
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Vineland Adaptive Behaviour Scale (VABS, Sparrow 2005)
The VABS assesses daily functioning and adaptive behaviour. Adaptive behaviours are everyday living skills like getting dressed, going to school, cleaning the house, etc. The expanded interview form of VABS can be used from 0 to 90 years of age. The subscale domains for which specific scores and indices can be calculated on VABS are communication, daily living skills, socialisation, motor skills and a maladaptive behaviour index. The scores are expressed in terms of standard scores, percentile ranks, adaptive levels and age equivalents. VABS scores were reported by Puig 2014..
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Social and Occupational Functioning Assessment Scale (SOFAS, APA 1994)
The SOFAS is a measure of an individual's social and occupational functioning. The total score ranges from 1 to 100 and a score of 0 is used to denote inadequate information. The score is not directly influenced by the individual's psychiatric symptoms and takes into account impairment in functioning due to general medical causes and mental disorders. The SOFAS was used by Holzer 2014.
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Life Skills Profile (LSP, Puig 2013)
The LSP assesses the real‐world life‐skills of adolescents with early onset schizophrenia. It includes 39 items each of which are scored 1 to 4. The range of the total score on the LSP can be between 39 to 156. The five subscales generated by the instrument are self‐care, interpersonal behaviour, communication‐social contact, nonpersonal social behaviour and autonomy. All items rely on basic, specific and observable behaviours. Lower scores indicate more dysfunction and poorer daily living skills. The LSP is usually scored according to the subjects' functioning over the preceding three months.The LPS was used Puig 2014.
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Self Consistency and Congruence Scale (SCSS) (Rogers 1959)
The SCSS is based on a scale (Rogers 1959) for measuring consistency between self and experience in psychotherapy. The scale consists of 35 items divided into three subscales ‐ self and experience disharmony, self flexibility and self inflexibility answered on a 5‐point Likert scale ranging from totally disagree to totally agree. This scale was used in the study by She 2016.
6.5. Quality of life scales
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Pediatric Quality of Life Scale (PedsQL) (Varni 1999)
The PedsQL rates the quality of life of children aged eight to 12 years based on responses related to the preceding month. The scale has a child‐ and a parent‐rated version. Koren 2015 used the PedsQL.
7. Missing outcomes
We found that many of the outcomes that we prespecified were not reported by the authors of these trials. None of the authors defined clinically important changes with regard to global state, mental state or global functioning. Mean endpoint scores for these outcomes were reported by several of the trials. For studies reporting a change in cognitive symptoms, there are no standardised and well‐accepted definitions of response or improvement, hence continuous scores were reported for various cognitive outcomes. However, clinically important changes in positive and negative symptoms as captured by common outcome measures like the PANNS and BPRS are well accepted but these were still not reported as categorical data. There were no data on the adverse effects of psychological therapies. Psychological therapies can cause adverse effects inadvertently. Certain psychological interventions in theory may change treatment adherence to medications and result in medication‐related adverse events. No data were available for medication‐related or nonmedication‐related adverse events during the studies. As will be described in the following section, the number of participants who left early from any particular study was reported by most of the studies. However, very few reported the number of hospitalisation episodes or days spent in the hospital. No economic data were reported.
8. Studies awaiting assessment
There are three studies awaiting assessment (Studies awaiting classification). We have written to the authors and we hope once we hear from the corresponding authors or the study is published, we will consider them for the next version of the review.
9. Ongoing studies
There are 13 ongoing studies which we could identify and they are described in the section Ongoing studies. Although study protocols were published a few years ago, reviewers couldn't find the full paper. Where possible, we made enquiries to the contact person for the study but were unable to get a response.
Excluded studies
We excluded 79 studies for various reasons that are mentioned in Characteristics of excluded studies. One of the studies was not randomised (Browning 2013). Many of the studies did not meet our age criteria and included only few patients in the adolescent age group, while the majority of the participants were adults. Some of the studies compared various service models and were outside the scope of the current review on psychological interventions. The authors of one of the excluded studies (McFarlane 2015) corresponded with us describing the difficulties in conducting a randomised trial in adolescents with psychosis.
Risk of bias in included studies
Risk of bias was analysed for all included studies. Potential sources of bias are described in the following paragraphs and Figure 2 and Figure 3. None of the studies were industry‐sponsored.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Allocation
All of the included studies were randomised trials. However, some of the studies did not report adequate details of randomisation. Calvo 2014 used computer‐generated randomisation sequence. Holzer 2014 followed a computer‐generated block randomisation method. Puig 2014 followed permuted blocks of with fixed size of eight participants allocated in a 4:4 ratio using a computer‐generated randomisation sequence. She 2016 used random number tables for randomisation. Ueland 2004 used sealed envelopes for randomisation and, as a result, was at high risk of bias. Details of the randomisation process was not described by Koren 2015 and Wykes 2007 and, as a result, have high risk of bias. Ueland 2004 used sealed envelopes for randomisation which is prone to high risk of bias. For the study by Puig 2014, only the outcome assessors were blinded and, as a result, there was an inadvertent risk of assessors getting to know about the allocation leading high risk of allocation bias. For all the other studies, the methodology of allocation concealment was not described by the authors and, as a result, these other studies have been classified as at 'unclear risk' for allocation bias.
Blinding
In four of the included studies (Calvo 2014, Holzer 2014, Puig 2014 and Wykes 2007), the authors clearly stated that the outcome assessments were done by raters who were blind to allocation status and, as a result, they were at low risk of detection bias. In the other three studies (Koren 2015, She 2016 and Ueland 2004) the authors have not explicitly stated the process of outcome assessment and, as a result, these studies had unclear risk of detection bias. Two studies (Calvo 2014, Holzer 2014) used the same therapist for both the intervention and control arm; in two studies (Ueland 2004 and Wykes 2007), a majority of the participants were recruited in the same inpatient services and, for one study (Puig 2014), the participants themselves were aware of the diagnosis and thus all these five studies were at a high risk of performance bias. The performance bias was unclear for two of the other studies (Koren 2015 and She 2016).
Incomplete outcome data
Attrition and loss to follow‐up were reported by six of the included studies (Calvo 2014; Holzer 2014; Koren 2015; Puig 2014; She 2016; Wykes 2007) and were not mentioned by Ueland 2004. Of the above studies which reported attrition of study participants, reasons for attrition were not clearly stated by Calvo 2014. Intention‐to‐treat analyses were done and reported by Holzer 2014, Puig 2014 and Wykes 2007 and these studies were at low risk of attrition bias. Other authors (Calvo 2014, Koren 2015, She 2016 and Ueland 2004) did not report on intention‐to‐treat analyses and, as a result, were at high risk of attrition bias.
Selective reporting
Multiple outcomes were reported by Ueland 2004 but not all participants completed all the measures. Similarly, Wykes 2007 did not report clearly results for several outcomes, although interaction analysis was reported for selected outcomes. Thus, Ueland 2004 and Wykes 2007 were at high risk of reporting bias. The other studies (Calvo 2014, Holzer 2014, Koren 2015, Puig 2014 and She 2016) reported all outcomes adequately and were at low risk of reporting bias.
Other potential sources of bias
None.
Effects of interventions
See: Summary of findings 1 COGNITIVE REMEDIATION THERAPY (CRG) + TREATMENT‐AS‐USUAL (TAU) compared to TAU (all short‐term) for psychosis in adolescents; Summary of findings 2 GROUP PSYCHOSOCIAL THERAPY (GPT) + TAU compared to TAU (all short‐term) for psychosis in adolescents; Summary of findings 3 STRUCTURAL GROUP THERAPY (SGT) + TAU compared to HANDICRAFT GROUP (HC) + TAU (all short‐term) for psychosis in adolescents; Summary of findings 4 COGNITIVE REMEDIATION PROGRAMME (CRP) + PSYCHOEDUCATIONAL TREATMENT PROGRAMME (PTP) compared to PTP (all medium‐term) for psychosis in adolescents; Summary of findings 5 COMPUTER‐ASSISTED COGNITIVE REMEDIATION PROGRAMME (CACR) compared to COMPUTER GAMES (CG, all short‐term) for psychosis in adolescents; Summary of findings 6 PSYCHOEDUCATIONAL (PE) + MULTIFAMILY TREATMENT (MFT) compared to NONSTRUCTURED GROUP THERAPY (NSGT, all long‐term) for psychosis in adolescents
For the six comparators, we have also presented separate 'Summary of findings' tables: summary of findings Table 1; summary of findings Table 2; summary of findings Table 3; summary of findings Table 4; summary of findings Table 5; summary of findings Table 6. For many of the binary outcomes that we had proposed to present in a SOF ('summary of findings' table), no data were available and hence indirect data from continuous scores were used, with appropriate downgrading of the level of evidence.
We have presented the two comparisons that assessed the absolute effects of psychological interventions (PI, i.e. comparing PI to treatment‐as‐usual or placebo) first, followed by comparisons where relative effects of psychological interventions were assessed (i.e. comparing PI with a sham therapy or another type of PI).
1. COMPARISON 1: COGNITIVE REMEDIATION THERAPY (CRT) + TREATMENT‐AS‐USUAL (TAU) vs TAU (all short‐term)
Two studies (Puig 2014, Wykes 2007) compared CRT with TAU (N = 90).
1.1 Global state: Average endpoint score (CGAS, high = good)
No global state measures were reported by Wykes 2007 , although the authors of this study reported in the text of the paper that the intervention did not show any effect on the global state of the participant. Puig 2014, however, did report on a 20‐week score on CGAS. Our analysis shows no clear difference between treatment groups for this outcome (MD ‐4.90, 95% CI ‐11.05 to 1.25; participants = 50; studies = 1; very low‐certainty, Analysis 1.1)
1.2 Mental state: Overall ‐ Average endpoint score (PANSS total, high = poor)
The authors of one of the studies (Puig 2014) reported mean endpoint total PANNS score. The total PANNS score at the end of 20 weeks showed that participants receiving TAU had clearly lower scores than those receiving CRT (MD 8.30, 95% CI 0.46 to 16.14; participants = 50; studies = 1; very low‐certainty; Analysis 1.2). The authors explained this apparently contradictory finding in the paper by pointing out that in spite of randomisation, the CRT group had a higher mean negative symptom score and total score on PANSS at baseline which could have contributed to this outcome.
1.3 Cognitive functioning: Clinically important change ‐ not attaining normal cognitive function
For one study (Wykes 2007), the primary outcomes reported were clinically important change in cognitive functions (memory, cognitive flexibility and planning as measured by: Digit span, Wisconsin Card Sorting Test (WCST) and Modified Six Elements Test (Analysis 1.3)). The study reported number of participants not attaining normal cognitive functioning for these domains.
1.3.1 Memory (Digit Span)
There was a clear difference, favouring the CRT group (RR 0.58, 95% CI 0.37 to 0.89; participants = 31; studies = 1; low‐certainty) as compared to TAU group at 3 months post‐treatment follow‐up.
1.3.2 Cognitive flexibility (WCST)
Our analysis found no clear difference between treatment groups for this outcome (RR 0.82, 95% CI 0.40 to 1.70; participants = 31; studies = 1).
1.3.3 Planning (Modified Six Elements Test)
Our analysis found no clear difference between treatment groups for this outcome (RR 0.94, 95% CI 0.34 to 2.60; participants = 31; studies = 1).
1.4 Cognitive functioning: Average endpoint score (various scales, high = poor)
One study (Puig 2014), reported on cognitive function outcomes using various scales. Our analysis found no clear difference between CRT and TAU group scores for any of the reported cognitive tests (Analysis 1.4).
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Verbal Memory (WMS III and RAVLT): MD 1.00, 95% CI ‐4.47 to 6.47; participants = 50; studies = 1
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Visual Memory (WMS III): MD 0.70, 95% CI ‐4.60 to 6.00; participants = 50; studies = 1
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Working Memory (WISC IV & WAIS III): MD 1.30, 95% CI ‐3.66 to 6.26; participants = 50; studies = 1
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Executive Functions (WCST, COWAT & TMT): MD 1.50, 95% CI ‐3.58 to 6.58; participants = 50; studies = 1
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Processing Speed: MD ‐2.00, 95% CI ‐10.92 to 6.92; participants = 50; studies = 1
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Cognitive Composite Score: MD 0.50, 95% CI ‐3.70 to 4.70; participants = 50; studies = 1
1.5 Global functioning: 1a. Average endpoint score (Life Skills Profile, high = good)
One study measured global functioning using the Life Skills Profile. Our analysis found no clear difference between treatment groups for this outcome (MD ‐2.00, 95% CI ‐11.29 to 7.29; participants = 50; studies = 1; Analysis 1.5).
1.6 Global functioning: 1b. Average endpoint score (VABS, high = good)
One study measured global functioning using VABS. Our analysis found no clear difference between treatment groups for this outcome (MD 5.90, 95% CI ‐3.03 to 14.83; participants = 50; studies = 1; very low‐certainty; Analysis 1.6).
1.7 Leaving the study early ‐ for any reason
Wykes 2007 reported that four young people left the CRT arm and five young people left the TAU at various stages of the treatment following recruitment into the study.
Puig 2014 reported that 10 young people left the 'cognitive remediation arm' and 10 people left the 'treatment‐as‐usual arm' and discontinued treatment. One person from the TAU arm was excluded from the final analysis as the diagnosis was changed to bipolar disorder. The post‐treatment assessment could be carried out with 15 young people in the CRT and 14 young people in the TAU. The final analyses included 50 of the 51 participants who were originally randomised.
When data from the two studies were combined, our analysis found there was no clear difference between the two treatment groups for number of participants who left the studies early (RR 0.93 95% CI 0.32 to 2.71; participants = 91; studies = 2; low‐certainty; Analysis 1.7).
1.8 Missing outcomes
Adverse events/effects, service use, social functioning, economics and quality life data were not reported for this comparison.
2. COMPARISON 2: GROUP PSYCHOSOCIAL THERAPY (GPT) + TAU (usual medication) vs TAU (usual medication, all short‐term)
One study (Koren 2015), compared GPT with TAU.
2.1 Global state: average endpoint score (CGAS, high = good)
Our analysis of reported data for this outcome found a clear difference, favouring GPT over TAU (MD 5.10, 95% CI 1.35 to 8.85; participants = 56; studies = 1; very low‐certainty; Analysis 2.1).
2.2 Mental state: Overall ‐ average endpoint score (PANSS total, high = poor)
Our analysis of reported data for this outcome found no clear difference between the treatment groups (MD ‐4.10, 95% CI ‐8.28 to 0.08; participants = 56; studies = 1; very low‐certainty; Analysis 2.2).
2.3 Quality of life: average endpoint score (PedsQL, high = good)
Our analysis of reported data for this outcome showed a clear difference, favouring GPT over TAU (MD 8.80, 95% CI 0.83 to 16.77; participants = 56; studies = 1; Analysis 2.3).
2.4 Leaving the study early ‐ for any reason
Our analysis of reported data found no clear difference in the number of participants leaving the study early from the GPT and TAU groups (RR 0.43, 95% CI 0.15 to 1.28; participants = 56; studies = 1; very low‐certainty; Analysis 2.4)
2.5 Missing outcomes
Adverse events/effects, service use, cognitive functioning, global functioning, social functioning and economic data were not reported for this comparison.
3. COMPARISON 3: STRUCTURAL GROUP THERAPY (SGT) + TAU (usual medication) vs HANDICRAFT GROUP (HC) + TAU (usual medication, all short‐term)
One study (She 2016), with a total of 48 participants compared SGT with HG.
3.1 Mental state: 1a. Overall ‐ average endpoint score (PANSS total, high = poor)
For this outcome, our analysis of reported data showed participants in the SGT group had clearly lower PANSS total scores at short‐term follow‐up (MD ‐2.57, 95% CI ‐4.47 to ‐0.67; participants = 48; studies = 1; very low‐certainty; Analysis 3.1).
3.2 Mental state: 1b. Specific: Positive symptoms ‐ average endpoint score (PANSS positive, high = poor)
Our analysis of reported data for this outcome found no clear difference between the treatment groups (MD ‐0.67, 95% CI ‐1.66 to 0.32; participants = 48; studies = 1; Analysis 3.2).
3.3 Mental state: 1c. Specific: Negative symptoms ‐ average endpoint score (PANSS negative, high = poor)
Our analysis of reported data for this outcome found no clear difference between the treatment groups (MD 0.12, 95% CI ‐0.87 to 1.11; participants = 48; studies = 1; Analysis 3.3).
3.4 Global functioning: average endpoint score (SCCS, high = good) ‐ skewed data
Data reported for this outcome were skewed and we have presented these data as 'other data'. These reported data for global functioning measuring average endpoint score on Self Consistency and Congruence Scale. (Analysis 3.4)
3.5 Leaving the study early ‐ for any reason
Noone had left the study early from either treatment group at six weeks. At 12 weeks, the number of participants who had left the GPT group was 5 out of 30 and from the HC group the number was 7 out of 30; our analysis found no clear difference for this outcome (RR 0.71, 95% CI 0.25 to 2.00; participants = 60; studies = 1; low‐certainty; Analysis 3.5).
3.6 Missing outcomes
Global state, adverse effects/events, cognitive functioning, service use, social functioning, economic and quality life data were not reported for this comparison.
4. COMPARISON 4: COGNITIVE REMEDIATION PROGRAMME (CRP) + PSYCHOEDUCATIONAL TREATMENT PROGRAMME (PTP) vs PTP (all medium‐term)
One study (Ueland 2004), with a total of 25 participants, compared a combination of PIs (CRP + PTP) with PTP alone.
4.1 Global state ‐ average endpoint score (GAS, high = good)
Our analysis of reported data for this outcome found no clear difference between the treatment groups (MD 1.60, 95% CI ‐6.48 to 9.68; participants = 25; studies = 1; very low‐certainty; Analysis 4.1).
4.2 Mental state: 1a. Overall ‐ average endpoint score (BPRS total, high = poor)
Total BPRS score showed a trend towards favouring CRP + PTP at the end of one year but our analysis of these average endpoint scores found no clear difference between treatment groups (MD ‐5.40 95% CI ‐16.42 to 5.62; participants = 24; studies = 1; very low‐certainty; Analysis 4.2).
4.3 Mental state: 1b. Overall ‐ average endpoint score (CBCL, high = poor)
Our analysis of reported data for this outcome found no clear difference between the treatment groups (MD ‐2.40, 95% CI ‐22.98 to 18.18; participants = 19; studies = 1; Analysis 4.3).
4.4 Mental state: 2a. Specific: Positive symptoms ‐ average endpoint score (BPRS positive, high = poor)
Our analysis of reported data for this outcome found no clear difference between the treatment groups (MD ‐2.30, 95% CI ‐7.95 to 3.35; participants = 24; studies = 1; Analysis 4.4).
4.5 Mental state: 2b. Specific: Negative symptoms ‐ average endpoint score (BPRS negative, high = poor ) ‐ (skewed data)
Data reported for this outcome were skewed and we have presented these data as 'other data'. These reported data on negative symptoms of mental state measuring average endpoint score on BPRS. (Analysis 4.5).
4.6 Cognitive functioning: average endpoint score (various tests, high = good)
On various tests of cognitive functioning, average endpoint scores were reported. Our analyses of reported data showed no clear differences between CRP + PTP group scores and PTP group scores for any of these tests at the one‐year follow‐up. Analysis 4.6.
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Attention: BMT: MD ‐1.30, 95% CI ‐6.58 to 3.98; participants = 25; studies = 1
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Attention: SPAN‐12: MD 2.40, 95% CI ‐2.67 to 7.47; participants = 25; studies = 1; very low‐certainty
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Attention: Continuous Performance test (CPT): MD ‐8.70, 95% CI ‐21.97 to 4.57; participants = 25; studies = 1
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Memory: Kimura Recurring Figures Test: MD 1.00, 95% CI ‐4.48 to 6.48; participants = 24; studies = 1
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Memory: Verbal Learning Paradigm: MD ‐2.80, 95% CI ‐10.98 to 5.38; participants = 24; studies = 1
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Executive function: WCST perseveration response: MD, 1.20 95% CI ‐4.85 to 7.25; participants = 25; studies = 1
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Executive function: Trail making test ‐ B: MD 4.50, 95% CI ‐9.07 to 18.07; participants = 24; studies = 1
4.7 Missing outcomes
Adverse events/effects, global functioning, social functioning, service use, attrition, economic and quality of life data were not reported for this comparison.
5. COMPARISON 5: COMPUTER‐ASSISTED COGNITIVE REMEDIATION PROGRAMME (CACR) versus COMPUTER GAMES (CG, all short‐term)
One study (Holzer 2014) with a total of 32 participants compared CACR with nontherapeutic CG.
5.1 Global state ‐ average endpoint score (HoNOSCA, high = good)
Our analysis of reported data for this outcome found no clear difference between the treatment groups (MD 2.00, 95% CI ‐1.85 to 5.85; participants = 32; studies = 1; very low‐certainty; Analysis 5.1).
5.2 Mental state: 1a. Overall ‐ average endpoint score (PANNS total, high = poor)
Our analysis of reported data for this outcome found no clear difference between the treatment groups (MD 3.70, 95% CI ‐10.68 to 18.08; participants = 32; studies = 1; very low‐certainty; Analysis 5.2).
5.3 Mental state: 1b. Specific: Positive symptoms ‐ average endpoint score (PANNS positive, high = poor)
Our analysis of reported data for this outcome found no clear difference between the treatment groups (MD 1.30, 95% CI ‐2.15 to 4.75; participants = 32; studies = 1; Analysis 5.3).
5.4 Mental state: 1c. Negative ‐ average endpoint score (PANNS negative, high = poor)
Our analysis of reported data for this outcome found no clear difference between the treatment groups (MD 1.20, 95% CI ‐4.60 to 7.00; participants = 32; studies = 1; Analysis 5.4).
5.5 Cognitive functioning: average endpoint score (RBANS, high = good)
For cognitive functioning, average endpoint scores for various domains on the RBANS (total, attention, immediate memory, delayed memory, visuospatial construction and language) were reported. Our analyses of these reported scores found no clear differences between treatment groups for any of these domains (Analysis 5.5).
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RBANS total: MD ‐8.70, 95% CI ‐17.40 to 0.00; participants = 32; studies = 1; very low‐certainty
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RBANS ‐ A (Attention): MD ‐7.90, 95% CI ‐19.07 to 3.27; participants = 32; studies = 1
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RBANS ‐ IM (Immediate Memory): MD ‐7.90, 95% CI ‐19.07 to 3.27; participants = 32; studies = 1
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RBANS ‐ DM (Delayed Memory): MD ‐4.20, 95% CI ‐16.58 to 8.18; participants = 32; studies = 1
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RBANS ‐ VC (Visuospatial Construction): MD 0.10, 95% CI ‐9.20 to 9.40; participants = 32; studies = 1
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RBANS ‐ L (Language): MD ‐13.40, 95% CI ‐25.42 to ‐1.38; participants = 32; studies = 1
5.6 Global functioning: Overall ‐ average endpoint score (SOFAS, high = good)
Analyses of average endpoint SOFAS scores showed no clear difference between treatment groups (MD ‐0.70, 95% CI ‐7.76 to 6.36; participants = 32; studies = 1; very low‐certainty; Analysis 5.6).
5.7 Leaving the study early ‐ for any reason
Three participants from the CACR group and one from CG group did not participate in the study until completion and left early due to lack of interest in the programme or being transferred to another treatment centre. Our analysis of these data found no clear difference in numbers leaving early from each group (RR 2.33, 95% CI 0.27 to 20.09; participants = 32; studies = 1; very low‐certainty; Analysis 5.7).
5.8 Missing outcomes
Adverse effects/events, social functioning, service use, economics and quality life data were not reported for this comparison.
6. COMPARISON 6: PSYCHOEDUCATIONAL (PE) + MULTIFAMILY TREATMENT (MFT) vs NONSTRUCTURED INTERVENTION (NSGT, all long‐term)
One study (Calvo 2014) with a total of 49 participants compared a combination of psychological interventions (PE + MFT) with a nonstructured intervention (NSGT).
6.1 Global state ‐ average endpoint score (CGAS, high = good, long term)
Our analysis of reported data for this outcome found no clear difference between the treatment groups (MD 3.38, 95% CI ‐4.87 to 11.63; participants = 49; studies = 1; very low‐certainty; Analysis 6.1).
6.2 Mental state: 1a. Overall ‐ average endpoint score (PANSS total, high = poor)
Our analysis of reported average endpoint PANSS total scores showed no difference between PE + MFT group and NGST group at two‐year follow‐up (MD ‐8.23, 95% CI ‐17.51 to 1.05; participants = 49; studies = 1; very low‐certainty; Analysis 6.2).
6.3 Mental state: 1b. Specific: Positive symptoms ‐ average endpoint score (PANSS positive, high = poor)
Our analysis of reported data for this outcome found no clear difference between the treatment groups (MD ‐0.85, 95% CI ‐6.65 to 4.95; participants = 49; studies = 1; Analysis 6.3).
6.4 Mental state: 1c. Specific: Negative symptoms ‐ average endpoint score (PANSS negative, high = poor)
Our analysis of reported data for this outcome found no clear difference between the treatment groups (MD ‐2.08, 95% CI ‐5.31 to 1.15; participants = 49; studies = 1; Analysis 6.4).
6.5 Service use: 1. Hospital admission: number of participants needing admission
Calvo 2014 reported numbers of participants needing hospital admission. Our analysis of reported two‐year data found no clear difference in the numbers admitted from each group (RR 0.84, 95% CI 0.36 to 1.96; participants = 49; studies = 1; low‐certainty; Analysis 6.5).
6.6 Service use: 2. Number of days in hospital (high = poor)
Our analysis of reported data found no clear difference in the number of days participants from each group spent in hospital (MD ‐1.81, 95% CI ‐10.13 to 6.51; participants = 49; studies = 1; very low‐certainty; Analysis 6.6).
6.7 Leaving the study early ‐ for any reason
Our analysis of reported attrition data found no clear difference in number of participants leaving the study early from each group (RR 0.52, 95% CI 0.10 to 2.60; participants = 55; studies = 1; low‐certainty; Analysis 6.7).
6.8 Missing outcomes
Adverse effects/events, cognitive functioning, global functioning, social functioning, economics and quality life data were not reported for this comparison.
Discussion
Summary of main results
1. Cognitive Remediation Therapy (CRT) + Treatment‐As‐Usual (TAU) versus TAU (all short‐term)
Two studies (Puig 2014; Wykes 2007 ) contributed data for a comparison of Cognitive Remediation Therapy (CRT) with Treatment‐as‐Usual (TAU). Both the studies were comparable and had similar inclusion criteria but used variable measures for outcomes so we could only combine attrition data for meta‐analyses (Analysis 1.7; low‐certainty).
Analysis of 20‐week data reported by Puig 2014, showed no clear difference in global state scores (Analysis 1.1; very low‐certainty) and a clear difference in mental state continuous scores favouring TAU (Analysis 1.2; very low‐certainty), this evidence suggesting adding CRT to TAU appears to have little or no effect on a participant's global state and TAU alone may be better for mental state. This apparently conflicting finding on the mental state outcome could be due to the baseline PANSS score being significantly lower in the control arm as compared to the intervention arm. The study thus does not provide any evidence favouring the use of cognitive remediation therapy in adolescents with psychosis as regards the outcome of mental state. (Wykes 2007) showed that in the medium term, clearly more participants in the CRT group showed improvement in short‐term memory as tested by the Digit Span Test at six months (Analysis 1.3; very low‐certainty) but other results from data reported by Puig 2014 showed no clear improvement in verbal memory, visual memory, working memory, processing speed, executive functioning and cognitive composite score in the short term at 20 weeks (Analysis 1.4). Attrition rates were similar (Analysis 1.7; very low‐certainty). However, these results are based on data from small studies where allocation and blinding were problematic, so these estimates of effect must be viewed with considerable caution. It is also likely that cognitive function, mental state and global state were interrelated in some way and standard measures are needed in future studies to be meaningfully compared.
2. Group Psychosocial Therapy plus TAU versus TAU (all short‐term)
One study contributed data for a comparison of Group Psychosocial therapy (GPT) plus usual medications with usual medications alone (TAU). There was a clear difference in the mean endpoint CGAS scores, GPT (very low‐certainty; Analysis 2.1), however, the same study did not find any clear difference in mental state scores on the PANSS (very low‐certainty; Analysis 2.2 ). There was a clear difference in quality of life scores (not a SOF outcome) measured (very low‐certainty; Analysis 2.3). The authors did not report random sequence generation, allocation concealment or blinding of participants and assessors. There was no clearly reported intention‐to‐treat analysis. These factors make the evidence of very low certainty (summary of findings Table 2). The reason for not finding clear differences in the psychopathology scores but finding a clear difference in the quality of life score is intriguing and could be because group therapy has more impact on interpersonal domains as opposed to the individual. The above diverse elements used in the group is likely to be engaging for adolescents and could hold the attention of young people who may be interested to learn to communicate with their peers. However, the nature of the intervention makes it difficult to understand the most therapeutic component of the psychological treatment that contributed to the positive results.
3. Structural Group Therapy + TAU versus Handicraft Group + TAU (all short‐term)
She 2016 compared structural group therapy with a handicraft group (both interventions were in addition to normal care). The study found a clear difference in mental state scores on PANSS between these interventions, favouring structured group therapy (very low‐certainty; Analysis 3.1) This study was conducted specifically in older adolescents with schizophrenia. Having a narrow age range of the participants made the study sample quite homogenous. The authors did not report binary outcome data for mental state or details regarding allocation concealment; also, participants were not blinded and no intention‐to‐treat analysis was reported. This made the evidence of very low certainty (summary of findings Table 3).
4. Cognitive Remediation Programme + Psychoeducational Treatment Programme (CRP + PTP) versus PTP (all medium‐term)
One study (Ueland 2004) compared CRP + PTP with PTP alone. No clear difference in the global state, mental state or cognitive functioning was found between the intervention and comparator arm even when the participants were followed up at the end of one year (very low‐certainty; Analysis 4.1; Analysis 4.2; Analysis 4.6). This lack of superiority of CRP could be because the comparator group, having received psychoeducation that may have indirectly influenced the positive, negative and cognitive symptoms by motivating participants to have a regular routine, plan their activities, improve medication adherence, reduced expressed emotions in family members and addressed their other day‐to‐day needs. The studies used 'sealed envelopes' as a method of randomisation and this has been often criticised for various methodological issues. The studies also did not report an intention‐to‐treat analysis which is routinely advocated as reducing bias. Many participants did not complete several of the questionnaires at many time points and this is not explained in the discussion. Using too many questionnaires with a small sample size poses an additional problem of spurious or chance associations due to the effects of multiple testing. It is advisable to do a sample size calculation a priori, based on the number of questionnaires to be used. Lack of details in the method of allocation concealment, method of blinding of participants and personnel, nonsignificant estimates of effect with wide confidence intervals and other factors make the evidence of very low certainty (summary of findings Table 4). The findings were of very low certainty as they were based on a single study with a small sample size.
5. Computer‐Assisted Cognitive Remediation Programme versus Computer Games (all short‐term)
Computerised therapies have been tested for psychiatric disorders and these may be particularly suitable for adolescents who are often more gadget‐friendly than adults. Similarly, over the years, many of the neuropsychological tests have been developed to be administered through computer (Lezak 1995). Use of a computer in cognitive remediation involving multiple cognitive tasks can be scored in real time to give feedback and reinforce participation in adolescents with psychosis. One study (Holzer 2014) compared computer‐assisted cognitive remediation to nontherapeutic computer games for adolescents with psychosis. Based on very low certainty of evidence, no clear difference in global state HoNOSCA scores was found between intervention and control arms following study completion (very low‐certainty; Analysis 5.1). Even on measurements of mental state using the PANSS, there was no clear difference between the two group's average endpoint scores (Analysis 5.2). Unavailability of binary outcomes except for attrition, lack of adequately described allocation concealment, and participants and personnel involved in the trial not being blind to the allocated intervention, all made the evidence of very low to low certainty (summary of findings Table 5). Failure to show efficacy of computerised CRP by the study should take into account the small sample size, leading to possible type II error. Moreover, the control arm of computer games may inadvertently have helped the adolescents use a diverse range of cognitive processes such as visual scanning, planning, memory and auditory processing, thus diluting any effect of the intervention. It would be interesting to compare CRP with other control treatments in the future.
Cognitive functioning was measured using RBANS ‐ Repeatable Battery for the Assessment of Neuropsychological Status (Randolph 1998). The baseline scores were different between the groups as regards the RBANS‐Language score with the control group scoring higher (Mann Whitney Z score 2.31, P < 0.05). The outcome assessments were done at the end of eight weeks. At the end of eight weeks, the RBANS score showed a difference in the RBANS‐Language subscale for the two groups, but, when this score was controlled for the baseline score using a Wilcoxon test, it lost its significance. The total score on RBANS showed improvement in both groups and did not show any clear difference between the two groups (very low‐certainty; Analysis 5.5). Again, the findings are very uncertain.
6. Psychoeducational + Multifamily Treatment (PE + MFT) versus Nonstructured Group Therapy (NSGT, all long‐term)
One study compared psychoeducational and multifamily treatment with nonstructured supportive treatment. The authors published the findings of a follow‐up of nine months and two years, respectively. The global state (very low‐certainty; Analysis 6.1) and mental state (very low‐certainty; Analysis 6.2) at two years did not differ between the groups. This study combined individual therapy and family group therapy and was feasible in an outpatient setting. Binary outcomes were not available for global state or mental state. The same therapists intervened for the intervention and comparator groups and proper intention‐to‐treat analyses were not reported. These factors made the results relating to global state and mental state of very low certainty. Service utilisation data as regards number of hospital admissions at the end of two years (low‐certainty; Analysis 6.5) and leaving the study early at the end of two years (low‐certainty; Analysis 6.7) did not show any difference between the groups.
Overall completeness and applicability of evidence
The review included evidence from seven studies (n = 319). Five of the seven studies reported short‐term outcomes (up to 6 months), one study had reported medium‐term follow‐up of one year duration and one study had reported longer‐term follow‐up of up to two years. A variety of interventions were studied including cognitive remediation therapy programme, computerised cognitive remediation, family therapy, psychoeducation and group therapy. The heterogeneity of the interventions made it difficult for us to combine findings of multiple studies together. All studies included mostly adolescent patients and a majority of the participants of the included studies were 17 years old or less, which makes this review relevant to this age group. All studies, except one, were conducted in developed countries and thus the evidence generated in this review should be used with caution in low‐ and middle‐income countries. Some authors did not publish means and standard deviations of scores following the intervention and these data could not be used in this review. It is interesting that none of the studies reported on the adverse events or harm associated with psychological interventions during the study period. This is a serious flaw in the reporting of studies covered in this review. Earlier literature (Lilienfeld 2007) have discussed the paucity of literature on the topic of adverse events or harm associated with psychological interventions and methodological problems in quantifying potential harm caused by therapy (Dimidjian 2010). Adolescents with psychosis are a very vulnerable group and we suggest that future clinical trials of psychological therapies for adolescents with psychosis should follow uniform adverse result reporting methods.
Quality of the evidence
Quality and style of reporting for many of the studies could have been improved (Figure 3). More than half of the studies had either not discussed the details of randomisation or had used suboptimal methods like ‘sealed envelopes’ for randomisation. Most studies were unclear about the allocation concealment.
The majority of the studies had small sample size and this increased the chances of bias due to unequal distribution of potential confounders between intervention and control arms. Small sample size has the added problem of multiple testing and positive results due to chance associations. However, some of the studies were well conducted and one of the studies had a long follow‐up of two years duration which is commendable.
Potential biases in the review process
The authors of the review tried to minimise bias in the review process by following standard guidelines of the Cochrane Schizophrenia Group and also the Cochrane Handbook. The search for literature was done centrally at the editorial centre of the Cochrane Schizophrenia Group and a record of the various steps of data acquisition, data extraction and analysis was systematically stored by the review team. We screened a large number of conference abstracts but these did not contribute significantly to the data.
Agreements and disagreements with other studies or reviews
Most reviews on treatment of adolescents with psychosis extrapolated findings from studies done on young adults (Stafford 2015). The National Institute of Clinical Excellence (NICE 2013) advocates use of culturally appropriate psychotherapies for children and young people with psychosis. It also mentions that psychological therapy should take into account the young person’s developmental level, emotional maturity, cognitive capacity, sight or hearing problems, and language difficulties. NICE recommends family therapy in adolescents with psychosis. We did not find any evidence in support of the use of family therapy for adolescents with psychosis in our review based on the studies specifically focused on adolescents. However we would like to reiterate that it is important to note lack of evidence for use of formal family therapy does not rule out the usefulness of therapeutic value of a supportive family for this group of young people. In our review, there was some evidence to support the use of group therapy for adolescents with psychosis based on low and very low quality of evidence. We cannot comment on Cognitive Behaviour Therapy (CBT) as a therapeutic modality for adolescents with psychosis as we did not find any randomised trials using CBT for adolescents with psychosis that met the inclusion criteria of the present review.
Study flow diagram.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Comparison 1: COGNITIVE REMEDIATION THERAPY (CRT) + TREATMENT‐AS‐USUAL (TAU) vs TAU (all short‐term), Outcome 1: Global state: 1a. Average endpoint score (CGAS, high = good)
Comparison 1: COGNITIVE REMEDIATION THERAPY (CRT) + TREATMENT‐AS‐USUAL (TAU) vs TAU (all short‐term), Outcome 2: Mental state: Overall ‐ average endpoint score (PANSS total, high = poor)
Comparison 1: COGNITIVE REMEDIATION THERAPY (CRT) + TREATMENT‐AS‐USUAL (TAU) vs TAU (all short‐term), Outcome 3: Cognitive functioning: 1. Clinically important change ‐ not attaining normal cognitive function
Comparison 1: COGNITIVE REMEDIATION THERAPY (CRT) + TREATMENT‐AS‐USUAL (TAU) vs TAU (all short‐term), Outcome 4: Cognitive functioning: 2. Average endpoint score (various scales, high = poor)
Comparison 1: COGNITIVE REMEDIATION THERAPY (CRT) + TREATMENT‐AS‐USUAL (TAU) vs TAU (all short‐term), Outcome 5: Global functioning: 1a. Average endpoint score (Life Skills Profile, high = good)
Comparison 1: COGNITIVE REMEDIATION THERAPY (CRT) + TREATMENT‐AS‐USUAL (TAU) vs TAU (all short‐term), Outcome 6: Global functioning: 1b. Average endpoint score (VABS, high = good)
Comparison 1: COGNITIVE REMEDIATION THERAPY (CRT) + TREATMENT‐AS‐USUAL (TAU) vs TAU (all short‐term), Outcome 7: Leaving the study early ‐ for any reason
Comparison 2: GROUP PSYCHOSOCIAL THERAPY (GPT) + TAU (usual medication) vs TAU (usual medicatoin, all short‐term), Outcome 1: Global state: average endpoint score (CGAS, high = good)
Comparison 2: GROUP PSYCHOSOCIAL THERAPY (GPT) + TAU (usual medication) vs TAU (usual medicatoin, all short‐term), Outcome 2: Mental state: Overall ‐ average endpoint score (PANSS total, high = poor))
Comparison 2: GROUP PSYCHOSOCIAL THERAPY (GPT) + TAU (usual medication) vs TAU (usual medicatoin, all short‐term), Outcome 3: Quality of life: average endpoint score (PedsQL, high = good)
Comparison 2: GROUP PSYCHOSOCIAL THERAPY (GPT) + TAU (usual medication) vs TAU (usual medicatoin, all short‐term), Outcome 4: Leaving the study early ‐ for any reason
Comparison 3: STRUCTURAL GROUP THERAPY (SGT) + TAU (usual medication) vs HANDICRAFT GROUP (HC) + TAU (usual medication, all short‐term), Outcome 1: Mental state: 1a. Overall ‐ average endpoint score (PANSS total, high = poor)
Comparison 3: STRUCTURAL GROUP THERAPY (SGT) + TAU (usual medication) vs HANDICRAFT GROUP (HC) + TAU (usual medication, all short‐term), Outcome 2: Mental state: 1b. Specific: Positive symptoms ‐ average endpoint score (PANSS positive, high = poor)
Comparison 3: STRUCTURAL GROUP THERAPY (SGT) + TAU (usual medication) vs HANDICRAFT GROUP (HC) + TAU (usual medication, all short‐term), Outcome 3: Mental state: 1c. Specific: Negative symptoms ‐ average endpoint score (PANSS negative, high = poor)
| Global functioning: average endpoint score on Self Consistency and Congruence Scale (SCCS, high = good) ‐ skewed data | ||||
| Study | Intervention | Mean | SD | N |
|---|---|---|---|---|
| SCSS total score | ||||
| She 2016 | Structural group therapy | 5.52 | 6.3 | 25 |
| Handicraft group | 0.04 | 3.1 | 23 | |
Comparison 3: STRUCTURAL GROUP THERAPY (SGT) + TAU (usual medication) vs HANDICRAFT GROUP (HC) + TAU (usual medication, all short‐term), Outcome 4: Global functioning: average endpoint score on Self Consistency and Congruence Scale (SCCS, high = good) ‐ skewed data
Comparison 3: STRUCTURAL GROUP THERAPY (SGT) + TAU (usual medication) vs HANDICRAFT GROUP (HC) + TAU (usual medication, all short‐term), Outcome 5: Leaving the study early ‐ for any reason
Comparison 4: COGNITIVE REMEDIATION PROGRAMME + PSYCHOEDUCATIONAL TREATMENT PROGRAMME (CRP + PTP) vs PTP (all medium‐term), Outcome 1: Global state ‐ average endpoint score (GAS, high = good)
Comparison 4: COGNITIVE REMEDIATION PROGRAMME + PSYCHOEDUCATIONAL TREATMENT PROGRAMME (CRP + PTP) vs PTP (all medium‐term), Outcome 2: Mental state: 1a. Overall ‐ average endpoint score (BPRS total, high = poor)
Comparison 4: COGNITIVE REMEDIATION PROGRAMME + PSYCHOEDUCATIONAL TREATMENT PROGRAMME (CRP + PTP) vs PTP (all medium‐term), Outcome 3: Mental state: 1b. Overall ‐ average endpoint score (CBCL, high = poor)
Comparison 4: COGNITIVE REMEDIATION PROGRAMME + PSYCHOEDUCATIONAL TREATMENT PROGRAMME (CRP + PTP) vs PTP (all medium‐term), Outcome 4: Mental state: 2a. Specific: Positive symptoms ‐ average endpoint score (BPRS positive, high = poor)
| Mental state: 2b. Specific: Negative symptoms ‐ average endpoint score (BPRS negative, high = poor ) ‐ (skewed data) | ||||
| Study | Intervention | Mean | SD | N |
|---|---|---|---|---|
| Ueland 2004 | CRP + PTP | 4.1 | 1.9 | 14 |
| PTP | 6.8 | 5.7 | 10 | |
Comparison 4: COGNITIVE REMEDIATION PROGRAMME + PSYCHOEDUCATIONAL TREATMENT PROGRAMME (CRP + PTP) vs PTP (all medium‐term), Outcome 5: Mental state: 2b. Specific: Negative symptoms ‐ average endpoint score (BPRS negative, high = poor ) ‐ (skewed data)
Comparison 4: COGNITIVE REMEDIATION PROGRAMME + PSYCHOEDUCATIONAL TREATMENT PROGRAMME (CRP + PTP) vs PTP (all medium‐term), Outcome 6: Cognitive functioning: average endpoint score (various tests, high = good)
Comparison 5: COMPUTER‐ASSISTED COGNITIVE REMEDIATION PROGRAMME (CACR) vs COMPUTER GAMES (CG, all short‐term), Outcome 1: Global state ‐ average endpoint score (HoNOSCA, high = good)
Comparison 5: COMPUTER‐ASSISTED COGNITIVE REMEDIATION PROGRAMME (CACR) vs COMPUTER GAMES (CG, all short‐term), Outcome 2: Mental state: 1a. Overall ‐ average endpoint score (PANSS total, high = poor)
Comparison 5: COMPUTER‐ASSISTED COGNITIVE REMEDIATION PROGRAMME (CACR) vs COMPUTER GAMES (CG, all short‐term), Outcome 3: Mental state: 1b. Specific: Positive symptoms ‐ average endpoint score (PANSS positive, high = poor)
Comparison 5: COMPUTER‐ASSISTED COGNITIVE REMEDIATION PROGRAMME (CACR) vs COMPUTER GAMES (CG, all short‐term), Outcome 4: Mental state: 1c. Negative ‐ average endpoint score (PANSS negative, high = poor)
Comparison 5: COMPUTER‐ASSISTED COGNITIVE REMEDIATION PROGRAMME (CACR) vs COMPUTER GAMES (CG, all short‐term), Outcome 5: Cognitive functioning: average endpoint score (RBANS, high = good)
Comparison 5: COMPUTER‐ASSISTED COGNITIVE REMEDIATION PROGRAMME (CACR) vs COMPUTER GAMES (CG, all short‐term), Outcome 6: Global functioning: Overall ‐ average endpoint score (SOFAS, high = good)
Comparison 5: COMPUTER‐ASSISTED COGNITIVE REMEDIATION PROGRAMME (CACR) vs COMPUTER GAMES (CG, all short‐term), Outcome 7: Leaving the study early ‐ for any reason
Comparison 6: PSYCHOEDUCATIONAL + MULTIFAMILY TREATMENT (PE + MFT) vs NONSTRUCTURED GROUP THERAPY (NSGT, all long‐term), Outcome 1: Global state ‐ average endpoint score (CGAS, high = good)
Comparison 6: PSYCHOEDUCATIONAL + MULTIFAMILY TREATMENT (PE + MFT) vs NONSTRUCTURED GROUP THERAPY (NSGT, all long‐term), Outcome 2: Mental state: 1a. Overall ‐ average endpoint score (PANSS total, high = poor)
Comparison 6: PSYCHOEDUCATIONAL + MULTIFAMILY TREATMENT (PE + MFT) vs NONSTRUCTURED GROUP THERAPY (NSGT, all long‐term), Outcome 3: Mental state: 1b. Specific: Positive symptoms ‐ average endpoint score (PANSS positive, high = poor)
Comparison 6: PSYCHOEDUCATIONAL + MULTIFAMILY TREATMENT (PE + MFT) vs NONSTRUCTURED GROUP THERAPY (NSGT, all long‐term), Outcome 4: Mental state: 1c. Specific: Negative symptoms ‐ average endpoint score (PANSS negative, high = poor)
Comparison 6: PSYCHOEDUCATIONAL + MULTIFAMILY TREATMENT (PE + MFT) vs NONSTRUCTURED GROUP THERAPY (NSGT, all long‐term), Outcome 5: Service use: 1. Hospital admission: number of participants needing addmission
Comparison 6: PSYCHOEDUCATIONAL + MULTIFAMILY TREATMENT (PE + MFT) vs NONSTRUCTURED GROUP THERAPY (NSGT, all long‐term), Outcome 6: Service use: 2. Number of days in hospital (high = poor)
Comparison 6: PSYCHOEDUCATIONAL + MULTIFAMILY TREATMENT (PE + MFT) vs NONSTRUCTURED GROUP THERAPY (NSGT, all long‐term), Outcome 7: Leaving the study early ‐ for any reason
| Method | Allocation: Randomised and described in detail in the study protocol and report. Appropriate measures to maintain allocation concealment needs to be implemented. Blinding: The trial should be double‐blind. Outcome Assessor: Researchers assessing outcome should be different from those who delivered the psychological interventions and should also be blind to the nature of the intervention. Duration: One year or more |
| Participants | Age: 13 to 18 years Gender: Equal representation of both genders Diagnosis: adolescents with psychosis as per clear operational criteria N = 200 Setting: Outpatient setting is preferred. Patients requiring admission to inpatient adolescent units may not be an ideal group to received structured therapy. A combination of inpatient and outpatients will make the study population heterogenous. |
| Intervention | Technique of psychotherapy: Cognitive remediation therapy, cognitive behaviour therapy, family therapy or group therapy. Duration of psychological intervention: at least 8 weeks Comparator: Treatment‐as‐usual |
| Outcome | Primary outcomes: Global state: Improved to significant degree Mental state: Significant clinical improvement as suggested by change of psychopathology score or relapse Global functioning: Significant change in global functioning as suggested by global functioning score or return to academic education or vocational training Leaving the study early: Intention‐to‐treat analysis should be conducted taking into account all participants in the intervention and comparator arms following randomisation even if they have left the study early. Comparative data for both groups should be presented. Service utilisation: Number of inpatient admissions and crisis presentations for one year following interventions Quality of life: Significant improvement in quality of life score Economic outcomes: Cost of interventions should be quantified. |
| COGNITIVE REMEDIATION THERAPY + TREATMENT‐AS‐USUAL compared to TREATMENT‐AS‐USUAL (all short‐term) for psychosis in adolescents | ||||||
| Patient or population: Adolescents with psychosis Intervention: COGNITIVE REMEDIATION THERAPY + TREATMENT‐AS USUAL (CRT + TAU) | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with TREATMENT‐AS‐USUAL (TAU) | Risk with COGNITIVE REMEDIATION THERAPY + TREATMENT‐AS‐USUAL (CRT + TAU) | |||||
| Global state: Average endpoint score CGAS (high score = good) | The mean endpoint global state score (CGAS) in the control group was 55.4 + 12.1 | The mean endpoint global state score (CGAS) in the intervention group was 4.9 lower | ‐ | 50 | ⊕⊝⊝⊝ | * data for prespecified outcome of importance: clinically important change (as categorical data) was not reported. |
| Mental state: Average endpoint score PANNS (high score = poor) | The mean endpoint mental state score (PANSS) in the control group was 54.2 + 12.0 | The mean endpoint mental state score (PANSS) in the intervention group was 8.30 higher (0.46 higher to 16.14 higher) | ‐ | 50 | ⊕⊝⊝⊝ | * data for prespecified outcome of importance: clinically important change (as categorical data) was not reported. |
| Cognitive functioning: clinically important change Not attaining normal cognitive function (Memory Digit Span) | Study population | RR 0.58 | 31 | ⊕⊝⊝⊝ | ||
| 1,000 per 1,000 | 580 per 1,000 | |||||
| Global functioning: Average endpoint VABS Score (high score = good) | The mean endpoint VABS score for the control arm was 73.5 + 19.5 | The mean endpoint VABS score for the intervention arm was 5.90 higher (3.03 lower to 14.83 higher) | 50 | ⊕⊝⊝⊝ Very Low 2,3,4,5,6 | * data for prespecified outcome of importance: clinically important change (as categorical data) was not reported. | |
| Adverse events: Clinically important effect | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data for this important outcome. |
| Service use: Hospital admission for any reason | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data for this important outcome. |
| Leaving the study early: For any reason | Study population | RR 0.93 | 91 | ⊕⊝⊝⊝ | ||
| 111 per 1,000 | 103 per 1,000 | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded by one level (the results were imprecise with the estimated change in mean CGAS score and the mean PANSS score had a wide confidence interval). 2 Downgraded by one level (the author reported that the study was a single‐blind study and likely the participants were not blind to the allocation status as the comparator arm was treatment‐as‐usual. This increased the risk of bias of the study findings). 3 Downgraded by one level (binary outcome was unavailable. We therefore employed the mean endpoint CGAS score, PANSS score and Composite Cognitive score as alternative indicators). 4 Downgraded by one level (majority of participants in one of the studies were recruited while they were inpatients. The comparator group was treatment‐as‐usual and the intervention arm was CRT. Therapists, patients and relatives were likely aware of the allocated arm. This design could pose a high risk of bias due to compromise in allocation concealment). 5 Downgraded by one level (data used are from one trial with small sample size). 6 Downgraded by one level (in one of the studies, there were fewer than 50% left the study early following randomisation. The study did not report the details of the intention‐to‐treat analysis). | ||||||
| GROUP PSYCHOSOCIAL THERAPY + TREATMENT‐AS‐USUAL compared to TREATMENT‐AS‐USUAL (all short‐term) for psychosis in adolescents | ||||||
| Patient or population: Adolescents with psychosis | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with TREATMENT‐AS‐USUAL (TAU) | Risk with GROUP PSYCHOSOCIAL THERAPY + TREATMENT‐AS‐USUAL (GPT + TAU) | |||||
| Global state: Mean endpoint score (CGAS, high score = good) | The mean endpoint global state score (CGAS) in the control group was 49.7 + 6.8 | The mean endpoint global state score (CGAS) in the intervention group was 5.1 higher | ‐ | 56 | ⊕⊝⊝⊝ | |
| Mental State: Mean endpoint total score on PANSS (high score = poor) | The mean endpoint score PANSS total score in the control group was 64.3 + 6.7 | The mean endpoint score PANSS total score in the intervention group was 4.1 lower | ‐ | 56 | ⊕⊝⊝⊝ | |
| Cognitive functioning: Attaining normal cognitive functioning ‐ Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on mental state. |
| Global functioning: Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on global functioning. |
| Adverse events: Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on adverse events |
| Service Use: Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on service utilisation. |
| Leaving the study early: For any reason | Study population | RR 0.43 | 56 | ⊕⊝⊝⊝ | ||
| 308 per 1,000 | 132 per 1,000 | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded by one level (the study did not report any details regarding random sequence generation and allocation concealment). 2 Downgraded by one level (the study did not report any details regarding blinding of participants and assessors). 3 Downgraded by one level (the authors have reported attrition in the intervention and control group and the number of participants who left the study early was fewer than 50%. However they have not been clear if the final analysis was done with intention‐to‐treat analysis where the outcome of all young people who were originally randomised were taken into account). 4 Downgraded by one level (binary outcome was unavailable. We therefore used continuous scores on CGAS (Global state) and PANSS (mental state) as an alternative indicator). | ||||||
| STRUCTURAL GROUP THERAPY + TREATMENT‐AS‐USUAL compared to HANDICRAFT GROUP + TREATMENT‐AS‐USUAL (all short‐term) for psychosis in adolescents | ||||||
| Patient or population: Adolescents with psychosis | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with HANDICRAFT GROUP + TREATMENT‐AS‐USUAL (TAU) | Risk with STRUCTURAL GROUP THERAPY + TRAETMENT‐AS‐USUAL (SGT + TAU) | |||||
| Global State: Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on global state. |
| Mental State: Mean endpoint total score on PANSS (high score = poor) | The mean endpoint PANSS score in the control group was 55.61 + 3.5 | The mean endpoint PANSS score in the intervention group was 2.57 lower | ‐ | 48 | ⊕⊝⊝⊝ | |
| Cognitive functioning: Attaining normal cognitive functioning ‐ Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on mental state. |
| Global functioning: Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on global functioning. |
| Adverse events: Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on adverse events. |
| Service Utilisation: Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on service utilisation. |
| Leaving the study early: For any reason | Study population | RR 0.71 | 60 | ⊕⊕⊝⊝ | ||
| 233 per 1,000 | 166 per 1,000 | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded by one level (significant number but fewer than 50% of participants were lost to follow‐up over the course of the trial. No mention of intention‐to‐treat analysis was found in the paper). 2 Downgraded by one level (binary outcome was unavailable. We therefore used continuous scores on PANSS (mental state) as an alternative indicator). 3 Downgraded by one level (data obtained from only one trial that had a small sample size). | ||||||
| COGNITIVE REMEDIATION PROGRAMME + PSYCHOEDUCATIONAL TREATMENT PROGRAMME compared to PSYCHOEDUCATIONAL TREATMENT PROGRAMME (all medium‐term) for psychosis in adolescents | ||||||
| Patient or population: Adolescents with psychosis | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with PSYCHOEDUCATIONALTREATMENT PROGRAMME (PTP) | Risk with COGNITIVE REMEDIATION PROGRAMME + PSYCHOEDUCATIONAL TREATMENT PROGRAMME (CRP + PTP) | |||||
| Global state: Average endpoint score GAS (high score = good) | The mean endpoint global state score (GAS) in the control group was 47.3 + 9.3 | The mean endpoint global state score (GAS) in the intervention group was 1.60 higher (6.48 lower to 9.68 higher) | ‐ | 25 | ⊕⊝⊝⊝ 1, 2, 3, 4 | * Data for prespecified outcome of importance: clinically important change (as categorical data) was not reported. |
| Mental state: Average endpoint score BPRS (high score = poor) | The mean endpoint BPRS scores in the control group was 43.3 + 14.6 | The mean endpoint BPRS scores in the intervention group was 5.40 lower (16.42 lower to 5.62 higher) | ‐ | 25 | ⊕⊝⊝⊝ | * Data for prespecified outcome of importance: clinically important change (as categorical data) was not reported. |
| Cognitive functioning: Mean endpoint score SPAN‐12 (high score = good) | The mean endpoint score on SPAN scores in the control group was 49.7 + 6.1 | The mean endpoint score on SPAN scores in the intervention group was 2.40 higher (2.67 lower to 7.47 higher) | ‐ | 25 | ⊕⊝⊝⊝ | * Data for prespecified outcome of importance: clinically important change (as categorical data) was not reported. |
| Global functioning: Clinically important change ‐ as defined by each of the studies | See comment | See comment | Not estimable | ‐ | See comment | For this comparison: no studies reported useable data on global functioning. |
| Adverse effects: Clinically important adverse effect ‐ as defined by each of the studies | See comment | See comment | Not estimable | ‐ | See comment | For this comparison: no studies reported useable data on adverse events. |
| Service use: Hospital admission for any reason | See comment | See comment | Not estimable | ‐ | See comment | For this comparison: no studies reported useable data for hospital admission. |
| Leaving the study early: For any reason | See comment | See comment | Not estimable | ‐ | See comment | For this comparison: no studies reported data for leaving the study early. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded by one level (allocation concealment and blinding of participants and raters not well explained). 2 Downgraded by one level (the authors analysed various outcome data for variable numbers of participants. Multiple outcome measures were reported but not all measures were completed by all participants. No intention‐to‐treat analysis was conducted and this posed a high risk of bias). 3 Downgraded by one level (the sample size for the studies were small. The estimate of effect was not significant with a relatively wide confidence interval that crossed the line of no effect). 4 Downgraded by one level (binary outcome was unavailable. We, therefore, employed BPRS score and Global State score as an alternative indicator). | ||||||
| COMPUTER‐ASSISTED COGNITIVE REMEDIATION PROGRAMME compared to COMPUTER GAMES (all short‐term) for psychosis in adolescents | ||||||
| Patient or population: Adolescents with psychosis | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with COMPUTER GAMES (CG) | Risk with COMPUTER‐ASSISTED COGNITIVE REMEDIATION PROGRAMME (CACR) | |||||
| Global state: Average endpoint score HoNOSCA (high score = good) | The mean endpoint global state score (HoNOSCA, 8 weeks) in the control group was 16.2 + 6.0 | The mean endpoint global state score (HoNOSCA, 8 weeks) in the intervention group was 2.0higher | ‐ | 32 | ⊕⊕⊝⊝ | * data for prespecified outcome of importance: clinically important change (as categorical data) was not reported. |
| Mental state: Average endpoint score PANNS (high score = poor) | The mean endpoint Mental state score (PANNS, 8 weeks) in the control group was 60.9 + 22.7 | The mean endpoint Mental state score (PANNS, 8 weeks) in the intervention group was 3.7higher | ‐ | 32 | ⊕⊕⊝⊝ | * data for prespecified outcome of importance: clinically important change (as categorical data) was not reported. |
| Cognitive functioning: Average endpoint score RBANS (high score = good) | The mean endpoint score RBANS score (8 weeks) in the control group was 92.3 + 14.4 | The mean endpoint score RBANS score (8 weeks) in the intervention group was 8.7 lower | ‐ | 32 | ⊕⊕⊝⊝ | * data for prespecified outcome of importance: clinically important change (as categorical data) was not reported. |
| Global functioning: Average endpoint score SOFAS (high score = good) | The mean endpoint global functioning score (SOFAS, 8 weeks) in the control group was 52.8 + 10.7 | The mean endpoint global functioning score (SOFAS, 8 weeks) in the intervention group was 0.7 lower | ‐ | 32 | ⊕⊕⊝⊝ | * data for prespecified outcome of importance: clinically important change (as categorical data) was not reported. |
| Adverse events: Clinically important change | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data for this important outcome. |
| Service use: Hospital admission | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data for this important outcome. |
| Leaving the study early: For any reason | Study population | RR 2.33 | 32 | ⊕⊕⊝⊝ | ||
| 71 per 1,000 | 166 per 1,000 | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded by one level (the participants for the intervention and control arm were trained by the same trainer. The sessions for both the groups were conducted in the same setting with the same frequency and duration. So the trainers and the adolescents were not blind to the group status. This confers high risk of bias, as allocation concealment may have been compromised, as the trainer and the adolescents were aware of the allocation status, although the outcome assessors were blind to the allocation status). 2 Downgraded by one level (the sample size of participants randomised was only 24. The magnitude of changes in the mean score of PANSS and HoNOSCA at the endpoint were both small and the confidence intervals were very wide for the mean endpoint scores for both HoNOSCA and BPRS making the results imprecise). 3 Downgraded by one level (the study did not report binary outcomes for mental state or cognitive functions. We therefore used continuous scores on HoNOSCA for global state, RBANS ‐ L (language) scores for cognitive functioning and SOFAS for global functioning as an alternative indicator). 4 Downgraded by one level (significant number but fewer than 50% of participants were lost to follow‐up over the course of the trial). | ||||||
| PSYCHOEDUCATIONAL + MULTIFAMILY TREATMENT compared to NONSTRUCTURED INTERVENTION (all long‐term) for psychosis in adolescents | ||||||
| Patient or population: Adolescents with psychosis | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with NONSTRUCTURED GROUP THERAPY (NSGT) | Risk with PSYCHOEDUCATIONAL + MULTIFAMILY TREATMENT (PE + MFT) | |||||
| Global state: Mean endpoint score CGAS (high score = good) | The mean endpoint global state score on CGAS (104 weeks) in the control group was 70.67 + 13.6 | The mean endpoint global state score on CGAS (104 weeks) in the intervention group was 3.38 higher | ‐ | 49 | ⊕⊝⊝⊝ | |
| Mental State: Mean end point score PANSS ‐ (high score = good) | The mean endpoint mental state score on PANSS (104 weeks) in the control group was 53.58 + 18.23 | The mean endpoint mental state score on PANSS (104 weeks) in the intervention group was 8.23 lower | ‐ | 49 | ⊕⊝⊝⊝ | |
| Cognitive functioning: Attaining normal cognitive functioning ‐ Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on mental state. |
| Global functioning: Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on global functioning. |
| Adverse events: Not reported | See comment | See comment | Not estimable | ‐ | See comment | No studies reported data on adverse events. |
| Service use: Number of participants needing admission | Study population | RR 0.84 | 49 | ⊕⊕⊝⊝ | ||
| 333 per 1,000 | 280 per 1,000 | |||||
| Leaving the study early: For any reason | Study population | RR 0.52 | 55 | ⊕⊕⊝⊝ | ||
| 143 per 1,000 | 74 per 1,000 | |||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded by one level (therapists were the same for intervention and control groups for each type of clients and were thus not blind to status of the participants increasing the risk of bias). 2 Downgraded by one level (although the study stated that the data were analysed using intention‐to‐treat analysis, it was strictly not the case at the end of two years, increasing the risk of bias). 3 Downgraded by one level (the magnitude of change in the mean score of CGAS at the endpoint was small and the confidence intervals were very wide for the mean endpoint scores for CGAS, making the results imprecise). 4 Downgraded by one level (binary outcome was unavailable. We therefore used continuous scores on CGAS (global state) and PANSS (mental state) as an alternative indicator). | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Global state: 1a. Average endpoint score (CGAS, high = good) Show forest plot | 1 | 50 | Mean Difference (IV, Fixed, 95% CI) | ‐4.90 [‐11.05, 1.25] |
| 1.2 Mental state: Overall ‐ average endpoint score (PANSS total, high = poor) Show forest plot | 1 | 50 | Mean Difference (IV, Fixed, 95% CI) | 8.30 [0.46, 16.14] |
| 1.3 Cognitive functioning: 1. Clinically important change ‐ not attaining normal cognitive function Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.3.1 Memory (Digit span) | 1 | 31 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.58 [0.37, 0.89] |
| 1.3.2 Cognitive flexibility (WCST) | 1 | 31 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.82 [0.40, 1.70] |
| 1.3.3 Planning (Modified Six Elements Test) | 1 | 31 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.94 [0.34, 2.60] |
| 1.4 Cognitive functioning: 2. Average endpoint score (various scales, high = poor) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.4.1 Verbal Memory (WMS III and RAVLT) | 1 | 50 | Mean Difference (IV, Fixed, 95% CI) | 1.00 [‐4.47, 6.47] |
| 1.4.2 Visual Memory (WMS III) | 1 | 50 | Mean Difference (IV, Fixed, 95% CI) | 0.70 [‐4.60, 6.00] |
| 1.4.3 Working Memory (WISC IV & WAIS III) | 1 | 50 | Mean Difference (IV, Fixed, 95% CI) | 1.30 [‐3.66, 6.26] |
| 1.4.4 Executive Functions (WCST, COWAT & TMT) | 1 | 50 | Mean Difference (IV, Fixed, 95% CI) | 1.50 [‐3.58, 6.58] |
| 1.4.5 Processing speed (Part A of the TMT) | 1 | 50 | Mean Difference (IV, Fixed, 95% CI) | ‐2.00 [‐10.92, 6.92] |
| 1.4.6 Cognitive Composite Score | 1 | 50 | Mean Difference (IV, Fixed, 95% CI) | 0.50 [‐3.70, 4.70] |
| 1.5 Global functioning: 1a. Average endpoint score (Life Skills Profile, high = good) Show forest plot | 1 | 50 | Mean Difference (IV, Fixed, 95% CI) | ‐2.00 [‐11.29, 7.29] |
| 1.6 Global functioning: 1b. Average endpoint score (VABS, high = good) Show forest plot | 1 | 50 | Mean Difference (IV, Fixed, 95% CI) | 5.90 [‐3.03, 14.83] |
| 1.7 Leaving the study early ‐ for any reason Show forest plot | 2 | 91 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.93 [0.32, 2.71] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 Global state: average endpoint score (CGAS, high = good) Show forest plot | 1 | 56 | Mean Difference (IV, Fixed, 95% CI) | 5.10 [1.35, 8.85] |
| 2.2 Mental state: Overall ‐ average endpoint score (PANSS total, high = poor)) Show forest plot | 1 | 56 | Mean Difference (IV, Fixed, 95% CI) | ‐4.10 [‐8.28, 0.08] |
| 2.3 Quality of life: average endpoint score (PedsQL, high = good) Show forest plot | 1 | 56 | Mean Difference (IV, Fixed, 95% CI) | 8.80 [0.83, 16.77] |
| 2.4 Leaving the study early ‐ for any reason Show forest plot | 1 | 56 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.43 [0.15, 1.28] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 3.1 Mental state: 1a. Overall ‐ average endpoint score (PANSS total, high = poor) Show forest plot | 1 | 48 | Mean Difference (IV, Fixed, 95% CI) | ‐2.57 [‐4.47, ‐0.67] |
| 3.2 Mental state: 1b. Specific: Positive symptoms ‐ average endpoint score (PANSS positive, high = poor) Show forest plot | 1 | 48 | Mean Difference (IV, Fixed, 95% CI) | ‐0.67 [‐1.66, 0.32] |
| 3.3 Mental state: 1c. Specific: Negative symptoms ‐ average endpoint score (PANSS negative, high = poor) Show forest plot | 1 | 48 | Mean Difference (IV, Fixed, 95% CI) | 0.12 [‐0.87, 1.11] |
| 3.4 Global functioning: average endpoint score on Self Consistency and Congruence Scale (SCCS, high = good) ‐ skewed data Show forest plot | 1 | Other data | No numeric data | |
| 3.4.2 SCSS total score | 1 | Other data | No numeric data | |
| 3.5 Leaving the study early ‐ for any reason Show forest plot | 1 | 60 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.71 [0.25, 2.00] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 4.1 Global state ‐ average endpoint score (GAS, high = good) Show forest plot | 1 | 25 | Mean Difference (IV, Fixed, 95% CI) | 1.60 [‐6.48, 9.68] |
| 4.2 Mental state: 1a. Overall ‐ average endpoint score (BPRS total, high = poor) Show forest plot | 1 | 24 | Mean Difference (IV, Fixed, 95% CI) | ‐5.40 [‐16.42, 5.62] |
| 4.3 Mental state: 1b. Overall ‐ average endpoint score (CBCL, high = poor) Show forest plot | 1 | 19 | Mean Difference (IV, Fixed, 95% CI) | ‐2.40 [‐22.98, 18.18] |
| 4.4 Mental state: 2a. Specific: Positive symptoms ‐ average endpoint score (BPRS positive, high = poor) Show forest plot | 1 | 24 | Mean Difference (IV, Fixed, 95% CI) | ‐2.30 [‐7.95, 3.35] |
| 4.5 Mental state: 2b. Specific: Negative symptoms ‐ average endpoint score (BPRS negative, high = poor ) ‐ (skewed data) Show forest plot | 1 | Other data | No numeric data | |
| 4.6 Cognitive functioning: average endpoint score (various tests, high = good) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 4.6.1 Attention: Backward Masking Task (BMT) | 1 | 25 | Mean Difference (IV, Fixed, 95% CI) | ‐1.30 [‐6.58, 3.98] |
| 4.6.2 Attention: Span of Apprehension Task (SPAN‐12) | 1 | 25 | Mean Difference (IV, Fixed, 95% CI) | 2.40 [‐2.67, 7.47] |
| 4.6.3 Attention: Continuous Performance Test (CPT) | 1 | 25 | Mean Difference (IV, Fixed, 95% CI) | ‐8.70 [‐21.97, 4.57] |
| 4.6.4 Memory: Kimura Recurring Figures Test | 1 | 24 | Mean Difference (IV, Fixed, 95% CI) | 1.00 [‐4.48, 6.48] |
| 4.6.5 Memory: Verbal Learning Paradigm | 1 | 24 | Mean Difference (IV, Fixed, 95% CI) | ‐2.80 [‐10.98, 5.38] |
| 4.6.6 Executive function: WCST perseveration response | 1 | 25 | Mean Difference (IV, Fixed, 95% CI) | 1.20 [‐4.85, 7.25] |
| 4.6.7 Executive function: Trail making test ‐ B | 1 | 24 | Mean Difference (IV, Fixed, 95% CI) | 4.50 [‐9.07, 18.07] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 5.1 Global state ‐ average endpoint score (HoNOSCA, high = good) Show forest plot | 1 | 32 | Mean Difference (IV, Fixed, 95% CI) | 2.00 [‐1.85, 5.85] |
| 5.2 Mental state: 1a. Overall ‐ average endpoint score (PANSS total, high = poor) Show forest plot | 1 | 32 | Mean Difference (IV, Fixed, 95% CI) | 3.70 [‐10.68, 18.08] |
| 5.3 Mental state: 1b. Specific: Positive symptoms ‐ average endpoint score (PANSS positive, high = poor) Show forest plot | 1 | 32 | Mean Difference (IV, Fixed, 95% CI) | 1.30 [‐2.15, 4.75] |
| 5.4 Mental state: 1c. Negative ‐ average endpoint score (PANSS negative, high = poor) Show forest plot | 1 | 32 | Mean Difference (IV, Fixed, 95% CI) | 1.20 [‐4.60, 7.00] |
| 5.5 Cognitive functioning: average endpoint score (RBANS, high = good) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 5.5.1 RBANS total | 1 | 32 | Mean Difference (IV, Fixed, 95% CI) | ‐8.70 [‐17.40, 0.00] |
| 5.5.2 RBANS ‐ A (Attention) | 1 | 32 | Mean Difference (IV, Fixed, 95% CI) | ‐1.90 [‐13.36, 9.56] |
| 5.5.3 RBANS ‐ IM (Immediate Memory) | 1 | 32 | Mean Difference (IV, Fixed, 95% CI) | ‐7.90 [‐19.07, 3.27] |
| 5.5.4 RBANS ‐ DM (Delayed Memory) | 1 | 32 | Mean Difference (IV, Fixed, 95% CI) | ‐4.20 [‐16.58, 8.18] |
| 5.5.5 RBANS ‐ VC (Visuospatial Construction) | 1 | 32 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐9.20, 9.40] |
| 5.5.6 RBANS ‐ L (Language) | 1 | 32 | Mean Difference (IV, Fixed, 95% CI) | ‐13.40 [‐25.42, ‐1.38] |
| 5.6 Global functioning: Overall ‐ average endpoint score (SOFAS, high = good) Show forest plot | 1 | 32 | Mean Difference (IV, Fixed, 95% CI) | ‐0.70 [‐7.76, 6.36] |
| 5.7 Leaving the study early ‐ for any reason Show forest plot | 1 | 32 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.33 [0.27, 20.09] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 6.1 Global state ‐ average endpoint score (CGAS, high = good) Show forest plot | 1 | 49 | Mean Difference (IV, Fixed, 95% CI) | 3.38 [‐4.87, 11.63] |
| 6.2 Mental state: 1a. Overall ‐ average endpoint score (PANSS total, high = poor) Show forest plot | 1 | 49 | Mean Difference (IV, Fixed, 95% CI) | ‐8.23 [‐17.51, 1.05] |
| 6.3 Mental state: 1b. Specific: Positive symptoms ‐ average endpoint score (PANSS positive, high = poor) Show forest plot | 1 | 49 | Mean Difference (IV, Fixed, 95% CI) | ‐0.85 [‐6.65, 4.95] |
| 6.4 Mental state: 1c. Specific: Negative symptoms ‐ average endpoint score (PANSS negative, high = poor) Show forest plot | 1 | 49 | Mean Difference (IV, Fixed, 95% CI) | ‐2.08 [‐5.31, 1.15] |
| 6.5 Service use: 1. Hospital admission: number of participants needing addmission Show forest plot | 1 | 49 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.84 [0.36, 1.96] |
| 6.6 Service use: 2. Number of days in hospital (high = poor) Show forest plot | 1 | 49 | Mean Difference (IV, Fixed, 95% CI) | ‐1.81 [‐10.13, 6.51] |
| 6.7 Leaving the study early ‐ for any reason Show forest plot | 1 | 55 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.52 [0.10, 2.60] |
