Training to recognise the early signs of recurrence in schizophrenia

Richard Morriss; Indira Vinjamuri; Mohammad Amir Faizal; Catherine A Bolton; James P McCarthy

doi:10.1002/14651858.CD005147.pub2

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Figure 1

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 2

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.

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Analysis 1.1

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 1 Relapse: 1. Relapse.

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Analysis 1.2

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 2 Relapse: 2. Time to first relapse.

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Analysis 1.3

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 3 Service use: 1a. Re‐hospitalisation.

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Analysis 1.4

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 4 Service use: 1b. Re‐hospitalisation (5‐7 year follow‐up).

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Analysis 1.5

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 5 Service use: 2. Time to re‐hospitalisation.

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Analysis 1.6

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 6 Mental state: general 1a. Average score (BPRS, high = bad).

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Analysis 1.7

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 7 Mental state: general 1b. Average score (PANSS, high = bad).

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Analysis 1.8

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 8 Mental state: general 1c. Average score (KGV, high = bad).

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Analysis 1.9

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 9 Mental state: specific 2. Average score in positive symptoms (various scales).

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Analysis 1.10

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 10 Mental state: specific 3. Average score in negative symptoms (various scales).

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Analysis 1.11

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 11 Social functioning: 1a. Not employed.

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Analysis 1.12

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 12 Social functioning: 2a. Average scores (various scales).

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Analysis 1.13

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 13 Social functioning: 2b. Average scores (various scales).

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Analysis 1.14

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 14 Quality of life: Average scores (various scales).

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Analysis 1.15

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 15 Satisfaction with care: 1a. Average endpoint scores (various scales).

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Analysis 1.16

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 16 Satisfaction with care: 1b. Average change scores (various scales).

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Analysis 1.17

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 17 Adverse events: 1. Lost to follow‐up.

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Analysis 1.18

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 18 Adverse events: 2. Death.

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Analysis 1.19

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 19 Knowledge: 1a. Average scores (various scales).

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Analysis 1.20

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 20 Knowledge: 1b. Average scores (various scales).

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Analysis 1.21

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 21 Knowledge: 1c. Average scores (various scales).

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Analysis 1.22

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 22 Burden of care: 1. Average scores (FBIS, high = bad).

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Analysis 1.23

Comparison 1 EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU), Outcome 23 Medication compliance: Not compliant to medication.

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Summary of findings for the main comparison. Early warning signs training and treatment as usual compared to treatment as usual for schizophrenia

Early warning signs training and treatment as usual compared to treatment as usual for schizophrenia
Patient or population: patients with schizophrenia Settings: secondary care Intervention: Early warning signs training and treatment as usual Comparison: treatment as usual
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Treatment as usual	Early warning signs training and treatment as usual
Relapse: Rate of relapse Follow‐up: 3 to 36 months	432 per 1000	229 per 1000 (155 to 341)	RR 0.53 (0.36 to 0.79)	1502 (15 studies)	⊕⊝⊝⊝ very low^{1, 2,3}
Relapse: Time to relapse Follow‐up: 12 to 18 months	See comment	See comment	HR 0.53 (0.27 to 1.06)	550 (6 studies)	⊕⊝⊝⊝ very low^{2, 3, 4}	The data were added to the meta‐analysis as generic inverse variance.
Service use: Rate of re‐hospitalisation Follow‐up: 2 to 36 months	385 per 1000	185 per 1000 (135 to 254)	RR 0.48 (0.35 to 0.66)	1457 (15 studies)	⊕⊝⊝⊝ very low^{2, 6, 7}
Service use: Time to re‐hospitalisation Follow‐up: 12 to 24 months	See comment	See comment	HR 0.58 (0.33 to 1.04)	1149 (6 studies)	⊕⊝⊝⊝ very low^{2, 3, 5}	The data were added to the meta‐analysis as generic inverse variance.
Satisfaction with care Follow‐up: 24 weeks to 12 months	See comment	See comment	Not estimable	See comment (3 studies)	⊕⊝⊝⊝ very low^{8, 9}	2 RCTs (92 participants) and 1 cluster RCT (56 clusters) report on satisfaction with care.¹⁰
Adverse events: Lost to follow‐up Follow‐up: 10 weeks to 24 months	105 per 1000	101 per 1000 (76 to 134)	RR 0.96 (0.72 to 1.28)	1495 (17 studies)	⊕⊝⊝⊝ very low^{3, 7, 11 ,16}
Economic burden (cost of care)	See comment	See comment	Not estimable	129 (2 studies)	⊕⊝⊝⊝ very low^{12, 13, 14}	Two studies report on costs of care, but data could not be pooled.¹⁵
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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). CI: Confidence interval; RR: Risk ratio; HR: Hazard ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹Eight studies had an unclear risk of bias for sequence generation and 13 for allocation concealment. One study did not use assessors that were blinded and in seven it was unclear. Eight studies had an unclear risk of bias for attrition and two studies had received funding from industry. ²There was high heterogeneity in the pooled results. ³The 95% confidence intervals are wide and include both significant benefit and harm of the intervention. ⁴The data were not provided for most studies and had to be imputed. Three studies had an unclear risk of bias for random sequence generation and all studies had an unclear risk for allocation concealment. In one study the assessors were not blinded and in another the risk of bias for blinding was unclear. In three studies there was an unclear risk of bias for attrition. ⁵The data were not provided for most studies and had to be imputed. Two studies had an unclear risk of bias for random sequence generation and two were unclear for allocation concealment. One study did not have assessors that were blinded and in another it was unclear. Three studies had an unclear risk of attrition bias. One study was funded by industry. ⁶Nine studies had an unclear risk of bias for sequence generation and 12 for allocation concealment. One study did not use assessors that were blinded and in seven it was unclear. One study had a high risk of attrition bias and eight studies had an unclear risk of bias for attrition. One study had received funding from industry. ⁷The funnel plot indicates that there may be the equivalent number of ’negative’ trials that have not been included in this analysis. ⁸Two studies had an unclear risk of bias for sequence generation and three for allocation concealment. One study did not use blind assessors and one study had an unclear risk of bias for attrition. Two studies were part funded by industry. ⁹Only three studies reported this outcome. ¹⁰The two RCTs found no significant difference in satisfaction with care between early warning signs training and treatment as usual, although the data may be skewed for one trial. The cluster RCT did find a significant difference in favour of early warning signs training. ¹¹Ten studies had an unclear risk of bias for sequence generation and fifteen for allocation concealment. One study did not use assessors that were blinded and in seven it was unclear. One study had a high risk of attrition bias and eight studies had an unclear risk of bias for attrition. Two studies had received funding from industry. ¹²One study had skewed data and the other did not report SDs. ¹³The two studies found very different results. ¹⁴This outcome included relatively few participants. ¹⁵Kuipers 1997 showed no significant difference between the mean cost of care for the early warning signs training group and standard care group, but the data was skewed. McDonell 2006 found that the mean costs of care were less in the early warning signs group ($1641) than the standard psychiatric group ($5199), no SDs were reported. ¹⁶ Some indication of publication bias from funnel plot.

Summary of findings for the main comparison. Early warning signs training and treatment as usual compared to treatment as usual for schizophrenia

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Table 1. Skewed and incomplete data

Outcome	Study	Results
Mental state: average score in positive symptoms (PAS positive, high = bad)	Drury 1996	The early warning signs group (N = 20) had a mean of 2.06 (SD 2.57) and the control group (N = 20) had a mean of 4.59 (SD 2.72).
Mental state: average score in positive symptoms (PAS negative, high = bad)	Drury 1996	The early warning signs group (N = 20) had a mean of 1.33 (SD 1.8) and the control group (N = 20) had a mean of 1.71 (SD 2.2).
Social functioning: average score (REHAB scale, high = bad)	Anzai 2002	The early warning signs group (N = 14) had a mean of 18.2 (SD 13) and the control group (N = 15) had a mean of 32.5 (SD 22.7).
Social functioning: average score (HoNOS scale, high = bad)	Bradley 2006	The early warning signs group (N = 25) had a mean of 9.26 (SD 4.63) and the control group (N = 24) had a mean of 7.66 (SD 4.85).
Social functioning: average score (SDSS, high = bad)	Chen 2003	The early warning signs group (N = 31) had a mean of 4.04 (SD 3.89) and the control group (N = 31) had a mean of 7.63 (SD 4.27).
Social functioning: average score (SDSS, high = bad)	Zhang 2004	The early warning signs group (N = 54) had a mean of 4.8 (SD 3) and the control group (N = 50) had a mean of 9.8 (SD 3.9).
Social functioning: average months of employment	Xiong 1994	The early warning signs group (N = 30) had a mean of 7.83 (SD 3) and the control group (N = 28) had a mean of 4.64 (SD 7.39).
Burden of care: average score (FBIS, high = bad)	Bradley 2006	The early warning signs group (N= 24) had a mean of 18.95 (SD 15.39) and the control group (N = 22) had a mean of 9.38 (SD 8.1).
Burden of care: average score (FAS, high = good)	Li 2003	The early warning signs group (N = 46) had a mean of 21 (SD 14.54) and the control group (N = 55) had a mean of 25.15 (SD 20).
Mean number of missed doses	Xiang 2001	The early warning signs group had a mean of 0.2 missed doses (SD 0.6) and the control group had a mean of 4.7 missed doses (SD 2.2).
Economic burden (cost of care)	Kuipers 1997	The early warning signs training group had a mean care package cost of £1220 (SD 736) and the standard treatment group had a mean care package cost of £1403 (SD 887) after 18 months follow‐up. There was no significant difference between the costs.
Economic burden (cost of care)	McDonell 2006	The mean cost of inpatient service utilisation was $5199 for the standard psychiatric care group and $1641 for the early warning signs training group at 3 years post‐randomisation.
FAS: Family Attitude Scale FIBS: Family Burden Interview Schedule HoNOS: Health of the Nation Outcome Scale PAS: Psychiatric Assessment Scale REHAB: Rehabilitation Evaluation Hall and Baker SD: standard deviation SDSS: Social disability screening scale

Table 1. Skewed and incomplete data

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Table 2. Comparison of nature of intervention of studies that reported primary outcome as relapse/ re‐hospitalisation

Study ID	EWS as primary focus	EWS delivered to patient only	EWS delivered to patient and carer/ health worker	EWS delivered to carer/ health worker only	EWS delivered individually	EWS delivered in groups	EWS promoting only help seeking from others	EWS promoting additional self‐directed coping
Anzai 2002	✗	✓	✗	✗	✗	✓	✗	✓
Bauml 2007	✗	✗	✓	✗	✗	✓	✗	✓
Bradley 2006	✗	✗	✓	✗	✗	✓	✗	✓
Buchkremer 1997	✗	✓	✗	✗	✗	✓	✗	✓
Chan 2007	✗	✓	✗	✗	not reported	not reported	✗	✓
Chen 2003	✗	✓	✗	✗	not reported	not reported	✗	✓
Chien 2004	✗	✗	✓	✗	✗	✓	✗	✓
Drury 1996	✗	✗	not reported	✗	✓	✓	✗	✓
Garety 2008	✓	✓ (CBT)	✗	✓ (family intervention)	✓ (CBT)	✓ (family intervention)	no (CBT) yes (family intervention)	✓ (CBT) no (family intervention)
Granholm 2005	✗	✓	✗	✗	✗	✓	✗	✓
Gumley 2003	✗	✓	✗	✗	✓	✗	✗	✓
Harris 2009	✗	✗	✗	✓	✓	✗	✗	✓
Herz 2000	✓	✗	✓	✗	✗	✓	✗	✓
Hogarty 1997a	✗	✗	✓	✗	✗	✓	✗	✓
Horan 2009	✗	✓	✗	✗	✗	✓	✗	✓
Kopelowicz 1998b	✗	✓	✗	✗	✗	✓	✗	✓
Kopelowicz 2003	✗	✗	✓	✗	✗	✓	✗	✓
Kuipers 1997	✗	✓	✗	✗	✓	✗	✗	✓
Li 2003	✗	✗	✗	✓	✓	optional	✗	✗
Liberman 1998	✗	✓	✗	✗	✓	✓	✗	✓
McDonell 2006	✗	✗	✓	✗	✗	✓	✗	✓
Merinder 1999	✗	✗	✓	✗	✗	✓	✗	✓
Norman 2002	✗	✓	✗	✗	✓	✓	✗	✓
Shin 2002	✗	✓	optional	✗	✓	✓	✗	✓
Shon 2002	✓	✓	✗	✗	unclear	✓	✗	✓
Tait 2002	✓ includes cognitive therapy	✓	✗	✗	✓	✗	✓	✗
Turkington 2006	✗	✗	✓	✗	✓	✗	✗	✓
Van Meijel 2006	✓	✓	✗	✗	✓	✗	✗	✓
Vreeland 2006	✗	✓	✗	✗	✗	✓	✗	✓
Weng 2005	✗	✓	✗	✗	✗	✓	✗	✓
Xiang 2001	✗	✓	✗	✗	✗	✓	✗	✓
Xiong 1994	✗	✗	✓	✗	✓	✓	✗	✓
Zhan 2003	✗	✓	✗	✗	not reported	not reported	✗	✓
Zhang 2004	✗	✗	✓	✗	✓	✓	✗	✓
CBT: cognitive behavioural therapy EWS: early warning signs

Table 2. Comparison of nature of intervention of studies that reported primary outcome as relapse/ re‐hospitalisation

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Table 3. Comparison of description of intervention of studies that reported primary outcome as relapse/ re‐hospitalisation

Study ID	Focus of intervention	At least one hour/ session focus on EWS	EWS intervention delivered by	No. of sessions	Control group
Anzai 2002	Community re‐entry program	yes	Ward Nurses	18 one‐hour sessions	Occupational rehabilitation
Bauml 2007	Psychoeducation of patients and relatives (reduce re‐hospitalisation and improve compliance)	yes	Psychiatrist or clinical psychologist	8 one‐hour groups, 4 sessions weekly and 4 monthly 8 bi‐weekly 90‐minute sessions for relatives	Outpatient treatment, antipsychotic medication
Bradley 2006	Multiple family group treatment	yes	Psychoeducation:Psychiatrist, psychologists, social workers, occupational therapists Family groups: Therapists	3 single family joining sessions. 2 half‐day psychoeducation sessions. Multiple family group fortnightly for 12 months	Appointments with case manager and doctor for medication and individual psychosocial rehabilitation. Family contact as required
Buchkremer 1997	Psychoeducational medication training and key person counselling	yes	Project staff	10 sessions, first 5 at weekly intervals and 5 at fortnightly intervals	1.Cognitive psychotherapy: 7 sessions weekly and 8 sessions fortnightly 2. Leisure time group activities led by students of psychology or educational sociology
Chan 2007	Psychoeducation & relapse prevention	no	Occupational therapist	Ten 50‐minute sessions over two weeks for patients	Traditional ward occupational therapy including work, rest, leisure activities
Chen 2003	Medication & symptom management training programme	not reported	Not reported	Not reported	Antipsychotic therapy
Chien 2004	Psychoeducation	yes	Trained psychiatric nurses	12 bi‐weekly 2‐hour sessions over 6 months for patients and families together	1. Mutual support group for families only 2. Standard outpatient care
Drury 1996	Cognitive Therapy	No	Not reported	8 hours a week – four individual and four group sessions, 2 sessions with family engagement	Recreation therapy, leisure and social activities outside the ward
Garety 2008	CBT or family intervention	No	Each session with 2 therapists ‐ mix of doctoral clinical psychologists and nurses all trained in CBT	9 months (intended minimum 12 months, max 20 months) – 1‐hour sessions with a mean number of 14.3 session	TAU‐ standard of care delivered according to national and local service protocols including antipsychotic medication.
Granholm 2005	Cognitive behavioural skills training	Yes	Each session led by 2 therapists ‐ mix of doctoral or senior graduate level psychologists	24 two‐hour weekly group sessions	TAU – continuation of prior treatment
Gumley 2003	Targeted CBT for relapse	yes	Clinical psychologist	5 session engagement phase between 0‐12 weeks; intensive targeted phase (2‐3 sessions per week) after for 12 months	Ongoing medication, regular psychiatric review, follow‐up from a key worker, access to multidisciplinary community mental health team
Harris 2009	Medication management training programme	yes	Not reported	Community mental health professionals (CMHPs; nurses, occupational therapists, social workers) received a 10‐day programme: 3 days assessment training, followed by seven fortnightly study days. These were followed by 1‐hour individual supervision sessions, at the CMHP’s workplace, every month for 6 months, giving a total educational input of 9 months.	Waiting list
Herz 2000	Relapse prevention	yes	Master's level nurse clinician or certified social worker	One‐hour weekly supportive group therapy OR 30‐45‐minute individual supportive therapy 90‐minute multifamily psychoeducation groups bi‐weekly for 6 months and monthly after	Individual supportive therapy and medication management biweekly for 15‐30 minutes
Hogarty 1997a	Personal therapy (relapse prevention) and/or family therapy (psychoeducation/ management)	yes	Personal and family therapy: master's level psychiatric nurse clinical specialists and doctoral‐ level clinical psychologists	30‐45‐minute weekly for about 3 years 1.9 additional monthly medication management sessions	Supportive therapy
Horan 2009	Symptom management	yes	Not reported	12 one‐hour groups that met twice weekly	Social cognitive intervention
Kopelowicz 1998b	Community re‐entry program	yes	2 trainers per session – from a multi‐disciplinary staff of 10	Eight 45‐minute group sessions, twice a day for 4 days in a week.	Occupational therapy
Kopelowicz 2003	Family assisted skills training program	yes	Nurses, psychologists and social workers	90‐minute sessions four times per week for 3 months. Weekly group sessions with families included	Case management by social workers and monthly 20‐minute psychiatric visits to see a psychiatrist
Kuipers 1997	CBT	Yes	Therapist	Weekly sessions that become fortnightly‐ up to one hour and up to nine months	Standard care‐ case management and medication
Li 2003	Comprehensive patient/ family education guide (CP/FEG)	yes	Ward Nurses	In hospital‐ Patient 8 hours; family member 36 hours. Post‐discharge‐ patient and family member 2 hours per month for 3 months.	Not reported
Liberman 1998	Social and Independent Living Skills Program consisting of basic conversation, recreation for leisure, medication management, and symptom management	yes	Occupational therapist and paraprofessionals	6 months of intensive, clinic‐based treatment 3 hours a day, 4 days per week.	Psychosocial occupational therapy
McDonell 2006	Multiple family group treatment	yes	clinicians	24 sessions in year 1 and 12 sessions in year 2	Outpatient services: medication management, case management, phone consultation, crisis services, group psychotherapy, occupational therapy, individual psychotherapy
Merinder 1999	Patient and relative psychoeducation	yes	not stated	8 weekly sessions separately for patients and relatives	Psychopharmacological treatment, psychosocial rehabilitation efforts, some supportive psychotherapy
Norman 2002	Stress management program	yes	Nurse case managers	12 weeks of group sessions, and 12 individual sessions	Social activities program similar in frequency and length to treatment group
Shin 2002	Psychoeducational group program with individual supportive therapy	yes	Group sessions – psychiatric social worker Individual sessions – Master’s degree student	10 weekly group sessions (90 minutes each) & individual sessions (45 minutes each)	Individual supportive therapy
Shon 2002	Self management educational group	Yes	2 psychiatric nurses & 2 social workers	12 group sessions (70 minutes each)	Non‐equivalent control group ‐ undefined
Tait 2002	EWS recognition and targeted cognitive therapy	yes	Therapist	5 one‐hour sessions on initial engagement and formulation Early signs monitoring questionnaire dispatched fortnightly for an average of 10 months Targeted cognitive therapy, intensive for a brief period, about 2‐3 sessions per week	Routine appointments with psychiatrist and key worker (community psychiatric worker, social worker or occupational therapist)
Turkington 2006	Modify patient's condition and family approach	yes	Trained Community Psychiatric Nurse	up to 6 hour‐long sessions of CBT and/or 3 sessions with carer	Care of community mental health teams
Van Meijel 2006	Relapse prevention plan using EWS monitoring	yes	Trained nurses	Therapy for a total of mean (SD) 155 (94) days	Care as usual
Weng 2005	Psychiatric rehabilitation	yes	Interdisciplinary teams	2 months, possibly weekly sessions	Standard inpatient services and activities
Xiang 2001	Medication & symptom management training programme	yes	Psychiatrist and a psychologist	90 to 120‐minute sessions, 3 sessions per week for 20 weeks	Antipsychotic medication and standard psychological intervention
Xiong 1994	Family based intervention	yes	Clinicians	1. Introduction‐ two to three 45‐minute sessions‐ family +/‐ patient 2. Monthly 45‐minute counselling with patient (average 8.1 contacts per year) and family and 90 minute family group 3. Maintenance‐ families seen once in 2‐3 months and monthly group meetings up to 18 months	2‐3 months of medication post discharge +/‐ out patient follow‐up
Zhan 2003	Medication & symptom management training programme	yes	Psychiatrist and a psychologist	60 to 90 minutes per session, 1 session per week for 12 weeks	Pharmacotherapy and standard psychological intervention
Zhang 2004	Life skills, medication & symptom management training programme	yes	Psychiatrist and psychiatric nurse	Group training for 90 to 120 minutes, 2 times a week. Then community follow‐up by nurses, number of sessions not reported	Conventional rehabilitation service (outpatient follow‐up every 3 months, or telephone counselling as needed)

Table 3. Comparison of description of intervention of studies that reported primary outcome as relapse/ re‐hospitalisation

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Comparison 1. EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Relapse: 1. Relapse Show forest plot	15	1502	Risk Ratio (M‐H, Random, 95% CI)	0.53 [0.36, 0.79]

1.1 training delivered to patient only	8	933	Risk Ratio (M‐H, Random, 95% CI)	0.43 [0.20, 0.92]
1.2 training delivered to carer/health professional only	2	78	Risk Ratio (M‐H, Random, 95% CI)	0.58 [0.24, 1.37]
1.3 training delivered to both patient and carer/health professional	6	491	Risk Ratio (M‐H, Random, 95% CI)	0.68 [0.46, 1.02]
2 Relapse: 2. Time to first relapse Show forest plot	6	550	hazards ratio (Random, 95% CI)	0.53 [0.27, 1.06]

2.1 training delivered to patient only	3	372	hazards ratio (Random, 95% CI)	0.26 [0.13, 0.53]
2.2 training delivered to both patient and carer/health professional	3	178	hazards ratio (Random, 95% CI)	1.00 [0.59, 1.68]
3 Service use: 1a. Re‐hospitalisation Show forest plot	15	1457	Risk Ratio (M‐H, Random, 95% CI)	0.48 [0.35, 0.66]

3.1 training delivered to patient only	7	791	Risk Ratio (M‐H, Random, 95% CI)	0.30 [0.14, 0.66]
3.2 training delivered to carer/health professional only	1	41	Risk Ratio (M‐H, Random, 95% CI)	0.53 [0.15, 1.82]
3.3 training delivered to both patient and carer/health professional	7	625	Risk Ratio (M‐H, Random, 95% CI)	0.64 [0.51, 0.79]
4 Service use: 1b. Re‐hospitalisation (5‐7 year follow‐up) Show forest plot	2	156	Risk Ratio (M‐H, Random, 95% CI)	0.82 [0.49, 1.36]

4.1 training delivered to patient only	1	108	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.79, 1.36]
4.2 training delivered to both patient and carer/health professional	1	48	Risk Ratio (M‐H, Random, 95% CI)	0.62 [0.42, 0.92]
5 Service use: 2. Time to re‐hospitalisation Show forest plot	6	1149	hazards ratio (Random, 95% CI)	0.58 [0.33, 1.04]

5.1 training delivered to patient only	3	409	hazards ratio (Random, 95% CI)	0.37 [0.07, 1.95]
5.2 training delivered to both patient and carer/health professional	3	740	hazards ratio (Random, 95% CI)	0.62 [0.46, 0.83]
6 Mental state: general 1a. Average score (BPRS, high = bad) Show forest plot	10		Mean Difference (Random, 95% CI)	‐4.55 [‐8.21, ‐0.90]

7 Mental state: general 1b. Average score (PANSS, high = bad) Show forest plot	3	385	Mean Difference (IV, Random, 95% CI)	‐5.89 [‐15.86, 4.09]

8 Mental state: general 1c. Average score (KGV, high = bad) Show forest plot	1		Mean Difference (Fixed, 95% CI)	‐2.6 [‐4.07, ‐1.13]

9 Mental state: specific 2. Average score in positive symptoms (various scales) Show forest plot	6		Mean Difference (IV, Random, 95% CI)	Subtotals only

9.1 BPRS (high = bad)	1	64	Mean Difference (IV, Random, 95% CI)	‐0.90 [‐3.52, 1.72]
9.2 PANSS positive (high = bad)	4	508	Mean Difference (IV, Random, 95% CI)	‐0.41 [‐2.70, 1.87]
9.3 SAPS (high = bad)	1	104	Mean Difference (IV, Random, 95% CI)	‐2.04 [‐3.22, ‐0.86]
10 Mental state: specific 3. Average score in negative symptoms (various scales) Show forest plot	7		Mean Difference (IV, Random, 95% CI)	Subtotals only

10.1 PANSS negative (high = bad)	4	508	Mean Difference (IV, Random, 95% CI)	‐0.74 [‐3.13, 1.64]
10.2 SANS (high = bad)	3	194	Mean Difference (IV, Random, 95% CI)	‐3.95 [‐15.25, 7.35]
11 Social functioning: 1a. Not employed Show forest plot	2	185	Risk Ratio (M‐H, Fixed, 95% CI)	0.68 [0.57, 0.82]

12 Social functioning: 2a. Average scores (various scales) Show forest plot	7		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

12.1 GAF (high = good)	2	88	Mean Difference (IV, Fixed, 95% CI)	2.51 [‐3.84, 8.85]
12.2 GAF‐DIS (high = good)	1	61	Mean Difference (IV, Fixed, 95% CI)	‐6.10 [‐12.34, 0.14]
12.3 ILSS (high = good)	1	84	Mean Difference (IV, Fixed, 95% CI)	0.35 [‐0.70, 1.40]
12.4 Time budget interview (high = good)	1	224	Mean Difference (IV, Fixed, 95% CI)	1.61 [‐4.04, 7.25]
12.5 SOFAS (high = good)	1	236	Mean Difference (IV, Fixed, 95% CI)	1.21 [‐2.71, 5.13]
12.6 SLOF (high = good)	1	64	Mean Difference (IV, Fixed, 95% CI)	27.5 [17.03, 37.97]
12.7 SAS (high = good)	1	80	Mean Difference (IV, Fixed, 95% CI)	‐0.43 [‐2.20, 1.34]
13 Social functioning: 2b. Average scores (various scales) Show forest plot	6		Mean Difference (Random, 95% CI)	Subtotals only

13.1 SFS (high = good)	1		Mean Difference (Random, 95% CI)	4.4 [‐3.16, 11.96]
13.2 GAS (high = good)	3		Mean Difference (Random, 95% CI)	1.92 [‐0.54, 4.38]
13.3 NOSIE (high = good)	3		Mean Difference (Random, 95% CI)	25.12 [5.75, 44.48]
14 Quality of life: Average scores (various scales) Show forest plot	4		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

14.1 QLS (high = good)	1	46	Mean Difference (IV, Fixed, 95% CI)	‐5.05 [‐16.12, 6.02]
14.2 LQLP (high = good)	1	48	Mean Difference (IV, Fixed, 95% CI)	‐0.40 [‐1.30, 0.50]
14.3 EuroQoL (high = good)	1	206	Mean Difference (IV, Fixed, 95% CI)	‐4.80 [‐10.79, 1.19]
14.4 LQoLS (high = good)	1	80	Mean Difference (IV, Fixed, 95% CI)	0.09 [‐0.24, 0.42]
15 Satisfaction with care: 1a. Average endpoint scores (various scales) Show forest plot	2		Mean Difference (Fixed, 95% CI)	Subtotals only

15.1 CALPAS (high = good)	1		Mean Difference (Fixed, 95% CI)	0.3 [0.12, 0.48]
15.2 IAPSRS (high = good)	1		Mean Difference (Fixed, 95% CI)	0.1 [‐0.11, 0.31]
16 Satisfaction with care: 1b. Average change scores (various scales) Show forest plot	1		Mean Difference (Fixed, 95% CI)	2.15 [‐9.66, 13.96]

16.1 VSSS (high = good)	1		Mean Difference (Fixed, 95% CI)	2.15 [‐9.66, 13.96]
17 Adverse events: 1. Lost to follow‐up Show forest plot	17	1495	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.72, 1.28]

18 Adverse events: 2. Death Show forest plot	4	462	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.29, 2.89]

19 Knowledge: 1a. Average scores (various scales) Show forest plot	4		Mean Difference (IV, Random, 95% CI)	Subtotals only

19.1 KASQ (patients, high = good)	1	61	Mean Difference (IV, Random, 95% CI)	1.60 [‐0.84, 4.04]
19.2 IS (patients, high = good)	1	40	Mean Difference (IV, Random, 95% CI)	0.96 [‐0.48, 2.40]
19.3 ITAQ (patients, high = good)	2	166	Mean Difference (IV, Random, 95% CI)	7.21 [0.94, 13.48]
20 Knowledge: 1b. Average scores (various scales) Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Subtotals only

20.1 SUMD (patients, high = bad)	1	81	Mean Difference (IV, Random, 95% CI)	‐1.18 [‐2.46, 0.10]
21 Knowledge: 1c. Average scores (various scales) Show forest plot	2		Mean Difference (Fixed, 95% CI)	Subtotals only

21.1 DAI (patients, high = good)	1		Mean Difference (Fixed, 95% CI)	1.4 [‐0.97, 3.77]
21.2 KASI (relatives, high = good)	1		Mean Difference (Fixed, 95% CI)	2.83 [0.93, 4.73]
22 Burden of care: 1. Average scores (FBIS, high = bad) Show forest plot	1	64	Mean Difference (IV, Random, 95% CI)	‐2.40 [‐7.10, 2.30]

23 Medication compliance: Not compliant to medication Show forest plot	4	374	Risk Ratio (M‐H, Fixed, 95% CI)	0.57 [0.42, 0.77]

Comparison 1. EARLY WARNING SIGNS TRAINING + TAU versus TREATMENT AS USUAL (TAU)

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