Scolaris Content Display Scolaris Content Display

Aumento de la dosis del antipsicótico versus cambio de antipsicótico para la falta de respuesta en la esquizofrenia

Appendices

Appendix 1. Previous searches

Search in 2014 and 2015

Electronic searches
1. Cochrane Schizophrenia Group’s Trials Register

On 10 June 2014 and 6 October 2015, the Trials Search Co‐ordinator (TSC) of the Cochrane Schizophrenia Group searched the Group's Registry of Trials using the following search strategies which have been developed based on literature review and consulting the authors of the review:

((("non respon*" or nonrespon* or "not respon*" or "no respon*" or unrespon* or fail* or unsuccess* or *resist* or persist* or residual or untreat* or refract* or ineffective or "not effective" or unchanged) or ((drug* or therap* or treat* or antipsychotic* or neuroleptic* or tranquili* or partial* or incomplete*) NEXT respon*) or ((poor or subsequen*) NEAR3 respon*)) and (((shift* or chang* or cross* or *taper* or overlap* or stay* or *continu* or remain* or combin* or ongoing or "on going") or switch*) and (dose* or dosage* or dosing))):ti,ab of REFERENCE or ((switch* or shift* or chang* or cross* or *taper* or overlap* or stay* or *continu* or remain* or combin* or ongoing or "on going") and (dose* or dosage* or dosing)):sin of STUDY.

The Cochrane Schizophrenia Group’s Registry of Trials is compiled by systematic searches of major resources (including AMED, BIOSIS, CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings (see Group Module). There is no language, date, document type, or publication status limitations for inclusion of records into the register.

Searching other resources
1. Reference searching

We inspected references of all included studies for further relevant studies.

2. Personal contact

We contacted the first author of each included study for information regarding unpublished trials.

Study flow diagram for trial selection up to March 2017
Figuras y tablas -
Figure 1

Study flow diagram for trial selection up to March 2017

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figuras y tablas -
Figure 2

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

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 3

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

Comparison 1 Increasing the antipsychotic dose versus switching the atipsychotic drug, Outcome 1 Global state: clinically relevant response – as defined by trial.
Figuras y tablas -
Analysis 1.1

Comparison 1 Increasing the antipsychotic dose versus switching the atipsychotic drug, Outcome 1 Global state: clinically relevant response – as defined by trial.

Comparison 1 Increasing the antipsychotic dose versus switching the atipsychotic drug, Outcome 2 Mental state: general mental state ‐ average endpoint score (BPRS total, high =poor).
Figuras y tablas -
Analysis 1.2

Comparison 1 Increasing the antipsychotic dose versus switching the atipsychotic drug, Outcome 2 Mental state: general mental state ‐ average endpoint score (BPRS total, high =poor).

Comparison 1 Increasing the antipsychotic dose versus switching the atipsychotic drug, Outcome 3 Mental state: negative symptoms ‐ average endpoint score (SANS, high = poor).
Figuras y tablas -
Analysis 1.3

Comparison 1 Increasing the antipsychotic dose versus switching the atipsychotic drug, Outcome 3 Mental state: negative symptoms ‐ average endpoint score (SANS, high = poor).

Table 1. Suggested design for future study

Methods

Randomisation: random
Allocation: concealed
Blinding: double blind
Duration: at least 2 weeks run‐in phase to confirm non response to initial treatment and at least 4 weeks' randomised double‐blind phase.
Setting: in‐ or out‐patients

Participants

Diagnosis: people with schizophrenia, schizoaffective disorder or schizophreniform disorder

N > 450
Gender: male and female
Age: mean 30 years (SD = 7.0), range 18 to 65 years

Interventions

All participants firstly receive treatment with one antipsychotic drug for at least 2 weeks. Those participants who do not at least minimally improve after 2 weeks, are considered non‐responders and are randomised to:

1. increasing the dose of the initial antipsychotic drug above the officially recommended dose range; or

2. switching the initial antipsychotic drug to another one with a different receptor profile; or

3. continuing treatment with the initial antipsychotic drug and at the same, initial dose (within the officially recommended dose range).

Outcomes

Response (defined as PANSS or BPRS decrease ≥ 50%)*

Relapse

Leaving the study early due to any reason

Leaving the study early due to side effects

General mental state: average change in general mental state scores

Adverse effects: at least one adverse effect; clinically important general adverse effects; sudden and unexpected death

Service use: time in hospital

Quality of life

All outcomes by time ‒ short term (up to 12 weeks), medium term (13 to 26 weeks) and long term (over 26 weeks)

Notes

*Primary outcome of interest

Figuras y tablas -
Table 1. Suggested design for future study
Summary of findings for the main comparison. Increasing the antipsychotic dose compared to switching the antipsychotic drug for non response in schizophrenia

Increasing the antipsychotic dose compared to switching the antipsychotic drug for non responsein schizophrenia

Patient or population: patients with non response in schizophrenia
Settings: inpatients
Intervention: increasing the antipsychotic dose
Comparison: switching the antipsychotic drug

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Switching the atipsychotic drug

Increasing the antipsychotic dose

Global state: Clinically relevant response – as defined by trial
Risk ratio
Follow‐up: mean 4 weeks

77 per 1000

125 per 1000
(13 to 1000)

RR 1.63
(0.17 to 15.99)

29
(1 study)

⊕⊝⊝⊝
very low1,2

Leaving the study early: Tolerabilityleaving the study early due to side effects

See comment

See comment

Not estimable

0
(0)

See comment

No studies reported on this outcome.

Leaving the study early: Acceptabilityleaving the study early due to any reason

See comment

See comment

Not estimable

0
(0)

See comment

No studies reported on this outcome,

General mental stateBPRS total score at endpoint*
Weighted mean difference
Follow‐up: mean 4 weeks

The mean general mental state ‒ BPRS total score at endpoint in the control groups was
38.2 points in BPRS

The mean general mental state ‐ BPRS total score at endpoint in the intervention groups was
2 higher
(4.2 lower to 8.2 higher)

29
(1 study)

⊕⊝⊝⊝
very low1,2

Data for prespecified outcome: Clinically important change were not reported.

Adverse effectsat least one adverse effect

See comment

See comment

Not estimable

0
(0)

See comment

No studies reported on this outcome.

Service usetime in hospital

See comment

See comment

Not estimable

0
(0)

See comment

No studies reported on this outcome.

Quality of lifeaverage change in quality of life

See comment

See comment

Not estimable

0
(0)

See comment

No studies reported on this outcome.

*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

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.

1 Imprecision: total (cumulative) sample size was just 29 participants and 95% confidence interval around the estimate of effect included no effect and appreciable benefit and appreciable harm; thus, very serious imprecision was present.
2 Publication bias: strongly suspected as there is only one study.

Figuras y tablas -
Summary of findings for the main comparison. Increasing the antipsychotic dose compared to switching the antipsychotic drug for non response in schizophrenia
Comparison 1. Increasing the antipsychotic dose versus switching the atipsychotic drug

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: clinically relevant response – as defined by trial Show forest plot

1

29

Risk Ratio (M‐H, Random, 95% CI)

1.63 [0.17, 15.99]

2 Mental state: general mental state ‐ average endpoint score (BPRS total, high =poor) Show forest plot

1

29

Mean Difference (IV, Random, 95% CI)

2.0 [‐4.20, 8.20]

3 Mental state: negative symptoms ‐ average endpoint score (SANS, high = poor) Show forest plot

1

29

Mean Difference (IV, Random, 95% CI)

3.40 [‐12.56, 19.36]

Figuras y tablas -
Comparison 1. Increasing the antipsychotic dose versus switching the atipsychotic drug