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Risperidone
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Figure 1

Risperidone

Logic framework model with potential causal pathways: risperidone treatment in persons with dual diagnosis.
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Figure 2

Logic framework model with potential causal pathways: risperidone treatment in persons with dual diagnosis.

PRISMA flow diagram of study selection from 2016 and 2017 searches
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Figure 3

PRISMA flow diagram of study selection from 2016 and 2017 searches

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 4

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.
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Figure 5

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

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 1 Mental state: 1. General: average endpoint scores (PANSS subscale, lower=better).
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Analysis 1.1

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 1 Mental state: 1. General: average endpoint scores (PANSS subscale, lower=better).

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 2 Mental state: 2. General: any change in general symptoms:.
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Analysis 1.2

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 2 Mental state: 2. General: any change in general symptoms:.

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 3 Mental state: 3. Specific: positive, negative symptoms ‐ average endpoint scores (PANSS subscales, lower = better):.
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Analysis 1.3

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 3 Mental state: 3. Specific: positive, negative symptoms ‐ average endpoint scores (PANSS subscales, lower = better):.

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 4 Mental state: 4. Specific: anxiety symptoms.
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Analysis 1.4

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 4 Mental state: 4. Specific: anxiety symptoms.

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 5 Substance use.
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Analysis 1.5

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 5 Substance use.

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 6 Subjective Well‐being: average endpoint scores (Subjective Well‐being under Neuroleptics scale, SWN scale, higher=better).
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Analysis 1.6

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 6 Subjective Well‐being: average endpoint scores (Subjective Well‐being under Neuroleptics scale, SWN scale, higher=better).

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 7 Craving for substances.
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Analysis 1.7

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 7 Craving for substances.

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 8 Adherence to antipsychotic medication: discontinued medication.
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Analysis 1.8

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 8 Adherence to antipsychotic medication: discontinued medication.

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 9 Adverse effects. 1. Movement disorders.
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Analysis 1.9

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 9 Adverse effects. 1. Movement disorders.

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 10 Adverse effects: 2. Non‐movement disorder related side‐effects.
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Analysis 1.10

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 10 Adverse effects: 2. Non‐movement disorder related side‐effects.

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 11 Leaving the study early.
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Analysis 1.11

Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 11 Leaving the study early.

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 1 Mental state: 1. Specific: Depression‐ change scores (HAM‐D, higher = better), short term (up to 6 months).
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Analysis 2.1

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 1 Mental state: 1. Specific: Depression‐ change scores (HAM‐D, higher = better), short term (up to 6 months).

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 2 Mental state: 2. Specific: Positive symptoms, total score‐ average endpoint scores (SADS‐C‐PD scale, lower=better), short term (up to 6 months).
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Analysis 2.2

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 2 Mental state: 2. Specific: Positive symptoms, total score‐ average endpoint scores (SADS‐C‐PD scale, lower=better), short term (up to 6 months).

Study

Intervention

Outcome (symptom subscore)

Mean

SD

N

Sevy 2011

Risperidone

Delusions

2.6

1.7

16

Sevy 2011

Olanzapine

2.7

1.6

21

Sevy 2011

Risperidone

Hallucinations

1.8

1.2

16

Sevy 2011

Olanzapine

2

1.6

21

Sevy 2011

Risperidone

Thought disorder

3.6

0.8

16

Sevy 2011

Olanzapine

4.5

2.6

21

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Analysis 2.3

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 3 Mental state: 3. Specific: Positive symptom subscales‐ average endpoint scores (SADS‐C‐PD subscores, lower=better), short term (up to 6 months)‐ skewed data.

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 4 Mental state: 4. Specific: Negative symptoms, subscales‐ average endpoint scores (SANS subscales, lower=better), short term (up to 6 months).
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Analysis 2.4

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 4 Mental state: 4. Specific: Negative symptoms, subscales‐ average endpoint scores (SANS subscales, lower=better), short term (up to 6 months).

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 5 Substance use: 1. Reduction of cannabis use‐change data (number of joints smoked/week, LOCF data, higher =better)‐ short term data (up to 6 months).
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Analysis 2.5

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 5 Substance use: 1. Reduction of cannabis use‐change data (number of joints smoked/week, LOCF data, higher =better)‐ short term data (up to 6 months).

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 6 Substance use: 2. Discontinued substance use, short term (up to 6 months).
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Analysis 2.6

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 6 Substance use: 2. Discontinued substance use, short term (up to 6 months).

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 7 Craving for substances: 1. Obsessive Compulsive Drug Use Scale‐ average endpoint score (OCDUS, lower=better)‐short term (up to 6 months).
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Analysis 2.7

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 7 Craving for substances: 1. Obsessive Compulsive Drug Use Scale‐ average endpoint score (OCDUS, lower=better)‐short term (up to 6 months).

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 8 Craving for substances: 2. Desires for Drug Questionnaire‐ average endpoint scores (DDQ, LOCF data, lower=better), short term (up to 6 months).
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Analysis 2.8

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 8 Craving for substances: 2. Desires for Drug Questionnaire‐ average endpoint scores (DDQ, LOCF data, lower=better), short term (up to 6 months).

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 9 Adverse effects.
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Analysis 2.9

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 9 Adverse effects.

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 10 Leaving study early: 1. Various reasons.
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Analysis 2.10

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 10 Leaving study early: 1. Various reasons.

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 11 Leaving study early: 2. Weeks in the study‐ average endpoint data (high=good), short term (up to 6 months).
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Analysis 2.11

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 11 Leaving study early: 2. Weeks in the study‐ average endpoint data (high=good), short term (up to 6 months).

Study

Intervention

Mean (number of weeks)

SD

N

Smelson 2006

Risperidone

207

142.9

76

Smelson 2006

Olanzapine

267.9

127.4

85

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Analysis 2.12

Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 12 Leaving study early: 3. Weeks in study‐ average endpoint data (high=good), short term (up to 6 months)‐ skewed data.

Comparison 3 RISPERIDONE versus PERPHENAZINE, Outcome 1 Leaving the study early: all cause discontinuation, long term (>12 months).
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Analysis 3.1

Comparison 3 RISPERIDONE versus PERPHENAZINE, Outcome 1 Leaving the study early: all cause discontinuation, long term (>12 months).

Comparison 4 RISPERIDONE versus QUETIAPINE, Outcome 1 Leaving the study early: all cause discontinuation, long term (>12 months).
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Analysis 4.1

Comparison 4 RISPERIDONE versus QUETIAPINE, Outcome 1 Leaving the study early: all cause discontinuation, long term (>12 months).

Comparison 5 RISPERIDONE versus ZIPRASIDONE, Outcome 1 Leaving the study early: all cause discontinuation, long term (>12 months).
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Analysis 5.1

Comparison 5 RISPERIDONE versus ZIPRASIDONE, Outcome 1 Leaving the study early: all cause discontinuation, long term (>12 months).

Table 4. Suggested design for future trial

Methods

Allocation: centralised sequence generation with table of random numbers or computer‐generated code, stratified by severity of illness, sequence concealed till interventions assigned.
Blinding: could be optional, depending on choice of outcome.
Duration: 12 months.

Participants

Diagnosis: schizophrenia and co‐occurring ongoing substance misuse (clinical criteria).
N = 300*.
Age: adults.
Sex: men and women.
Setting: any.

Interventions

1. Risperidone: clinically indicated dose. N = 150.

2. Olanzapine: clinically indicated dose. N = 150.

Outcomes

Global state: CGI‐I and CGI‐S.

Substance use: pragmatic binary/continuous measure.

Well‐being: pragmatic binary/continuous measure.

Craving: pragmatic binary/continuous measure.

Service outcomes: re‐hospitalisation, days in hospital, time attending psychiatric outpatient clinic.

Quality of life: important change.
Adverse effects: including mortality, weight change and extrapyramidal symptoms.
Satisfaction with care: patients/carers.

Leaving the study early.
Economic data.

Other routine data, such as incidents with the police,

Notes

* size of study to detect a 10% difference in improvement with 80% certainty.

For all outcomes there should be binary cut‐off points of clinically important improvement, defined before the study starts.

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Table 4. Suggested design for future trial
Summary of findings for the main comparison. RISPERIDONE versus CLOZAPINE ‐ all data short term for people with severe mental illness and co‐occurring substance misuse

RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months) for people with severe mental illness and co‐occurring substance misuse

Patient or population: for people with serious mental illness and co‐occurring substance misuse
Setting:
Intervention: Risperidone
Comparison: Clozapine

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with Clozapine

Risk with Risperidone

Mental state: positive symptomsaverage endpoint score (PANSS positive subscale, lower = better)

The mean positive symptoms (PANSS positive subscale, lower = better) in the intervention group was 0.9 higher (2.21 lower to 4.01 higher)

36
(1 RCT)

⊕⊝⊝⊝
very low1 2

No trial reported "improvement in symptoms of severe mental illness" ‒ this continuous measure is the nearest proxy for this.

Substance use: improvement(at least 20% reduction in use, TLFB scale)

Study population

RR 1.00
(0.30 to 3.35)

14
(1 RCT)

⊕⊝⊝⊝
very low3 4

429 per 1000

429 per 1000
(129 to 1000)

Moderate

429 per 1000

429 per 1000
(129 to 1000)

Subjective well‐being: Subjective well‐being under neuroleptics scaleaverage endpoint scores (SWN scale, higher = better)

The mean subjective well‐being under neuroleptics scale score (SWN scale, higher = better) in the intervention group was 6 lower (14.82 lower to 2.82 higher)

36
(1 RCT)

⊕⊝⊝⊝
very low1 2

Craving for substances: Marijuana Craving Questionnaireaverage endpoint scores (MCQ, lower = better)

The mean craving for substances score on the Marijuana Craving Questionairre (MCQ, lower = better) in the intervention group was 7 higher (2.37 higher to 11.63 higher)

28
(1 RCT)

⊕⊝⊝⊝
very low1 2

Adherence to antipsychotic medication: discontinued medication

Study population

RR 4.05
(0.21 to 78.76)

36
(1 RCT)

⊕⊝⊝⊝
very low1 2

0 per 1000

0 per 1,000
(0 to 0)

Moderate

0 per 1,000

0 per 1,000
(0 to 0)

Adverse effects. 1. Movement disorders ‐ any extrapyramidal

Study population

RR 2.71
(0.30 to 24.08)

50
(2 RCTs)

⊕⊝⊝⊝
very low5 6

Many adverse effects reported ‒ none designated 'clinically important' (extrapyramidal used as proxy).

0 per 1000

0 per 1000
(0 to 0)

Moderate

0 per 1000

0 per 1000
(0 to 0)

Leaving the study earlyany reason

Study population

RR 0.49
(0.10 to 2.51)

45
(2 RCTs)

⊕⊝⊝⊝
very low5 6

318 per 1000

156 per 1000
(32 to 799)

Moderate

386 per 1000

189 per 1000
(39 to 968)

*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).

CI: Confidence interval; RR: Risk ratio; OR: Odds ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

1 High risk of performance bias and detection bias

2 Sample size is very small, optimal information size (OIS) not met to detect 25% difference

3 Performance bias, attrition bias, selective outcome reporting

4 Sample size is very small (n = 14)

5 High risk of performance bias, detection bias, attrition bias and selective outcomes reporting

6 Total sample size is very small (n<300), total event rate is very low and optimum information size (OIS) is not met

Figures and Tables -
Summary of findings for the main comparison. RISPERIDONE versus CLOZAPINE ‐ all data short term for people with severe mental illness and co‐occurring substance misuse
Summary of findings 2. RISPERIDONE versus OLANZAPINE ‒ short‐ and long‐term data for people with severe mental illness and co‐occurring substance misuse

RISPERIDONE versus OLANZAPINE‐ all data short term (up to 6 months) for people with severe mental illness and co‐occurring substance misuse

Patient or population: people with serious mental illness and co‐occurring substance misuse
Setting: In and outpatients, United States
Intervention: Risperidone
Comparison: Olanzapine

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with Olanzapine

Risk with Risperidone

Mental state: 2. Specific‐ Positive symptoms, total score‐ average endpoint scores (SADS‐C‐PD scale, lower = better)

The mean positive symptoms total score at endpoint (SADS‐C‐PD scale, lower = better) in the intervention group was 1.5 lower (3.82 lower to 0.82 higher)

37
(1 RCT)

⊕⊝⊝⊝
very low1 2

Substance use: 1. Reduction of cannabis use‐change data (number of joints smoked/week)

The reduction of cannabis joints smoked (number of joints smoked/week‐short term data, up to 6 months) in the intervention group was 0.4 higher (4.72 lower to 5.52 higher)

41
(1 RCT)

⊕⊝⊝⊝
very low3 4

Subjective well‐being

No trial reported on this important outcome for participants with a co‐occurring substance use disorder

Craving for substances: 2. Drug Desires Questionnaire‐ average endpoint scores (DDQ, lower = better)

The mean endpoint. Drug Desires Questionnaire‐ endpoint scores (DDQ, lower = better), short term, up to 6 months‐in the intervention group was5 higher (4.86 lower to 14.86 higher)

41
(1 RCT)

⊕⊝⊝⊝
very low2 3

Adherence to antipsychotic medication: number of missed doses, average endpoint data, short term (up to 6 months)

no useable data available for this outcome

Adverse effects: Parkinsonism ‐ average endpoint score (SAS, high = worse)

The mean adverse effects: ‐ Parkinsonism‐ average endpoint score (SAS, high = worse)‐ short‐term‐ up to 6 months in the intervention group was 0.08 lower (1.21 lower to 1.05 higher)

16
(1 RCT)

⊕⊝⊝⊝
very low2 5

Leaving study early: any reason

Study population

RR 0.68
(0.34 to 1.35)

77
(2 RCTs)

⊕⊝⊝⊝
very low4 6

357 per 1000

243 per 1000
(121 to 482)

Moderate

411 per 1000

279 per 1000
(140 to 554)

*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).

CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 High risk for performance bias, allocation concealment, unknown risk for attrition and slective reporting

2 Very low sample size, optimal information size (OIS) not met

3 High risk of attrition bias, study sponsored by pharmaceutical industry

4 Very low sample size, optimal information criterion not met, CI crosses both appreciable harm and benefit

5 High attrition risk, high other risk of funding by pharmaceutical industry, all other risk items unclear risk of bias

6 High risk of performance, attrition and funding bias. Several domains with unclear risk of bias

Figures and Tables -
Summary of findings 2. RISPERIDONE versus OLANZAPINE ‒ short‐ and long‐term data for people with severe mental illness and co‐occurring substance misuse
Summary of findings 3. RISPERIDONE versus PERHENAZINE ‒ long‐term data for people with severe mental illness and co‐occurring substance misuse

RISPERIDONE versus PERPHENAZINE‐long term data (>12 months) for people with severe mental illness and co‐occurring substance misuse

Patient or population: people with severe mental illness and co‐occurring substance misuse
Setting: Outpatients, United States
Intervention: RISPERIDONE
Comparison: PERPHENAZINE

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with PERPHENAZINE

Risk with RISPERIDONE

Leaving the study early: any reason

Study population

RR 1.05
(0.92 to 1.20)

281
(1 RCT)

⊕⊕⊝⊝
low1 2

750 per 1000

788 per 1000
(690 to 900)

Moderate

750 per 1000

788 per 1000
(690 to 900)

*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).

CI: Confidence interval; RR: Risk ratio; OR: Odds ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

1 High risk of attrition bias, but this does not affect this particular outcomes

2 Optimal information size criterion is met but the estimate includes no effect with both appreciable harm and benefit

Figures and Tables -
Summary of findings 3. RISPERIDONE versus PERHENAZINE ‒ long‐term data for people with severe mental illness and co‐occurring substance misuse
Summary of findings 4. RISPERIDONE versus QUETIAPINE ‒ short‐ and long‐term data for people with severe mental illness and co‐occurring substance misuse

RISPERIDONE versus QUETIAPINE‐ short and long term data (up to 6months and > 12 months) for people with severe mental illness and co‐occurring substance misuse

Patient or population: people with severe mental illness and co‐occurring substance misuse
Setting: Outpatients, United States
Intervention: RISPERIDONE
Comparison: QUETIAPINE

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with QUETIAPINE

Risk with RISPERIDONE

Leaving the study early: 1. any reason, long term (>12 months)

Study population

RR 0.96
(0.86 to 1.07)

294
(1 RCT)

⊕⊕⊝⊝
low3 4

825 per 1000

792 per 1000
(709 to 883)

Moderate

825 per 1000

792 per 1000
(709 to 883)

*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).

CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

1 Risk of bias unclear across all groups and with high risk of funding bias

2 Sample size meets optimal information threshold/ required sample size to detect 25% difference from control group in in PANSS score; at alpha of 0.05 and power of 80%.

3 Outcome not affected by risk of attrition bias

4 Optimal information criterion not met, estimate includes both appreciable harm and benefit

Figures and Tables -
Summary of findings 4. RISPERIDONE versus QUETIAPINE ‒ short‐ and long‐term data for people with severe mental illness and co‐occurring substance misuse
Summary of findings 5. RISPERIDONE versus ZIPRASIDONE ‒ long‐term data (> 12 months) for people with severe mental illness and co‐occurring substance misuse

RISPERIDONE versus ZIPRASIDONE‐ all data long term data (>12 months) for people with severe mental illness and co‐occurring substance misuse

Patient or population: people with severe mental illness and co‐occurring substance misuse
Setting: Outpatients, United States
Intervention: RISPERIDONE
Comparison: ZIPRASIDONE

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with ZIPRASIDONE

Risk with RISPERIDONE

Leaving the study early: any reason

Study population

RR 0.96
(0.85 to 1.10)

240
(1 RCT)

⊕⊕⊝⊝
low1 2

819 per 1000

787 per 1000
(696 to 901)

Moderate

819 per 1000

787 per 1000
(696 to 901)

*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).

CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

1 Risk of attrition bias high but this does not affect this outcome

2 Optimal information size criterion met but estimate includes both appreciable harm and benefit. Total sample size small

Figures and Tables -
Summary of findings 5. RISPERIDONE versus ZIPRASIDONE ‒ long‐term data (> 12 months) for people with severe mental illness and co‐occurring substance misuse
Table 1. Assessment of risk of bias

Sequence generation

  • Low: investigators described a random component in the sequence generation process such as the use of random number table, coin tossing, cards or envelope shuffling etc.

  • High: investigators described a non‐random component in the sequence generation process such as the use of odd or even date of birth, algorithm based on the day/date of birth, hospital or clinic record number.

  • Unclear: insufficient information to permit judgment of the sequence generation process.

Allocation concealment

  • Low: participants and the investigators enrolling participants cannot foresee assignment, e.g. central allocation; or sequentially numbered, opaque, sealed envelopes.

  • High: participants and investigators enrolling participants can foresee upcoming assignment, e.g. an open random allocation schedule (e.g. a list of random numbers); or envelopes were unsealed or non­opaque or not sequentially numbered.

  • Unclear: insufficient information to permit judgment of the allocation concealment or the method not described.

Blinding of participants and personnel

  • Low: blinding of the participants, key study personnel, and unlikely that the blinding could have been broken, or lack of blinding unlikely to introduce bias. No blinding in the situation where non‐blinding is not likely to introduce bias.

  • High: no blinding, incomplete blinding and the outcome is likely to be influenced by lack of blinding. Blinding of participants and key study personnel attempted but likely that blinding could have been broken and the outcome is likely to be influenced by lack of blinding.

  • Unclear: insufficient information to permit judgment of 'low risk' or 'high risk', or otherwise the study did not address this outcome.

Blinding of outcome assessment

  • Low: no blinding of the outcome assessment but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding, or blinding of outcome assessment ensured and unlikely that blinding could have been broken.

  • High: no blinding of outcome assessment and outcome measurement is likely to be influenced by lack of blinding, or blinding of outcome assessment but likely that blinding could have been broken and outcome measurement is likely to be influenced by lack of blinding.

  • Unclear: insufficient information to permit judgement of 'low risk' or 'high risk', or the study did not address this outcome.

Incomplete outcome data

  • Low: no missing outcome data, reasons for missing outcome data unlikely to be related to true outcome, or missing outcome data balanced in number across groups.

  • High: reason for missing outcome data likely to be related to true outcome, with either imbalance in number across groups or reasons for missing data.

  • Unclear: insufficient reporting of attrition or exclusions.

Selective reporting

  • Low: a protocol is available which clearly states the primary outcome as the same as in the final trial report.

  • High: the primary outcome differs between the protocol and final trial report.

  • Unclear: no trial protocol is available or there is insufficient reporting to determine if selective reporting is present.

Other forms of bias

  • Low: there is no evidence of bias from other sources.

  • High: there is potential bias present from other sources (e.g. fraudulent activity, extreme baseline imbalance or bias related to specific study design).

  • Unclear: insufficient information to permit judgment of adequacy or otherwise of other forms of bias.

Figures and Tables -
Table 1. Assessment of risk of bias
Table 2. Scales, diagnostic instruments and other outcome measures used in included studies

Diagnostic tools

Abbreviation

Source of scale/ instrument

Study using instrument

Results reported or usable data for re‐analysis/ quantitative synthesis or qualitative results/data only

Structured Clinical Interview for DSM Disorders

SCID‐I

First 1994

Akerele 2007; Sevy 2011; Swartz 2008; van Nimwegen 2008

Not an outcome measure

Mental state scales

Brief Psychiatric Rating Scale

BPRS

Lukoff 1986

Noordsy 2010

No results or usable data reported or obtained

Clinical Global Impression scale

CGI

Guy 1976

Akerele 2007; Noordsy 2010

No results or usable data reported or obtained

Hamilton Depression Rating Scale

HAM‐D

Hamilton 1960

Akerele 2007

Results reported; usable data for quantitative synthesis

Positive and Negative Syndrome Scale

PANSS

Kay 1986

Akerele 2007;Greenspan 2005; Machielsen 2014; Swartz 2008

Results reported; usable data for quantitative synthesis

Schedule for Affective Disorders and Schizophrenia ‒ Change Version with Psychosis and Disorganization items

SADS‐C‐PD

Endicott 1978

Sevy 2011

Results reported; usable data for quantitative synthesis

Schedule for the Assessment of Negative Symptoms

SANS

Andreasen 1982

Noordsy 2010

No results or usable data reported or obtained

Substance use scales

Addiction Severity Index

ASI

McLellan 1980; McLellan 1992

Akerele 2007

No results or usable data reported or obtained

Composite International Diagnostic Interview

CIDI

Robins 1988

Machielsen 2014

Not an outcome measure

Substance Use Questionnaire

SUQ

Sevy 2011, Locally derived instrument/ non‐validated

Sevy 2011

Results reported, used together with urine testing; usable data for quantitative synthesis

Time‐Line Follow‐Back

TLFB

Sobell 1992

Noordsy 2010

Results reported in dichotomised format for quantitative synthesis

Quantitative Substance Use Inventory

Locally derived instrument/ non‐validated

Akerele 2007

Non‐validated scale

Subjective‐Wellbeing Scales

Subjective Well‐being Under Neuroleptics Scale

SWN

de Haan 2002; Naber 1995

Machielsen 2014; van Nimwegen 2008

Results reported; usable data for quantitative synthesis

Craving for substances measures

Cocaine Craving Report

Weddington 1990

Akerele 2007

No usable data for quantitative synthesis

Desires for Drug Questionnaire

DDQ

Franken 2002

van Nimwegen 2008

Results reported; usable data for quantitative synthesis

Marijuana Craving Report

Weddington 1990

Akerele 2007

No usable data for quantitative synthesis

Marijuana Craving Questionnaire

MCQ

Heishman 2009

Machielsen 2014

Results reported; usable data for quantitative synthesis

Obsessive Compulsive Drug Use Scale

OCDUS

Dekker 2012

Machielsen 2014;van Nimwegen 2008

Results reported; usable data for quantitative synthesis

Adverse effect scales

Abnormal Involuntary Movement Scale

AIMS

National Institute of Mental Health 1988

Akerele 2007

No results or usable data reported or obtained

Barnes Akathisia Rating Scale

BARS

Barnes 1989

Brunette 2011

No results or usable data reported or obtained

Simpson Angus Scale

SAS

Simpson 1970

Akerele 2007

Results reported; usable data for quantitative synthesis

Other measures (categorical or time to event)

Urine assay for cannabis and cocaine use (proportion of treatment group positive per week)

Akerele 2007

No usable data for quantitative synthesis

Number of participants with improvement in substance use (categorised as improved or not‐improved versus unchanged)

Noordsy 2010

Results reported; usable data for quantitative synthesis (dichotomised)

Days of self‐reported drug use in past week

Akerele 2007

No usable data for quantitative synthesis

Weeks in treatment

Akerele 2007; Smelson 2006

Results reported; usable data for quantitative synthesis

Number of participants not completing the study

Akerele 2007; Machielsen 2014; Noordsy 2010; Sevy 2011; Swartz 2008

Results reported, usable data for quantitative synthesis

Compliance with medication (missed doses)

Akerele 2007

No usable data for quantitative synthesis

Figures and Tables -
Table 2. Scales, diagnostic instruments and other outcome measures used in included studies
Table 3. Excluded randomised and quasi randomised studies and their relevant comparisons

Study tag

Participants

Comparison

Relevant review

Primary problem

Co‐morbidity

Note (reasons for exclusion)

Blin 1996

schizophrenia

Excludes participants with alcohol or drug abuse in past year

Excludes comorbidity

risperidone, haloperidol, methotrimeprazine

Gaebel 2010

schizophrenia, schizoaffective disorder

Excludes participants with alcohol or drug abuse in past year

Excludes comorbidity

risperidone, olanzapine, conventional antipsychotics vs. risperidone long‐acting injectable (RLAI),or quetiapine

Green 2001

schizophrenia

cannabis use disorder

Excluded as this was a study protocol, authors contacted for unpublished data, no response

risperidone vs. clozapine

Harvey 2007

bipolar type I disorder

No measure of substance use

Excludes comorbidity

risperidone, quetiapine

Ikuta 2014

schizophrenia, schizophreniform, psychosis not otherwise specified

No measure of substance use

Excludes comorbidity

risperidone, aripirazole

Kerfoot 2011

schizophrenia

Co‐occurring substance use in subgroup of 44.9%

No comparison of study medication, mainly a prognostic study of the impact of substance use

risperidone, quetiapine, perphenazine, olanzapine, ziprasidone

Liemburg 2011

schizophrenia

No measure of substance use

Excludes comorbidity

risperidone, aripiprazole

Liu 2008

mental disorders due to alcohol use

substance induced mental disorders

Exclusion criterion

risperidone, olanzapine

Suggested review: risperidone versus other antipsychotics for substance induced psychosis

NCT00063349

schizophrenia

Co‐occurring cannabis use disorder

Study protocol, authors contacted for unpublished data no response

risperidone, clozapine

NCT00130923

schizophrenia, schizoaffective disorder

Co‐occurring alcohol use disorder (abuse or dependence)

Comparison of same medication (risperidone) in different preparations (oral vs depot)

oral risperidone, depot risperidone

NCT00169026

schizophrenia, schizoaffective disorder

Co‐occurring alcohol and substance use disorder

Study protocol, study terminated, authors contacted for unpublished data no response

clozapine, conventional antipsychotics, atypical antipsychotics

NCT00498550

schizophrenia, schizoaffective disorder

Co‐occurring cannabis use disorder

Study protocol, authors contacted no data provided

clozapine, conventional antipsychotics, atypical antipsychotics

Nejtek 2008

bipolar I and II disorder, recent manic or mixed episode with or without psychosis

co‐occurring cocaine or methamphetamine use disorder

Only 8.3% of total sample had psychotic features and 15.9% had bipolar type II disorder.

risperidone, quetiapine

Suggested review: Risperidone versus other antipsychotics in bipolar disorder with co‐occurring substance use disorders

Perlis 2006

bipolar I disorder with mania or mixed states

Excludes participants with recent substance use

Excludes comorbidity. Excludes bipolar disorder with psychotic features.

risperidone or olanzapine

Rezayat 2014

bipolar disorder, acute mania

Excludes participants with drug or alcohol use in past 3 months

Excludes comorbidity

aripiprazole, risperidone

Rubio 2006a

schizophrenia

Co‐occurring substance use disorders

Quasi‐randomisation

risperidone long‐acting depot, zuclopenthixol long‐acting depot

Rubio 2006b

schizophrenia

Co‐occurring substance use disorders

Quasi‐randomisation

risperidone (oral), zuclopenthixol (oral), zuclopenthixol long acting depot

Sachs 2002

bipolar with current manic or mixed episode

Study excludes participants with drug or alcohol in past 1 months

Excludes comorbidity

mood stabiliser augmentation with risperidone, haloperidol or placebo

Sajatovic 2002

psychotic disorders: schizoaffective disorder, bipolar I disorder, major depressive disorder, delusional disorder, Alzheimer's dementia, schizophreniform disorder, vascular dementia, and substance abuse dementia

No subgroups with substance use reported

Excludes comorbidity. Authors contacted for unpublished data, no response.

risperidone, quetiapine

Smulevich 2005

bipolar I disorder

Excludes participants with recent substance use

Excludes comorbidity

haloperidol, risperidone, placebo

van Nimwegen 2008a

schizophrenia, schizophreniform, schizoaffective disorder

No measure of substance use

Excludes comorbidity

haloperidol, risperidone, placebo

Yatham 2007

bipolar I and II

Excludes participants with drug or alcohol use in past 3 months.

Excludes comorbidity

continuation of oral risperidone, olanzapine, quetiapine or switch to long‐acting injectable LAI risperidone

Zhangyue 2005

schizophrenia or schizophrenia‐like illnesses

Excludes participants with alcohol or substance dependence

Quasi‐randomisation.Excludes comorbidity.

aripiprazole versus risperidone

Figures and Tables -
Table 3. Excluded randomised and quasi randomised studies and their relevant comparisons
Comparison 1. RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mental state: 1. General: average endpoint scores (PANSS subscale, lower=better) Show forest plot

1

36

Mean Difference (IV, Fixed, 95% CI)

2.70 [‐2.14, 7.54]

2 Mental state: 2. General: any change in general symptoms: Show forest plot

1

14

Risk Ratio (M‐H, Random, 95% CI)

0.14 [0.01, 2.34]

3 Mental state: 3. Specific: positive, negative symptoms ‐ average endpoint scores (PANSS subscales, lower = better): Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Subtotals only

3.1 Mental state: Positive symptoms ‐ average endpoint score (PANSS positive subscale, lower=better)

1

36

Mean Difference (IV, Random, 95% CI)

0.90 [‐2.21, 4.01]

3.2 Mental state: Negative symptoms ‐ average endpoint score (PANSS negative subscale, lower=better)

1

36

Mean Difference (IV, Random, 95% CI)

4.0 [0.79, 7.21]

4 Mental state: 4. Specific: anxiety symptoms Show forest plot

1

14

Risk Ratio (M‐H, Random, 95% CI)

3.0 [0.14, 63.15]

5 Substance use Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

5.1 Substance use: Improvement (at least 20% reduction in use, TLFB scale)

1

14

Risk Ratio (M‐H, Random, 95% CI)

1.0 [0.30, 3.35]

5.2 Substance use: Discontinued substance use

1

28

Risk Ratio (M‐H, Random, 95% CI)

1.13 [0.41, 3.12]

6 Subjective Well‐being: average endpoint scores (Subjective Well‐being under Neuroleptics scale, SWN scale, higher=better) Show forest plot

1

36

Mean Difference (IV, Random, 95% CI)

‐6.0 [‐14.82, 2.82]

7 Craving for substances Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Subtotals only

7.1 Craving for substances: 1. Specific: current craving‐ average endpoint scores (Marijuana Craving Questionairre, MCQ, lower=better)

1

28

Mean Difference (IV, Random, 95% CI)

7.00 [2.37, 11.63]

7.2 Craving for substances: 2. Specific: past week craving‐ average endpoint scores (Obsessive Compulsive Drug Use Scale, OCDUS, lower=better)

1

28

Mean Difference (IV, Random, 95% CI)

14.20 [4.45, 23.95]

8 Adherence to antipsychotic medication: discontinued medication Show forest plot

1

36

Risk Ratio (M‐H, Random, 95% CI)

4.05 [0.21, 78.76]

9 Adverse effects. 1. Movement disorders Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

9.1 any extrapyramidal side‐effects

2

50

Risk Ratio (M‐H, Random, 95% CI)

2.71 [0.30, 24.08]

9.2 akathisia

1

14

Risk Ratio (M‐H, Random, 95% CI)

2.0 [0.23, 17.34]

10 Adverse effects: 2. Non‐movement disorder related side‐effects Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

10.1 Cardiovascular: palpitations

1

14

Risk Ratio (M‐H, Random, 95% CI)

3.0 [0.14, 63.15]

10.2 Cardiovascular: hypotension

1

14

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.02, 7.02]

10.3 Central nervous system: headache

1

14

Risk Ratio (M‐H, Random, 95% CI)

0.2 [0.01, 3.54]

10.4 Central Nervous System: somnolence

1

14

Risk Ratio (M‐H, Random, 95% CI)

0.2 [0.03, 1.30]

10.5 Dermatological: acne

1

14

Risk Ratio (M‐H, Random, 95% CI)

3.0 [0.14, 63.15]

10.6 Endocrinological: decreased libido

1

14

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.02, 7.02]

10.7 Ear and labarynthine: ear canal blockage

1

14

Risk Ratio (M‐H, Random, 95% CI)

3.0 [0.14, 63.15]

10.8 Gastrointestinal: abdominal pain

1

14

Risk Ratio (M‐H, Random, 95% CI)

3.0 [0.14, 63.15]

10.9 Gasstrointesinal: elevated liver function tests

1

14

Risk Ratio (M‐H, Random, 95% CI)

3.0 [0.14, 63.15]

10.10 Gastrointestinal: hypersalivation

1

14

Risk Ratio (M‐H, Random, 95% CI)

0.11 [0.01, 1.74]

10.11 General adverse effects: fatigue

1

14

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.02, 7.02]

10.12 Injuries: sprain

1

14

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.02, 7.02]

10.13 Metabolic: increased appetite

1

14

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.02, 7.02]

10.14 Metabolic: weight gain

1

14

Risk Ratio (M‐H, Random, 95% CI)

1.0 [0.19, 5.24]

10.15 Musculosceletal: ankle pain

1

14

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.02, 7.02]

10.16 Musculosceletal: knee and foot pain

1

14

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.02, 7.02]

10.17 Musculosceletal: muscle twitch

1

14

Risk Ratio (M‐H, Random, 95% CI)

3.0 [0.14, 63.15]

10.18 Renal: urinary retention

1

14

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.02, 7.02]

10.19 Renal: urinary urgency

1

14

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.02, 7.02]

11 Leaving the study early Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

11.1 any reason

2

45

Risk Ratio (M‐H, Random, 95% CI)

0.49 [0.10, 2.51]

11.2 due to inefficacy

1

14

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

Figures and Tables -
Comparison 1. RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months)
Comparison 2. RISPERIDONE versus OLANZAPINE

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mental state: 1. Specific: Depression‐ change scores (HAM‐D, higher = better), short term (up to 6 months) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Subtotals only

1.1 short‐term (up to 6 months)

1

22

Mean Difference (IV, Random, 95% CI)

‐0.11 [‐0.78, 0.56]

2 Mental state: 2. Specific: Positive symptoms, total score‐ average endpoint scores (SADS‐C‐PD scale, lower=better), short term (up to 6 months) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Subtotals only

2.1 short term, up to 6 months)

1

37

Mean Difference (IV, Random, 95% CI)

‐1.5 [‐3.82, 0.82]

3 Mental state: 3. Specific: Positive symptom subscales‐ average endpoint scores (SADS‐C‐PD subscores, lower=better), short term (up to 6 months)‐ skewed data Show forest plot

Other data

No numeric data

4 Mental state: 4. Specific: Negative symptoms, subscales‐ average endpoint scores (SANS subscales, lower=better), short term (up to 6 months) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Subtotals only

4.1 Negative symptoms: Affective flattening

1

39

Mean Difference (IV, Random, 95% CI)

0.5 [‐0.17, 1.17]

4.2 Negative symptoms: alogia

1

39

Mean Difference (IV, Random, 95% CI)

0.40 [‐0.22, 1.02]

4.3 Negative symptoms: avolition‐apathy

1

39

Mean Difference (IV, Random, 95% CI)

‐0.10 [‐0.73, 0.53]

4.4 Negative symptoms: asociality‐anhedonia

1

39

Mean Difference (IV, Random, 95% CI)

‐0.10 [‐0.80, 0.60]

5 Substance use: 1. Reduction of cannabis use‐change data (number of joints smoked/week, LOCF data, higher =better)‐ short term data (up to 6 months) Show forest plot

1

41

Mean Difference (IV, Random, 95% CI)

0.40 [‐4.72, 5.52]

6 Substance use: 2. Discontinued substance use, short term (up to 6 months) Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

6.1 Substance use: 2. Stopped using cannabis (Urine testing and Substance Use Questionnaire)

1

37

Risk Ratio (M‐H, Random, 95% CI)

1.19 [0.68, 2.08]

6.2 Substance use: 2. Stopped using alcohol (Substance Use Questionnaire)

1

37

Risk Ratio (M‐H, Random, 95% CI)

1.31 [0.73, 2.36]

7 Craving for substances: 1. Obsessive Compulsive Drug Use Scale‐ average endpoint score (OCDUS, lower=better)‐short term (up to 6 months) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Subtotals only

7.1 short‐term (up to 6 months)

1

41

Mean Difference (IV, Random, 95% CI)

1.30 [‐3.51, 6.11]

8 Craving for substances: 2. Desires for Drug Questionnaire‐ average endpoint scores (DDQ, LOCF data, lower=better), short term (up to 6 months) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Subtotals only

8.1 Short‐term (up to 6 months)

1

41

Mean Difference (IV, Random, 95% CI)

5.0 [‐4.86, 14.86]

9 Adverse effects Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

9.1 Movement disorders: Parkinsonism‐ average endpoint score (SAS, high = worse)‐ short‐term (up to 6 months)

1

16

Mean Difference (IV, Random, 95% CI)

‐0.08 [‐1.21, 1.05]

9.2 Non‐movement disorder related side‐effects: Weight gain‐ average endpoint score (BMI, lower=better)‐ short term (up to 6 months)

1

37

Mean Difference (IV, Random, 95% CI)

‐1.0 [‐3.99, 1.99]

10 Leaving study early: 1. Various reasons Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

10.1 any reason, short term (up to 6 months)

2

77

Risk Ratio (M‐H, Random, 95% CI)

0.68 [0.34, 1.35]

10.2 any reason, long term (> 12 months)

1

299

Risk Ratio (M‐H, Random, 95% CI)

1.07 [0.94, 1.21]

10.3 readmission, short term (up to 6 months)

1

28

Risk Ratio (M‐H, Random, 95% CI)

1.0 [0.07, 14.45]

10.4 intolerable adverse effects, short term (up to 6 months)

1

28

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.5 participant loss of interest, short term (up to 6 months)

1

28

Risk Ratio (M‐H, Random, 95% CI)

0.43 [0.14, 1.33]

11 Leaving study early: 2. Weeks in the study‐ average endpoint data (high=good), short term (up to 6 months) Show forest plot

1

28

Mean Difference (IV, Random, 95% CI)

0.0 [‐3.35, 3.35]

12 Leaving study early: 3. Weeks in study‐ average endpoint data (high=good), short term (up to 6 months)‐ skewed data Show forest plot

Other data

No numeric data

Figures and Tables -
Comparison 2. RISPERIDONE versus OLANZAPINE
Comparison 3. RISPERIDONE versus PERPHENAZINE

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Leaving the study early: all cause discontinuation, long term (>12 months) Show forest plot

1

281

Risk Ratio (M‐H, Random, 95% CI)

1.05 [0.92, 1.20]

Figures and Tables -
Comparison 3. RISPERIDONE versus PERPHENAZINE
Comparison 4. RISPERIDONE versus QUETIAPINE

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Leaving the study early: all cause discontinuation, long term (>12 months) Show forest plot

1

294

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.86, 1.07]

Figures and Tables -
Comparison 4. RISPERIDONE versus QUETIAPINE
Comparison 5. RISPERIDONE versus ZIPRASIDONE

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Leaving the study early: all cause discontinuation, long term (>12 months) Show forest plot

1

240

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.85, 1.10]

Figures and Tables -
Comparison 5. RISPERIDONE versus ZIPRASIDONE