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Meta-Analysis
. 2018 Jan 22;1(1):CD011057.
doi: 10.1002/14651858.CD011057.pub2.

Risperidone versus other antipsychotics for people with severe mental illness and co-occurring substance misuse

Henk S Temmingh  1 , Taryn Williams, Nandi Siegfried, Dan J Stein
Affiliations
Meta-Analysis

Risperidone versus other antipsychotics for people with severe mental illness and co-occurring substance misuse

Henk S Temmingh et al. Cochrane Database Syst Rev. .

Abstract

Background: Up to 75% of people with serious mental illness (SMI) such as schizophrenia and bipolar disorder have co-occurring substance use disorders (dual diagnosis). Dual diagnosis can have an adverse effect on treatment and prognosis of SMI.

Objectives: To evaluate the effects of risperidone compared to treatment with other antipsychotics (first-generation and other second-generation antipsychotics) used in people with serious mental illness and co-occurring substance misuse.

Search methods: On 6 January 2016 and 9 October 2017, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (including trial registers).

Selection criteria: We selected randomised trials of risperidone versus any other antipsychotic in people with SMI and substance abuse (dual diagnosis). We included trials meeting our inclusion criteria and reporting useable data. We excluded trials that either did not meet our inclusion criteria or met our inclusion criteria but did not report any useable data.

Data collection and analysis: We independently inspected citations and selected studies. For included studies, we independently extracted data and appraised study quality. For binary outcomes we calculated the risk ratios (RRs) and their 95% confidence intervals. For continuous outcomes we calculated the mean differences (MDs) and their 95% confidence intervals. We pooled data using random-effects meta-analyses and assessed the quality of evidence, creating a 'Summary of findings' table using the GRADE approach.

Main results: We identified eight randomised trials containing a total of 1073 participants with SMI and co-occurring substance misuse. Seven of these contributed useable data to the review. There was heterogeneity in trial design and measurement. Risperidone was compared to clozapine, olanzapine, perphenazine, quetiapine and ziprasidone. Few trials compared risperidone with first-generation agents. Few trials examined participants with a dual diagnosis from the outset and most trials only contained separate analyses of subgroups with a dual diagnosis or were secondary data analyses of subgroups of people with a dual diagnosis from existing larger trials.For risperidone versus clozapine we found no clear differences between these two antipsychotics in the reduction of positive psychotic symptoms (1 randomised controlled trial (RCT), n = 36, mean difference (MD) 0.90, 95% CI -2.21 to 4.01, very low quality evidence), or reduction in cannabis use (1 RCT, n = 14, risk ratio (RR) 1.00, 95% CI 0.30 to 3.35, very low quality evidence), improvement in subjective well-being (1 RCT, n = 36, MD -6.00, 95% CI -14.82 to 2.82, very low quality evidence), numbers discontinuing medication (1 RCT, n = 36, RR 4.05, 95% CI 0.21 to 78.76, very low quality evidence), extrapyramidal side-effects (2 RCTs, n = 50, RR 2.71, 95% CI 0.30 to 24.08; I² = 0%, very low quality evidence), or leaving the study early (2 RCTs, n = 45, RR 0.49, 95% CI 0.10 to 2.51; I² = 34%, very low quality evidence). Clozapine was associated with lower levels of craving for cannabis (1 RCT, n = 28, MD 7.00, 95% CI 2.37 to 11.63, very low quality evidence).For risperidone versus olanzapine we found no clear differences in the reduction of positive psychotic symptoms (1 RCT, n = 37, MD -1.50, 95% CI -3.82 to 0.82, very low quality evidence), reduction in cannabis use (1 RCT, n = 41, MD 0.40, 95% CI -4.72 to 5.52, very low quality evidence), craving for cannabis (1 RCT, n = 41, MD 5.00, 95% CI -4.86 to 14.86, very low quality evidence), parkinsonism (1 RCT, n = 16, MD -0.08, 95% CI -1.21 to 1.05, very low quality evidence), or leaving the study early (2 RCT, n = 77, RR 0.68, 95% CI 0.34 to 1.35; I² = 0%, very low quality evidence).For risperidone versus perphenazine, we found no clear differences in the number of participants leaving the study early (1 RCT, n = 281, RR 1.05, 95% CI 0.92 to 1.20, low-quality evidence).For risperidone versus quetiapine, we found no clear differences in the number of participants leaving the study early (1 RCT, n = 294, RR 0.96, 95% CI 0.86 to 1.07, low-quality evidence).For risperidone versus ziprasidone, we found no clear differences in the number of participants leaving the study early (1 RCT, n = 240, RR 0.96, 95% CI 0.85 to 1.10, low-quality evidence).For many comparisons, important outcomes were missing; and no data were reported in any study for metabolic disturbances, global impression of illness severity, quality of life or mortality.

Authors' conclusions: There is not sufficient good-quality evidence available to determine the effects of risperidone compared with other antipsychotics in people with a dual diagnosis. Few trials compared risperidone with first-generation agents, leading to limited applicability to settings where access to second-generation agents is limited, such as in low- and middle-income countries. Moreover, heterogeneity in trial design and measurement of outcomes precluded the use of many trials in our analyses. Future trials in this area need to be sufficiently powered but also need to conform to consistent methods in study population selection, use of measurement scales, definition of outcomes, and measures to counter risk of bias. Investigators should adhere to CONSORT guidelines in the reporting of results.

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Conflict of interest statement

Henk Temmingh has received a speaker honorarium from Pharma Dynamics and was a recipient of the Harry Crossley Clinical Fellowship that provided support for travel and subsistence during his sabbatical.

Taryn Williams has no known conflicts of interest outside her employment by the MRC Unit on Anxiety and Stress Disorders.

Nandi Siegfried provides technical consultation on the efficacy of drugs at the request of a managed care organization, and receives an honorarium. Nandi has not appraised risperidone in this work.

Dan Stein has received research grants or consultancy honoraria (or both) from AstraZeneca, Eli Lilly, GlaxoSmithKline, Lundbeck, Orion, Pfizer, Pharmacia, Roche, Servier, Solvay, Sumitomo, and Wyeth.

Figures

1
1
Risperidone
2
2
Logic framework model with potential causal pathways: risperidone treatment in persons with dual diagnosis.
3
3
PRISMA flow diagram of study selection from 2016 and 2017 searches
4
4
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
5
5
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
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).
1.2
1.2. Analysis
Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 2 Mental state: 2. General: any change in general symptoms:.
1.3
1.3. Analysis
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):.
1.4
1.4. Analysis
Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 4 Mental state: 4. Specific: anxiety symptoms.
1.5
1.5. Analysis
Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 5 Substance use.
1.6
1.6. Analysis
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).
1.7
1.7. Analysis
Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 7 Craving for substances.
1.8
1.8. Analysis
Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 8 Adherence to antipsychotic medication: discontinued medication.
1.9
1.9. Analysis
Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 9 Adverse effects. 1. Movement disorders.
1.10
1.10. Analysis
Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 10 Adverse effects: 2. Non‐movement disorder related side‐effects.
1.11
1.11. Analysis
Comparison 1 RISPERIDONE versus CLOZAPINE ‐ all data short term (up to 6 months), Outcome 11 Leaving the study early.
2.1
2.1. Analysis
Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 1 Mental state: 1. Specific: Depression‐ change scores (HAM‐D, higher = better), short term (up to 6 months).
2.2
2.2. Analysis
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).
2.4
2.4. Analysis
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).
2.5
2.5. Analysis
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).
2.6
2.6. Analysis
Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 6 Substance use: 2. Discontinued substance use, short term (up to 6 months).
2.7
2.7. Analysis
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).
2.8
2.8. Analysis
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).
2.9
2.9. Analysis
Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 9 Adverse effects.
2.10
2.10. Analysis
Comparison 2 RISPERIDONE versus OLANZAPINE, Outcome 10 Leaving study early: 1. Various reasons.
2.11
2.11. Analysis
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).
3.1
3.1. Analysis
Comparison 3 RISPERIDONE versus PERPHENAZINE, Outcome 1 Leaving the study early: all cause discontinuation, long term (>12 months).
4.1
4.1. Analysis
Comparison 4 RISPERIDONE versus QUETIAPINE, Outcome 1 Leaving the study early: all cause discontinuation, long term (>12 months).
5.1
5.1. Analysis
Comparison 5 RISPERIDONE versus ZIPRASIDONE, Outcome 1 Leaving the study early: all cause discontinuation, long term (>12 months).
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