Risperidone versus other antipsychotics for people with dual diagnosis of a psychiatric disorder and an alcohol or drug use disorder

What is dual diagnosis?

Dual diagnosis is a term used to describe people who have both a psychiatric disorder and an alcohol or drug use disorder. Up to 75% of people with a serious mental illness (SMI) are dual diagnosis. It has been suggested that one of the reasons behind the high levels of substance use in people with SMI is due to 'self-medication', with patients taking additional drugs in order to counter their distressing symptoms. People with a dual diagnosis have been shown to have more complications in their treatment, including higher rates of relapse and re-hospitalisation, more contact with legal and forensic services, higher levels of psychotic symptoms, more risk-taking behaviour, greater levels of side-effects to antipsychotics and lower medication adherence. Antipsychotics are the main treatment for SMI. It has been suggested that second-generation antipsychotics (SGAs) such as risperidone may be superior to older, first-generation antipsychotics (FGAs) in improving negative affective states, reducing drug craving, improving subjective well-being, and may lead to fewer side-effects and hence greater medication adherence. Such improvements in symptoms may lead to less self-medication with alcohol and drugs, and improved overall mental states. However it remains unclear to what extent risperidone, one of the first atypical antipsychotics to be manufactured, is superior to other antipsychotics for dual diagnosis.

Who may be interested in this review?

Mental health care practitioners who treat people with SMI and dual diagnosis, and who prescribe antipsychotics for these conditions. People who use mental health services and their families who may be involved in their treatment and care.

What does this review aim to answer?

How effective and safe is risperidone compared to other antipsychotics for treating people with a dual diagnosis?

Which studies were included in the review?

We conducted searches for relevant randomised studies in January 2016 and October 2017. We found eight randomised controlled trials with 1073 participants who had a dual diagnosis. The majority of participants were adults over 18 years (4 participants were 17 years). Risperidone was compared to clozapine, olanzapine, perphenazine, quetiapine and ziprasidone.

What does the evidence from the review tell us?

We found no great effect favouring risperidone over any of the other comparison medications. Very limited data were available for side-effects; and again, we found no real differences between risperidone and other antipsychotics. Overall the quality of the evidence available was graded as low to very low, and currently there is not sufficient evidence to indicate risperidone is superior or inferior to other antipsychotics in the treatment of people with severe mental illness and co-occurring substance misuse.

What should happen next?

More high-quality research is needed. Future research should include samples sufficiently large to detect meaningful clinical differences in outcomes.

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.

Read the full 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 strategy: 

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.

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