Chlorpromazine versus metiapine for schizophrenia

The aim of this review was to find good quality evidence for comparing the efficacy of chlorpromazine versus metiapine for schizophrenia.

Background

Schizophrenia is a common disabling and enduring mental illness worldwide. People with schizophrenia often experience positive symptoms such as delusions and hallucinations, and negative symptoms such as apathy (lack of interest) and loss of emotion.

Antipsychotic medicines have been successful for treating the positive symptoms but the negative symptoms remain difficult to treat and usually do not respond to routine antipsychotics. In addition, antipsychotic medicines often have unpleasant side effects.

Chlorpromazine is a widely available and inexpensive antipsychotic introduced in the 1950s and considered the benchmark treatment for schizophrenia worldwide. Initial research indicated that chlorpromazine helped global improvement and was effective at preventing relapse compared with placebo (dummy treatment). However, some of chlorpromazine's side effects, particularly incidence of movement disorders, are reported as severe or debilitating. Metiapine is a relatively newer antipsychotic medicine, reporting to be effective at treating the symptoms of schizophrenia while causing fewer side effects. However, there is currently no good quality information concerning metiapine's effectiveness directly compared to chlorpromazine.

Searching for evidence

In November 2015, the Information Specialist of the Cochrane Schizophrenia group searched their specialised register for relevant clinical trials. The search identified four reports. We inspected these reports and found they referred to three trials, randomising people with schizophrenia to receive chlorpromazine or metiapine.

Main results

Our review now includes three studies with 161 participants. The studies revealed no real differences between chlorpromazine and metiapine for improvement in global state or incidence of parkinsonism (an umbrella term for symptoms such as tremor (shaking), bradykinesia (slow movement), rigidity (stiffness), and postural instability (difficulty in balancing). No data were reported for our other main areas of interest: mental state, service use, satisfaction with treatment, behaviour or cost of care.

Conclusions

We cannot draw firm conclusions from the data provided. The number of studies and number of participants in each study is small, all studies are also short term. Therefore, we rated the reported evidence as very low quality. However, metiapine is not a highly prescribed or used antipsychotic medicine, so although our evidence is poor, it probably will remain the best available evidence as it is unlikely new trials comparing metiapine with chlorpromazine will be conducted in the future.

Authors' conclusions: 

Chlorpromazine has been the mainstay treatment for schizophrenia for decades, yet available evidence comparing this drug to metiapine fails to provide high-quality trial based data. However, the need to determine whether metiapine is more or less effective than chlorpromazine seems to be lacking in clinical relevance and future research on this comparison seems unlikely.

Read the full abstract...
Background: 

Chlorpromazine, a widely available and inexpensive antipsychotic drug, is considered the benchmark treatment for schizophrenia worldwide. Metiapine, a dibenzothiazepine derivative, has been reported to have potent antipsychotic characteristics. However, no evidence currently exists on the effectiveness of chlorpromazine in treatment of people with schizophrenia compared to metiapine, a newer antipsychotic.

Objectives: 

To compare the effect of chlorpromazine versus metiapine for the treatment of people with schizophrenia

Search strategy: 

We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials in November 2015 and 2016.

Selection criteria: 

All randomised controlled trials (RCTs) focusing on chlorpromazine versus metiapine for adults with schizophrenia. We included trials meeting our selection criteria and reporting useable data.

Data collection and analysis: 

We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference between groups and its 95% CI. We employed a random-effects model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE.

Main results: 

We included three studies randomising 161 people with schizophrenia. Data were available for only two of our seven prestated main outcomes. Clinically important improvement in global state was measured using the Clinical Global Impression (CGI). There was no clear difference between chlorpromazine and metiapine groups (2 RCTs, n = 120, RR 1.11, 95% CI 0.84 to 1.47, very low quality evidence) and numbers of participants with parkinsonism at eight weeks were similar (2 RCTs, n = 70, RR 0.97, 95% CI 0.46 to 2.03, very low quality evidence). There were no useable data available for the other key outcomes of clinically important improvement in mental state, readmission due to relapse, satisfaction with treatment, aggressive or violent behaviour, or cost of care.

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