Pimozide for schizophrenia or related psychoses

People with schizophrenia have ‘positive symptoms’ such as hearing voices and seeing things (hallucinations) and fixed strange beliefs (delusions). People with schizophrenia also have ‘negative symptoms’ such as tiredness, apathy and loss of emotion. Antipsychotic drugs are the main treatment for the symptoms of schizophrenia and can be grouped into older drugs (first generation or ‘typical’) and newer drugs (second generation or ‘atypical’). Pimozide is a ‘typical’ antipsychotic drug that was first introduced in the late 1960s and was given to people with schizophrenia. Pimozide is thought to be effective in treating the positive and negative symptoms of schizophrenia or similar mental health problems such as delusional disorder, but it produces serious side effects such as muscle stiffness, tremors and slow body movements. Pimozide may also cause heart problems and has been linked to sudden unexplained death. Monitoring the heart via electrocardiogram is now required before and during treatment with pimozide. It is well known that people with mental health problems suffer from physical illnesses such as heart disease and diabetes and can die on average twenty years younger than those in the general population.
An update search for this review was carried out 28 January 2013; the review now includes 32 studies that assess the effects of pimozide for people with schizophrenia or similar mental health problems. Pimozide was compared with other antipsychotic drugs, placebo (‘dummy’ treatment) or no treatment. Results suggest that pimozide is probably just as effective as other commonly used ‘typical’ antipsychotic drugs (for outcomes such as treating mental state, relapse, leaving the study early). No studies included delusional disorders, so no information is available on this group of people. No evidence was found to support the concern that pimozide causes heart problems (although this may be result of the fact that the studies were small and short term and the participants did not receive doses above recommended limits of 20 mg/d). Pimozide may cause less sleepiness than other typical antipsychotic drugs, but it may cause more tremors and uncontrollable shaking. The claim that pimozide is useful for treating people with negative symptoms also is not supported and proven. However, the quality of evidence in the main was low or very low quality, studies were small and of short duration and were poorly reported. Large-scale, well-conducted and well-reported studies are required to assess the effectiveness of pimozide in the treatment of schizophrenia and other mental health problems such as delusional disorder.

This plain language summary has been written by a consumer, Benjamin Gray (Service User and Service User Expert, Rethink Mental Illness).

Authors' conclusions: 

Although shortcomings in the data are evident, enough overall consistency over different outcomes and time scales is present to confirm that pimozide is a drug with efficacy similar to that of other, more commonly used antipsychotic drugs such as chlorpromazine for people with schizophrenia. No data support or refute its use for those with delusional disorder.

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Background: 

Pimozide, formulated in the 1960s, continues to be marketed for the care of people with schizophrenia or related psychoses such as delusional disorder. It has been associated with cardiotoxicity and sudden unexplained death. Electrocardiogram monitoring is now required before and during use.

Objectives: 

To review the effects of pimozide for people with schizophrenia or related psychoses in comparison with placebo, no treatment or other antipsychotic medication.

A secondary objective was to examine the effects of pimozide for people with delusional disorder.

Search strategy: 

We searched the Cochrane Schizophrenia Group's Register (28 January 2013).

Selection criteria: 

We sought all relevant randomised clinical trials (RCTs) comparing pimozide with other treatments.

Data collection and analysis: 

Working independently, we inspected citations, ordered papers and then re-inspected and assessed the quality of the studies and of extracted data. For homogeneous dichotomous data, we calculated the relative risk (RR), the 95% confidence interval (CI) and mean differences (MDs) for continuous data. We excluded data if loss to follow-up was greater than 50%. We assessed risk of bias for included studies and used GRADE to rate the quality of the evidence.

Main results: 

We included 32 studies in total: Among the five studies that compared pimozide versus placebo, only one study provided data for global state relapse, for which no difference between groups was noted at medium term (1 RCT n = 20, RR 0.22 CI 0.03 to 1.78, very low quality of evidence). None of the five studies provided data for no improvement or first-rank symptoms in mental state. Data for extrapyramidal symptoms demonstrate no difference between groups for Parkinsonism (rigidity) at short term (1 RCT, n = 19, RR 5.50 CI 0.30 to 101.28, very low quality of evidence) or at medium term (1 RCT n = 25, RR 1.33 CI 0.14 to 12.82, very low quality of evidence), or for Parkinsonism (tremor) at medium term (1 RCT n = 25, RR 1 CI 0.2 to 4.95, very low quality of evidence). No data were reported for quality of life at medium term.

Of the 26 studies comparing pimozide versus any antipsychotic, seven studies provided data for global state relapse at medium term, for which no difference was noted (7 RCTs n = 227, RR 0.82 CI 0.57 to 1.17, moderate quality of evidence). Data from one study demonstrated no difference in mental state (no improvement) at medium term (1 RCT n = 23, RR 1.09 CI 0.08 to 15.41, very low quality evidence); another study demonstrated no difference in the presence of first-rank symptoms at medium term (1 RCT n = 44, RR 0.53 CI 0.25 to 1.11, low quality of evidence). Data for extrapyramidal symptoms demonstrate no difference between groups for Parkinsonism (rigidity) at short term (6 RCTs n = 186, RR 1.21 CI 0.71 to 2.05, low quality of evidence) or medium term (5 RCTs n = 219, RR 1.12 CI 0.24 to 5.25, low quality of evidence), or for Parkinsonism (tremor) at medium term (4 RCTs n = 174, RR 1.46 CI 0.68 to 3.11, very low quality of evidence). No data were reported for quality of life at medium term.

In the one study that compared pimozide plus any antipsychotic versus the same antipsychotic, significantly fewer relapses were noted in the augmented pimozide group at medium term (1 RCT n = 69, RR 0.28 CI 0.15 to 0.50, low quality evidence). No data were reported for mental state outcomes or for extrapyramidal symptoms (EPS). Data were skewed for quality of life scores, which were not included in the meta-analysis but were presented separately.

Two studies compared pimozide plus any antipsychotics versus antipsychotic plus placebo; neither study reported data for outcomes of interest, apart from Parkinsonism at medium term and quality of life using the Specific Level of Functioning scale (SLOF); however, data were skewed.

Only one study compared pimozide plus any antipsychotic versus antipsychotics plus antipsychotic; no data were reported for global state and mental state outcomes of interest. Data were provided for Parkinsonism (rigidity and tremor) using the Extrapyramidal Symptom Rating Scale (ESRS); however, these data were skewed.

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