Switching antipsychotic curbs cannabis use in schizophrenia

 

Switching antipsychotic curbs cannabis use in schizophrenia

Heavy cannabis use is particularly troubling in patients already struggling with schizophrenia. This study provides the first evidence from a randomised controlled trial that switching such patients to the antipsychotic clozapine may help reduce their cannabis use without adverse effects on psychiatric symptoms. 

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A randomized trial of clozapine versus other antipsychotics for cannabis use disorder in patients with schizophrenia.

Brunette M.F., Dawson R., O’Keefe C.D. et al.
Journal of Dual Diagnosis: 2011, 7 (1–2), p. 50–63.
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Heavy cannabis use is particularly troubling in patients already struggling with schizophrenia. This study provides the first evidence from a randomised controlled trial that switching such patients to the antipsychotic clozapine may help reduce their cannabis use without adverse effects on psychiatric symptoms.

Summary Studies have found that 13% to 42% of people with schizophrenia have at some time also been dependent on or abused cannabis, many more than in the general population. Cannabis use disorder has been associated with clinical exacerbations, non-compliance with treatment, poor global functioning, and increased relapse and rehospitalisation rates.

While the older ‘typical’ antipsychotic medications do not appear to curb substance use in patients with schizophrenia, preliminary findings, and a theoretical rationale based on the drug’s effects on the brain, suggest that the atypical antipsychotic clozapine may help both with psychotic symptoms and cannabis and other substance abuse.

The authors tested this by recruiting 31 adult schizophrenic outpatients; generally their symptoms were not severe and had responded to treatment. Usually they had been referred to the study by clinicians at two US clinics. Typically patients were employed single white men in their 30s. All were also diagnosed with a cannabis use disorder and had used the drug at least five days out of the past 21. In practice the average was nearly five days and about a dozen joints a week, and about 8 in 10 were diagnosed as dependent on the drug. Half also were problem drinkers.

All the patients were being prescribed antipsychotics other than clozapine. A randomly selected 15 were transitioned over four weeks to clozapine instead. Over 12 weeks in total, the study’s interviewers assessed the patients’ use of cannabis, alcohol, and other substances, psychiatric symptoms, and experience of medication side effects, to test whether the switch to clozapine had led to improvements.

Main findings

Taking in to account differences in pre-study cannabis use, patients switched to clozapine on average smoked 4–5 joints of cannabis less per week, a medium effect size of 0.6, though with the small samples the difference was not statistically significant. Psychiatric symptoms improved in both sets of patients to roughly the same degree, and once a single ‘outlier’ heavy drinker had been eliminated from the analysis, excessive drinking rates too were similar. Some side effects were more common among patients switched to clozapine. Two patients in each group stopped taking their medications before the study ended. All the patients taking clozapine diligently took their medication as did all but three left on their existing medications.

The authors’ conclusions

Clozapine may curb cannabis use more than continued treatment with other antipsychotics in patients with schizophrenia and co-occurring cannabis use disorders. Clozapine’s lack of impact on psychiatric symptoms may reflect the overall moderate levels of psychiatric symptoms in this group of patients without treatment-refractory psychosis. The magnitude of the effect of clozapine suggests a clinically meaningful role for this medication, but the small size of the study sample limits the conclusions that can be drawn. Once an outlier had been removed, drinking was not affected. Changes in drinking were unrelated to changes in cannabis use, suggesting decreased cannabis use was not at the expense of increased drinking.

Although effective treatments for cannabis use disorder in schizophrenia are badly needed, clozapine’s side-effect profile severely restricts its use. If it can definitively be shown to decrease cannabis use in patients with schizophrenia, it may be appropriate to expand the routine use of clozapine beyond treatment-refractory psychosis to stable outpatients with a co-occurring cannabis use disorder.

The question posed by this study was whether it is worth switching schizophrenic patients to clozapine to curb their excessive cannabis use, when their psychiatric symptoms are already relatively well controlled by their current antipsychotics. If they prove valid in replications and larger trials, the results leave patients and their doctors to make a judgement call between what may be a quite substantial reduction in cannabis use (in the study, by over a third) at the cost of more undesirable side effects – though not so troubling in this study as to lead to early termination or refusal to take the pills. A clincher might have been if the fall in cannabis use and/or clozapine itself could be shown to have improved patients’ psychiatric health, but over the short time of the trial, there was no such effect.

Unfortunately, while we know that clozapine was compared to other antipsychotics, we do not know which ones. Neither do we know whether any impact on cannabis use was a short-lived ‘halo effect’ of trying a new drug, or would persist through to routine use over many months and years. The authors comment on the difficulty of recruiting such patients to clinical trials, a difficulty which in turn raises questions over how typical the patients were of all schizophrenic patients who frequently use cannabis.

This draft entry is currently subject to consultation and correction by the study authors and other experts.

Last revised 16 November 2013. First uploaded 16 November 2013