For schizophrenia that is treatment resistant, clozapine is the standard drug therapy. The high use of clozapine for this condition is largely based on one study conducted by Kane and colleagues that demonstrated its effectiveness. However, since then many clinical trials have been conducted for other second generation antipsychotics. In addition to this fact, clozapine is also noted to have many side effects. Thus, the researchers of this study found it necessary to conduct a meta-analysis to evaluate if clozapine is still the most effective treatment available for treatment-resistant schizophrenia. In order to conduct the meta-analysis, the researchers studied 40 single and double blind randomized clinical trials of adults with treatment-resistant schizoaffective disorder, schizophreniform disorder, or schizophrenia. The drugs involved in the studies were clozapine, haloperidol, olanzapine, and risperidone.
The results of the pairwise meta-analysis showed that olanzapine, clozapine and risperidone were significantly effective as therapies for treatment-resistant schizophrenia. Clozapine, however, was not the most effective of all the drugs. The data showed some inconsistencies due to sampling bias found in the trials. In addition, many of the clinical trials that the researchers would have liked to include in the study were unblinded and thus excluded. Therefore, it can be concluded that evidence for which antipsychotic medication is best for patients with treatment-resistant schizophrenia is limited. More research needs to be conducted to compare clozapine with second generation antipsychotics.
I found this article to be interesting because the researchers conducting this study took it upon themselves to question standard practices. I think it is important to continue studying treatments that are considered “standard” because it allows for continuous improvement in prescribing. If we never questioned ourselves, therapies would never be improved. In this case, clozapine had been shown to be more effective than first generation antipsychotics. However, its effectiveness was not proven over second generation antipsychotics. With the emergence of these newer drugs, I think it is important to reevaluate the situation and compare therapies. With this in mind, as future pharmacists we should try to always stay up to date on such research so that we are able to advise prescribers and patients on the most effective drug available for the indication being treated.
Samara M, Dold M, Gianatsi M, et al. Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment-Resistant Schizophrenia. Jama Psychiatry. 2016; published ahead of print.