For many years, researchers have found that clozapine is substantially more effective than other antipsychotic medications in patients with treatment-resistant schizophrenia. See this tip and this JAMA article. However, some more recent studies and studies comparing clozapine with second-generation antipsychotic medications have not found clozapine to more effective. This has been surprising. A concern with these recent studies has been that, when medications are readily available, patients who enroll in randomized controlled trials are often not representative of the larger population with the illness. Therefore, it can be more informative to examine cohort studies that compare patients treated naturalistically with clozapine against a group of other patients. High quality cohort studies had been shown to provide information that has similar validity to randomized controlled trials. Researchers used this cohort approach with clozapine, and found that despite clozapine patients being more severely ill, clozapine was associated with lower hospitalization risk and better symptom and illness outcomes. Clozapine was also associated with greater risk for weight gain and type two diabetes.
See the resource below to learn more.