Effective and underprescribed: what about clozapine?

Competing interest statement

Conflict of interest: the authors declare no potential conflict of interest.

Clinical psychiatry, especially pharmacological- based treatment regimens still face the problem of high rates of partial or non-responders to the various treatment strategies. So in schizophrenia, a serious psychiatric disease with regard to overall impairment of patients up to three-quarters will experience a relapse after their first episode and one-fifth is facing long-term symptoms often leading to disability and dramatically reduced quality of life and psychosocial outcome.[1-3]

Solid evidence suggests that Clozapine is the most effective antipsychotic drug for schizophrenics who do not respond to treatment with first- or second-generation antipsychotics.[4] So approximately 60% of those who are considered treatment-resistant will respond to clozapine and its clinical use is supported by studies with various designs showing the positive outcomes and reduced hospitalization rates.[5,6] In addition to its utility in schizophrenia, accumulating evidence supports clozapine’s utility for a variety of other disorders and psychopathologic symptoms, such as hostility and aggression.[7] There is also solid evidence in other psychiatric and neuropsychiatric diseases like treatment-resistant bipolar disorder, [8] Lewy body dementia psychosis[9] and psychosis in borderline personality disorder. [10] The work of Wahid et al. published in Mental Illness, Volume 9, Issue 2 (2017), contributes to that bride indication implications of clozapine use.[11]

Having that positive evidence in mind there still is a dark side in the clinical use. Because of the sometimes serious somatic side effects of clozapine like myocarditis, cardiomyopathy, seizures and especially the severe neutropenia risk the Federal Food and Drug Administration mandated the monitoring of blood draws when using clozapine. That is likely one main reason that the use of clozapine in the US has been steadily declining.[12]

Knowing all antipsychotic medication strategies to have potentially serious side effects and looking at the overall reduced survival rates of schizophrenics the (in most cases good to manage) clinical use of clozapine should stay in mind of every prescriber facing the challenges in treatment of schizophrenic and psychotic-associated diseases.