Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine

Abstract

Clozapine, a dibenzodiazepine developed in 1961, is a multireceptorial atypical antipsychotic approved for the treatment of resistant schizophrenia. Since its introduction, it has remained the drug of choice in treatment-resistant schizophrenia, despite a wide range of adverse effects, as it is a very effective drug in everyday clinical practice. However, clozapine is not considered as a top-of-the-line treatment because it may often be difficult for some patients to tolerate as some adverse effects can be particularly bothersome (i.e. sedation, weight gain, sialorrhea etc.) and it has some other potentially dangerous and life-threatening side effects (i.e. myocarditis, seizures, agranulocytosis or granulocytopenia, gastrointestinal hypomotility etc.). As poor treatment adherence in patients with resistant schizophrenia may increase the risk of a psychotic relapse, which may further lead to impaired social and cognitive functioning, psychiatric hospitalizations and increased treatment costs, clozapine adverse effects are a common reason for discontinuing this medication. Therefore, every effort should be made to monitor and minimize these adverse effects in order to improve their early detection and management. The aim of this paper is to briefly summarize and provide an update on major clozapine adverse effects, especially focusing on those that are severe and potentially life threatening, even if most of the latter are relatively uncommon.

The impact of social, national and community-based health insurance on health care utilization for mental, neurological and substance-use disorders in low- and middle-income countries: a systematic review

“…Across studies from China, insurance coverage was associated with the increased prescription of ACM and anti-epileptic medication but the reduced provision of Clozapine and ECT for Schizophrenia; although importantly, prescription for all these drugs across all insurance groups was higher than globally recommended [28,32,35,37,39,42,43]. Each of these drugs is associated with negative side effects including the impairment of cognitive capacity, while clozapine is principally recommended for use with treatment resistant schizophrenia and is associated with increased cardiovascular risk and psychotic relapse and the potential for agranulocytosis [46]. There appears to be an improved alignment to global treatment recommendations amongst the insured, with the overprovision of unnecessary services to those paying out-of-pocket.…”

A Rational Use of Clozapine Based on Adverse Drug Reactions, Pharmacokinetics, and Clinical Pharmacopsychology

“…On the other hand, psychiatric textbooks and review articles call ADRs "side effects" and do not explain these two classes of limitations in the field. Similarly, recent review articles [9][10][11] stressed that clozapine is prone to cause ADRs but do not explain these advances in knowledge of ADRs.…”

<p>The Effect of Liver and Kidney Disease on the Pharmacokinetics of Clozapine and Sildenafil: A Physiologically Based Pharmacokinetic Modeling</p>

“…10 Among these risks is clozapine-induced agranulocytosis; thus, treatment with clozapine demands regular monitoring of white blood counts and absolute neutrophil counts, and in the US, the FDA instructs that patients on clozapine treatment be enrolled in a computer-based registry. 11,12 Sexual dysfunction is popular among patients receiving clozapine, and is the most aggravating side effect, resulting in a negative impact on patients and their desire to continue medication. 13 Hyperprolactinemia is considered to be the main element for this side effect.…”