Clozapine Safety, 35 Years Later

Abstract

Clozapine is the best treatment option in several clinical circumstances, including treatment-resistant schizophrenia, non treatment-resistant schizophrenia, suicide risk in schizophrenia spectrum disorders, aggressiveness or violence in psychiatric patients, psychosis in Parkinson's disease, prevention and treatment of tardive dyskinesia. However, clozapine is associated with many serious side effects. Furthermore, monitoring requirements, i.e., frequent blood draws and frequent visits, discourage clozapine use. Therefore, the drug is underused. The only way to avoid the underuse of clozapine is full awareness of its side effects and competence to minimize them. The aim of the paper is reviewing the safety profile of clozapine and the suggested strategies in the management of its side effects, including neutropenia, eosinophilia, seizures, myocarditis, weight gain, diabetes, metabolic syndrome, hypersalivation, fever, constipation, ileus, urinary incontinence, sweating. The neuropsychiatric side effects of clozapine are not discussed in this review.

Clozapine for Treating Pharmacoresistant Schizophrenia among Elders

“…Other side effects, such as sedation, hypotension, weight gain, agitation, increase of blood glucose and lipid level, were detected in this research. This finding is in accordance with other researchers in this field [11][12][13]. Watchful monitoring of side effects of clozapine used in elderly is unevitable [12,13].…”

“…The results ofthis observatory study show the potential of clozapine to clinical improvement of symptoms in senior patients with pharmacoresistant schizophrenia, this result is in accordance with other authors [9,11]. Average CGI-S 12 week score was 3,6 with range from 3 to 4.…”

“…Treatment with clozapine is adviced in treatment of pharmacoresistant schizophrenia worldwide [2,5,6]. However, clozapine is associated with many serious side effects which should be taken into account -such as severe and potentially lethal neutropenia, eosinophilia, seizures, myocarditis, weight gain, diabetes, metabolic syndrome, hypersalivation, fever, constipation, ileus, urinary incontinence, sweating [11]. There are no contraindications for using clozapine in elderly, however, clozapine treatment in the elderly requires a careful geriatric assessment [12].…”

Update on Typical and Atypical Antipsychotic Drugs

“…Unfortunately, clozapine has numerous side effects, including agranulocytosis; eosinophilia and fever at treatment onset; sedation; metabolic side effects, including hyperlipidosis, type II diabetes, and weight gain; major motor and myoclonic seizures; myocarditis; hypersalivation; urinary incontinence; sweating; constipation; and ileus (49). These have contributed to gross underutilization in the United States compared to other advanced countries (50).…”

Pharmacological and behavioral management of some often-overlooked clozapine-induced side effects

“…There are other significant side effects, such as diabetes mellitus, weight gain, metabolic syndrome, ileus, and other more trivial side effects such as fever, drowsiness, sedation, and eosinophilia (Raja, 2011). Most of these side effects are not specific to clozapine and are common in other second-generation antipsychotics.…”