Autonomic Nervous System Related Adverse Effects Developed During Clozapine Treatment

The purpose of this study was to investigate the prevalence and course of autonomic nervous system related adverse effects(ARAEs) reported in patients treated with clozapine. The study population comprised ninety-one patients treated with clozapine at Seoul National University Hospital Treatment-Resistant Schizophrenia Clinic. Medical records were reviewed for the prevalence and course of 14 ARAEs related to clozapine treatment. ARAEs with the prevalence greater than 10% were selected and analyzed for their relationship with the demographic variables of the subjects and for the distribution of the duration of treatment and daily dosage of clozapine. Eighty-one (97.8%) patients experienced at least one ARAE during treatment with clozapine. The most frequently occurring ARAE was hypersalivation, followed by constipation, tachycardia, orthostatic hypotension, nausea, diaphoresis, urinary frequency, enuresis, vomiting, blurred vision, dry mouth, diarrhea, urinary incontinence and urinary retention. None of the 7 selected frequently occurring ARAEs had a significant relationship with the age or sex of the subjects. Most of them developed within 8 weeks of clozapine treatment and at a clozapine dose of under 200 mg/day. Among the total of 248 events attributed to ARAEs, 35 events required additional medication to alleviate the symptoms, 8 required other types of medical intervention, and 3 required reduction of clozapine dose. There was no case that necessitated withdrawal of clozapine therapy. The findings from this study suggest that almost all patients treated with clozapine experienced one or more ARAEs. Most of them occurred during the initial phase of treatment and were managed without further medical treatment.