Clozapine and the gastrointestinal tract

Abstract

Clozapine is one of psychiatry’s most valuable medicines, improving outcomes for many people with schizophrenia whose illness has not responded adequately to other treatments. However, clozapine’s well-established advantages come at a price: a troublesome adverse-effect profile. Clozapine-induced gastrointestinal hypomotility (CIGH) is one of the most common—and serious—of these adverse effects, ranging in severity from mild constipation to fatal bowel obstruction and/or ischaemia. Mortality from these serious gastrointestinal complications is increasingly being reported in the literature.

Most patients remain on clozapine for many years, sometimes compulsorily under mental health legislation. As compulsory treatment abrogates the usual patient right to self-determine the balance of risks and benefits, the prescriber has an even greater responsibility than usual to monitor and manage adverse effects.

This thesis comprises a broad-ranging investigation into the epidemiology, aetiology, prevention, and treatment of CIGH. The objective is to improve the understanding, and consequently the management, of this important, but poorly understood and under-researched adverse effect.