Significant weight loss following clozapine use, how is it possible? A case report and review of published cases and literature relevant to the subject

Abstract

It has been repeatedly shown that clozapine is more efficacious than other antipsychotics in the management of treatment-resistant schizophrenia. However, clozapine is associated with a number of side effects including weight gain. Antipsychotic-induced weight gain has been linked with a number of untoward events including psychological factors such as stigma and low self-esteem, and physical factors such as metabolic syndromes and untimely death. The mechanism underlying antipsychotic (including clozapine)-induced weight gain is not clearly understood, although it is said to involve several brain areas, several neurotransmitters, neuropeptides and genetic factors. To some individuals however, clozapine use is associated with significant weight loss (13.5-50% of body weight). The observed weight loss in these groups of patients has not been attributed to any underlying diagnosable physical disorders. There have been a handful cases published with this phenomenon, which seems to be contrary to what is expected when clozapine is prescribed. From the currently published cases three groups emerge - those who lost weight simply by taking clozapine, those who lost weight due to improved mental state, engaging in diet and increased exercise, and those for whom weight loss was a sign of a poor response to clozapine. A case of JX who has a diagnosis of schizoaffective disorder is presented. JX lost over 26% of her body weight when she was prescribed clozapine. A detailed review of other published cases is undertaken. The underlying mechanisms involving weight loss are discussed and the implications to clinicians are highlighted. Coordinated studies to examine these groups of patients may provide some insight, not only in the mechanism of clozapine-induced weight loss, but also in the better management of patients with treatment-resistant schizophrenia involving clozapine use.

Antipsychotic Drugs: From Receptor-binding Profiles to Metabolic Side Effects

“…In many models, clozapine may not affect or even decrease weight, partially explained by its sedative effects [34]. Despite the positive association of clozapine administration and weight gain in humans, clozapine may also induce weight loss to some individuals, possibly underpinning genetic factors or variable therapeutic response [39].…”

Clozapine-induced Weight Loss and Stuttering in a Patient with Schizophrenia

“…Moreover, weight loss is often found to be associated with poor response to treatment. [ 3 ] In addition, in our case-patient did not respond to 600 mg of clozapine.…”

“…[ 7 ] Most of the literature mentioning clozapine-induced weight gain are dependent on naturalistic studies without proper control and presence of preexposure with multiple adipogenic antipsychotics; such as olanzapine or quetiapine which often gives biased results. [ 3 ] In addition, obesity can be attributed to an unhealthy lifestyle, personal genetic profile, as well as the effects of comedications or medical disorders. [ 8 ] Moreover, evidence also shows that having a certain genetic type of 5HT2c (−759 C/T, T allele rather than C allele) protects against antipsychotic-induced weight gain.…”

“…Reasons behind the phenomenon could be due to physical exercise secondary to improved mental status, but the particular receptor-based mechanism is yet to be explored. [ 3 ]…”

Psychophysiological Status in Overweight Individuals

“…It was established [14] that neurotransmitters and neuropeptides contribute to the inclination to obesity through a complex chain of reactions.…”