Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556
USA

Back

Drug Induced Weight Gain, an Impediment to Successful Pharmacotherapy: Focus on Antipsychotics

Author(s): T. Baptista, J. Zarate, R. Joober, C. Colasante, S. Beaulieu, X. Paez and L. Hernandez

Affiliation: Department of Physiology, P.O.Box 93, Los Andes University Medical School, Mérida, 5101-A, Venezuela.

Keywords: antipsychotics, appetite, cortisol, gonadal steroids, histamine, insulin, neurotransmitters, obesity, prolactin

Abstract:

The antipsychotic drugs (APDs) are fundamental tools in current psychiatric practice. A new generation of agents, the atypical APDs, represents an important progress in the treatment of psychotic disorders. Unfortunately, some of them induce excessive body weight gain (BWG), obesity, hyperglycemia and dyslipidemia in the following order: clozapine ≅ olanzapine > quetiapine > risperidone > ziprasidone = aripiprazole. Appetite stimulation is probably the main mechanism of BWG and this is strongly correlated with the APD affinity for H1 (histaminergic) and a1 (adrenergic) receptors. A composed ratio of the APD affinity for diverse neurotransmitters involved in food intake (FI) regulation correlates with BWG as well. Endocrine/metabolic mechanisms, such as the activation of the hypothalamus-pituitary-adrenal axis, changes in insulin sensitivity (by conventional and atypical agents), hyperprolactinemia and gonadal dysfunction (by conventional APDs and risperidone) may also be involved. Importantly, patients with schizophrenia may have a genetically-based predisposition to appetite dysregulation, insulin resistance and endocrine imbalance involving gonadal steroids. Excessive BWG must be prevented or attenuated by proper drug selection, combining or switching agents, nutritional assistance and physical exercise. Amantadine, metformin and reboxetine proved to significantly lessen APD-induced BWG. Notwithstanding this, novel strategies are necessary to treat this side effect in a clinical population particularly prone to poor compliance and under a high risk of negative drug interaction.

Reprint ePrint Rights & PermissionsPrintExport

Article Details

VOLUME: 5
ISSUE: 3
Page: [279 - 299]
Pages: 21
DOI: 10.2174/1389450043490514