Pharmacological Management of Atypical Antipsychotic-Induced Weight Gain

• Published in: CNS drugs Vol. 22; no. 6; pp. 477 - 495
• Main Authors: Baptista, Trino, ElFakih, Yamily, Uzcátegui, Euderruh, Sandia, Ignacio, Tálamo, Eduardo, de Baptista, Enma Araujo, Beaulieu, Serge
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-01-2008; Adis International; Wolters Kluwer Health, Inc; Springer Nature B.V
• Subjects: Amantadine; Amino acids; Animals; Anti-Obesity Agents - therapeutic use; Antipsychotic Agents - adverse effects; Antipsychotic drugs; Antipsychotics; Appetite; Aripiprazole; Biological and medical sciences; Care and treatment; Clinical trials; Clozapine; Cognitive ability; Complications and side effects; Diabetes; Drug therapy; Drug toxicity and drugs side effects treatment; Drugs; Food; General and cellular metabolism. Vitamins; Humans; Medical sciences; Medicine; Medicine & Public Health; Mental illness; Metabolism; Metformin; Miscellaneous (drug allergy, mutagens, teratogens...); Neurology; Neurosciences; Obesity - chemically induced; Obesity - drug therapy; Olanzapine; Patient outcomes; Patients; Peptides; Pharmacology. Drug treatments; Pharmacotherapy; Physical activity; Physical training; Physiology; Psychiatry; Psychopharmacology; Psychotic Disorders - drug therapy; Psychotropic drugs; Quetiapine; Reboxetine; Review Article; Risk factors; Risperidone; Schizophrenia; Sibutramine; Substance abuse treatment; Topiramate; Weight control; Weight gain; Weight Gain - drug effects; Ziprasidone; United States; Olanzapine; Metformin; Clozapine; Risperidone; Quetiapine; Human; Treatment; Atypical antipsychotic; Neuroleptic; Toxicity; Pharmacotherapy; Review; Weight gain
• ISSN: 1172-7047; 1179-1934
• DOI: 10.2165/00023210-200822060-00003

Excessive bodyweight gain was reported during the 1950s as an adverse effect of typical antipsychotic drug treatment, but the magnitude of bodyweight gain was found to be higher with the atypical antipsychotic drugs that were introduced after 1990. Clozapine and olanzapine produce the greatest bodyweight gain, ziprasidone and aripiprazole have a neutral influence, and quetiapine and risperidone cause an intermediate effect. In the CATIE study, the percentage of patients with bodyweight gain of >7% compared with baseline differed significantly between the antipsychotic drugs, i.e. 30%, 16%, 14%, 12% and 7% for olanzapine, quetiapine, risperidone, perphenazine (a typical antipsychotic) and ziprasidone, respectively (p < 0.001).
Appetite stimulation is probably a key cause of bodyweight gain, but genetic polymorphisms modify the bodyweight response during treatment with atypical antipsychotics.
In addition to nutritional advice, programmed physical activity, cognitive-behavioural training and atypical antipsychotic switching, pharmacological adjunctive treatments have been assessed to counteract excessive bodyweight gain. In some clinical trials, nizatidine, amantadine, reboxetine, topiramate, sibutramine and metformin proved effective in preventing or reversing atypical antipsychotic-induced bodyweight gain; however, the results are inconclusive since few randomized, placebo-controlled clinical trials have been conducted. Indeed, most studies were short-term trials without adequate statistical power and, in the case of metformin, nizatidine and sibutramine, the results are contradictory. The tolerability profile of these agents is adequate.
More studies are needed before formal recommendations on the use of these drugs can be made. Meanwhile, clinicians are advised to use any of these adjunctive treatments according to their individual pharmacological and tolerability profiles, and the patient’s personal and family history of bodyweight gain and metabolic dysfunction.