A typical Antipsychotic Induced Weight Gain: Pathophysiology and Management

Abstract

There is compelling evidence that patients with schizophrenia are prone to gain weight. In addition, atypical antipsychotic (AAP) drugs also induce weight gain. All antipsychotic drugs produce weight gain but the potential varies. Many studies overwhelmingly confirm that AAP drugs produce substantially more weight gain in comparison to conventional antipsychotic drugs. Clozapine and olanzapine have the most weight inducing potential. Even ziprasidone, which is considered to be weight neutral, and aripiprazole a dopamine modulator produce weight gain in some. The pathophysiology of weight gain is complicated. Many neurohormones, neuropeptides, gut hormones, as well as adipose tissue and hair root derived hormones interact with environmental factors to produce weight gain. Management of weight gain is a difficult problem. Basic to treatment is an understanding of the etiology. Drug induced obesity provides a unique opportunity to psychiatrists to understand this clinically important problem. In the absence of this knowledge, prevention is the best hope. Education, diet control and simple behavioral measures may prevent excessive weight gain. In those with weight gain, treatment can be attempted with pharmacotherapy with careful monitoring of the side effects.

Dopamine D2-like Receptors Are Expressed in Pancreatic Beta Cells and Mediate Inhibition of Insulin Secretion

“…Interestingly, treatment with L-dopa alters insulin secretion in patients with Parkinson disease (10,57,58). Moreover, antipsychotic (neuroleptic) drugs blocking dopamine receptors may cause hyperinsulinemia (59), hypoglycemia (60), increase appetite, and obesity (61,62) and are associated with diabetes (61,63,64). Therefore, dopamine action on beta cells might have relevant implications for the study of obesity and diabetes, in particular in situations where dopamine transmission is altered.…”

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia, Part 2: Long-term treatment of schizophrenia

“…Behaviour and life style are an important part of weight maintenance in psychiatric patients. Therefore, physicians should encourage patients to increase their physical activity gradually and stepwise in combination with dietary restriction to obtain negative energy balance (Ananth et al 2004).…”

Diretrizes da Federação Mundial das Sociedades de Psiquiatria Biológica para o tratamento biológico da esquizofrenia. Parte 2: tratamento de longo prazo

“…Comportamento e estilo de vida são aspectos importantes para a manutenção do peso entre os pacientes psiquiátricos. Os médicos devem incentivar os pacientes a aumentar suas atividades físicas gradualmente, aliando a isso restrições alimentares para que se possa atingir um balanço energético negativo (Ananth et al, 2004).…”

“…O efeito da perda de peso foi confirmado por meio de um tratamento de inclusão com 100 a 300 mg/dia de amantadina por 3 a 6 meses em 12 pacientes que ganharam peso excessivamente enquanto recebiam olanzapina (Floris et al, 2001) e numa investigação duplo-cega, com duração de 16 semanas, avaliando 60 pacientes com esquizofrenia, psicose esquizofreniforme ou transtorno bipolar, comparados ao grupo-placebo (Deberdt et al, 2005). A amantadina, um agonista dopaminérgico, pode exacerbar os sintomas psicóticos (Ananth et al, 2004). A nizatidina, um bloqueador de receptores histamínicos H2 periférico, que provavelmente age pela indução da saciedade relacionada ao aumento da secreção de colecistocinina e da diminuição da produção de ácido gástrico, tem sido citada por diminuir o ganho de peso quando administrada em doses de 300 mg/dia entre os pacientes que recebem olanzapina (Sachetti et al, 2000).…”