Possible mechanisms of atypical antipsychotic induced weight gain and preventive treatment options

Antipsychotic induced weight gain is regarded as more than 7% weight gain after the initiation of the drug. Weight gain takes place in a very high degree with clozapine and olanzapine, high degree with quetiapine, zotepine, chlorpromazine and tioridazine, moderate degree with risperidone and sertindole, low degree with ziprasidone, amisulpride, haloperidol, şuphenazine, pimozide, and molindone. Patients receiving antipsychotic usually gain a large part of their body weight in the first 12-month period. Patients with low body mass index prone to gain weight than those with high body mass index. On the other hand, it seems to be no significant effect of drug dose on weight gain. The underlying mechanisms of the antipsychotic induced weight gain are not exactly known. Environmental, genetic and behavioral factors have been implicated in the development of this side effect. Carbohydrate starvation and reduction in metabolic rate due to sedation have been blamed for antipsychotic induced weight gain. Especially eating behavior was investigated in this regard. In the hypothalamus, the interactions between arcuate nucleus, paraventricular nucleus, neuropeptides in the dorsomedial area and peripherally acting leptin, ghrelin, cholecystokinin, orexin, melanin stimulating hormone are responsible for the behavior of eating in general. Among the genes associated with antipsychotic induced weight gain, leptin, tumor necrosis factor alpha (TNF ?), brain-derived neurotrophic factor (BDNF), dopaminergic system, serotonergic system, histaminergic system, adrenergic system, Peroxisome proliferator activated receptor (PPAR), Insulin Receptor Substrate-1 (IRS–1), cytochrome P450 system, G-protein system and synaptic signal transduction genes come to the forefront. The effects of antipsychotic drugs on receptor affinities such as serotonin receptors that are 5 - HT1A and 5-HT2C, 5-HT6, 5-HT7, histamine receptors that are H1, H2, H3, muscarinic acetylcholine receptors, dopaminergic receptor that is D2, adrenoceptors that are ?1, ?2 may play a role in weight gain. If the patients have risk factors like obesity, family history of diabetes, hyperglycemia care should be taken in the choice of antipsychotic drugs. In case of risk factors, principally, weight monitoring at regular intervals is required in the patients who started treatment with atypical antipsychotics. Determination of weight gain provide to give attention to the other side effects. Fasting blood glucose, liver enzymes, cholesterol levels, thyroid hormones, prolactin and insulin levels should be examined at baseline, 3, 6, 12 months and measurements of height, weight, blood pressure, breast circumference recommended to be repeated in monthly controls. The follow-up of male and elderly patients’ blood glucose and weight need to be maintained more carefully. In case of an increase in weight, clinical follow-up strategies like transition to a lower risk of psychotropic drug, the implementation of a healthy diet regime, doing 30–60 minutes of exercise a day, should be performed. Family members and other persons involved in the care of the patient must be informed and given the necessary training about the risk of weight gain. Orlistat, sibutramine, şuoxetine, topiramate, amantadine, nizatidine, cimetidine, metformin, and modafinil have been implicated to be effective in the studies investigating the drugs that can be used in the treatment of weight gain.