Two classes of medications may increase body weight. One class is designed to increase body weight or increase appetite in cachexic patients, and this class includes four approved products (oxandrolone, dronabinol, megestrol, and growth hormone). The second class of medications increases body weight as a side effect of treating other conditions, and this class includes many antipsychotics, certain antidepressants, certain antiepileptic agents, insulin, and peroxisome proliferator-activated receptor (PPAR) gamma agonists.

The anabolic steroid oxandrolone is a synthetic derivative of testosterone, which was approved for the treatment of wasting in 1964. The weight gain indication is primarily based on a six-week clinical trial in a population with heterogeneous clinical backgrounds. Longer-term clinical data have not been published. Dronabinol is the synthetic version of the cannabinoid tetrahydrocannabinol, the major active ingredient in Cannabis sativa. Dronabinol was first approved for the treatment of nausea and vomiting and later extended to anorexia associated with acquired immunodeficiency syndrome (AIDS) in 1992. The appetite-enhancing effect of marijuana smoking is also well documented.

Megestrol is a synthetic progesterone derivative, and it is also indicated for the treatment of anorexia, cachexia, and weight loss in AIDS patients. In several clinical trials where change of body composition was determined, megestrol appears to increase fat mass. Growth hormone is approved for the treatment of wasting and cachexia in AIDS. A small increase in lean body mass may be associated with growth hormone treatment.

There are other medications officially approved to treat psychiatric disorders but are associated with significant weight gain as a major side effect. For example, many atypical antipsychotics such as clozapine, olanzapine, and risperidone and some typical antipsychotics such as thioridazine and chlorpromazine cause severe weight gain on chronic use. The mechanism of antipsychotics-induced weight gain is not entirely clear, although it has been proposed that multiple brain receptors targeted by antipsychotics mediate the weight gain side effect. Only a few antipsychotics (such as zaprasidone and molindone) appear to have minimal effect on body weight.

Some antidepressants such as amitriptyline and lithium are associated with long-term weight gain. The antidepressant-induced weight gain cannot be explained solely by the improvement in depressive symptoms. In the case of some selective serotonin reuptake inhibitors, short-term weight loss is often followed by small or inconsistent weight gain. The exact mechanism of antidepressant-induced weight gain has not been elucidated.

Several antiepileptic agents such as valproate, carbamazepine, and gabapentin are associated with weight gain. However, topiramate and zonisamide cause weight loss. The divergent effects of different antiepileptic agents on body weight may be related to the different mechanisms of these agents affecting neural activity.

Antidiabetic treatment based on intensive insulin therapy and insulin secretagogues such as sunfonylureas or thiazolidinedione (TZD) is generally accompanied by weight gain. The insulin-induced weight gain may be attributed to the anabolic effect of insulin and increased appetite. TZD-induced weight gain may be attributable to TZD's ability to promote adipocyte diferentiation.

Drug-induced weight gain can be a serious side effect and may jeopardize effective medical therapy. Weight gain may be lessened or prevented by diet, exercise, or selection of an effective therapy with less weight gain potential.

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