A majority of patients who suffer from mental illness are treated with serotonin regulating FDA approved medications. Some of these medications also block histamine transmission, increase blood prolactin levels, induce insulin resistance, hyperlipidemia, and promote sedation. All of which lead to weight gain and obesity. Many of these drugs are generally safe and effective but do carry the risk of a long term side effect in that acute and gradual weight gain of 10-30 pounds over a few months to a year of treatment. The detrimental gain of 7% of pre-drug weight is reported with many antipsychotics, mood stabilizers and some antidepressants. This weight gain may subsequently add to medical co-morbidity ( ie diabetes, hypertension, osteoarthritis, coronary artery diseasem, hyperlipidemia… ) This therapeutic manipulation of brain serotonin functioning may be associated with abnormal increases in carbohydrate cravings, consumption and weight gain. It is possible that insulin resistance occurs as a direct effect or as an indirect effect of weight gain, particularly in patients prone to weight gain or diabetes due to genetic loading. Leptin, a chemical associated with feedback signaling that reduces appetite and adipose tissue growth may also become insensitive. These multiple insults may lead to the worst weight gain in patients taking clozapine, olanzapine, and mirtazapine.