Metabolic disturbances and cardiovascular disease are important causes of morbidity and mortality in patients with severe mental illnesses. Antipsychotic medications are the drug of the choice for patients with schizophrenia. However, some antipsychotic drugs have a high tendency to cause weight gain and metabolic abnormalities, therefore increasing the risk of obesity, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. These findings have led to an increased interest in looking into the relationships between schizophrenia, antipsychotic drugs, metabolic dysregulation, and cardiovascular disease. Although some neurotransmitter receptor-binding affinities are correlated with specific metabolic abnormalities, the exact mechanisms underlying antipsychotic-induced adverse metabolic effects are still unclear. The receptor affinity of antipsychotic drugs for histamine H 1, serotonin 5-HT 2C and 5-HT 1A, muscarinic M 3, dopamine D 2, and adrenergic receptors might be involved in causing metabolic dysregulation. Low-potency first-generation antipsychotic drugs are associated with a higher potential to cause weight gain and metabolic disturbance than are high-potency first-generation antipsychotics. Second-generation antipsychotic drugs carry different risks of causing weight gain and metabolic dysregulation: clozapine and olanzapine have the highest risk; quetiapine and risperidone a moderate risk; and aripiprazole, amisulpride, and ziprasidone the lowest risk. The psychiatric literature has recommended follow-up for metabolic and cardiovascular risk factors, but many antipsychotic-treated patients have not received the recommended regular monitoring for these risk factors. Psychiatrists need to educate and motivate this group of patients to make healthy lifestyle changes. If these lifestyle changes fail, these patients need to receive drug interventions. Adding medications (such as metformin, topiramate, and amantadine) or switching to another antipsychotic drug should be considered to decrease the risk of antipsychotic-induced weight gain and metabolic abnormalities. In conclusion, this review is intended to describe the adverse metabolic and cardiovascular effects related to antipsychotic medications, to explore their possible underlying mechanisms, and to recommend how to monitor and manage those iatrogenic side effects.
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