Metabolic adverse effects, including alterations in glucose metabolism, lipid abnormalities, and weight gain, are of great concern for patients treated with antipsychotic medications. These metabolic effects may occur in any patient, but are particularly concerning in children and adolescents, in drug-naive patients, or in patients with first-episode schizophrenia. The alterations seen in glucose metabolism include hyperglycemia, type 2 diabetes mellitus, or diabetic ketoacidosis and coma; whereas hypercholesterolemia, hypertriglyceridemia, and low high-density lipoprotein cholesterol level are possible lipid abnormalities associated with antipsychotic use.
Despite varying degrees of risk of alterations in metabolic parameters, it is important to emphasize that all antipsychotic agents pose a higher risk of clinically significant weight gain (greater than or equal to 7% of baseline body weight) than placebo.1 Antipsychotic medications are not the only factor that results in metabolic effects, as patients with severe mental illness are at increased risk for these abnormalities because of lifestyle choices and limited access to and participation in medical care.
Collectively, these effects are even more concerning because they are components of the metabolic syndrome and are associated with up to a 6-fold increase in the risk of type 2 diabetes and death from coronary heart disease.1,2 Despite these risks and the increased need for monitoring in this population, patients who have psychiatric illnesses typically receive less frequent medical care. In some cases, psychiatrists may be the only clinicians who manage a psychiatric patient’s care, and therefore they must aim to ensure appropriate monitoring of metabolic parameters when antipsychotic medications are used. Furthermore, consultation with other providers, including pharmacists, may be necessary to optimize the monitoring and management of these metabolic parameters according to established recommendations. Parameters are checked at baseline and at every follow-up visit in both adult and pediatric patients who receive antipsychotic medications (Table 1).
It is important to recognize the physical and psychological consequences of adverse effects associated with treatment nonadherence. An understanding of the differences between the metabolic risks with each antipsychotic may help guide medication selection so that the risks versus the benefits can be appropriately evaluated and treatment nonadherence can be minimized. Note that no single mechanism explains any of the metabolic effects seen with antipsychotic medications. Histamine, serotonin, dopamine, and muscarinic receptors, along with several others, are thought to play a role in these adverse effects. Lipid abnormalities can be independent of weight gain, and switching to an antipsychotic with lower metabolic risk may not lead to weight loss. Table 2 compares the risks of metabolic abnormalities among various antipsychotics based on available evidence in adults. While there are limitations to available data, this may be used as a guide for prescribers when selecting an agent.
While monitoring of atypical antipsychotics for metabolic effects has been well studied, there is controversy surrounding the need to monitor typical antipsychotics for the same effects. Leucht and colleagues3 conducted a meta-analysis that demonstrates the need to eliminate the dichotomy between typical and atypical antipsychotics with regard to potential weight gain. One finding suggests that if a patient is treated with chlorpromazine, a low-potency typical antipsychotic, the risk of weight gain is greater than with quetiapine and nearly similar to that of clozapine.
Dr. Bostwick is Associate Chair and Clinical Associate Professor, Department of Clinical Pharmacy, University of Michigan College of Pharmacy and Clinical Pharmacist in Psychiatry, Michigan Medicine, Ann Arbor; Dr. Murphy is Clinical Pharmacy Specialist – Mental Health, VA Ann Arbor Healthcare System. The authors report no conflicts of interest concerning the subject matter of this article.
1. De Hert M, Detraux J, van Winkel R, et al. Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nat Rev Endocrinol. 2011;8:114-126.
2. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27:596-601.
3. Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013;382:951-962.
4. Bak M, Fransen A, Janssen J, et al. Almost all antipsychotics result in weight gain: a meta-analysis. PLoS One. 2014;9:e94112.