Melatonin for SGA-induced metabolic syndrome

Abstract

Second-generation antipsychotics (SGAs) such as quetiapine are among the most commonly prescribed drugs in the United States, with much of their use for off-label conditions rather than for schizophrenia or bipolar disorder. Initially considered safer than the typical antipsychotics, SGAs are well known to cause metabolic syndrome, with olanzapine and clozapine carrying the highest risks. Second-generation antipsychotics (SGAs) such as quetiapine are among the most commonly prescribed drugs in the United States, with much of their use for off-label conditions rather than for schizophrenia or bipolar disorder. Initially considered safer than the typical antipsychotics, SGAs are well known to cause metabolic syndrome, with olanzapine and clozapine carrying the highest risks. Patients taking SGAs are counseled about smoking cessation as well as careful management of weight, blood pressure, lipids, and glucose. Several studies have evaluated the potential effects of melatonin on SGA-induced metabolic syndrome, as the supplement has decreased both systolic and diastolic blood pressure along with LDL cholesterol in patients with non-SGA induced metabolic syndrome.1.J Pineal Res. 2011; 50: 261-266Crossref PubMed Scopus (201) Google Scholar In the first study, researchers compared the effects of sustained-release melatonin 5 mg daily with placebo on components of the metabolic syndrome associated with SGA use. Fifty patients met the inclusion criteria, and 44 completed the 8-week study. Participants were between the ages of 18. years and 45 years, had started on the SGA within 3 months, and had a diagnosis of either schizophrenia or bipolar disorder type I. The SGAs included clozapine (n = 2), olanzapine (n = 14), quetiapine (n = 15), or risperidone (n = 13). Participants took melatonin and placebo at 8:00 pm. The mean age of participants was 29.5 years, with an equal distribution between men and women. More patients in the melatonin groups received SGAs with a moderate (versus high) risk of metabolic syndrome. After adjusting for these and other baseline differences, researchers found that patients with bipolar disorder who took melatonin had less weight gain, lower triglycerides, and lower diastolic blood pressures. Weight gain was greater with melatonin among patients taking clozapine or olanzapine, although this gain may have been an increase in total body water. Metabolic benefits were not observed in patients with schizophrenia, and psychiatric symptoms in both diseases were unchanged with the use of melatonin.2.Bipolar Disorders. 2014; https://doi.org/10.1111/bdi.12196Crossref Scopus (85) Google Scholar Another study of new-onset schizophrenia randomized 48 participants to receive melatonin 3 mg at 8:00 pm or placebo along with olanzapine for 8 weeks. Of those participants, 36 had at least one follow-up assessment. Participants receiving melatonin had less weight gain, a smaller increase in waist circumference, and slightly lower triglycerides than those taking placebo. In addition, in this study improvements in the Positive and Negative Syndrome Scale, a tool to assess the symptom severity in schizophrenia, were identified with melatonin use.3.J Psychiatr Res. 2014; 53: 133-140Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar Although these findings are interesting, health professionals should recognize the trends in overprescribing SGAs and consider alternative drugs with neutral metabolic effects, such as aripiprazole. Potential mechanisms for benefits with melatonin may involve the suprachiasmatic nucleus, the area of the hypothalamus responsible for regulation of circadian rhythms. Encourage patients who develop metabolic syndrome secondary to SGAs to maintain heart-healthy behaviors to reduce their cardiovascular risk. Melatonin, in dosages of 3 mg and 5 mg taken at 8:00 pm, has demonstrated modest effects on lessening the syndrome, although studies are small and of short duration, with some conflicting findings.