Acta Medica Iranica 2014. 52(10):734-739.

Melatonin decreases olanzapine induced metabolic side-effects in adolescents with bipolar disorder: a randomized double-blind placebo-controlled trial.
Ali Mostafavi, Mahmoud Solhi, Mohammad-Reza Mohammadi, Mehdi Hamedi, Maryam Keshavarzi, Shahin Akhondzadeh


Olanzapine is the frequently prescribed drug in children and adolescents with bipolar disorder, but unfortunately it has metabolic side-effects. On the other hand, in a number of melatonin studies on sleep cycle, regulation of metabolic abnormalities has been reported. Therefore, we aimed to study effects of melatonin in reducing metabolic side-effects of olanzapine in 11-17 year-old patients with bipolar disorder. Seventy-seven 11-17 year-old outpatients entered into the study after their initial diagnosis of bipolar mood disorder by a psychiatrist. After assessing inclusion and exclusion criteria, 48 patients consented to participate in the study. Of this number, 24 patients were allocated to olanzapine, lithium carbonate, and melatonin and 24 patients were allocated to olanzapine, lithium carbonate, and placebo. Young mania rating scale was performed at baseline. Before treatment initiation and at sixth and twelfth weeks after treatment, Lipid profile, Fasting Blood Sugar (FBS), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were measured. ANOVA with repeated measure and independent sample t-test were used for data analysis. Nineteen patients in each group completed the study and yielded data for analysis.  ANOVA with repeated measure showed that FBS and Triglyceride (TG) (especially in boys) demonstrated greater increase in the placebo group compared to the melatonin group but the differences were not statistically significant. Melatonin significantly inhibited the rise in Total Cholesterol levels compared to placebo (P=0.032). Mean SBP rose more slowly in the melatonin group (1.05mmHg) compared to placebo (6.36 mmHg) (P=0.023). The trends in DBP did not show any significant pattern. Administration of melatonin along with olanzapine and lithium carbonate could significantly inhibit the rise in cholesterol level and SBP compared to placebo. The effect of melatonin on TG was more obvious in boys. Melatonin was more effective in prevention of SBP rise.


Metabolic Syndrome; Olanzapine; Melatonin; Bipolar disorder

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