Table 2.
Pharmacological studies comparing melatonin versus placebo to prevent/reverse atypical antipsychotic-induced metabolic syndrome
| Studies | Sample | Treatment (dosage) | Trial duration (weeks) | Results |
|---|---|---|---|---|
| Raskind et al9 | 44 rats | 11 patients, olanzapine (2 mg/kg/day) | 8 | Higher weight in the olanzapine group than in each of the other groups (all P<0.001) |
| 11 patients, melatonin | Total visceral fat pad weight was increased ~37% (P<0.001) by olanzapine and restored to control levels by olanzapine + melatonin | |||
| 11 patients, olanzapine + melatonin | Nocturnal plasma melatonin concentrations in week 7 of treatment were suppressed 55% (P<0.001) in the olanzapine-treated rats, relative to control treatment, and were restored to normal by olanzapine + melatonin treatment | |||
| 11 patients, placebo | Nocturnal locomotor activity was decreased 32% (P<0.001) by olanzapine and addition of melatonin treatment did not alter this decrease | |||
| Romo-Nava et al26 | 44 patients (20 with bipolar disorder and 24 with schizophrenia) | 20 patients, slow-release melatonin (5 mg) | 8 | Decrease in diastolic BP (5.1 vs 1.1 mmHg for placebo, P=0.003) and attenuated weight gain (1.5 vs 2.2 kg for placebo, P=0.04) in melatonin group |
| 24 patients, placebo | Waist circumference changes between the placebo and melatonin groups (1.9 vs 2.2, respectively, P=0.05) | |||
| Antipsychotics (clozapine, olanzapine, quetiapine, risperidone) | In the bipolar disorder, but not in the schizophrenia group, strong beneficial metabolic effects of melatonin in comparison to placebo on fat mass (0.2 vs 2.7 kg, respectively, P=0.032) and diastolic BP (5.7 vs 5.5 mmHg, respectively, P=0.001) were observed | |||
| Concomitant medications (lithium, valproate, SSRI, benzodiazepines) | ||||
| Modabbernia et al34 | 48 patients (first-episode schizophrenia) | 24 patients, melatonin (3 mg) | 8 | Melatonin was associated with significantly less weight gain (MD =3.2 kg, P=0.023), increase in waist circumference (MD =2.83 cm, P=0.041), in body mass index (MD =1.07 kg/m2, P=0.024), and triglyceride concentration (MD =62 mg dL−1, P=0.09) than the placebo |
| 48 patients, olanzapine (5–25 mg) | Changes in cholesterol, insulin, and blood sugar concentrations did not differ significantly between the two groups | |||
| 24 patients, placebo (24) | ||||
| 48 patients, clonazepam (2 mg) | ||||
| Mostafavi et al21 | 48 patients (bipolar disorder) | 24 patients, (olanzapine, lithium carbonate, and melatonin) | 12 | Fasting blood sugar and triglyceride demonstrated greater increase in the placebo group compared with the melatonin group, but the differences were not statistically significant |
| 24 patients (olanzapine, lithium carbonate, and placebo) | Melatonin significantly inhibited the rise in total cholesterol levels compared with placebo (P=0.032) | |||
| Mean systolic BP rose more slowly in the melatonin group (1.05 mmHg) compared with placebo (6.36 mmHg) (P=0.023) The trends in diastolic BP did not show any significant pattern |
Abbreviations: BP, blood pressure; MD, mean difference; SSRI, selective serotonin reuptake inhibitors.