Therapeutic use of melatonin in schizophrenia: A systematic review

Table 2 Metabolic outcomes

Ref.	Sample size (sex) melatonin; control	Age (yr) melatonin; control	Dose, duration	Diagnosis	Inclusion criteria	Study design	Outcomes	Significant findings related to melatonin	Risk of bias
Borba et al[23], 2011	14 (8 M, 6 F); 6 (5 M, 1 F)	49 ± 7; 56 ± 9	8 mg/d Ramelton or placebo for 8 wk	SCZ (n = 11), SZA (n = 9)	Diagnosis of SCZ (as per DSM-IV criteria); aged between 18-65 yr; BMI > 27 kg/m2, insulin resistance or any component of metabolic syndrome or a BMI of > 30 kg/m2	Double-blind, placebo-controlled pilot trial	Waist circumference (cm), abdominal fat as measured by DEXA, glucose metabolism, C-reactive protin, lipids, psychopathology (PANSS; HDRS, HCQoL), sleep quality (SSS, FSI, MOSSS), adverse effects (SATEE)	Total cholesterol; cholesterol-to-HDL ratio; LDL particle number: Melatonin < Placebo	High
								Adverse effects: Melatonin vs control group: drowsiness (57% vs 33%), heart burn (21% vs 0%), cough (21% vs 0%), akathisia (21% vs 0%), increased urinary frequency (14% vs 0%), problems with memory or concentration (21% vs 0%)
								Arthralgia/myalgia and anxiety: Placebo > Melatonin
Modabbernia et al[24], 2014	18 (13 M, 5 F); 18 (12 M, 6 F)	32.7 ± 7.3; 32.8 ± 8.2	3 mg/d melatonin + Olanzapine or placebo + Olanzapine for 8 wk	SCZ (n = 36)	Diagnosis of SCZ (as per DSM-IV criteria); aged between 18-65 yr; in their first-episode eligible for starting olanzapine	Randomized, double- blind, placebo-controlled, and parallel-group study	Anthropometric measures, BP, FBS, fasting plasma insulin, Psychopathology (PANSS)	Weight, BMI and Waist circumference: Melatonin < Placebo	Some concerns
								PANSS total score: Melatonin < Placebo
Romo-Nava et al[25], 2014	20 (10 M, 10 F); 24 (12 M, 12F)	Overall: 29.5 ± 8.3	5 mg/d CR melatonin or placebo for 8 wk	SCZ (n = 24); BP (n = 20)	Diagnosis of SCZ or BP type I (as per DSM-IV criteria); aged between 18-45 yr, initiated treatment with SGAs < 3 mo	Double-blind, placebo-controlled study	Anthropometric measures, body composition, BP, Lipids, Glucose, PANSS, CGI-S. BPD only: HDRS, YMRS. Schizophrenia only: CDS	Weight gain, waist circumference, DBP, fat mass, triglycerides: Melatonin (BP only) < Placebo	Some concerns

BMI: Body mass index; BP: Bipolar disorder; BP: Blood pressure; CDS: Calgary depression scale; CGI-S: Clinical Global Impression-Severity of Illness; CR: Controlled-release; DEXA: Dual-energy x-ray absorptiometry; DSM-IV: Diagnostic and Statistical Manual of Mental Disorders, fourth edition; F: Female; FBS: Fasting blood sugar; FSI: Fatigue scale inventory; HCQoL: Heinrichs-Carpenter Quality of Life Scale; HDL: High-density lipoprotein; HDRS: Hamilton Depression Rating Scale; LDL: Low-density lipoprotein; M: Male; MOSSS: Medical outcomes study sleep scale; PANSS: Positive and Negative Syndrome Scale; SATEE: Systematic assessment for treatment emergent events; SCZ: Schizophrenia; SGA: Second generation antipsychotics; SSS: Stanford sleepiness scale; SZA: Schizoaffective disorder; YMRS: Young mania rating scale.