Modabbernia 2014.

Study characteristics
Methods	Study design: Randomized controlled trial Study grouping: Parallel group How were participants recruited: Academic psychiatric hospital Type of RCT: Double‐blind
Participants	Baseline characteristics Melatonin + olanzapine Sex (N, % female, % male): female 5 (28%), male 13 (72%) Age (mean, SD): 32.7 (SD 7.3) years Number of participants: 18 Placebo + olanzapine Sex (N, % female, % male): female 6 (33%), male 12 (67%) Age (mean, SD): 32.8 (SD 8.2) years Number of participants: 18 Overall Sex (N, % female, % male): female 11 (31%), male 25 (69%) Age: not reported Number of participants: 36 Inclusion criteria: Age 18 to 65 years, first episode schizophrenia (DSM‐IV‐TR), ability to take medicine orally, eligible for starting olanzapine Exclusion criteria: Married women who are at reproductive age, history of taking olanzapine in the recent 3 months, history of allergy or intolerance to olanzapine, history of significant head trauma (causing loss of consciousness more than 5 minutes or neurological or cognitive sequels). Liver, kidney, cerebrovascular or cardiovascular disease, diabetes, metabolic syndrome, cancer. Using antiepileptic (other than benzodiazepines for sleep), antihypertensive, anticoagulant, anti‐platelet drugs, using inhibitors or stimulants of hepatic isoenzymes that metabolize melatonin or olanzapine (e.g. omeprazole, rifampin, fluvoxamine, ciprofloxacin, carbamazepine, modafinil), delirium, need for administration of other antipsychotics. Substance abuse Pretreatment: Placebo group had slightly lower PANSS score, lower fasting glucose, lower cholesterol at baseline.
Interventions	Intervention characteristics Melatonin + olanzapine Class of drug: Hormone Dose: 3 mg Frequency: Daiily Duration: 8 weeks Who delivered the intervention? Nurse guided, when staying at Hospital. At home used pill pack was monitored. Type of intervention: Pharmacological Placebo + olanzapine Class of drug: Placebo Dose: ‐ Frequency: Daily Duration: 8 weeks Who delivered the intervention? Nurse guided, when staying at Hospital. At home used pill pack was monitored. Type of intervention: Pharmacological
Outcomes	Fasting blood sugar Outcome type: Continuous Reporting: Partially reported Unit of measure: mg/dL Direction: Lower is better Data value: Endpoint Notes: Values reported at 8 weeks are mean and SEM, not SD. BMI Outcome type: Continuous Reporting: Partially reported Unit of measure: kg/m2 Direction: Lower is better Data value: Endpoint Notes: Values reported at 8 weeks are mean and SEM, not SD. Cholesterol Outcome type: Continuous Waist circumference Outcome type: Continuous Diastolic blood pressure Outcome type: Continuous Systolic blood pressure Outcome type: Continuous Drop‐outs Outcome type: Dichotomous Reporting: Fully reported Direction: Lower is better Data value: Endpoint
Identification	Sponsorship source: Grant from Guilan University of Medical Sciences to Prof MJ Modabbernia (grant number 9277). Country: Iran Setting: Academic psychiatric hospital Comments: SEM is reported for outcomes instead of SD Authors name: Amirhossein Modabbernia Institution: Department of Psychiatry, Shafa Hospital, Guilan University of Medical Sciences, Rasht, Iran Email: amirh899@gmail.com Address: 15 Khordad Ave, Rasht 41939‐55599, Iran
Notes	Trial registration: https://clinicaltrials.gov/ct2/show/NCT01593774Publication: J Psychiatr Res. 2014 Jun;53:133‐40. doi: 10.1016/j.jpsychires.2014.02.013.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Judgement comment: Random number generator used.
Allocation concealment (selection bias)	Low risk	Judgement comment: Treatment allocation was conceal from the study participants and physicians who rated them using sequentially numbered and opaque envelops.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Judgement comment: Participants, physicians, and statistician were blinded. The study states that those blinded to allocation include: patients, their family members, the evaluator, statistician and those responsible for administering the intervention. There was insufficient information to determine how blinding was tested.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Judgement comment: clinical evaluators were blinded. The study states that treatment allocation and clinical evaluation were done by different individuals.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Judgement comment: Numbers do not match: in section 3.1 7 patients in each group were said to have dropped out, out of a total of 24, but the data is for N=18 participants per group. Reasons for drop‐out do not reveal obvious differences in reasons related to treatment.
Selective reporting (reporting bias)	Low risk	Judgement comment: Protocol available and outcomes match those reported.
Other sources of bias	Low risk	No other sources of bias identified.