Gupta 2004b.

Methods	Randomized, double‐blind, parallel, placebo‐controlled trial
Participants	Inclusion criteria: children of either sex, aged 3‐12 years, valproate monotherapy, confirmed diagnosis of epilepsy according to the International Classification of Epileptic Seizures, seizure free for ≥ 6 months Exclusion criteria: children with a history of psychiatric or other progressive neurological disorder, or a chronic haematological, cardiac, hepatic, renal, or thyroid disorder N: 31 (1 lost to follow‐up) M: 18; F: 12 Type of seizures: absence (8); complex partial (5); generalized tonic‐clonic seizures (14); Lennox‐Gastaut syndrome (3) Concurrent AED treatment: valproate monotherapy. Participant on sodium valproate (10 mg/kg/day) monotherapy for the last 6 months, and, at the time of inclusion in the study, with serum blood levels in the range 75‐125 μg/mL Seizure frequency: all participants were seizure free for at ≥ 6 months Duration of the trial (including follow‐up): 8 weeks
Interventions	Melatonin (fast release) compared with placebo (see text for more details)
Outcomes	Adverse events: authors state that "no adverse event warranting discontinuation of the therapy was observed" Quality of life: assessed by the QOLCE questionnaire. Valproic acid + melatonin group: intragroup P value = 0.08; valproic acid + placebo group: intragroup P value = 0.16
Notes	Reasons for lost to follow‐up (1 participant) were reported Authors performed no intergroup statistical evaluation between valproic acid + melatonin and valproic acid + placebo
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomization code list prepared by a statistician, not connected to the study. Computer‐generated permutations of code numbers for the treatment groups
Allocation concealment (selection bias)	Low risk	Placebo and melatonin tablets were identical in shape, size, colour, and packaging
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Blinding not explicitly reported (insufficient information to permit judgement)
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Missing to follow‐up reported. No intention‐to‐treat analysis
Selective reporting (reporting bias)	High risk	Each participant has a daily diary to record any adverse events or unusual symptoms observed immediately. In results section, authors only state that "no adverse event warranting discontinuation of the therapy was observed"
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Blinding not explicitly reported (insufficient information to permit judgement)
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Blinding not explicitly reported (insufficient information to permit judgement)