Barekatain 2005.

Methods	Study design: 2‐week, double‐blind, randomised, parallel‐group study
Participants	Diagnosis: BMD‐I most recent episode manic, hospitalised for treatment Method of diagnosis: expert psychiatrist diagnosed BMD‐I (manic episode) based on DSM‐IV and CIDI Age: for valproate + lithium, median = 29.8 (SD = 10.3) years; for valproate + risperidone, median = 31.4 (SD = 10.1) years; range = not described (18‐65 years allowed) Sex: females; males Location: Noor University hospital, Isfahan, Iran Co‐morbidities: substance abuse in (8 for lithium, 13 for risperidone) Adjunctive therapy: not described Adjunctive medication: in addition to the main drugs, only 1‐4 mg/day oral clonazepam (Sobhan Darou Iran) or lorazepam (Wyeth‐Ayerst Lab USA) were permitted to be administered during the study. For severe agitation, intramuscular lorazepam was allowed.
Interventions	Participants were randomly assigned to either: Experimental arm n = 23 Duration: 2 weeks Treatment protocol: 20 mg/kg per day sodium valproate three times daily at days 1‐14. Lithium capsules (300 mg) were administered three times daily at days 1‐5. If the participant's body weight was below 45 kg, lithium was used twice daily. After measuring serum lithium concentration at days 5 and 10, if lithium level was below 0.8 mEq/L, the dosage of lithium was adjusted by 300 mg increment in dosage at days 6 and 11 Therapist/face‐to‐face contact: not described Comparator arm n = 23 Duration: 2 weeks Treatment protocol: 20 mg/kg per day sodium valproate three times daily at the days 1‐14. Risperidone was administered once daily in 2 mg capsules (matching those capsules used for lithium) at days 1‐2, and twice daily at days 3‐14." Therapist/face‐to‐face contact: not described
Outcomes	Timepoints for assessment: 4, 8, 14 days Primary outcomes: Mean of YMRS scores from baseline to endpoint (day 14) Secondary outcomes: Withdrawal Adverse events Additional medication required 50% reduction in baseline YMRS Remission – YMRS ≤ 12 CGI – ‘much improved’ or ‘very much improved’ Mean dose of benzodiazepine used for each participant Mean weight of the participants Change in YMRS – Day 4 Change in YMRS ‐ Day 8 CGI severity change
Notes	Date of study: 2003 Funding source: not described Declarations of interest among the primary researchers: not described
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Randomized" ‘46 cases were enrolled in two groups, equally
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	Low risk	Double‐blind Total number of placebo capsules (matched for lithium and risperidone) were equally ad‐ ministered per day for each participant in both groups. Assessment by "by a trained blind psychiatry resident
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	During the study, a total number of 7 participants (30.4%) dropped out in each group: between 4th and 7th days, four participants (17.4%) discontinued the study in each group;
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Unclear risk	None identified