Mahmoudi‐Gharaei 2012.

Methods	Randomised single‐blind trial
Participants	Number of total participants/type of patients: 30 participants randomised. Inpatient study Inclusion criteria: Sex: male and female Age‐group : children and adolescents (11 ‐ 18 years) Diagnosis: diagnosis of current bipolar disorder I (BD) according to the DSM‐IV‐TR in the manic or mixed phase (with or without psychotic features), eligible for adding adjunctive therapy, who were treated with lithium + risperidone at therapeutic doses for at least 4 weeks were selected. Other: in the context of the study centre, children and adolescents with BD are regularly initiated on two agents (lithium + risperidone) together. Therefore, those patients who received the above combination for at least 4 weeks and met the criteria for adjunctive therapy entered the study. Indications for receiving adjunctive therapy included experiencing a recurrent episode, or relapse evaluation by 1 child and adolescent psychiatrist. Exclusion criteria: (i) Comorbidity of mental retardation, pervasive developmental disorder, seizure disorder, anorexia nervosa according to clinical assessment; (ii) a severe mental illness requiring ECT or other treatment modalities during trial; (iii) any contraindication to the study drugs; (iv) current substance abuse or dependence within 3 months; (v) pregnancy; (vi) clinically significant medical illness; (vii) body weight under 30 kg; (viii) positive personal or family history of nephrolithiasis
Interventions	Location: Iran, hospital site in Tehran Study duration: Not stated Treatment groups: 1. Lithium + risperidone + valproate: valproate was initiated at a dose of 10 mg/kg in divided doses with increase of 5 mg/kg every 3 days to a maximum daily dose of 20 – 30 mg/kg or as tolerated. Mean dose: 927.27 (SD 134.83) Maximum dose: 1200; lithium and risperidone were kept stable. 2.Lithium + risperidone + topiramate: topiramate was initiated at a dose of 25 mg/day; dosage was increased by 25 mg every 3 days to a maximum dose of 200 mg/day or increased as tolerated. Mean dose: 177.08 (SD 31.00) Maximum dose: 250; lithium and risperidone were kept stable Concomitant medications: Concomitant treatments with haloperidol injections (as needed for severe agitation) and biperiden (in the event of facing EPS symptoms) were allowed. Participants were not allowed to have any other concomitant treatments, including medications for their comorbid illnesses Length of study: 6 weeks Randomisation: 15 patients randomised to lithium, risperidone, and valproate 15 patients randomised to lithium, risperidone, and topiramate
Outcomes	Outcomes: 1. Changes on YMRS scale 2. Changes on the CGI scale Study withdrawals were reported
Funding	"Funding sources supported by Teheran University of Medical Scienes"
Conflict of interest	Not stated
Notes	Study focused on children/teenagers between 11 – 18 years of age
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: No comment on randomisation procedure in text. We contacted the authors but received no reply.
Allocation concealment (selection bias)	Unclear risk	Comment: No comment on randomisation concealment in text. We contacted the authors but received no reply.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "Single‐blind" Comment: No comment on the nature of the single blind (who exactly was blind). No comment on procedures to maintain blinding. We contacted the authors but received no reply. However, as a single‐blind study, either the participants or medical staff must be unblinded.
Blinding of outcome assessment (detection bias) Efficacy	Unclear risk	Quote: "Single‐blind" Comment: No comment on the nature of the single blind (who exactly was blind). No comment on procedures to maintain blinding. We contacted the authors but received no reply.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: In all groups dropout rate was below 30%.
Selective reporting (reporting bias)	Unclear risk	Comment: No pre‐published protocol found. We are therefore unable to assess the bias.
Other bias	High risk	Comment: Group receiving adjunctive topiramate had significantly different baseline characteristics (more hospitalisations).