Szobot 2008.

Study characteristics
Methods	6‐week cross‐over trial with 2 interventions SODAS MPH placebo Group A: receiving SODAS MPH dosage: 0.3, 0.7 and 1.2 mg/kg/d for weeks 1, 2 and 3 and placebo for weeks 3, 4, and 6 Group B: receiving placebo for weeks 1, 2, and 3, and SODAS MPH dosage: 0.3, 0.7 and 1.2 mg/kg/d for weeks 4, 5, and 6
Participants	Number of participants screened: 25 from a previous ADHD/substance misuse trial and 15 through advertising Number of participants included: 16 (100% boys) Number of participants followed up: 16 Number of withdrawals: 2 (both from group A; withdrawal rate 12.5%) Diagnosis of ADHD: DSM‐IV (combined 12 (75%), hyperactive/impulsive (n = 1), inattentive 3 (18.75%)) Mean age: group A 17.5 years (SD 2.33), group B 17.38 (SD 2.2) IQ: group A 79.43 (SD 16.66), group B 84.75 (SD 21.16) MPH‐naive: 100% Ethnicity: European‐Brazilian (group A 3 (37.5%), group B 7 (87.5%)) Country: Brazil Setting: outpatient clinic Comorbidity: CD (group A 100%, group B 75%); ODD (group A 25%, group B 37.5%); depression (group A 12.5%, group B 25%) Comedication: yes (marijuana and cocaine); group A: marijuana (100%) and cocaine (50%); group B: marijuana (87.5%) and cocaine (37.5%) Other sociodemographics: divorced parents (group A 37.5%, group B 50%); socioeconomic group A + B + C (group A 50%, group B 87.5%); group D + E (group A 50%, group B 12.5%) Inclusion criteria 15‐21 years of age Male Current diagnosis of abuse of marijuana or cocaine (K‐SADS‐E and MINI) Current diagnosis of ADHD: K‐SADS‐E Stimulant‐naive Exclusion criteria Absence of responsible adult ‐ to inform on childhood psychopathology and to take responsibility for medication and/or the need for inpatient care for substance misuse or psychiatric comorbidity Primary psychiatric condition requiring immediate treatment (e.g. moderate/severe depression)
Interventions	Participants were randomly assigned to 1 of 2 possible drug condition orders of MPH and placebo Mean SODAS MPH dosage: 0.3, 0.7 and 1.2 mg/kg/d for weeks 1, 2 and 3 for group A, and for weeks 4, 5 and 6 for group B Administration schedule: morning dose time points Duration of each medication condition: 3 weeks Washout before trial initiation: no Medication‐free period between interventions: 24 h Titration period: none Treatment compliance: "Study compliance was assessed by self‐report, mother’s report and pill counting"
Outcomes	ADHD symptoms K‐SADS‐E, for diagnosis SNAP‐IV Serious AEs Barkley Side Effect Rating Scale (SERS) Non‐serious AEs Barkley Side Effect Rating Scale (SERS)
Notes	Sample calculation: not stated Ethics approval: "The project was approved by the Institutional Review Board (IRB) of Hospital de Clinicas de Porto Alegre (approved as an IRB by the Office for Human Research Protections, United States of America, IRB 00000921" Comments from trial authors "In the present trial, SODAS MPH was significantly superior to placebo in reducing ADHD symptoms and improving global functioning for all main outcome measures (SNAP‐IV and CGI scores)" "No treatment effect on illicit substance use disorders was noted, and MPH‐SODAS was well tolerated, despite causing greater appetite reduction than was seen with placebo" Key conclusions of trial authors SODAS MPH was more effective than placebo in reducing ADHD symptoms in a non‐abstinent outpatient sample of adolescents with comorbid substance use disorders RCTs, with larger samples and substance use disorder interventions, are recommended Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: no Any withdrawals due to AEs: 1 withdrawal resulted from a participant feeling "worse", "more restless" Funding source: "The ADHD outpatient program receives research support from Bristol‐Myers Squibb, Eli‐Lilly, Janssen‐Cilag and Novartis" Email correspondence with trial authors: May 2014. We received supplemental information from trial authors
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	"One of the investigators (LAR) randomized the 16 subjects into groups A or B and prepared weekly blisters of medications for each participant"
Allocation concealment (selection bias)	High risk	Not stated
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"A pharmacist packaged mPH‐SODAS and matching placebo in capsules so that the MPH‐SODAS and placebo could not be visually differentiated"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	From author correspondence: "all persons who evaluated outcome measures were blinded"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No information Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): unclear
Selective reporting (reporting bias)	Unclear risk	No protocol identified