Findling 2007.

Study characteristics
Methods	4‐week, double‐blind, randomised, placebo‐controlled, cross‐over trial with 4 interventions (MPH at 3 different doses, in the morning and at midday): 5 mg 10 mg 15 mg placebo Phases Participants were assigned to receive, at random, 1 of 6 possible dosing orders that included the following: placebo, 5 mg, 10 mg, 15 mg placebo, 10 mg, 15 mg, 5 mg 5 mg, placebo, 10 mg, 15 mg 5 mg, 10 mg, 15 mg, placebo 10 mg, 15 mg, placebo, 5 mg 10 mg, 15 mg, 5 mg, placebo Schedules were designed in such a way that participants did not receive the 15 mg dose before the 10 mg dose, so in the event that a participant experienced AEs while taking a lower dose, the 15 mg dose was not administered
Participants	Number of participants screened: not stated Number of participants included: 20 Number of participants followed up: 16 (12 boys, 4 girls) Number of withdrawals: 4 Demographic data regarding the 16 who completed the trial: Diagnosis of ADHD: DSM‐IV (combined (94%), inattentive (6%)) Age: mean 10.43 years (range 5‐17) IQ: > 70 MPH‐naive: not stated Ethnicity: white (75%), African American (6%), Hispanic (19%) Country: USA Setting: outpatient clinic Comorbidity: bipolar (100%), ODD (50%), CD (25%), enuresis (12.5%), encopresis (12.5%) Comedication: 100% divalproex sodium. Some received clonidine for sleep at night Other sociodemographics: none. No statistically significant differences in distribution based on sex, ethnicity, age group, rate/proportion of comorbid ODD or comorbid CD were found between 6 dosing order groups Inclusion criteria 5‐17 years of age Individuals meeting DSM‐IV criteria for a diagnosis of bipolar spectrum disorder and a comorbid diagnosis of ADHD were eligible for trial participation Treated with fixed doses of mood stabilisers at the time of trial enrolment for ≥ 5 days before receiving trial medication Eligible if trial physician’s clinical assessment indicated the need for a psychostimulant for treatment of "dysfunctional residual symptoms of ADHD" Exclusion criteria Mental disability Pervasive developmental disorder Inability to swallow pills History of alcohol or other substance abuse or dependence within 6 months before enrolment Active neurological or other medical condition suspected to be related to mood symptoms Pregnant female patients, those intending to become pregnant and sexually active female patients who were using an inadequate form of birth control were not permitted to participate Participation required a negative qualitative pregnancy test within 2 weeks of receiving the first dose of double‐blind treatment for female patients of childbearing potential Significant symptoms of mania (Young Mania Rating Scale score > 13) or depression (CDRS‐R > 40) during the week before enrolment and anticipated dosing changes for mood‐stabilising agents Individuals receiving a tricyclic antidepressant or antipsychotic agent and those with symptoms of psychosis or suicidal ideation Female patients nursing an infant and patients experiencing significant medical or neurological illness were not permitted to participate
Interventions	Participants were randomly assigned to 1 of 6 possible drug condition orders of MPH (5 mg twice/d, 10 mg twice/d, 15 mg twice/d) and placebo Mean MPH dosage: not provided, as the trial compares MPH at different doses Administration schedule: morning and midday Duration of each medication condition: 1 week Washout before trial initiation: not stated Medication‐free period between interventions: between lunchtime dose and morning dose the following day Titration period: none. Dosing schedules were designed in such a way that patients did not receive the 15 mg dose before the 10 mg dose, so in the event that a participant experienced AEs while on a lower dose, the 15 mg dose was not administered Treatment compliance: 1 of 20 screened participants was withdrawn from the trial because of poor compliance. Among the 16 who participated, no compliance issues were reported
Outcomes	ADHD symptoms ADHD‐RS‐IV: rated weekly by parents CPRS (48‐item): rated weekly General behaviour CPRS, Conduct problem subscale Non‐serious AEs CDRS‐R: rated weekly Young Mania Rating Scale: rated weekly. Side Effects/Behavior Monitoring Scale: rated weekly at the trial visit Resting BP and pulse recorded each week Weight documented at baseline and at end of trial
Notes	Sample calculation: yes Ethics approval: yes Comments from trial authors (limitations) Small sample size Full consideration of dosing order effects was not possible because of the modest size of this trial cohort Key conclusion of trial authors Euthymic youths with bipolar disorder and ADHD may benefit from short‐term concomitant treatment with MPH Comment from review authors All participants have a bipolar disorder Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: no Any withdrawals due to AEs: yes; 2 Funding source: Stanley Medical Research Institute Email correspondence with trial authors: November 2013. We wrote to the trial author twice to request a copy of the protocol and information about sample size and allocation concealment but have not received a response.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	A random numbers table was generated and was used by a pharmacist to assign dose orders to participants. Counterbalancing was applied in such a way that as each dose order was used, its number was eliminated from the next dose order assignment.
Allocation concealment (selection bias)	Low risk	Placebo and MPH in identical capsules. No participants were discontinued from this trial because of broken integrity of the blind.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	At the conclusion of the 4‐week trial, trial physician, participant and participant's guardian determined a "best dose week", taking into consideration behaviour ratings and reports of any AEs. After all assessments had been completed, the trial blind was broken to reveal the dose that had been prescribed during the previously identified best dose week. No participants were discontinued from this trial because of broken integrity of the blind.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"After all of the assessments had been completed, the study blind was then broken to reveal the dose that had been prescribed during the previously identified 'best dose week'"
Incomplete outcome data (attrition bias) All outcomes	Low risk	All data present Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): no
Selective reporting (reporting bias)	Unclear risk	No protocol identified