Findling 2015.
| Methods | Study design: multicentre, randomised, double‐blind, placebo‐controlled study | |
| Participants |
Diagnosis: bipolar affective disorder type 1, currently in manic or mixed episode Method of diagnosis: children aged 7 to 17 years meeting unmodified DSM IV, criteria for BP‐I currently in a manic or mixed episode, scoring 20 on the YMRS Age: for lithium, median 11.5 (SD = 2.9) years, for placebo, median 11.2 (SD = 3.0) years Sex: lithium: 31 female; 22 male, placebo: 13 female; 15 male Location: outpatient participants were enrolled at 1 of 10 academic medical centres in the United States that are experienced in paediatric psychiatric care Co‐morbidities: children were ineligible if they: were clinically stable on a medication regimen for BP‐I; diagnosed with schizophrenia or schizoaffective disorder, a pervasive developmental disorder, anorexia nervosa, bulimia nervosa, obsessive compulsive disorder, substance dependence, symptoms of mania that were attributable to a general medical condition or secondary to use of medications or general medical condition including neurologic disease, diabetes mellitus, thyroid dysfunction, or renal dysfunction that might be adversely affected by lithium; had clinically significant abnormal laboratory assessments that could influence the efficacy or safety of lithium or would complicate interpretation of study results; had evidence of serious homicidal/suicidal ideation or active hallucinations and delusions such that in the treating physician’s opinion it would not be appropriately safe for the participant to participate in this study; or had concomitant prescription of overthe‐counter medication or nutritional supplements that would interact with lithium or affect the participant’s physical or mental status. Adjunctive therapy: none Adjunctive medication: "participants with comorbid attention‐deficit/hyperactivity disorder were able to receive psychostimulants after 4 weeks of double‐blind therapy at the treating physician’s discretion. Melatonin (up to 3 mg) at bedtime was permitted to treat insomnia." |
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| Interventions | Participants were randomly assigned to either: Experimental arm ‐ lithium N = 53 Duration: 8 weeks Treatment protocol: "Starting dose of lithium (supplied as 300 mg, regular‐release capsules) was either 600 or 900 mg/d. Participants weighing, 30 kg started with 600 mg/day; all other participants began lithium therapy with 900 mg/day. Dose increases of 300 mg/day could occur at study visits and via telephone call during the middle of the first week of randomised treatment unless the participant had the following: had met dosing response criteria (defined as a CGI 25 score ≥2 and a 50% decrease in the YMRS score from baseline assessment); experienced1 adverse effect that significantly affected functioning that was at least of moderate severity; had a serum lithium level 1.4 mEq/L; or if the dose exceeded 40 mg/kg/day (with the exception of participants weighing, 23 kg, who could receive up to 900 mg/day)." Therapist/face‐to‐face contact: not described Comparator arm ‐ placebo N = 28 Duration: 8 weeks Treatment protocol: "Participants randomised to receive placebo were pre‐assigned to a maximum dose at randomisation to maintain the integrity of the blind. Adherence to study medication was monitored by using a dosing diary and pill counts." |
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| Outcomes |
Timepoints for assessment: weekly Primary outcome:
Secondary outcome:
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| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "Participants were enrolled into the study and were randomized to receive lithium or matching placebo in a 2 (lithium): 1 (placebo) allocation ratio. Stratification factors included study site, age at randomization (7–11 years and 12–17 years), and gender (male and female). The randomization list was created by an unblinded BPCA data coordinating centre (DCC) statistician. Unblinded site staff members were provided randomization assignments via an electronic data capture system." |
| Allocation concealment (selection bias) | Low risk | double‐blinded |
| Blinding (performance bias and detection bias) All outcomes | Low risk | "Participants randomized to receive placebo were preassigned to a maximum dose at randomization to maintain the integrity of the blind." |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | All participants included in analysis lithium 16/53 did not complete 8 weeks ‐ all reasons given Placebo 7/28 did not complete 8 weeks ‐ all reasons given |
| Selective reporting (reporting bias) | Low risk | Comprehensively reported |
| Other bias | Low risk | None identified |