Small 1991.

Methods	Study design: double‐blind, randomised controlled study, parallel
Participants	Diagnosis: bipolar disorder, manic or mixed phases Method of diagnosis: examination of the patient and independent interviews with relatives using SADS. Patients met DSM‐ III‐R" criteria for a manic episode with or without coexisting symptoms of depression. Age: for lithium, median = 42.6 years (SD = not described); for carbamazepine, median = 34.3 years (SD = not described ) range = 22‐73 years Sex: lithium 13 women; 11 men, carbamazepine 14 women; 10 men. Location: Indiana University School of Medicine, Indianapolis Comorbidities: not described Adjunctive medication: "As during the washout phase, the only adjuvant medications that were allowed were chloral hydrate and amobarbital with repeated efforts to withdraw them after the first 3 weeks with double‐blind medications." Adjunctive therapy: not described
Interventions	Participants were randomly assigned to either: Experimental arm ‐ lithium N = 24 Duration: 8 weeks Treatment protocol: "2 week washout were randomly assigned to treatment with lithium carbonate (300 mg) plus carbamazepine placebo tablets Medications were prescribed in initial dosages of one or two capsules and tablets daily, with dosage increments every 3 to 4 days until trough plasma lithium ion levels (10 to 12 hours after the last dose) were between 0.6 and 1.5 mmol/L and plasma carbamazepine levels were between 25 and 50 μ/L. Dosages were increased to ceiling levels or dosage‐limiting side effects. The "blind" of the attending clinicians was preserved by providing dummy plasma levels of lithium or carbamazepine, as was done in the study by Lerer et al." Therapist/face‐to‐face contact: as above Comparator arm ‐ carbamazepine N = 24 Duration: 8 weeks Treatment protocol: 2 week washout "Patients were randomly assigned to carbamazepine (200 mg tablets) and lithium placebo capsules. Medications were prescribed in initial dosages of one or two capsules and tablets daily, with dosage increments every 3 to 4 days until trough plasma lithium ion levels (10 to 12 hours after the last dose) were between 0.6 and 1.5 mmol/L and plasma carbamazepine levels were between 25 and 50 μ/L. The latter was primarily a measure of the parent compound without separation of the epoxide metabolite. Dosages were increased to ceiling levels or dosage‐limiting side effects. The "blind" of the attending clinicians was preserved by providing dummy plasma levels of lithium or carbamazepine, as was done in the study by Lerer et al."
Outcomes	Timepoints for assessment: weekly Primary outcome: MRS Secondary outcome: Depression and mania scale Hamilton depression rating scale BPRS CGI GAS Shopsin‐Gershon Social Behaviour Checklist Use of additional medication Adverse events Withdrawal Length of stay in the study
Notes	Funding source: this study was supported in part MH40930 from the National Institute of Mental Health, Bethseda, Md.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"randomised"
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	Low risk	Placebo tablets "The "blind" of the attending clinicians was preserved by providing dummy plasma levels of lithium or carbamazepine, as was done in the study by Lerer et al. The clinical ratings of psychopathology were done by blinded clinicians who were not informed of the randomised treatment that was assigned nor were these clinicians involved in patient management."
Incomplete outcome data (attrition bias) All outcomes	Low risk	48/52 completed
Selective reporting (reporting bias)	Low risk	Well reported
Other bias	Low risk	None identified