Tohen 2011.

Study characteristics
Methods	Study design: Randomized controlled trial Study grouping: Parallel group How were participants recruited: Patients were recruited in Japan, China, Taiwan, South Korea and the USA in both in‐patient and out‐patient settings. Type of RCT: Double blind for 6 weeks, followed by 18 weeks open label
Participants	Baseline characteristics Placebo Sex (N, % female, % male): female 37 (53%), male 33 (47%) Age (mean, SD): 32.02 (SD 11.50) years Number of participants: 70 Ethnicity: East Asian 70 (100%) Olanzapine Sex (N, % female, % male): Age (mean, SD): 33.31 (SD 10.57) years Number of participants: 140 Ethnicity: East Asian 139 (99%), African 1 (1%) Overall Sex (N, % female, % male): female 114 (54%), male 96 (46%) Age (range and mean, SD): 18 to 61, 32.88 (SD 10.88) years Number of participants: 210 Ethnicity: East Asian (99.5% ), African (0.5% ) Inclusion criteria: Meet diagnostic criteria for major depressive episode and bipolar I disorder (DSM‐IV‐TR), HAM‐D score >=18, age 18 to 64 years, informed consent, tested negative for pregnancy if female, using contraception if of childbearing age, not breastfeeding, birth control use for male patients, at least 1 manic or mixed episode within the past 6 years, YMRS total score <=8. Exclusion criteria: Investigator site personnel, Lilly employee, previously withdrawn or completed this study or another study investigating olanzapine, received drug treatment in past 30 days with drug that has not received regulatory approval, participated in another trial or drug research including olanzapine within 1 month, used olanzapine and treatment withdrawn because of side effects, bipolar depression considered to be treatment‐resistant to olanzapine or olanazapine+SSRI, experiencing current episode of bipolar depression > 90 days in duration, pregnant or nursing, serious unstable illness, history or diagnosis of diabetes mellitus, prolactin level > 200 ng/mL (full list of exclusion criteria available upon request) Pretreatment: No significant differences observed. Similar baseline severity of illness.
Interventions	Intervention characteristics Placebo Class of drug: placebo Dose: ‐ Frequency: daily Duration: 6 weeks Who delivered the intervention? Not reported Type of intervention: control Olanzapine Class of drug: antipsychotic Dose: 5‐10 mg Frequency: daily Duration: 6 weeks Who delivered the intervention? Not reported Type of intervention: Pharmacological
Outcomes	Fasting blood sugar Outcome type: Continuous Unit of measure: mmol/l Direction: Lower is better Data value: Endpoint Notes: Baseline data were not available. BMI Outcome type: Continuous Cholesterol Outcome type: Continuous Unit of measure: mmol/l Direction: Lower is better Data value: Endpoint Notes: Baseline data were not available. Waist circumference Outcome type: Continuous Diastolic blood pressure Outcome type: Continuous Unit of measure: mm Hg Systolic blood pressure Outcome type: Continuous Unit of measure: mm Hg Direction: Lower is better Data value: Endpoint Drop out Outcome type: Adverse event Unit of measure: number MADRS Outcome type: Continuous Data value: Endpoint
Identification	Sponsorship source: This study was funded by Eli Lilly and Company Country: Patients were recruited in Japan, China, Taiwan, Korea and the USA (outcomes are shown for China) Setting: 64 study centers; inpatient and outpatient Comments: ‐ Authors name: Mauricio Tohen Institution: University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA Email: Email: tohen@uthscsa.edu Address: UT Health Science Center, Division of Mood and Anxiety Disorders, 7526 Louis Pasteu
Notes	Noortje Uphoff on 22/08/2019 18:29 Population Population characteristics for China only. Data from Taiwan not extracted.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Assignment to treatment groups was determined by a computer‐generated random sequence using an interactive voice response system." Judgement comment: Computer‐generated sequence used.
Allocation concealment (selection bias)	Low risk	Judgement comment: Minimal number of Lilly personnel saw randomization table and these people were not involved in administering medication or monitoring patients.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Judgement comment: Double‐blinded. Participant discontinued from study if unblinded. System in place for emergency unblinding in case of adverse events.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Judgement comment: Outcome assessors were blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Judgement comment: Reasons for drop‐out were monitored (data not available by country but adverse events similar in the two overall groups). Drop‐out rates were similar between groups; 23% in placebo and 25% in olanzapine group.
Selective reporting (reporting bias)	Low risk	Judgement comment: Protocol available and outcomes match those reported in study report. One additional outcome collected and reasons for deviation from protocol are discussed.
Other sources of bias	High risk	Judgement comment: Study funded by pharmaceutical company Eli Lilly and Company and study authors are either employees of the company and/or stockholders or received grants from the same company.