Rothschild 2004b.

Study characteristics
Methods	Randomised, double‐blind comparison Random assignment was 2:2:1 for olanzapine, placebo, and olanzapine fluoxetine combination, respectively
Participants	124 participants. DSM‐IV diagnosis (unclear how) Major depression with psychotic features Inpatients for at least 1 week. No data about prior treatment for current episode
Interventions	2004a: olanzapine (5 to 20 mg, clinically titrated; mean 11.9 mg) vs olanzapine (5 to 20 mg, clinically titrated; mean 12.4 mg) plus fluoxetine (20 to 80 mg, clinically titrated; mean 23.5 mg) vs placebo 2004b: same procedure: olanzapine (mean 14.0 mg) vs olanzapine (mean 13.9 mg) plus fluoxetine (mean 22.6 mg) 3 to 9 days' screening; probably no washout period Treatment period: 8 weeks Additional medication: 30 mg a day diazepam equivalent for no more than 5 consecutive days or 10 cumulative days
Outcomes	Dichotomous data: study author defined: response is reduction in HAMD‐24 ≥ 50% at endpoint. Remission is HAMD‐24 ≤ 8 for 2 consecutive visits Continuous data: symptom reduction: no ITT data; global response: no ITT data; QOL: no data Overall dropout rate: yes Dropout due to adverse effects: no ITT data Mortality rate: probably 0
Notes	Washout unclear 23 investigators randomly assigned at least 1 participant. Excluded patient characteristics not described Dropouts in study "a": 28%; lost before baseline + 1 visit: 7% (were excluded from results; included in our data); 24% in study "a" are LOCF (last observation carried forward; in our data not counted as dropouts). Some of these LOCFs are counted as responders; total non‐completers (LOCF included) 28 + 7 + 24 = 59% Dropouts in study "b": 38%; lost before baseline + 1 visit: 9% (were excluded from results; included in our data); LOCF in study "b": 6%; total non‐completers 28 + 9 + 6 = 53% Completers in study "a": 41%; in study "b": 47%
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	As reported: "patients were randomly allocated"; no further information
Allocation concealment (selection bias)	Unclear risk	As reported: "patients were randomly allocated"; no further information
Blinding (performance bias and detection bias) of participants	Low risk	As reported: "double blind therapy. Dose adjustments in all study arms with 'capsules' (assuming identical capsules because the study is double blind)"
Blinding (performance bias and detection bias) of personnel	Low risk	As reported: "double blind therapy"
Blinding (performance bias and detection bias) of outcome assessors	Unclear risk	No explicit information
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Dropouts described in general terms. Very high dropout rate
Selective reporting (reporting bias)	Unclear risk	No protocol available. According to study authors, the olanzapine‐fluoxetine group was designed as a exploratory pilot arm. However, in the conclusions, it is stated that an olanzapine/fluoxetine combination was well‐tolerated treatment associated with significant and quick reduction in depressive (and psychotic) symptoms in 1 trial. With ITT data, this difference is seen in 1 study to be not statistically significant, and in the other study, to be barely significant. Pooling of these 2 studies would result in no significance. Study authors discuss as a limitation the absence of a fluoxetine arm. They state that they cannot rule out that the effect of fluoxetine/olanzapine was due to fluoxetine. So this should have been mentioned in the conclusion
Other bias	High risk	High dropout rate of 47.2% reduces the internal validity of the study High placebo response is contradictory to the literature