Table 2.

Randomized controlled trials in major depressive episode with mixed features in bipolar disorders

Study	Duration (wk)	Medication	Primary measure	Definition	Results	Remark
Tohen et al.19) (2014)	6	Olanzapine (n=690) vs. placebo (n=524)	Changes from baseline in MADRS	BD I depression with 0, 1 or 2, ≥3 manic symptoms	−3.76 (p=0.002) vs. −3.20 (p<0.001) vs. −3.44 (p=0.002) for 0, 1 or 2, ≥3 manic symptoms	Post-hoc analysis
McIntyre et al.20) (2015)	6	Lurasidone 20–120 mg (n=182) vs. placebo (n=90)	Changes from baseline in MADRS	BD I depression (MADRS ≥20, YMRS ≤12) with YMRS ≥4	−15.7 vs. −10.9 (p=0.001)	Post-hoc analysis
Patkar et al.21) Pae et al.22) (2012)	6	Ziprasidone (40–160 mg/day) vs. placebo (n=72)	Changes from baseline in MADRS	BD II or MDD with 2 or 3 manic criteria	Ziprasidone > placebo (p=0.0038), BD II > MDD (p=0.036)
Benazzi et al.18) (2009)	8	Olanzapine (5–20 mg/day, n=351) vs. OFC (6/25, 6/50, 12/50 mg/day, n=82) vs. placebo (n=355)	Response (≥50% reduction) in MADRS and <2 concurrent (hypo)manic symptoms	BD I depression with ≥2 manic symptoms	OFC vs. olanzapine: OR=2.00 (95% CI, 0.96–4.19); OFC vs. placebo: OR=3.91 (95% CI, 1.80–8.49); olanzapine vs. placebo: OR=1.95 (95% CI, 1.14–3.34)	Post-hoc analysis

MADRS, Montgomery–Åsberg Depression Rating Scale; BD, bipolar disorder; YMRS, Young Mania Rating Scale; MDD, major depressive disorder; OFC, olanzapine+fluoxetine; OR, odds ratio; 95% CI, 95% confidence interval.