Table 3 Efficacy of selected antipsychotics for depressive symptoms in bipolar disorder: Summary of selected studies
MADRS Total Score | CGI-BP-D | |||||
|---|---|---|---|---|---|---|
Study Design | Baseline | Change From Baseline | MADRS Remitters* | Baseline | Change From Baseline | |
Asenapine | ||||||
(current post hoc analysis) | Design: randomized, double-blind, placebo- and olanzapine-controlled study in bipolar I disorder patients experiencing manic or mixed episodes | Baseline MADRS total score ≥20 Asenapine: 24.0 ± 3.5 Olanzapine: 25.0 ± 4.4 Placebo: 26.0 ± 4.7 | LS mean ± SE at day 21 Baseline MADRS total score ≥20 Asenapine: -13.6 ± 1.6 (P = 0.009 vs placebo) Olanzapine: -10.6 ± 1.3 Placebo: -7.0 ± 1.8 | Percentage at day 21 Baseline MADRS total score ≥20 Asenapine: 70% (P = 0.01 vs placebo) Olanzapine: 48% Placebo: 33% | Baseline MADRS total score ≥20 Asenapine: 3.9 ± 0.9 Olanzapine: 3.8 ± 0.8 Placebo: 3.8 ± 0.9 | LS mean ± SE at day 21 Baseline MADRS total score ≥20 Asenapine: -1.4 ± 0.2 (P = 0.020 vs placebo) Olanzapine: -1.3 ± 0.2 (P = 0.038 vs placebo) Placebo: -0.7 ± 0.2 |
Duration: 3 wk | Baseline CGI-BP-D severity score ≥4 Asenapine: 20.0 ± 6.9 Olanzapine: 20.0 ± 7.2 Placebo: 22.0 ± 7.5 | Baseline CGI-BP-D severity score ≥4 Asenapine: -9.9 ± 1.3 (P = 0.030 vs placebo) Olanzapine: -8.8 ± 1.0 Placebo: -5.4 ± 1.6 | Baseline CGI-BP-D severity score ≥4 Asenapine: 67% Olanzapine: 69% (P = 0.026 vs placebo) Placebo: 41% | Baseline CGI-BP-D severity score ≥4 Asenapine: 4.4 ± 0.6 Olanzapine: 4.2 ± 0.5 Placebo: 4.3 ± 0.5 | Baseline CGI-BP-D severity score ≥4 Asenapine: -1.6 ± 0.2 Olanzapine: -1.7 ± 0.2 Placebo: -1.2 ± 0.2 | |
Treatment: Asenapine 5-10 mg BID Olanzapine 5-20 mg QD Placebo | Mixed episode at baseline Asenapine: 17.0 ± 6.3 Olanzapine: 17.0 ± 6.9 Placebo: 19.0 ± 7.4 | Mixed episode at baseline Asenapine: -8.5 ± 0.8 (P = 0.040 vs placebo) Olanzapine: -7.2 ± 0.7 Placebo: -5.8 ± 1.1 | Mixed episode at baseline Asenapine: 77% (P = 0.026 vs placebo) Olanzapine: 74% (P = 0.036 vs placebo) Placebo: 56% | Mixed episode at baseline Asenapine: 3.1 ± 1.3 Olanzapine: 3.2 ± 1.1 Placebo: 3.4 ± 1.1 | Mixed episode at baseline Asenapine: -1.0 ± 0.1 Olanzapine:-0.9 ± 0.1 Placebo:-0.7 ± 0.2 | |
Aripiprazole | ||||||
Thase et al[22] | Design: randomized, double-blind, placebo-controlled study in bipolar I disorder patients experiencing a major depressive episode without psychotic features | Aripiprazole: 29.1 Placebo: 28.5 | Adjusted mean ± SE at week 8 Not significant vs placebo (actual change not reported) | Percentage at week 8 Aripiprazole: 30% Placebo: 28% | Aripiprazole: 4.3 Placebo: 4.3 | Adjusted mean ± SE at week 8 Not significant vs placebo (actual change not reported) |
Duration: 8 wk | ||||||
Treatment: Aripiprazole 5-30 mg (n = 186) Placebo (n = 188) | ||||||
Thase et al[22] | Design: randomized, double-blind, placebo-controlled study in bipolar I disorder patients experiencing a major depressive episode without psychotic features | Aripiprazole: 29.6 Placebo: 29.4 | Adjusted mean ± SE at week 8 Not significant vs placebo (actual change not reported) | Percentage at week 8 Aripiprazole: 26% Placebo: 29% | Aripiprazole: 4.4 Placebo: 4.5 | Adjusted mean ± SE at week 8 Not significant vs placebo (actual change not reported) |
Duration: 8 wk | ||||||
Treatment: Aripiprazole 5-30 mg (n = 187) Placebo (n = 188) | ||||||
Olanzapine & olanzapine-fluoxetine | ||||||
Tohen et al[18] | Design: randomized, double-blind, placebo-controlled study in bipolar I disorder patients with MADRS total score ≥20 | Olanzapine: 32.6 Olanzapine-fluoxetine: 30.8 Placebo: 31.3 | Mean ± SE at week 8 Olanzapine: -15.0 ± 0.7 (P = 0.002 vs placebo) Olanzapine-fluoxetine: -18.5 ± 1.3 (P < 0.001 vs placebo) Placebo: -11.9 ± 0.8 | Percentage at week 8 Olanzapine: 33% (P = 0.02 vs placebo) Olanzapine-fluoxetine: 49% (P < 0.001 vs placebo) Placebo: 25% | Olanzapine: 4.9 ± 0.8 Olanzapine-fluoxetine: 4.8 ± 0.7 Placebo: 4.8 ± 0.8 | Mean ± SE at week 8 Olanzapine: -1.6 ± 0.1 (P = 0.004 vs placebo) Olanzapine-fluoxetine: -2.2 ± 0.2 (P < 0.001 vs placebo) Placebo:-1.2 ± 0.1 |
Duration: 8 wk | ||||||
Treatment: Olanzapine 5-20 mg (n = 370) Olanzapine-fluoxetine 6-12 mg and 25-50 mg (n = 86) Placebo (n = 377) | ||||||
Quetiapine | ||||||
Thase et al[20] | Design: randomized, double-blind, placebo-controlled in bipolar I or II disorder patients experiencing a major depressive episode | Quetiapine 300 mg: 31.1 ± 5.7 Quetiapine 600 mg: 29.9 ± 5.6 Placebo: 29.6 ± 5.4 | LS mean ± SE at last assessment Quetiapine 300 mg: -16.9 ± 1.0 (P < 0.001 vs placebo) Quetiapine 600 mg: -16.0 ± 1.0 (P = 0.001 vs placebo) Placebo: -11.9 ± 1.0 | Percentage at last assessment Quetiapine 300 mg: 52% (P < 0.05 vs placebo) Quetiapine 600 mg: 52% (P < 0.01 vs placebo) Placebo: 37% | NA | NA |
Duration: 8 wk | ||||||
Treatment: Quetiapine 300 mg (n = 172) Quetiapine 600 mg (n = 169) Placebo (n = 168) | ||||||
Calabrese et al[19] | Design: randomized, double-blind, placebo-controlled in bipolar I or II disorder patients experiencing a major depressive episode | Quetiapine 300 mg: 30.4 ± 5.0 Quetiapine 600 mg: 30.3 ± 5.3 Placebo: 30.6 ± 5.3 | Mean at last assessment Quetiapine 300 mg: -16.4 (P < 0.001 vs placebo) Quetiapine 600 mg: -16.7 (P < 0.001 vs placebo) Placebo: -10.3 | Percentage at last assessment Quetiapine 300 mg: 53% (P < 0.001 vs placebo) Quetiapine 600 mg: 53% (P < 0.001 vs placebo) Placebo: 28% | NA | NA |
Duration: 8 wk | ||||||
Treatment: Quetiapine 300 mg (n = 181) Quetiapine 600 mg (n = 180) Placebo (n = 181) | ||||||
Ziprasidone | ||||||
Liebowitz et al[24] | Design: open-label in bipolar II disorder patients experiencing a major depressive episode | Ziprasidone: 28.5 ± 5.0 | Mean change ± SD at week 8 Ziprasidone: 13.2 ± 9.0 (P < 0.0001 vs baseline) | NA | NA | NA |
Duration: 8 wk | ||||||
Treatment: Ziprasidone 20 mg QD -60 mg BID (n = 30) | ||||||