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Table 4 Placebo-controlled trials for acute depression in bipolar disorder

From: Bipolar depression: a major unsolved challenge

TreatmentsSubjects (n)Responders/subjects (%)RR [95%CI]
DrugPlacebo
Anticonvulsants
[10 trials, 3 agents]
1281313/657
[47.6%]
181/624
[29.0%]
1.61
[1.39–1.87]
Antidepressants
[12 trials, 11 agents]
1895383/803
[48.9%]
419/1092
[38.4%]
1.32
[1.07–1.62]
Antipsychotics
[13 trials, 6 agents]
60442135/3859
[55.3%]
904/2185
[41.4%]
1.28
[1.09–1.51]
Lithium
[1 trial, 1 agent]
26585/136
[62.5%]
72/129
[55.8%]
1.12
[0.92–1.37]
Pooled/totals
[36 trials, 21 agents]
94852926/5455
[54.4%]
1576/4030
[39.4%]
1.37
[1.30–1.44]
  1. Dropout rates (average: 32.9% [28.0–37.8]) were similar across treatments and with drug or placebo. Response typically involved ≥ 50% improvement in depression symptom ratings. By separate random-effects meta-analysis, antidepressants were statistically more effective than placebo (RR = 1.32 [1.07–1.87]; z = 2.65, p = 0.008), as were the other agents (RR = 1.34 [1.17–1.53]; z = 431, p < 0.0001). The overall weighted average drug vs. placebo difference (RR = 1.37) was highly significant (χ2 = 196, p < 0.0001). Antidepressant dose averaged 172 [146–198] mg/day imipramine-equivalent (Baldessarini 2013). Antidepressant monotherapy trials yielded greater drug/placebo differences than with addition to a mood-stabilizer (RR = 1.64 [1.05–2.56] vs. 1.18 [0.96–1.46]). Of note, in 23/36 trials (63.9%) drug was not statistically superior to placebo. Results are ranked by drug/placebo Risk Ratios (RR). [References: Nemeroff et al. (2001); Tohen et al. (2003); Shelton and Stahl (2004); Agosti and Stewart (2008); McElroy et al. (2010); McGirr et al. (2016); Yatham et al. (2018); Vázquez et al. (2017a); Baldessarini et al. (2019b)]