SUMMARY

• The Food and Drud Administration (FDA) approval of CAPLYTA was based upon positive results of two short-term (6-week), placebo-controlled trials in patients with bipolar depression.^1,2
• Suppes et al (2023)¹ conducted a 6-week, phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of CAPLYTA as adjunctive treatment to lithium or valproate in patients with major depressive episodes (MDEs) associated with bipolar I or bipolar II disorder.
  • At day 43, CAPLYTA 42 mg adjunctive to lithium or valproate (n=177) showed a statistical improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) total score compared to placebo adjunctive to lithium or valproate (n=175), with a least square mean difference (LSMD) of -2.4 (95% confidence interval [CI]: -4.42 to -0.37; effect size=-0.27; P=0.021).
• Calabrese et al (2021)² conducted a 6-week, phase 3, randomized, double-blind, placebo-controlled, multinational study to evaluate the efficacy and safety of CAPLYTA in patients with MDEs associated with bipolar I or bipolar II disorder.
  • At day 43, CAPLYTA 42 mg (n=188) showed a statistical improvement in MADRS total score compared to placebo (n=189), with an LSMD of -4.6 (95% CI: -6.34 to -2.83; effect size=-0.56; P<0.0001).
  • A statistically significant improvement in MADRS total score compared to placebo was observed as early as day 8, with an LSMD of -1.3 (95% CI: -2.27 to -0.31; P=0.010).³

BACKGROUND

The FDA approval of CAPLYTA was based upon positive results of two short-term (6-week), placebo-controlled trials in patients with bipolar depression. In one study, CAPLYTA was given as monotherapy and, in the second study, CAPLYTA was given as adjunctive therapy with lithium or valproate.^1,2 

CLINICAL DATA

Suppes et al (2023)¹ conducted a phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of CAPLYTA as adjunctive treatment to lithium or valproate in patients with MDEs associated with bipolar I or bipolar II disorder. Patients were randomized (1:1:1) to receive CAPLYTA 28 mg (n=176), CAPLYTA 42 mg (n=177), or placebo (n=175) for 6 weeks; this was followed by a 2-week safety follow-up period. The primary efficacy endpoint was the change from baseline to day 43 in MADRS total score.

• At day 43, CAPLYTA 42 mg adjunctive to lithium or valproate showed a statistical improvement in MADRS total score compared to placebo adjunctive to lithium or valproate, with an LSMD of -2.4 (95% CI: -4.42 to -0.37; effect size=-0.27; P=0.021).

Calabrese et al (2021)² conducted a phase 3, randomized, double-blind, placebo-controlled, multinational study to evaluate the efficacy and safety of CAPLYTA in patients with MDEs associated with bipolar I or bipolar II disorder. Patients were randomized (1:1) to receive either CAPLYTA 42 mg (n=188) or placebo (n=189) for 6 weeks; this was followed by a 2-week safety follow-up period. The primary efficacy endpoint was the change from baseline to day 43 in MADRS total score.

• At day 43, CAPLYTA 42 mg showed a statistical improvement in MADRS total score compared to placebo, with an LSMD of -4.6 (95% CI: -6.34 to -2.83; effect size=-0.56; P<0.0001).
• A statistically significant improvement in MADRS total score compared to placebo was observed as early as day 8, with an LSMD of -1.3 (95% CI: -2.27 to -0.31; P=0.010).³ 

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 07 October 2025.