Proven antidepressant efficacy in bipolar I and bipolar II depression as monotherapy or when added to lithium or valproate
Significant symptom relief in a broad range of adult patients with bipolar depression regardless of bipolar I or II1-3*†
Monotherapy
Adjunctive with Lithium or Valproate
improvement
from baseline1
CAPLYTA 42 mg (n=188)
Placebo (n=188)
improvement
from baseline1
CAPLYTA 42 mg + lithium or valproate (n=174)
Placebo + lithium or valproate (n=174)
Monotherapy
improvement
from baseline1
CAPLYTA 42 mg (n=188)
Placebo (n=188)
Adjunctive with Lithium or Valproate
improvement
from baseline1
CAPLYTA 42 mg + lithium or valproate (n=174)
Placebo + lithium or valproate (n=174)
LSM=least squares mean; MADRS=Montgomery-Asberg Depression Rating Scale.
*Monotherapy study placebo-subtracted difference was -4.6 (95% CI, -6.3, -2.8). Mean baseline MADRS total scores for CAPLYTA 42 mg and placebo were 30.8 and 30.3, respectively. There was a 40% improvement from baseline in the placebo group. Adjunctive therapy study placebo-subtracted difference was -2.4 (95% CI, -4.4, -0.4). Mean baseline MADRS total scores for CAPLYTA 42 mg and placebo were 32.2 and 32.1, respectively. There was a 45% improvement from baseline in the placebo + lithium or valproate group.1
†The MADRS total score ranges from 0 to 60. Higher scores reflect greater symptom severity.
Study design
Monotherapy study: 6-week study that randomized 381 patients to either CAPLYTA 42 mg or placebo. Patients were generally moderately to markedly ill. Median age was 45 years (range 18 to 72 years). 58% were female, 91% were Caucasian, and 8% were African American.1 The primary efficacy measure was the change from baseline in MADRS total score. The MADRS is a 10-item clinician-rated scale with total scores ranging from 0 (no depressive features) to 60 (maximum score).
Adjunctive therapy study: 6-week study that randomized 529 patients to lithium or valproate with either CAPLYTA 28 mg (two-thirds of the recommended daily dose), CAPLYTA 42 mg, or placebo. Patients were generally moderately to markedly ill. Median age was 46 years (range 18 to 75 years). 58% were female, 88% were Caucasian, and 11% were African American. The treatment effect in the CAPLYTA 28 mg group (vs placebo) was not statistically significant.1
Full chart description
This graph depicts the change from baseline in MADRS total score over 6 weeks for patients receiving CAPLYTA 42 mg or placebo as monotherapy or adjunctive therapy with lithium or valproate.
In the monotherapy study, patients on CAPLYTA saw a 16.7‑point reduction at 6 weeks compared to 12.1‑point reduction with placebo. In the adjunctive therapy study, patients on CAPLYTA saw a 16.9‑point reduction at 6 weeks compared to 14.5‑point reduction with placebo.
MADRS scale description
†The MADRS total score ranges from 0 to 60. Higher scores reflect greater symptom severity. Each item is scored from 0 to 6, with 0 being the least severe and 6 being most severe. The symptoms scored are: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts.1,2
A higher score represents a more severe condition. Usual cutoffs: 0-6 normal, 7-19 mild, 20-34 moderate, 35-60 severe.
References: 1. CAPLYTA prescribing information. 2. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382-389.
View data on weight change
CAPLYTA separated from placebo as early as week 1 and continued to week 6 with no titration required1,2
Change in MADRS total score in monotherapy study1,2
- CAPLYTA—the maintenance dose is the starting dose
*P=nominal. The weekly time points prior to week 6 were not powered for statistical comparison and are descriptive only.
†The primary endpoint was the change from baseline to Week 6 in score on the Montgomery-Asberg Depression Rating Scale (MADRS).2 Baseline MADRS Total Score: CAPLYTA (42 mg): 30.8; placebo 30.3.1
Full chart description
This graph depicts the change from baseline in MADRS total score by week over a 6-week period for patients receiving CAPLYTA 42 mg or placebo as monotherapy.
Patients on CAPLYTA saw a 16.7-point reduction at Week 6 compared to 12.1‑point reduction with placebo.
Improvement observed in all individual MADRS item scores in bipolar depression (bipolar I and II) in the monotherapy study at week 64
Limitation: These are exploratory endpoints; results require cautious interpretation.
Improvement based on least squares mean change from baseline on individual MADRS items scored 0-6.
*Patients who were at risk for suicide were excluded from the clinical trials.
This graph depicts the improvement based on least squares mean change from baseline to week 6 on individual MADRS items.
Patients on CAPLYTA saw a 2.3-point reduction in reported sadness compared to 1.7-point reduction with placebo; 2.1-point reduction in apparent sadness compared to 1.7-point reduction with placebo; 1.6-point reduction in inner tension compared to 1.1-point reduction with placebo; 2.1-point reduction in reduced sleep compared to 1.4-point reduction with placebo; 1.6-point reduction in reduced appetite compared to 1.2-point reduction with placebo; 1.7-point reduction in concentration difficulties compared to 1.4-point reduction with placebo; 1.8-point reduction in lassitude compared to 1.4-point reduction with placebo; 1.8-point reduction in inability to feel compared to 1.3-point reduction with placebo; 1.5-point reduction in pessimistic thoughts compared to 1.1-point reduction with placebo; 0.3-point reduction in suicidal thoughts compared to 0.1-point reduction with placebo.
See key secondary endpoint data for CAPLYTA
Helpful tools & resources
References: 1. CAPLYTA prescribing information. 2. Calabrese JR, Durgam S, Satlin A, et al. Efficacy and safety of lumateperone for major depressive episodes associated with bipolar I or bipolar II disorder: a phase 3 randomized placebo-controlled trial. Am J Psychiatry. Published online September 23, 2021. doi:10.1176/appi.apj.2021.20091339. 3. Data on File. 2021. 4. McIntyre RS, Durgam S, Kozauer SG, et al. The efficacy of lumateperone on symptoms of depression in bipolar I and bipolar II disorder: Secondary and post hoc analyses [published online ahead of print, 2023 Jan 12]. Eur Neuropsychopharmacol. 2023;68:78-88. doi:10.1016/j.euroneuro.2022.12.012