Clinical Summary
Clinical Summary: The Effect of Lurasidone on Anxiety Symptoms in Patients With Bipolar Depression: A Post Hoc Analysis
Anxiety symptoms and sleep disturbance are common during bipolar depression and add clinical burden, yet clinicians often have little bipolar-specific evidence to guide treatment of these symptoms. This analysis asks a practical question: when treating bipolar I depression with lurasidone, how much improvement occurs in psychic and somatic anxiety, and does reduced sleep identify patients with a stronger anxiolytic response?
Design
This post hoc analysis included pooled data from 2 placebo-controlled studies of lurasidone as monotherapy (20–60 mg/d and 80–120 mg/d, conducted from April 2009 to February 2012) and as adjunctive therapy (20–120 mg/d, conducted from May 2009 to January 2012) flexibly dosed with lithium or valproate
N
n = 824
Population
adult patients with bipolar I depression
Duration
6 weeks of double-blind treatment
Key Findings
- Lurasidone improved psychic anxiety more than placebo over 6 weeks in both treatment settings: in monotherapy, LSM = −4.82 ± 0.37 for lurasidone vs −2.97 ± 0.28 for placebo, P < .001, with 95% CI for between treatment group difference: −2.69, −1.00; in adjunctive therapy, LSM = −5.56 ± 0.41 for lurasidone vs −4.26 ± 0.42 for placebo, P = .009, with 95% CI for between treatment group difference: −2.27, −0.32.
- Lurasidone also improved somatic anxiety more than placebo: in monotherapy, LSM = −1.89 ± 0.17 for lurasidone vs −1.37 ± 0.23 for placebo, P = .048, with 95% CI for between treatment group difference: −1.04, −0.01; in adjunctive therapy, LSM = −2.22 ± 0.22 for lurasidone vs −1.47 ± 0.23 placebo, P = .006, with 95% CI for between treatment group difference: −1.29, −0.23.
- Baseline decrease in sleep identified a subgroup with stronger anxiolytic benefit during lurasidone monotherapy: for overall anxiety, the interaction was P = .010, F2, 428 = 4.69, and when baseline decrease in sleep was present the effect sizes were Cohen d = 0.47 for the pooled dose group, d = 0.55 for 20–60 mg/d, and Cohen d = 0.38 for 80–120 mg/d.
- The same sleep-related moderation was seen for anxiety subcomponents during monotherapy: for psychic anxiety, the interaction was P = .018, F2, 428 = 4.03, with Cohen d = 0.50 for the pooled dose group, Cohen d = 0.58 for 20–60 mg/d, and Cohen d = 0.42 for 80–120 mg/d; for somatic anxiety, the interaction was P = .032 for baseline YMRS item 4 “decrease in sleep” interaction with treatment, F2, 428=3.47, with effect size of 0.3 overall and Cohen d = 0.35 for 20–60 mg/d versus Cohen d = 0.24 for 80–120 mg/d.
- Antidepressant benefit with lurasidone monotherapy persisted across anxiety severity strata: for MADRS improvement in the lower anxiety group (HAM-A total < 14, n = 223), treatment effect size was 0.53, P = .001, t444 = −3.3, with 95% CI for between treatment group difference: −8.15, −2.07; for the higher anxiety group (n = 262), treatment effect size was 0.39, P = .005, t444 = −2.8, with 95% CI for between treatment group difference: −6.39, −1.16.
Clinical Bottom Line
In bipolar I depression with comorbid anxiety symptoms, lurasidone reduced both psychic and somatic anxiety over 6 weeks as monotherapy and as adjunctive therapy with lithium or valproate. Reduced sleep at baseline marked a subgroup with stronger anxiolytic response to lurasidone monotherapy, especially in the 20–60 mg/d range.
Practice Implications
- When choosing treatment for bipolar depression with prominent anxiety symptoms, consider lurasidone as an option that improved both psychic and somatic anxiety components, not just depressive symptoms.
- Assess sleep disturbance at baseline, particularly YMRS item 4 “decrease in sleep,” because its presence was associated with greater anxiety improvement during lurasidone monotherapy.
- Do not assume higher baseline anxiety rules out antidepressant benefit with lurasidone monotherapy; MADRS improvement was significant in both lower anxiety and higher anxiety groups.
- Track functioning alongside mood and anxiety: changes from baseline in HAM-A were significantly associated with change in SDS score (P < .001, F1, 396 = 167.97), and in monotherapy the HAM-A–SDS mediation remained significant after accounting for MADRS improvement (P = .044, F1,395 = 4.08).
