Bipolar depression is a challenging condition to treat. Treatment options are often limited. Olanzapine-fluoxetine combination and quetiapine have demonstrated efficacy in this phase.Mood stabilisers often do not provide enough antidepressant activity. Would Lurasidone , an atypical agent, with with high affinity for D2, 5-HT2A, and 5-HT7 receptors (antagonist), moderate affinity for 5-HT1A receptors (partial agonist), and no appreciable affinity for H1 and M1 receptors, be effective in bipolar depression? Would the 5HT7 antagonism make it a useful antidepressant?
505 patients with bipolar I depression (DSM-IV-TR criteria, more than 4 weeks and less than 12 months in duration), with or without rapid cycling, without psychotic features underwent randomisation in this, double-blind, placebo-controlled, fixed- flexible dose, parallel-group mono therapy study. After a 3 day washout period, participants received 6 weeks of treatment with lurasidone, at flexible daily doses of either 20–60 mg or 80–120 mg, or 6 weeks of placebo .The primary efficacy endpoint was the mean change from baseline to week 6 in MADRS total score.
Nearly 75% completed the study ( similar across all three groups). At week 6, lurasidone was more effective on the primary outcome measure than placebo. Superiority was seen from week two onwards. The effect size was 0.51
51-53% achieved response in lurasidone groups compared with 30% with placebo . 40-42% achieved remission in lurasidone groups compared with 25% in placebo group.Lurasidone versus placebo difference in MADRS scores was 4.6 which is similar to that reported for quetiapine.
Discontinuation due to adverse events was similar across all three groups. Adverse reactions rated as “severe” was 9.8% with the lurasidone 20–60 mg, 8.4% with and 80–120 mg groups and 6% with placebo .
Limitations: Excluded patients with serious psychiatric or medical comorbidity/ active suicidal ideation: may have reduced the generalisability.
Conclusions: Lurasidone significantly improved depressive symptoms in patients with bipolar depression. It showed significantly greater improvement in the MADRS from week 2. FDA has approved Lurasidone for bipolar depression ( mono therapy as well as adjunct with Lithium and valproate).
Summary of the article:
Loebel A, Cucchiaro J, Silva R, Kroger H, Hsu J, Sarma K, Sachs G. Am J Psychiatry. 2014 Feb 1;171(2):160-8