EFFICACY AND SAFETY OF ADJUNCTIVE LURASIDONE IN TREATMENT RESISTANT UNIPOLAR DEPRESSION : AN OPEN-LABEL SINGLE-ARM PILOT STUDY

Abstract Background Major depressive disorder (MDD) is a recurrent, chronic, and disabling disorder worldwide. Antidepressant treatment is an important evidence-based therapy. However, the response rate of antidepressant therapy is unsatisfied. Lots of evidence indicates atypical antipsychotic is an efficient choice for adjunctive therapy for patient with treatment resistant depression (TRD), but only aripiprazole, quetiapine and brexpiprazole are indicated. Lurasidone is a novel atypical antipsychotic as a serotonin-dopamine modulator. Its pharmacological mechanism may be beneficial for depressed mood with few notable adverse effects. The efficacy and safety of lurasidone adjunctive therapy in MDD is not yet well established. Objectives This clinical study aimed to explore efficacy and safety of lurasidone as adjunctive therapy for TRD patients. Methods This is an 8-week open-label single-arm study, enrolled TRD cases. Use lurasidone as adjunctive drug treated with antidepressant. We select Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impression- severity (CGI-S), Clinical Global Impression- Improvement (CGI-I) as assessment tools. Evaluation were done at baseline, week 2, week 4, and week 8, included efficacy and safety. Results This is an interim report. Totally 17 patients enrolled, 7 males and 10 females, mean age was 39.0 (SD: 10.2) year-old, 58.8% were married, 35.3% were single, 47.1% employed, 41.2% were housewife, 58.8% were college/university graduated, 23.5% had suicide attempt history, mean number of previous MDE was 2.7 (SD: 1.9), mean duration of current MDE was 18.4 (SD: 4.3) weeks. Preliminary results indicated a trend of reduction of MADRS, and CGI (MADRS: P=0.001; CGI-S: P=0.002; CGI-I: P=0.004). The score of MADRS reduced from 32.6 (SD: 3.0) to 23.0 (SD: 2.62). The response rate was 52.9%, but the remission rate was 0%. Mean maximal dose of lurasidone was 35.3 (SD: 8.8) mg/day. Three mild adverse events were observed: sedation, nausea, weight gain. Discussion & Conclusion This pilot study found in a sample of TRD patients, suggest that lurasidone may be an effective and safe adjunctive drug. Our 8-week study found a response rate of 52.9%. The observed effect size on reducing depressive symptoms is substantial and clinically relevant. The findings should be interpreted with caution, as this is a single-arm small sample size study. Further double- blinded, randomized, placebo-controlled study is needed. References Trisha S, Robert S, Josephine C, et al. Lurasidone for the treatment of Major depressive disorder with mixed features: A Randomized, Double-Blind, Placebo-Controlled Study. Am J Psychiatry 2016; 173:400- 407.