PracticeUpdate Conference Series European Congress of Psychiatry 2019

Lurasidone Safe, Effective for Major Depressive DisorderWith Mixed Features Study of 12 weeks also showed lurasidone treatment to be well-tolerated, with onlyminor metabolic changes observed. T he atypical antipsychotic lurasidone has shown efficacy and tolera- bility in patients with major depressive disorder with mixed features in a recent study presented at this meeting. Typically, lurasidone is used for treating patients with schizophrenia, bipolar disorder or bipolar depression. Stephen Stahl, MD, PhD, from the University of California in San Diego and colleagues reported in their conference abstract that their study evaluated the efficacy and tolerability of longer term treatment with lurasidone in patients with major depressive disorder with mixed features. The study took place in the United States and enrolled patients with major depressive disorder who presented with two or three manic symptoms and who had completed 6 weeks of a double-blind, placebo-controlled treat- ment with lurasidone in dosages of 18.5 to 56 mg per day. The research reported by Dr. Stahl and colleagues was a 12-week, open-label extension study. Patients already on lurasidone continued taking it while the original placebo group was switched to lurasidone. The primary efficacy measure was the Montgomery-Åsberg Depression Rating Scale (MADRS). A total of 48 patients entered the open-label extension study, with different groups having a different mean MADRS score at the beginning of the open-label phase of the trial. The mean score was 15.0 for those who continued on lurasidone (n=29) and 24.1 for those who switched from lurasidone to placebo (n=19). The remaining 9 patients (18.8%) discontinued the trial prematurely. Among patients who remained on the lurasidone, the mean change in total MADRS scores from baseline to week 12 was –4.1 (observed cases) and –3.3 (last observation carried forward). For those switched from placebo to lurasidone, the mean change in MADRS score was –11.2 (observed cases) and –9.7 (last observation carried forward). In the study, adverse events affecting at least 5% of patients were akathisia (10.4%); diarrhea (8.3%); upper respiratory infection (8.3%); and headache, sedation, nausea, or fatigue (6.3% each). Regarding metabolic parameters, median changes from the beginning of the open-label extension to the end of the 12 weeks in the lurasidone- lurasidone group were: cholesterol –6.5mg/dL, triglycerides –3.5mg/dL and hemoglobin (Hb)A1c +0.15%. For those switched from placebo to lurasidone, cholesterol increased by 1.5 mg/dL, triglycerides by 20.0 mg/dL and HbA1c by 0.30%. The study cohort experienced no clinically significant changes in body weight. Treatment-emergent mania or hypomania as an adverse event occurred in 2 patients (4.2%). Stahl and colleagues concluded that treatment with lurasidone (18.5–56 mg daily) was generally safe and well-tolerated for up to 12 weeks in patients with major depressive disorder with mixed features. They also stated that they observed continued improvement in depressive symptoms.

that determining the appropriate point to initiate antidepressant therapy among patients suffering from depressive symptoms remains an important clinical quandary. “Some guidelines discourage the use of medication for mild depression, and certainly some clinicians express reluctance to prescribe medication for milder forms of depression,” he pointed out. In addition, “patient beliefs about being able to over- come depression through willpower or lifestyle changes are also a barrier to the use of medication for less severe forms of depression. “Although this statistically sophisticated review only had a half dozen studies with data on the acute phase of depression treatment,” he noted, “the results strongly indicated that antidepressants were effective regardless of depression severity. While this research might affect future treatment guidelines and recommendations, it should be balanced with the very extensive problem of patient non-adherence to medication regimens. Patients with mild symptoms would seem to be among the most likely to discontinue medication treatment since, by definition, mild symptoms are those which do not cause significant disruption in their lives.”

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EPA 2019 • PRACTICEUPDATE CONFERENCE SERIES 11