Sunovion Pharmaceuticals Inc. has announced results from the first placebo-controlled study in adults with major depressive disorder (MDD) who presented with a limited number of associated manic symptoms (mixed features). This study demonstrated that Latuda® (lurasidone HCl) significantly reduced depressive symptoms in adults with MDD with mixed features when compared to placebo. The study results were presented at the 168th Annual Meeting of the American Psychiatric Association (APA). LATUDA is an atypical antipsychotic agent indicated in the United States for the treatment of adult patients with major depressive episodes associated with bipolar I disorder (bipolar depression) both as monotherapy and as adjunctive therapy with lithium or valproate, and for the treatment of adult patients with schizophrenia.
"The presence of manic symptoms in patients with MDD is associated with greater levels of anxiety, increased risk for suicide attempt, substance abuse and functional disability," said Gary Sachs, M.D., Founding Director of the Bipolar Clinic and Research Program at Massachusetts General Hospital in Boston, Massachusetts. "This novel study provides the first placebo-controlled evidence of an effective treatment in this patient population."
In this randomized, double-blind, placebo-controlled, 6-week clinical trial, adults patients with MDD with a limited number of manic symptoms (mixed features) were randomized to receive 6 weeks of treatment with flexibly-dosed LATUDA 20 - 60 mg/day (N=109) or placebo (N=102). The primary efficacy endpoint in the study was change from baseline at Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. The key secondary endpoint was change from baseline at Week 6 in the Clinical Global Impression, Severity (CGI-S) score, which assessed global severity of illness.
Results from the study showed that treatment with LATUDA was associated with a statistically significant reduction in MADRS total scores at the end of the study (Week 6) compared with placebo (-20.5 vs. -13.0; p<0.0001; Cohen's d effect size=0.80), with separation from placebo starting at the first post-baseline assessment (Week 1). In addition, patients treated with LATUDA experienced a statistically significant reduction in change from baseline at Week 6 in CGI-S scores compared with placebo (-1.83 vs. -1.18; p<0.0001; Cohen's d effect size=0.60), with separation from placebo starting at Week 2, as well as significant differences from placebo on all other secondary efficacy endpoints, including manic symptoms (based on Young Mania Rating Scale assessment).
LATUDA was generally well-tolerated with low rates of change in weight and metabolic parameters and had an overall discontinuation rate that was lower than placebo (6.4% vs. 14.7%). The most common adverse events (AEs) reported with an incidence ≥ 5% and greater than placebo in patients receiving LATUDA vs. placebo were nausea (6.4% vs. 2.0%) and somnolence (including the combined terms hypersomnia, hypersomnolence, sedation and somnolence) (5.5% vs. 1.0%).
"These results demonstrate that LATUDA significantly reduced depressive symptoms in adult patients with an often severe form of depression, MDD with mixed features," said Antony Loebel, M.D., Executive Vice President and Chief Medical Officer, Sunovion Pharmaceuticals Inc., Head of Global Clinical Development for Sumitomo Dainippon Pharma Group. "We believe this is an important finding as patients with this condition may not respond adequately to standard antidepressant treatment."
About Major Depressive Disorder with Mixed Features
Research suggests that manic symptoms below the threshold criteria for hypomania (mixed features) occurs in at least 25% of individuals with MDD.1,2 Patients with MDD with mixed features often have greater symptom severity and higher rates of depressive episode recurrence, inadequate treatment response to standard antidepressants, increased risk for suicide attempt, anxiety disorders and substance abuse, and greater overall associated disability.1,2,3,4,5,6,7 Patients with MDD with mixed features have an increased risk for the development of a future bipolar disorder diagnosis.8 Given increased understanding regarding this form of depression, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders introduced a new "mixed features" specifier for patients who present with a limited set of manic symptoms during a major depressive episode.9 To date, no controlled trials have been conducted for psychotropic agents in this patient population.8