Studies: Lurasidone effective for treating depression associated with bipolar disorder

Lurasidone HCl (Latuda) reduces depressive symptoms in adult patients with bipolar depression when used as monotherapy and adjunctive therapy to lithium or valproate. This flexibility is important given the multiple unmet needs of patients with bipolar depression, according to two phase 3 studies published recently in TheAmerican Journal of Psychiatry.

In the first study, adult patients with bipolar depression in the double-blind, randomized, placebo-controlled, 6-week monotherapy clinical trial were randomly assigned to receive 6 weeks of treatment with lurasidone flexibly dosed within two dose ranges, 20 mg/day to 60 mg/day (N=166) and lurasidone 80 mg/day to 120 mg/day (N=169), or placebo (N=170). 

In the monotherapy study, adverse events reported with an incidence ≥5% (and greater than placebo) in at least one of the lurasidone 20 mg/day to 60 mg/day, lurasidone 80 mg/day to 120 mg/day and placebo groups were nausea, headache, akathisia, somnolence, sedation, dry mouth, and vomiting. 

In the second study, adult patients with bipolar depression in the double-blind, randomized, placebo-controlled, 6-week adjunctive clinical trial were randomized to receive 6 weeks of adjunctive treatment with lurasidone (N=183) or placebo (N=165) (added to background treatment with lithium or valproate). 

In this adjunctive therapy study, adverse events reported with an incidence ≥5% (and greater than placebo) in patients receiving lurasidone versus placebo were nausea, somnolence, tremor, akathisia, and insomnia. 

The primary end point in both studies was change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score at week 6.  The key secondary end point was change from baseline at week 6 in the Clinical Global Impression, Bipolar Severity of Depression (CGI-BP-S) score, which assessed global severity of depressive symptoms.

Other secondary end points included responder rates; rates of remission; Hamilton Anxiety Rating Scale (HAM-A); Sheehan Disability Scale (SDS); Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16); and Quality of Life, Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF). 

“These studies demonstrated that [lurasidone] significantly reduced depressive symptoms in adult patients with bipolar depression, both as monotherapy and as adjunctive therapy with lithium or valproate,” said Antony Loebel, MD, executive vice president and chief medical officer at Sunovion, the manufacturer of Latuda.

Bipolar disorder is a serious mental illness characterized by severe and debilitating mood swings that affects approximately 10.4 million adults in the United States. Bipolar depression refers to the depressive phase of bipolar disorder. When symptomatic, most people with bipolar disorder spend most time in the depressive phase.

Major depressive episodes associated with bipolar disorder have been shown to result in significant impairment in work, family, and social function. Bipolar depressive episodes are also associated with increased direct and indirect healthcare costs, as well as an increased risk of suicide.

“Many of the most commonly used mood stabilizers, antidepressants and antipsychotic agents actually have little data to support their efficacy in treating bipolar depression,” said Dr. Loebel. “The dearth of data means that healthcare providers must often exercise a ‘trial-and-error’ approach to managing their patients’ symptoms.  This can be frustrating, time-consuming, and costly for patients and the healthcare system. Very few medications have been approved as monotherapy treatment and no medications to date have been approved as adjunctive treatment of bipolar depression, despite the fact that mood stabilizers [such as lithium or valproate] are a mainstay treatment for people with bipolar disorder. The last FDA approval of any medication for bipolar depression occurred in 2006; there is a pressing need for additional effective and safe treatment options for this severely disabling and difficult to treat condition.” 

Latuda was approved by FDA in June 2013 for the treatment of bipolar depression.