Data Released Backing Lurasidone’s New Indication

Lurasidone (Latuda), a medication originally approved to treat schizophrenia, was approved in June by the Food and Drug Administration (FDA) to alleviate depression associated with bipolar I disorder (Psychiatric News, August 6, 2013). In the October 30, 2013, AJP In Advance, Sunovion Pharmaceuticals, lurasidone’s developer, released data showing how the drug received approval to remedy this difficult-to-treat condition.

Lurasidone is one of three medications approved to treat bipolar I depression; the others are quetiapine and combinational olanzapine-fluoxetine. Lurasidone inhibits dopamine 2 receptor–associated mechanisms and has the capability to bind to multiple serotonin receptors (5-HTs).

Antony Loebel, M.D., lead author and executive vice president at Sunovion, told Psychiatric News that because of lurasidone’s pharmacology, the company believed that the drug originally approved to treat schizophrenia could also be effective in treating depression.

“Lurasidone has a unique set of effects at several key receptors that are thought to facilitate antidepressant effects, based on animal models,” said Loebel. “These include high affinity for 5HT7 receptors where lurasidone acts as an antagonist and moderate affinity for 5HT1A receptors where it acts as a partial agonist.”

Loebel explained that these antidepressant effects were confirmed in Sunovion’s schizophrenia trials, in which data showed improvement in associated depressive symptoms in patients taking lurasidone.

He stated that the company believed that there was an unmet need for relieving depressive symptoms associated with bipolar disorder. Thus, said Loebel, the company saw lurasidone as a “very promising and different” molecular candidate to remedy bipolar I depression.

To assess lurasidone’s efficacy and safety, researchers at Sunovion conducted a global recruitment of over 500 participants who were experiencing major depressive symptoms with a diagnosis for bipolar I disorder, in accordance with DSM-IV-TR criteria. Participants were given 20 mg to 120 mg per day of lurasidone or placebo for six weeks. Changes in depression were measured by the Montgomery Asberg Depression Rating Scale (MADRS), and depression severity was measured by the Clinical Global Impression Scale for Bipolar Illness (CGI-BP). In addition, participants were evaluated for adverse events and changes in metabolic profiles.

Results showed that lurasidone reduced MADRS scores 31 percent more than placebo did and decreased CGI-BP scores by more than 38 percent compared with placebo. In addition, those given lurasidone showed improvement in anxiety symptoms and patient-reported quality of life and functional impairment.

The most frequent adverse events reported by participants were nausea, headache, restlessness, and drowsiness. Discontinuation rates due to adverse events were similar among both active and placebo groups. In addition, no significant changes in weight, lipids, and measures of glycemic controls were observed in either group.

“This placebo-controlled, multicenter study clearly demonstrated the efficacy and safety of lurasidone in patients with bipolar depression,” stated Loebel. “These results suggest that lurasidone is an important new treatment option for patients with this disorder.”

Loebel informed Psychiatric News that more studies are under way that will observe the long-term safety and efficacy of lurasidone, in addition to studies that will investigate the drug’s efficacy in adolescents with bipolar disorder. The studies are scheduled to begin this year.

R.H. Belmaker, M.D., a faculty member in the Bipolar Clinic at Hadassah Medical Center in Israel and author of an accompanying editorial for Loebel’s manuscript, told Psychiatric News that lurasidone is not very different from other compounds in its class—besides the “current” perception of its having fewer metabolic side effects.

“Past experiences have taught clinician scientists that not all side effects are revealed in phase 3 studies,” stated Belmaker. “I was involved in olanzapine trials decades ago, and at the time we were not aware of the metabolic side effects that are now quite prominent.”

Though lurasidone will be added to the armamentarium for depression associated with bipolar I disorder, Belmaker concluded that only time will reveal whether the medication is a safe first-line option for this complex illness. ■

“Lurasidone Monotherapy in the Treatment of Bipolar I Depression: A Randomized, Double-Blind, Placebo-Controlled Study” is posted at http://ajp.psychiatryonline.org/article.aspx?articleid=1763708.