Session Explores Use of Lurasidone in Bipolar Depression

Treating the episodes of depression for patients with bipolar disorder has long been a challenge, particularly for those patients with the more severe form of the disease, bipolar I. Patients whose depression results from bipolar disorder often do not respond to standard antidepressants; in fact, for those patients who have not experienced an initial manic episode, this can offer the first clue to a diagnosis.

Still, as Henry Chung, MD, chief medical officer at Montefiore Medical Center outlined Monday during “Examining the Treatment and Care of Bipolar Depression,” it is common for standard antidepressants to be prescribed alongside mood stabilizers, such as lithium. Mood stabilizers are the main treatment for bipolar disorder, and work to keep patients from cycling in and out of the manic and depressive episodes that characterize the disease.

Use of antidepressants in treating bipolar depression is controversial, however. Not only do these drugs have no effect on some patients, but it is believed that for others, their use can trigger the onset of a manic episode.

In June 2013, the FDA expanded its indication for the antipsychotic lurasidone, marketed as Latuda, for use in bipolar disorder, either as a monotherapy or in combination with lithium or valproate. (It was first approved for schizophrenia.)¹ Dr Chung and Joseph Calabrese, MD, director of the Mood Disorders Program at University Hospitals Case Medical Center, Case Western Reserve School of Medicine, presented data on lurasidone Monday during the US Psychiatric and Mental Health Congress in Orlando, Florida. Their presentation was sponsored by Sunovion Pharmaceuticals.¹

Lurasidone has been praised in some circles for relative safety and especially for its lack of adverse cardiometabolic effects, although apparently the FDA does not permit Sunovion to specifically market this aspect. However, in April 2014 writer David Allen, MD, noted that while the drug was superior to other antipsychotics in terms of cardiometabolic effects, the fact that Sunovion had sought FDA approval to prove its effects on biopolar depression did not mean other, less expensive drugs in the same class would not do the same thing.²

Still, Sunovion has the data on lurasidone, which were published in a pair of studies that appeared in the same issue of The American Journal of Psychiatry earlier this year.^3,4 In the study of lurasidone as a monotherapy, patients were given doses that ranged from 20 mg to 120 mg per day. Treatment resulted in significantly greater endpoint reduction in depression severity scores for both the group taking 20 mg to 60 mg as the group taking the larger doses, compared with placebo.³ Dr Calabrese noted in his remarks that this suggests a smaller dose is indicated for most patients.

Both lurasidone groups also experienced improvements in anxiety compared with placebo, improvements in patient-reported quality-of-life and functional improvement measures.³ In both studies, the main side effects were somnolence (sleepiness), akathisia (restlessness), and nausea. As with other antipsychotics, a boxed warning appears on the label. (Dr Calabrese is listed as a co-author on the study.)^3,4

In his portion of the presentation, Dr Chung outlined the toll that bipolar depression takes on patients in terms of lost productivity and costs to the healthcare system. He presented data showing direct and indirect costs of the disease were $151 billion in 2009. Reducing episodes of depression in these patients, he said, has the potential to trim their overnight hospital stays, visits to the emergency department, and other costs to the system.

The comorbidities associated with severe mental illness are gaining more attention, Dr Chung said. As community health clinics have begun to integrate primary medical care into their services under health care reform, there’s been a growing awareness of the overlay between mental illness and cardiovascular conditions, including the number of mental health patients who have heart attacks, he said.

A patient’s overall cardiometabolic profile would be a consideration for how long a patient might remain on lurasidone, in addition to how well the drug is helping with symptoms of depression. “At no time have we had more incentive to look at both things together,” he said.

References

1. Sunovion Pharmaceuticals Inc. announces FDA approval of Latuda (lurasidone HCl) as monotherapy and adjunctive therapy in adult Patients with bipolar depression [press release]. Marlborough, MA: Sunovion Pharmaceuticals; June 28, 2013. http://www.sunovion.com/news/latuda-press-room.html
2. Allen D. Latuda and bipolar depression. Family and Dysfunction and Mental Health blog. http://davidmallenmd.blogspot.com/2014/04/latuda-and-bipolar-depression.html. Published April 8, 2014. Accessed September 23, 2014.
3. Loebel A, Cucchiaro J, Silva R, Kroger H, Hsu J, Sarma K, Sachs G. Lurasidone monotherapy in the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Am J Psychiatry 2014;171(2):160-168.
4. Loebel A, Cucchiaro J, Silva R, Kroger H, Sarma K, Xu J, Calabrese JR. Lurasidone as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Am J Psychiatry 2014;171(2):169-177.