Lurasidone May Work Better as Monotherapy in Older Patients With Bipolar Depression
Abstract
A post-hoc assessment of a pair of clinical studies found that when combined with a mood stabilizer, lurasidone was not superior to placebo in adults over 55.
As bipolar disorder progresses in older patients with the illness, episodes of depression can become more impairing. Yet, few studies have compared the efficacy of the available bipolar depression treatments in older adults.
Even as the global population of adults aged 55 and over climbs, Martha Sajatovic, M.D., says data are sparse on which of the medications that are approved for adults are best for older patients.
“The presumption is that results from clinical trials in younger patients will generalize to the older adult population; however, this is not certain,” Martha Sajatovic, M.D., a professor of psychiatry at Case Western Reserve University School of Medicine, and colleagues wrote August 29 in the Journal of Clinical Psychiatry.
In 2013, the Food and Drug Administration approved lurasidone for the treatment of bipolar I depression in adults after two studies revealed that using the antipsychotic as a monotherapy and add-on agent to a mood stabilizer reduced depressive symptoms in adults without weight gain.
Sajatovic wanted to know if older adults respond differently to lurasidone, so she and her colleagues performed a post-hoc analysis of the data obtained by Sunovian Pharmaceuticals Inc., the manufacturers of lurasidone (Latuda), during the original clinical trials.
This analysis included data collected from 83 older adults in the monotherapy trial (56 on lurasidone [20 mg/day to 120 mg/day] and 27 on placebo) and 53 in the adjunctive trial (27 taking lurasidone [20mg/day to 120 mg/day] plus lithium or valproate and 26 taking placebo in addition to lithium or valproate).
At the end of the six-week trial, the patients taking lurasidone monotherapy showed an improvement of 14.8 points on the Montgomery-Åsberg Depression Rating Scale (MADRS) and 1.7 points on the Clinical Global Impressions scale for use in bipolar illness (CGI-BP). These findings were similar to those drawn from the 2013 monotherapy trial (15.4 point MADRS improvement and 1.7 point CGI-BP improvement among all adults 18 to 75)—suggesting both groups of adults had comparable responses to the medication.
In the adjunctive analysis, the 27 patients taking lurasidone plus lithium or valproate had an average improvement of 13.9 points on the MADRS and 1.4 points on the CGI-BP—similar to the outcomes of the 26 older patients taking a mood stabilizer and placebo (11.1 point improvement on the MADRS and 0.9 point improvement on the CGI-BP).
As was demonstrated in the original trials, both monotherapy and adjunctive therapy with lurasidone were found to be safe and well tolerated in the older adult population, with minimal metabolic effects.
“It’s still important to monitor a patient’s health and be aware of other medical comorbidities, but these findings provide the first concrete data that lurasidone is well tolerated and improves depression in older patients,” Sajatovic said.
Sajatovic added that the lack of superiority for adjunctive lurasidone over placebo may be due to older patients having been on a mood stabilizer for a longer period, which may dampen the effects of an augmenting agent. The low number of participants in the adjunctive trial may also have made it difficult to identify a statistical difference between the two groups, she said.
“I don’t think the results of the adjunctive portion of this analysis will affect clinical decision making, especially since we have a limited number of options to treat bipolar I depression,” Jonathan Meyer, M.D., an assistant clinical professor of psychiatry at University of California, San Diego, who specializes in the pharmacokinetics and side effects of antipsychotics, told Psychiatric News. Meyer, who is also a member of the Psychiatric News PsychoPharm editorial board, was not involved with this study.
Meyer noted that while a prospective analysis of lurasidone in older adults with bipolar depression would be ideal, it may be difficult to convince the government or industry to commit to a large, controlled trial of medications for bipolar disorder in a limited age bracket. A post-hoc analysis may not offer definitive conclusions that affect clinical practice, but such analysis can identify signals that are worth pursuing in future studies, he said.
“We need to try and make the most out of the data that are available. In that regard, it is helpful that newer clinical trials generally don’t have upper age limits, which makes it possible to extract some useful information,” Sajatovic said.
“Given its good tolerability profile, lurasidone should remain in the armamentarium of potentially useful agents to use alone or in combination therapy,” Meyer said.
This analysis was supported by Sunovion Pharmaceuticals Inc. ■
