HOLLYWOOD, FLA. – Lurasidone as monotherapy in the dosage range of either 20-60 mg/day* or 80-120 mg/day significantly improved functioning and quality-of-life in patients with bipolar depression, a post hoc analysis has shown.
In a previously published study of 318 patients randomized to either lurasidone dosage groups or placebo, the drug’s association at both dose ranges with reduced Montgomery-sberg Depression Scale total scores and Clinical Global Impressions scale for bipolar depression severity scores from baseline to week 6 was significant. The study also noted that both lurasidone groups had significant improvements in patient-reported measures of quality of life and functional impairment, compared with the placebo group (P less than .001 for each) (Am. J. Psychiatry 2014;171:160-8).
The findings led Dr. Terence A. Ketter, professor of psychiatry and chief of the bipolar disorders clinic at Stanford (Calif.) University, to wonder how the improvements in functionality and quality of life had happened in such relatively short order.
"It kind of makes sense that it’s related to the mood improvement," Dr. Ketter said in an interview during a poster session at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.
To investigate further, Dr. Ketter and his colleagues performed a mediation regression analysis using data from phase III of the original trial. The results were that reduced depressive symptoms from baseline to week 6 mediated the effect of lurasidone on Sheehan Disability Scale functional recovery and Quality of Life Enjoyment and Satisfaction Questionnaire scores at week 6 (P less than .05 for each).
"This suggests that, at least in the first 6 weeks, most of the improvement [in functionality and quality of life] is related to the improvement in depressive symptoms," Dr. Ketter said. "Functional recovery is something that takes months, and it may be that beyond this by a month or two, you’re looking at a degree of mood improvement by duration interaction to get functional improvement." He added that there likely would be a "huge improvement" in cognition, simply because of the removal of depressive symptoms.
"Is it enough to be able to go out and get a job? Well, maybe not. Maybe you need things to integrate for months before you can go out and work." But, he added, over time, the less interference with one’s cognitive ability, the greater likelihood that person is employable.
In the original study in bipolar I patients, "the company wanted to know which was the right dose," Dr. Ketter said. "As it turned out, both worked. The higher one was a little bit harder to tolerate, but not horribly so."
As a result, Dr. Ketter said the drug has a "pretty flexible label." In his own practice, he said he starts patients on monotherapy with lurasidone 20 mg/day at dinner time, titrating upward in 20-mg increments each week until his patients reach the dosage that works best for them. "The average dose seems to be about 60 mg/day," he said.
Lurasidone, a second-generation antipsychotic, originally was approved by the Food and Drug Administration in 2010 to treat schizophrenia in adults; the indication was expanded in 2013 to include bipolar I, either as monotherapy or as an adjunct to lithium or valproate.
Because of its relatively low impact on metabolic function and its low sedative effect, compared with other second-generation antipsychotics, Dr. Ketter said he favors using lurasidone in his patients. "It’s like an easier to use quetiapine," he noted.
This study was supported by Sunovion Pharmaceuticals. Dr. Ketter disclosed that he has received funding from Sunovion, as well as from AstraZeneca Pharmaceuticals, Cephalon, Eli Lilly, and others.
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*Correction, 7/2/2014: An earlier version of this story misstated the lurasidone dosage range.