There are no published pediatric data on lurasidone or ketamine, although both seem promising. Lurasidone has been approved for adults, and a study being done in youngsters is not specific for bipolar disorder. Children with schizophrenia, psychosis, autism disorders, Asperger’s syndrome, and refractory major depressive disorder also can enroll.
A recently published adult study, PREVAIL 2 (Program to Evaluate the Antidepressant Impact of Lurasidone), comprised 505 patients with bipolar I depression. They were randomized to once-daily, flexibly dosed lurasidone at either 20-60 mg/day or 80-120 mg/day, or to placebo.
After 6 weeks, depression scores fell in both the 20- to 60-mg/day group (–15.4; effect size = 0.51) and the 80- to 120-mg/day group (–15.4; effect size =0.51), compared with placebo (–10.7).
Similarly, lurasidone treatment resulted in significantly greater endpoint reduction in Clinical Global Impressions-Bipolar Scale depression severity scores for both the 20- to 60-mg/day group (–1.8; effect size = 0.61) and the 80- to 120-mg/day group (–1.7; effect size = 0.50), compared with placebo (–1.1). Both lurasidone groups also experienced significant improvements compared with placebo in anxiety symptoms, and in patient-reported measures of quality of life and functional impairment. Response rates were 53% for the active group and 30% for the placebo group, with remission rates of 42% vs. 40%.
"The effect size was similar for the high and low doses, about 0.5, which is not terrible," Dr. Carlson said. "Discontinuation rates were fairly low, suggesting that it may be worth pursuing."
The main side effects were nausea, headache, akathisia, and somnolence, but very few changes were found in weight, lipids, or measures of glycemic control.
"Ketamine is something we’ve been hearing a lot about," Dr. Carlson said. "If we can come up with a way to give it that’s not intravenous and make it last for a while, it could be really valuable."
One study found that adults randomized to ketamine had significantly greater improvements in depression scores after 24 hours than did those who had midazolam.
The study comprised 73 patients. Response rates at 24 hours were 64% vs. 28% for placebo – with patients taking ketamine more than twice as likely to respond in the adjusted analysis.
The response was highest in the first 3 days after infusion; by day 7, it had dropped to about 45%. A review also highlighted ketamine's 'Achilles heel' – it just hasn’t got staying power. The paper looked at effect sizes in two depression studies and found that they peaked around 2 or 3 days after infusion. But 2 weeks later, the effect size was just about the same as with placebo.
"It’s a really interesting drug, and it does appear to hold some promise," Dr. Carlson said.
Dr. Carlson noted that she has received research funding from Bristol-Myers Squibb, GlaxoSmithKline, Merck & Co., Otsuka America Pharmaceutical, Pfizer, and Schering-Plough.