Advances in Pharmacotherapies for Youth Reported at AACAP Meeting

The American Academy of Child and Adolescent Psychiatry (AACAP) held its 63rd annual meeting in New York last month. The conference featured several pharmaceutical industry reports on pharmacological therapies for psychiatric disorders in youth, a select few of which are presented below.

Lurasidone Shows Promise in Adolescents With Schizophrenia

Lurasidone (brand name Latuda)—which is approved by the Food and Drug Administration for the treatment of schizophrenia in adults—may also decrease symptoms of schizophrenia in adolescents without major weight gain and other metabolic effects, data presented by Sunovion Pharmaceuticals Inc. suggests.

“We are pleased that the efficacy and tolerability profile of Latuda for patients with schizophrenia were similar in adolescents to that previously seen in adults across multiple studies,” said Antony Loebel, M.D., executive vice president and chief medical officer of Sunovion in a press release.

According to Sunovion, these findings may help Latuda gain approval for use in children, providing a viable option to treat young patients without the strong risk of weight gain at an early age.

A total of 326 adolescents with schizophrenia aged 13 to 17 were randomly assigned to take Latuda (40 mg/day or 80 mg/day) or placebo for six weeks. Compared with placebo, 40 mg and 80 mg lurasidone daily doses were associated with marked improvements in subjects’ Positive and Negative Syndrome Scale (PANSS) scores after six weeks, with about 62 percent and 65 percent improving by at least 20 percent in the low- and high-dose groups, respectively.

Latuda was generally well tolerated by the patients in the low- and high-dose groups, with somnolence, nausea, akathisia, and vomiting among the most common side effects.

While patients taking placebo and 40 mg of lurasidone showed no difference in weight gain over the course of the six-week study, those in the 80 mg group gained an average of 1.1 pounds. There were no clinically meaningful changes in metabolic parameters (cholesterol, glucose, triglycerides) among the three groups. The patients taking 80 mg lurasidone daily did show a slight increase in triglyceride levels relative to the other groups.

Latuda has also been approved for the treatment of major depressive disorder and bipolar I disorder in adults. According to Sunovion, the FDA has accepted the company’s supplemental New Drug Application for treating adolescents with schizophrenia.

Vortioxetine Appears to Be Well Tolerated by Youth With Depression

Only two antidepressants are approved for pediatric depression, the selective serotonin reuptake inhibitors fluoxetine (children and adolescents) and escitalopram (adolescents only). Vortioxetine, which was approved in 2013 for depression in adults, might offer a novel pathway of treatment in younger patients, as this drug is a serotonin modulator (it both stimulates and inhibits serotonin receptors).

At the 2015 AACAP meeting, preliminary data from a two-week clinical study exploring the safety and pharmacokinetics of vortioxetine in children aged 7 to 17 were presented. The data suggested that the agent is well tolerated in youth. This year, researchers from H. Lundbeck A/S and their collaborators followed reported results from a 24-week open label extension study.

Forty-one children and adolescents who had participated in the original two-week trial continued taking vortioxetine (5 mg/daily to 20 mg/daily). All participants in the trial had previously been diagnosed with a depressive or anxiety disorder, and 18 patients had comorbid attention-deficit/hyperactivity disorder.

After 24 weeks, 35 patients (85 percent) reported at least one adverse event, though the type and severity matched what has been seen in adults; headache, nausea, and sedation were the most commonly reported side effects. The incidence and severity of adverse events decreased over time, as assessed by the 45-item Pediatric Adverse Events Rating Scale administered at baseline, day 14, and day 182.

Children and adolescents also experienced improvements in depression and anxiety as measured by the Clinical Global Impressions-Severity of Illness and -Global Improvement scales.

Tetrabenzine Derivative May Improve Tourette's Symptoms With Less Risk

Tetrabenzine is approved to treat hyperkinetic movement symptoms in Huntington's disease and has also been used off-label for other motor problems, such as the tics associated with Tourette's syndrome. Many patients who take tetrabenzine experience uncomfortable side effects including risks of fatigue, insomnia, akathisia, anxiety, and depression.

An open-label pilot study of 23 adolescents aged 12 to 18 with Tourette's tested the efficacy and safety of a related drug called deutetrabenzine. According to researcher Barbara Coffey, M.D., of the Icahn School of Medicine at Mount Sinai in New York, who presented the study results, slight modifications to deutetrabenzine may provide metabolic advantages that will decrease the number of doses given to patients and potentially reduce side effects.

The participants received an initial dose of 6 mg deutetrabenzine daily (titrated up to 36 mg depending on tolerance) over six weeks, followed by a two-week washout period and a final assessment at the eight-week mark.

At the study’s conclusion, the participants had an average 37 percent decrease in their Yale Global Tic Severity Scale (YGTSS) score, with improvements seen both in motor tics and verbal tics. Improvements were also seen in depressive symptoms and obsessive-compulsive symptoms; such symptoms frequently co-occur in Tourette’s patients.

The safety profile was also positive, as almost all the side effects were mild to moderate, and only one participant withdrew due to adverse events. Fatigue, headaches, and irritability were the most common effects reported.

This study was sponsored by Auspex, which is a wholly owned subsidiary of Teva Pharmaceutical Industries, Israel. ■