The drug is approved for adults with depression, but exceptionally high placebo responses rendered its effects in children not statistically significant.
Sarah Atkinson, MD
Pediatric patients with major depressive disorder (MDD) did not benefit from either low or high doses of desvenlafaxine when compared to young people who took a placebo, a short-term double-blind study found.
“Results do not support efficacy of desvenlafaxine in the treatment of depression in children ages 7 to 17,” corresponding author Sarah Atkinson, MD, Finger Lakes Clinical Research, Rochester, New York, told MD Magazine.
Longer term, the findings highlight the importance of understanding placebo-response in pediatric MDD trials and continuing to work to identify effective treatments for young people, Atkinson said.
Desvenlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI) marketed by Pfizer Inc. as Pristiq, has been approved for adults with major depressive disorder. Doses of 50 mg to 400 mg have been found to be effective, although no additional benefit was shown at greater than 50 mg per day. Adverse reactions and discontinuations were more frequent at higher doses, Atkinson said.
As for treating depression in young people, only limited medications are approved by the US Food and Drug Administration, she said.
The recent study sponsored by Pfizer is the second short-term investigation of desvenlafaxine for children and adolescents. The first produced similar results, although it differed slightly by considering just high dose desvenlafaxine and adding a positive control arm along with a placebo.
“Both the desvenlafaxine treatment arm and the positive control arm — fluoxetine – did not separate in a statistically significant manner from placebo,” Atkinson said.
No new safety signals were identified for desvenlafaxine in either study, she said.
The current study focused on children aged 7 to 11 years old and adolescents aged 12 to 17. Evaluators screened 573 young people and assigned 363 to treatment in one of three groups: 121 took desvenlafaxine at high exposure, 122 took desvenlafaxine at low exposure; and 120 took a placebo. The low exposure group received 20, 30, or 35 mg/day based on their weight; the higher exposure group received 25, 35, or 50 mg/day.
A total of 59 patients discontinued treatment early due to adverse events or requests to drop out of the study. Two patients, both in the desvenlafaxine low exposure group, reported severe adverse events that the investigator considered related to the treatment. One adolescent experienced a tension headache and initial insomnia while a second had a suicide attempt.
The participants were assessed after eight weeks using the Children's Depression Rating Scale-Revised (CDRS-R).
“Overall, the profile of change from baseline in CDRS-R score during the course of the 8-week treatment phase was similar for the three treatment groups,” the team, which included researchers from Pfizer and Johns Hopkins University in Baltimore, reported.
The placebo group showed a large response across all measures of efficacy, they said.
“This likely reduced the ability to detect a statistically significant difference between the desvenlafaxine low exposure, desvenlafaxine high exposure, and placebo groups,’’ the authors wrote.
The large placebo group response may have been due to administering the CDRS-R, the team speculated. Interaction between the clinician and the patient could have provided a therapeutic effect comparable to a cognitive behavior therapy session, the authors said.
As for why desvenlafaxine was shown to be effective in adults but not in pediatric patients, Atkinson said such differing outcomes aren’t well understood.
“Most multisite pediatric MDD trial programs have failed to demonstrate efficacy of drugs that have been shown to treat depression adults,” she noted.
Possible contributing factors include higher placebo response rates among pediatric patients, the possible therapeutic effects of participating in a clinical trial, differences in etiology of MDD between children and adults, and differences in developmental stages, among other issues.
“Pediatric depression can lead to significant impairment in a child’s academic, family, and peer relationships that negatively impacts well-being and the developmental trajectory may be interrupted,” Atkinson said regarding the importance of treatments for young patients with depression.
There is increased risk for substance abuse, conduct disorders, suicidal behavior, and recurrence of MDD in this population, she added.
No further trials of desvenlafaxine are planned for this age group, Atkinson said.
The study, “Desvenlafaxine Versus Placebo in the Treatment of Children and Adolescents with Major Depressive Disorder,” was published in the Journal of Child and Adolescent Psychopharmacology.