Ketamine Appears Safe and Effective for Adolescents With Treatment-Resistant Depression

A single dose of intravenous ketamine appears to reduce depressive symptoms within 24 hours in adolescents with treatment-resistant depression, suggests a small study in AJP in Advance. These improvements lasted for at least two weeks.

Jennifer Dwyer, M.D., of Yale University and colleagues enrolled 17 adolescents aged 13 to 17 years in a four-week trial. All the teens had a diagnosis of major depressive disorder, as determined by the Schedule for Affective Disorders and Schizophrenia for School-Age Children, and had failed to respond to at least one antidepressant treatment. The participants had failed an average of 3.24 prior treatments, and the average length of their current depressive episode was 21 months.

The study employed a crossover design. The participants randomly received a single infusion of either ketamine (0.5 mg/kg over 40 minutes) or midazolam (0.045 mg/kg over 40 minutes) and then received the other compound two weeks later. Midazolam was chosen as the placebo compound since like ketamine, it can produce dissociative symptoms but has no antidepressant effects. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) 1, 2, 3, 5, 7, 10, and 14 days post-infusion.

The adolescents who received ketamine had significantly greater reductions in MADRS scores after 24 hours compared with those who received midazolam (average MADRS reduction of 18 points compared with 9 points). Overall, 76% of the adolescents who received ketamine achieved a treatment response (defined as a >50% reduction in their MADRS scores) within three days, compared with 35% of participants who received midazolam.

The adolescents who received ketamine experienced greater increases in blood pressure and more dissociative symptoms in the first hour after infusion than those who received midazolam. Both effects were transient, however, disappearing within a few hours. No serious adverse effects emerged in any of the participants.

“This trial provides promising initial data on the feasibility, preliminary efficacy, and safety of intravenous ketamine in adolescent depression,” Dwyer and colleagues wrote. “However, additional data on long-term safety and efficacy are needed before any recommendations regarding integration into care in non-research pediatric populations can be made.”

To read more on this topic, see the Psychiatric News article “Researchers Look to Extend Benefits of Ketamine.”

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