Study Finds Intravenous Ketamine May Be Safely Used for Depression in Adolescents

A study has found that intravenous ketamine is effective in reducing symptoms of depression in the short term and is well tolerated among adolescents suffering from depression. Yale Child Study Center’s Jennifer B. Dwyer and her fellow researchers stated that case reports proposed early potential effectiveness of intranasal ketamine in bipolar depression and intravenous ketamine in depression in adolescents.

The researchers also revealed that an intravenous (“IV”) ketamine open-label trial that was conducted recently, which recruited 13 adolescents with treatment-resistant depression, also proposed that ketamine could be efficacious in this population. However, the lack of placebo in the trial complicated the results’ interpretation. The researchers note that placebo response rates in depression trials were high, especially in pediatric depression trials, which is why it’s important to distinguish genuine drug effects from general effects.

For their study, the researchers recruited 17 adolescents aged 13 to 17 and carried out a randomized clinical trial that was placebo-controlled to evaluate the effectiveness and safety of IV ketamine in adolescents. During the study, they administered one IV infusion of either midazolam or ketamine to the participants who had diagnoses of major depressive disorder before administering the alternate compound 14 days later.

Prior to the study, participants had tried one or a few antidepressant medications for the condition and met the severity criterion on the Depression Rating Scale-Revised Score for children, with a 0.4 score. Their score on the Montgomery-Åsberg Depression Rating Scale a day after the drug had been administered served as the primary outcome measure.

During the first three days after the ketamine infusion had been administered, a higher proportion of participants showed response to midazolam vs. ketamine, at 35% and 76% respectively. The results demonstrated a substantial decrease in symptoms of depression 24 hours after the ketamine infusion. The researchers also conducted a secondary analysis which showed that the treatment gains associated with ketamine remained a fortnight after treatment.

In their report, the researchers note that no severe adverse events were observed. However, ketamine was associated with self-limited dissociative symptoms that impacted participant blinding. They added that further research was needed to better distinguish the longevity of ketamine’s antidepressant responses, both in the intermediate and long-term.

They also note that future studies should pay attention to safety monitoring in this population and neurodevelopmental context. The researchers assert that additional data on the effectiveness and safety of ketamine is required before any recommendations on integration into care can be made.

The study was reported in the “American Journal of Psychiatry.”

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