Ketamine’s Impact on Depression Symptoms Over Time

A recent study⁤ published ‍in The British Journal of Psychiatry indicates that IV ketamine can provide rapid relief from sadness for adults battling treatment-resistant depression, while improvements in suicidal thoughts may take weeks to manifest.

Researchers⁢ found that apparent and reported sadness ‍were the most improved‍ symptoms one day after ketamine infusion.However,noticeable improvement in suicidal⁤ ideation was only observed ‍21 days post-infusion.

Manivel Rengasamy,MD,assistant professor of psychiatry at the University of pittsburgh School of Medicine,explained to‍ Healio ⁤that previous studies have demonstrated ketamine’s⁣ effectiveness in⁣ reducing overall ⁣depression severity,particularly within the first 24 ‍hours.

Rengasamy ⁢and his team conducted‍ a secondary analysis of a ⁤double-blind, randomized, controlled study⁣ to investigate the immediate and delayed effects of ketamine on specific depression symptoms, ⁤using network ⁢analyses.

The analysis included 152 adults with treatment-resistant depression, ⁤with an ‍average age of 34.3 years. The participants, 62.5% women and 81.5% white, had not responded to at least ⁢one FDA-approved ⁤antidepressant. At ‍the start of the study, 38.8%⁣ reported suicidal ideation.

Participants were randomly assigned to receive either a single⁣ 40-minute IV infusion of 0.5 mg/kg⁣ ketamine (n‍ =‍ 103) ⁣or a saline placebo (n = 49).

Symptom severity was measured using Montgomery-Åsberg Depression Rating Scale (MADRS) scores, ‍ranging from zero to⁢ six, with higher scores indicating greater severity. Measurements were taken during an early period ⁤(baseline to 24 hours post-infusion) ⁣and a late period (5 to 30 days ⁤post-infusion).

The ketamine group showed the greatest effects on apparent and reported sadness 24 hours‍ after infusion, compared to the control group. Significant differences were also noted in⁢ pessimistic⁤ thoughts,inability to feel,concentration difficulties,lassitude,and reduced sleep. ⁣(Cohen’s d 0.39-0.65; ⁢ P < .05).

Network analyses indicated ⁢a strong correlation between ⁣reported and⁢ apparent sadness before and 24 hours ⁢after infusion. Symptoms were also more interconnected following ketamine administration.

Improvements in sadness and lassitude persisted to day 5,while improvement in apparent sadness⁣ lasted until day 12⁣ (Cohen’s d > 0.56; P < .05).

Significant differences in suicidal thoughts between the control and ⁤intervention groups were only observed on ‍day 21 (Cohen’s d ‍= 0.44; P < .05).

Rengasamy noted the unexpected finding that overall depressive symptoms were more closely connected after ketamine treatment. He also expressed surprise that differences ⁤in suicidal ‍ideation were detected a month after a single⁣ infusion,given that approximately 40% of the⁢ sample reported such ideation.

The researchers acknowledged limitations, including ⁢potential underestimation of ketamine’s effect sizes in late-period analyses due to a digital cognition intervention for the placebo group between days 2 and 5.

Rengasamy suggests that clinicians⁣ should note ketamine’s rapid improvement⁤ of sadness symptoms promptly after infusion, as⁤ well ⁣as⁣ the potential for sustained improvement⁢ in other areas,⁣ such as suicidality, up ⁢to a month later.Future research should explore the impact of repeated ketamine doses on individual symptoms over time, with more detailed assessments, time‍ points, and larger participant samples, ⁣he ⁢added.

For more information, Manivel‍ Rengasamy, MD, can be reached ⁢at psychiatry@healio.com.