How much ketamine is the right dosage for Treatment Resistant Depression?

Medical Reviewer: Nima A. Fahimian, MD

Published:

Abstract

Numerous placebo-controlled studies have demonstrated the ability of ketamine, an NMDA receptor antagonist, to induce rapid (within hours), transient antidepressant effects when administered intravenously (IV) at subanesthetic doses (0.5 mg/kg over 40 min). However, the optimal antidepressant dose remains unknown. We aimed to compare to active placebo the rapid acting antidepressant properties of a broad range of subanesthetic doses of IV ketamine among outpatients with treatment resistant depression (TRD). A range of IV ketamine doses were compared to active placebo in the treatment of adult TRD over a 3-day period following a single infusion over 40 min. This was an outpatient study conducted across six US academic sites. Outpatients were 18–70 years old with TRD, defined as failure to achieve a satisfactory response (e.g., less than 50% improvement of depression symptoms) to at least two adequate treatment courses during the current depressive episode.

Following a washout period, 99 eligible subjects were randomly assigned to one of the five arms in a 1:1:1:1:1 fashion: a single intravenous dose of ketamine 0.1 mg/kg (n = 18), a single dose of ketamine 0.2 mg/kg (n = 20), a single dose of ketamine 0.5 mg/kg (n = 22), a single dose of ketamine 1.0 mg/kg (n = 20), and a single dose of midazolam 0.045 mg/kg (active placebo) (n = 19). The study assessments (HAM-D-6, MADRS, SDQ, PAS, CGI-S, and CGI-I) were performed at days 0, 1, 3 (endpoint), 5, 7, 14, and 30 to assess the safety and efficacy. The overall group × time interaction effect was significant for the primary outcome measure, the HAM-D-6. In post hoc pairwise comparisons controlling for multiple comparisons, standard dose (0.5 mg/kg) and high dose (1 mg/kg) of intravenous ketamine were superior to active placebo; a low dose (0.1 mg/kg) was significant only prior to adjustment (p = 0.02, p-adj = 0.14, d = −0.82 at day 1). Most of the interaction effect was due to differences at day 1, with no significant adjusted pairwise differences at day 3. This pattern generally held for secondary outcomes. The infusions of ketamine were relatively well tolerated compared to active placebo, except for greater dissociative symptoms and transient blood pressure elevations with the higher doses. Our results suggest that there is evidence for the efficacy of the 0.5 mg/kg and 1.0 mg/kg subanesthetic doses of IV ketamine and no clear or consistent evidence for clinically meaningful efficacy of lower doses of IV ketamine.

Read more about the trial here.

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As someone who has struggled with depression for years, I was skeptical about trying alternative treatment options. However, the team at Bespoke Treatment made me feel comfortable and supported throughout the entire process. Not only did their TMS therapy provide significant relief for my depression symptoms, but I also had a positive experience with their ketamine therapy. The staff was incredibly knowledgeable and took the time to answer all of my questions and address any concerns I had.

I can't recommend this place enough. I had an incredible experience with the treatment I received here. From the administrative staff to the medical team, I really appreciated the outstanding care and attention I received and always felt listened to. There was never any sense of rushing or a "one size fits all" approach, which is sadly very much the norm elsewhere. I highly recommend coming here for the excellent quality of services, professionalism, and warmth that are so important when you're needing mental health treatment.

TMS was amazing for me . I loved my treatments , the doctors, the staff as well as the office itself. Its an amazing place to go for your wellbeing . Everyone is super nice, kind and extremely professional. The place is very easy to get to with available parking. Basically no stress. I felt very comfortable with my technician and all his knowledge about TMS . I also loved Dr. Fahimian . He is extremely educated and knowable in his field. His patience in taking his time to answer all my questions and concerns were highly appreciated.

I was severely depressed when starting treatment. I could not handle meds and had big hopes that TMS would work. It absolutely did wonders for lifting my depression. I have my life back. I have motivation to do things and energy to achieve goals. I really wasn’t sure if the TMS method would work, but it did and I am forever grateful. It even helped with my ruminating thoughts. I’m able to be in the moment and get back into doing things I enjoy. I highly recommend TMS to anyone who needs it.

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