6 Research Papers to Read About Oral Ketamine for Depression | ISHA Health

Science of Ketamine

6 Research Papers to Read About Oral Ketamine for Depression | ISHA Health

Written by

Isha Team


July 3, 2022


October 27, 2023

Ketamine, originally developed as an anesthetic, has gained ground as an effective intervention for mental health conditions such as treatment-resistant depression, major depressive disorders, bipolar depression, PTSD, obsessive-compulsive disorders, and general anxiety disorder. Esketamine intranasal spray was approved by the US Food and Drug Administration (FDA) in March 2019.

Oral Ketamine is considered the most convenient and least expensive formulation of ketamine in patients with depression. It tends to cause fewer side effects as it gets absorbed slower than via other routes. It is the most appealing route for many in terms of its ease of use and high accessibility. Let’s look at some of the research papers about oral ketamine and depression.

1. A systematic review by Rosenblat et al assessed oral ketamine for unipolar and bipolar depression and demonstrates the efficacy of oral ketamine with good tolerability. Two randomized controlled trials (RCTs) indicated significant improvement in depressive symptoms after 2-6 weeks of treatment with oral ketamine. The rapid antidepressant effect after 24 hours of oral ketamine treatment, antidepressant effects, and efficacy in TRD were demonstrated in retrospective studies. This systematic study concludes that oral Ketamine has significant antidepressant effects with good tolerability.

2. Case reports also indicate the efficacy of oral ketamine in TRD(treatment-resistant depression) and of beneficial effects of oral ketamine.

3. In a double-blind randomized and controlled trial, Jafarina et al evaluated the efficacy and safety of oral ketamine versus diclofenac to alleviate mild to moderate depression in chronic pain patients, Oral ketamine was more effective and superior to diclofenac in a trial of 6 weeks in 40 patients. Hamilton Depression Rating Scale (HDRS) and depression subscale for depression (HADSDepression) scores assessed reduction in depressive symptoms at week 3 and week 6 after intervention with oral ketamine. So, this trial concludes oral ketamine is more effective for patients with depression and chronic pain.

4. Arabzadeh et al conducted a double-blinded controlled trial with 81 patients with major depressive disorder (MDD) to check the antidepressant effect of oral ketamine. These patients were scored with the Hamilton Depression Rating Scale (HDRS) at intervals of 2, 4, and 6 weeks after the start of the trial. General linear model repeated measures indicated a significant effect of oral ketamine for time × treatment interaction when measured by Hamilton Depression Rating Scale (HDRS) score. An early improvement was demonstrated in the ketamine group (approximately 85.4%) compared to the placebo group (42.5%). No significant adverse effects were observed in this trial. This trial suggests oral ketamine combined with sertraline is effective for major depressive disorder.

5. In a randomized, double-blind, placebo-controlled study by Domany et al of patients with treatment-resistant depression (TRD), 41 patients received either oral ketamine or placebo thrice/ week for a duration of 21 days. They were evaluated at baselines, 40 minutes, 240 minutes after administration, and 3rd, 7th, 14th, and 21st days. Changes in symptoms of depression were measured on Montgomery–Åsberg Depression Rating Scale (MADRS). The Ketamine group showed a significant reduction in depressive symptoms at all intervals in comparison with the controlled group, which showed improvement at 40 min after administration.  MADRS score in the Ketamine group was reduced by 12.5 on day 21, and in the placebo, it was reduced by 2.49 points only. Ketamine rapidly ameliorated symptoms of depression in patients with TRD with mild and transient side effects.

6. Another study on the efficacy of oral ketamine combined with psychotherapy indicates that pharmacotherapy with a low dose of Ketamine effectively improved the symptoms of patients with treatment resistant depression. The average PHQ-9 score of the patients was 17.9 which decreased to 9.5 after two sessions of ketamine enhanced psychotherapy with 75mg of oral ketamine.

To conclude, multiple studies indicate the effectiveness of oral ketamine in treatment-resistant depression (TRD), unipolar or bipolar depression, and major depressive disorder (MDD), particularly when it is combined with psychotherapy. Many researchers in the world are studying oral ketamine for various mental health conditions. We will keep you updated when new research papers come out.

Isha health provides online ketamine therapy in the comfort and privacy of your home. Once you reach the maintenance phase, its positive effects last for about a week or even longer in many cases. About 60-70% of patients with treatment-resistant depression (TRD) respond to ketamine-assisted therapy, and many people feel improvement in depressive symptoms within 24 hours. The sleep, appetite, and libido of patients are usually not affected. An experienced team of clinicians provides sessions via telemedicine to make this treatment safely accessible.

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