Ketamine Repository

Over the last two decades, there has been significant research into ketamine’s use in treating depression and other mental illnesses. Initially, research was focused on learning more about the antidepressant effects of Ketamine itself. Today, more research has expanded into ketamine’s use as an adjunct to traditional therapy for two main reasons. 

  1. Psychotherapy by expert clinicians has been shown to be more effective for the mental health disorders we treat than medications alone. Barriers to treatment success usually involve fear, avoidance, rigid thinking, or failure to open up to a therapist.  
  2. Despite Ketamine’s effectiveness, the studies have shown limited duration of symptom relief. The highest quality studies show clinical improvement anywhere from 1 to 7 days. 

The results thus far suggest a synergistic effect, meaning Ketamine and psychotherapy have the potential to work better together than separately.

The possible benefits of Ketamine Assisted Psychotherapy

Ketamine-Assisted Psychotherapy

Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data and Outcomes in Three Large Practices Administering Ketamine with Psychotherapy

Journal of Psychoactive Drugs (2019)
Jennifer Dore, Brent Turnipseed, Shannon Dwyer, Andrea Turnipseed, Julane Andries, German Ascani, Celeste Monnette, Angela Huidekoper, Nicole Strauss & Phil Wolfson

Explores KAP within an analytical framework examining three distinct clinical practices that use similar methods. The authors present demographic and outcome data from 235 patients. Their findings suggest that KAP is an effective method for decreasing depression and anxiety in a private practice setting, especially for older patients and those with severe symptom burden. 

Augmenting the Treatment of PTSD with Ketamine—a Review

Current Treatment Options in Psychiatry (2019)
Duek, O., Kelmendi, B., Pietrzak, R.H. et al.

Ketamine may affect memory reconsolidation, learning and more specifically, and extinction learning. Small studies suggest that it may act as an enhancer for extinction-based psychotherapies for PTSD.

PTSD Augmented Psychotherapy With Ketamine (KPE) – First Results

Biological Psychiatry (2019)
Duek, O ; Levy, I ; Li, Yt ; Gordon, C ; Kelmendi, B ; Harpaz-Rotem, I

A small study that divided PTSD patients into two groups, one receiving Ketamine, the other Midazolam. The treatment protocol consisted of 7 daily sessions of prolonged exposure therapy with Ketamine or Midazolam. After 90 days follow-up, ketamine PTSD symptoms were lower than midazolam.

Single Versus Repeated Sessions of Ketamine-Assisted Psychotherapy for People with Heroin Dependence.

Journal of Psychoactive Drugs (2007)
Krupitsky, Evgeny M ; Burakov, Andrei M ; Dunaevsky, Igor V ; Romanova, Tatyana N ; Slavina, Tatyana Y ; Grinenko, Alexander Y

A prior study found that one ketamine-assisted psychotherapy session was significantly more effective than active placebo in promoting abstinence (Krupitsky et al. 2002). In this study of the efficacy of single versus repeated sessions of ketamine-assisted psychotherapy in promoting abstinence in people with heroin dependence. At one-year follow-up, survival analysis demonstrated a significantly higher rate of abstinence in the multiple KAP group.

Ketamine psychotherapy for heroin addiction: immediate effects and two-year follow-up.

Journal of Substance Abuse Treatment (2002)
Evgeny Krupitsky M.D.,Ph.D. Andrey Burakov M.D. Tatyana Romanova M.A. Igor Dunaevsky M.D. Rick Strassman M.D.  Alexander Grinenko M.D.

Seventy detoxified heroin-addicted patients were randomly assigned to one of two groups receiving ketamine psychotherapy (KAP) involving two different doses of ketamine, psychedelic and sub-psychedelic. High dose KAP produced a significantly greater rate of abstinence in heroin addicts within the first two years of follow-up, a greater and longer-lasting reduction in craving for heroin, as well as greater positive change in nonverbal unconscious emotional attitudes than did low dose KAP.

Ketamine for Depression

Efficacy and Safety of Ketamine in Bipolar Depression: A Systematic Review

Revista de Psiquiatría y Salud Mental – Journal of Psychiatry and Mental Health (2017)
Alberich S., Martínez-Cengotitabengoa M., López P., et al.

This a systematic review of 10 studies on the efficacy and safety of ketamine as treatment of bipolar depression. According to data, ketamine appears to be an effective and safe treatment for bipolar depression. Adverse effects observed tended to completely disappear within the first hour of therapy. 

Efficacy of Ketamine in the Rapid Treatment of Major Depressive Disorder: A Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Studies

Neuropsychiatric Disease and Treatment (2016)
Han Y., Chen J., Zou D., et al.

Nine high-quality studies that included 368 patients were selected to compare the efficacy of ketamine to placebo. The therapeutic effects at 24 hours, 72 hours, and day 7 were found to be significantly better than placebo. 

Ketamine Administration in Depressive Disorders: A Systematic Review and Meta-Analysis

Psychopharmacology (2014)
Fond G, Loundou A, Rabu C, et al.

This meta-analysis confirms ketamine’s efficacy in depressive disorders based on 9 studies with a total of 192 patients. Depression scores were significantly decreased in the ketamine groups compared to those in the control groups. Three of four studies found a significant decrease of suicidal thoughts.

Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial

The American Journal of Psychiatry (2013)
Murrough J.W., Iosifescu D.V., Chang L.C., Al Jurdi R.K., Green C.E., Perez A.M., et. al.

This was a high quality, well-designed randomized controlled trial. Patients with treatment-resistant major depression experiencing a major depressive episode were randomly assigned under double-blind conditions to receive either ketamine or midazolam. The primary outcome was change in depression severity 24 hours after drug administration, as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). The ketamine group had greater improvement in the MADRS score than the midazolam group 24 hours after treatment.

Post-Traumatic Stress Disorder

Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder

A Randomized Clinical Trial

JAMA Psychiatry (2014)
Feder A, et al.

A single dose of ketamine resulted in the rapid reduction of symptoms of posttraumatic stress disorder in a proof-of-concept, randomized, double-blind study of 41 patients with chronic PTSD. Scores of PTSD symptom severity 24 hours after receiving Ketamine were significantly improved compared with midazolam.

Impact of oral ketamine augmentation on hospital admissions in treatment-resistant depression and PTSD: a retrospective study

Psychopharmacology (2017)
Hartberg, John; et al.

This was a retrospective review of patients receiving long-term oral ketamine for treatment-resistant depression and post-traumatic stress disorder. Hospital records of 37 patients who received oral ketamine treatment were reviewed to compare the number and duration of psychiatric hospital admissions before and after treatment. Following treatment, inpatient hospital days were reduced by 70%, and hospital admissions were reduced by 65%. 

Repeated ketamine infusions for antidepressant-resistant PTSD: Methods of a multicenter, randomized, placebo-controlled clinical trial

Contemporary Clinical Trials (2019)
Abdallah CG, Roache JD, Averill LA, et al.

This ongoing study is the only trial of therapeutic effects of ketamine for PTSD and the first placebo-controlled trial to determine the dose-related effects of repeated ketamine on PTSD.