WholeMind Healing Pathways
Ketamine Research
The use of ketamine for depression and the treatment of mental illnesses extends back at least 50 years, but in the last decade, we have seen a resurgence of interest.
Ketamine research has primarily focused on depression, with a minor interest in treating addiction. Despite this limited scope of research, ketamine clinics across the world are seeing very positive results while treating an extensive range of ailments, not just depression and addiction.
It is essential to know that the underlying causes of depression and chronic pain, often linked to trauma, are also the underlying causes of many other mental health disorders.
Ketamine (With no Integration) For Depression and Suicide
(Wilkinson et al., 2018) (Number of Participants-167): A single infusion of ketamine for patients with acute suicidal ideation/thoughts (SI) showed a persistent decrease in SI for seven days following infusion. 60% reported no SI at all at seven days. Participants also showed a reduction in reported depression for the same period.
(Bahji et al., 2021): Review of Randomized Controlled Trials (RCT)comparing the effectiveness of esketamine (nasal) vs. ketamine IV Infusions. They found that intravenous ketamine consistently outperformed esketamine when comparing the effectiveness of reducing depression. Among intravenous Ketamine studies, with a total of 1,011 patients, no patients reported side effects that caused death, injury, or hospitalization.
(Price et al., 2022) (Number of Participants-809): Researchers compared the effectiveness of IV ketamine treatment in individuals with Treatment-Resistant Depression (TRD) and individuals who had depression but did not meet the TRD criteria (>two failed depression drug trials). Ketamine was found to have a greater effect in TRD individuals and to have a consistent reduction of depression symptoms across all psychiatric populations.
Ketamine with Therapy/Integration (KAP) for Depression
(Drozdz, et al., 2022)(Number of Participants-603): This study reviewed literature summarizing evidence regarding ketamine-assisted psychotherapy (ketamine with integration). Seventeen articles that included 603 participants were reviewed, and researchers found combined treatments can produce clinically significant reductions in pain, anxiety, and depression while also increasing rapport, treatment engagement, and promoting abstinence from addictive substances. Despite variances in the route of administration, psychotherapy provided before, during, and after ketamine treatment can maximize and prolong benefits for months or years.
(Dore, et al., 2019) (Number of Participants-253): This research reviews three distinct practices with data from 253 patients utilizing ketamine-assisted psychotherapy. Researchers found that KAP is an effective method for decreasing depression and anxiety in the private practice setting, especially in older patients and those with more severe symptoms. Ketamine can benefit patients with a wide variety of diagnoses when administered with psychotherapy. Harnessing the psychedelic properties, or “side effects,” of ketamine to enhance the effectiveness of psychotherapy. Ketamine can be administered by intramuscular injections (IM) in the office setting without IV access. Ketamine has been proven safe over decades and is ideal for office use.
Ketamine with Therapy/Integration (KAP) for Addiction
As a preface to this research, we would like to highlight the effectiveness (or lack thereof) of substance abuse treatment without ketamine. The success of individuals participating in substance abuse treatment is typically measured by evaluating their sobriety one year after treatment. The average rate of one year of sobriety for individuals across the spectrum of ages, genders, and substances is 5-7%. Krupitsky's control group correlates this in the first research article.
Ketamine is currently not widely utilized for the treatment of substance abuse, but the excellent research by Krupitsky and others shows the vast potential for its use in treating addiction.
(Krupitsky et al., 2002)(Number of Participants-70): Study of Ketamine Assisted Psychotherapy, single treatment session, for detoxed patients addicted to heroin. A randomized trial with two groups, low-dose (active control) vs. high-dose ketamine (2mg/Kg), who received one infusion and one KAP session within 3-5 days of infusion. The first key takeaway was that at three months, fewer high-dose participants had relapsed (50% vs. 60%). Secondly, 18% remained sober for two years vs. less than 5% in the control group.
(Krupitsky et al., 2011)(Number of Participants-59): A follow-up to the study above, the researchers compared the effectiveness of a single high-dose ketamine infusion vs. three high-dose ketamine infusions with both groups receiving KAP post-treatment. The participants were post-discharge from a hospital for opioid withdrawal. At one year, the high-dose group had an abstinence rate of 50% vs. 22% in the low-dose group. These numbers support the original 2002 results and suggest there is a dose-dependent response to KAP for opioid addiction.
Oral Ketamine for Depression
(Swainson et al., 2022): This paper discusses the safety of oral ketamine in comparison to other routes and formulations of ketamine, such as Spravato. The authors of this paper suggest that the safety risks associated with ketamine (e.g., high blood pressure and addiction) are overstated and have not been sufficiently studied. This paper goes on to suggest that the use of oral ketamine is relatively safe and appropriate for use in patient's homes and in therapists' offices. These ideas are important because access to IV and IM ketamine in clinics is not available to some patients, either due to geographic location or financial means.
(Mathai et al., 2024) (n=11,441): This large study tracked outcomes from patients receiving in-home oral lozenge/troche ketamine along with telemedicine integration. The researchers found that almost 60% of patients had a 50% reduction in depression symptoms, with around 20% experiencing full remission from their depression. The researchers also closely tracked the safety of in-home ketamine and found that only 5% of patients experienced any adverse effects, with most being mild in nature. A very small percentage of patients did experience increased suicidal ideation (0.7%). Overall, the use of in-home ketamine with telemedicine support and care was found to be effective and safe. While oral ketamine is effective in treating depression at a lower cost, it less effective than intramuscular or intravenous ketamine.