In a systematic review and meta-analysis of four studies investigating combined use of psychotherapy and ketamine for PTSD, results showed that all the studies showed a significant reduction in PTSD symptom scores.
Overall, the treatment was “highly effective, as seen by the significant improvements in symptoms on multiple measures,” Aaron E. Philipp-Muller, BScH, Centre for Neuroscience Studies, Queen’s University, Kingston, Ont., and colleagues write.
Furthermore, the study “demonstrates the potential feasibility of this treatment model and corroborates previous work,” the investigators write.
However, a limitation they note was that only 34 participants were included in the analysis.
The findings were published online in the Journal of Clinical Psychiatry.
Emerging treatment
Ketamine is an “emerging treatment for a number of psychopathologies, such as major depressive disorder and PTSD, with a higher response than other pharmacologic agents,” the researchers write.
It is hypothesized that ketamine rapidly facilitates long-term potentiation, “thereby allowing a patient to disengage from an established pattern of thought more readily,” they write.
However, ketamine has several drawbacks, including the fact that it brings only 1 week of relief for PTSD. Also, because it must be administered intravenously, it is “impractical for long-term weekly administration,” they note.
Pharmacologically enhanced psychotherapy is a potential way to prolong ketamine’s effects. Several prior studies have investigated this model using other psychedelic medications, with encouraging results.
The current investigators decided to review all literature to date on the subject of ketamine plus psychotherapy for the treatment of PTSD.
To be included, the study had to include patients diagnosed with PTSD, an intervention involving ketamine alongside any form of psychotherapy, and assessment of all patients before and after treatment using the Clinician-Administered PTSD Scale (CAPS) or the PTSD Checklist (PCL).
Four studies met inclusion criteria. Of these, two were of “moderate” quality and two were of “low” quality, based on the GRADE assessment. The studies encompassed a total of 34 patients with “diverse traumatic experiences” and included several types of ketamine administration protocols, including one used previously for treating depression and another used previously for chronic pain.
The psychotherapy modalities also differed between the studies. In two studies, patients received 12 sessions of trauma interventions using mindfulness-based extinction and reconsolidation therapy; in a third study, patients received 10 weekly sessions of prolonged exposure therapy; and in the fourth study, patients received five daily sessions of exposure therapy.
Across the studies, the psychotherapies were paired differently with ketamine administration, such as the number of ketamine administrations in conjunction with therapy.
Despite the differences in protocols, all the studies of ketamine plus psychotherapy showed a significant reduction in PTSD symptoms, with a pooled standardized mean difference (SMD) of –7.26 (95% CI, –12.28 to –2.25; P = .005) for the CAPS and a pooled SMD of –5.17 (95% CI, –7.99 to –2.35; P < .001) for the PCL.
The researchers acknowledge that the sample size was very small “due to the novelty of this research area.” This prompted the inclusion of nonrandomized studies that “lowered the quality of the evidence,” they note.
Nevertheless, “these preliminary findings indicate the potential of ketamine-assisted psychotherapy for PTSD,” the investigators write.