Active mechanisms of ketamine-assisted psychotherapy: A systematic review.
Isak Joneborg, Yena Lee, Joshua D Di Vincenzo, Felicia Ceban, Shakila Meshkat, Leanna M W Lui, Farhan Fancy, Joshua D Rosenblat, Roger S McIntyre
Journal of affective disorders October 15, 2022 DOI: 10.1016/j.jad.2022.07.030 via PubMed
Summary
A systematic review of five randomized-controlled trials found that ketamine-assisted psychotherapy (KAP) had a significant positive effect on primary outcome measures for adults with substance use disorders and treatment-resistant depression, but the data is mixed. The single trial examining KAP for treatment-resistant depression found no benefit. The review notes a lack of large, replicated clinical trials and no studies actively examining mechanisms of action. Evidence suggests temporary neural changes caused by ketamine, such as NMDAR inhibition and increased synaptic neuroplasticity, may affect treatment outcomes. Preliminary findings also suggest adjunct psychotherapy, changes in perspective, and spirituality may play a role.
Study at a glance
| Characteristics | Systematic review Randomized Peer reviewed |
|---|---|
| Population | Adults with treatment-resistant depression or substance use disorders |
| Intervention | Ketamine-assisted psychotherapy |
| Topics | Ketamine |
| Keywords | Mood disorders Psychedelics Psychotherapy Rapid acting antidepressants |
| Key finding | Ketamine-assisted psychotherapy had a significant positive effect on primary outcome measures compared to controls, but the data is mixed and the single trial for treatment-resistant depression found no benefit. |
Abstract
Few studies have evaluated the efficacy of ketamine-assisted psychotherapy (KAP) in the treatment of treatment-resistant depression (TRD) and substance use disorders (SUD). A systematic review of clinical trials reporting on the efficacy of KAP and discussing mechanisms of action, identified on PubMed and PsycInfo. Five randomized-controlled trials reported on the efficacy of KAP treatment and discussed active mechanisms. Four of the studies treated adults with SUD and a single study treated adults with TRD. Overall, KAP had a significant positive effect on primary outcome measures compared to controls, however, the data is mixed. The study examining KAP for TRD found no benefit. Lack of large, replicated clinical trials. No studies actively examining mechanisms of action. Evidence suggests that temporary neural changes caused by ketamine such as n-methyl-d-aspartate receptor (NMDAR) inhibition and increase of synaptic neuroplasticity affect treatment outcomes of KAP. Based on reports of preliminary findings, we speculate that adjunct psychotherapy, changes in perspective, and spirituality may also play a role.