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

doi:10.1016/j.jad.2022.07.030

Active mechanisms of ketamine-assisted psychotherapy: A systematic review

J Affect Disord. 2022 Oct 15:315:105-112. doi: 10.1016/j.jad.2022.07.030. Epub 2022 Jul 26.

Authors

Isak Joneborg¹, Yena Lee², Joshua D Di Vincenzo², Felicia Ceban³, Shakila Meshkat⁴, Leanna M W Lui⁵, Farhan Fancy⁶, Joshua D Rosenblat⁷, Roger S McIntyre⁸

Affiliations

¹ Department of Psychology, Lund University, Lund, Sweden; Brain and Cognition Discovery Foundation, Toronto, ON, Canada.
² Brain and Cognition Discovery Foundation, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
³ Brain and Cognition Discovery Foundation, Toronto, ON, Canada; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
⁴ Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
⁵ Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Institute of Medical Studies, University of Toronto, Toronto, ON, Canada.
⁶ Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Institute of Medical Studies, University of Toronto, Toronto, ON, Canada.
⁷ Brain and Cognition Discovery Foundation, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁸ Brain and Cognition Discovery Foundation, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Institute of Medical Studies, University of Toronto, Toronto, ON, Canada. Electronic address: roger.mcintyre@uhn.ca.

PMID: 35905796
DOI: 10.1016/j.jad.2022.07.030

Abstract

Background: Few studies have evaluated the efficacy of ketamine-assisted psychotherapy (KAP) in the treatment of treatment-resistant depression (TRD) and substance use disorders (SUD).

Methods: A systematic review of clinical trials reporting on the efficacy of KAP and discussing mechanisms of action, identified on PubMed and PsycInfo.

Results: 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.

Limitations: Lack of large, replicated clinical trials. No studies actively examining mechanisms of action.

Conclusion: 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.

Keywords: Ketamine; Mood disorders; Psychedelics; Psychotherapy; Rapid acting antidepressants; Substance-use.

Publication types

Review
Systematic Review

MeSH terms

Adult
Depressive Disorder, Treatment-Resistant* / drug therapy
Humans
Ketamine*
Psychotherapy
Receptors, N-Methyl-D-Aspartate
Treatment Outcome

Substances

Receptors, N-Methyl-D-Aspartate
Ketamine