Toward Synergies of Ketamine and Psychotherapy

Abstract

Ketamine is a dissociative drug that has been used medically since the 1970s primarily as an anesthetic agent but also for various psychiatric applications. Anecdotal reports and clinical research suggest substantial potential for ketamine as a treatment in conjunction with psychological interventions. Here, we review historical and modern approaches to the use of ketamine with psychotherapy, discuss the clinical relevance of ketamine's acute psychoactive effects, propose a unique model for using esketamine (one isomeric form of ketamine) with Acceptance and Commitment Therapy (ACT), and suggest considerations for moving medication-assisted psychotherapy forward as a field.

Keywords: ACT; dissociation; esketamine; ketamine; psychedelic; psychotherapy; therapy.

Figure 1

Functional units for existing models combining ketamine with psychotherapy. Each circle indicates a single experience of ketamine, with circle size corresponding to relative theoretical emphasis on the nature of the experience. Bracketed lines are used to indicate optimal windows of psychotherapeutic intervention. (A) shows the strategy of high-dose “psychedelic therapy,” involving significant preparation before and integration after a limited number of drug sessions, which themselves are largely inner-directed, rather than primarily relational, experiences. (B) shows the model of low-dose “psycholytic therapy,” in which ongoing psychotherapy coincides with ketamine administration, making use of acute drug effects that are thought to facilitate the quality of therapy. The two former approaches are examples of “experience-oriented” frameworks, such as KAP. (C) is representative of “plasticity-oriented” strategies, wherein psychotherapy is delivered after the period of acute drug effects but within “critical periods” of neural adaptation that are thought to facilitate the uptake and efficacy of behavioral interventions.

Figure 2

Proposed design for a pilot investigation of esketamine with Acceptance and Commitment Therapy (ACT) for treatment-resistant depression. Current esketamine dosing protocols call for twice weekly dosing during a 4-week induction phase, followed by weekly dosing during a maintenance phase in weeks 5 through 8. Patients receive an initial dose of 56 mg, followed by repeated doses of 56 mg or 84 mg based on treatment response (i.e., efficacy and tolerability). After initial study procedures, participants will be randomized to receive treatment as usual (plain circle) or esketamine in conjunction with ACT (circle with bracketed line) during the induction phase of treatment. Both study arms will follow the same clinical procedures for maintenance treatment and subsequent follow-up.