Ketamine-Assisted Psychotherapy

Definitions/Description

Ketamine assisted psychotherapy (KAP) is a heterogeneous psychotherapeutic practice that incorporates the use of ketamine, a dissociative anesthetic, to treat psychiatric conditions and substance-use disorders. It falls under the broader category of psychedelic-assisted psychotherapy, which also encompasses therapeutic use of substances like psilocybin and MDMA.

• Prior clinical studies exploring KAP have used various psychotherapies including cognitive-behavioral, motivational enhancement, mindfulness-based, functional analytic, and existentially oriented therapies among many others.[1]
• Given the variability between approaches, KAP should be viewed as a general term for psychotherapy performed proximally or concurrently with ketamine dosing, which could include one or a few ketamine doses, or more commonly repeated doses interspersed with therapy.

It is not known whether the therapeutic effects of ketamine are primarily attributable to the subjective (i.e., dissociative) effects of the drug, its biological activity at glutamatergic NMDA-receptors (including enhanced neuroplasticity), or some combination of these with concurrent therapeutic interventions. Data suggest both the neuropharmacological effects and first-person experience may play a role in therapeutic benefits.

• The traditional, or biochemical, model of ketamine therapy generally consists of multiple infusions over several weeks followed by maintenance dosing once or twice weekly.
  • In the case of depression, the antidepressant effect of ketamine lasts approximately one week and evidence for long-term remission without maintenance therapy is lacking. Of 54% of patients who responded to ketamine treatment at outpatient infusion clinics, fewer than 25% maintained a response after 3 months without maintenance infusions. [2]
  • Recent research found that repeated IV ketamine dosing (without concurrent talk therapy) in patients with nonpsychotic treatment-resistant depression was well tolerated and noninferior to electroconvulsive therapy.[3]
• KAP is distinct from medical models of ketamine therapy that are typically administered in a supervised setting without psychotherapy or exploration of the experience.
  • Recent systematic reviews of KAP have generally described favorable results, but comparisons between studies remain limited due to variance in administration route/dosing, psychotherapy modality, treatment length, indication, and outcome measures.[4][5][6] There remains a gap in the literature for a large-scale randomized controlled trial that quantifies the additive contribution of psychotherapy.