Active mechanisms of ketamine-assisted psychotherapy: A systematic review

Joneborg, Isak; Lee, Yena; Vincenzo, Joshua D. Di; Ceban, Felicia; Meshkat, Shakila; Lui, Leanna M.W.; Fancy, Farhan; Rosenblat, Joshua D.; McIntyre, Roger S.

doi:10.1016/j.jad.2022.07.030

Cited by 25 publications

(13 citation statements)

References 22 publications

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“…At this stage, there is not sufficient evidence to support a particular sequencing protocol for future ketamine and psychotherapy studies, but this area is important to resolve. A systematic review by Joneborg et al 51 discussed possible mechanisms for the efficacy of combined use of ketamine and psychotherapy, although only a small number of studies were identified that had reported on this topic. This review also noted that despite possible synergistic effects, evidence for this possibility remained speculative.…”

Section: Discussionmentioning

confidence: 99%

Ketamine and psychotherapy for the treatment of psychiatric disorders: systematic review

et al. 2023

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Background Ketamine is an effective short-term treatment for a range of psychiatric disorders. A key question is whether the addition of psychotherapy to ketamine treatment improves outcomes or delays relapse. Aim To identify all studies combining psychotherapy with ketamine for the treatment of psychiatric disorders to summarise their effects and make recommendations for future research. Method The review protocol was prospectively registered with PROSPERO (registration number CRD42022318120). Potential studies were searched for in MEDLINE, Embase, PsycINFO, SCOPUS, the Cochrane library and Google Scholar. Eligible studies combined ketamine and psychotherapy for the treatment of psychiatric disorders and did not use case reports or qualitative designs. Key findings relating to psychotherapy type, diagnosis, ketamine protocol, sequencing of psychotherapy and study design are reported. Risk of bias was assessed using modified Joanna Briggs critical appraisal tools. Results Nineteen studies evaluating 1006 patients were included in the systematic review. A variety of supportive individual and group, manualised and non-manualised psychotherapies were used. The majority of studies evaluated substance use disorders, post-traumatic stress disorder and treatment-resistant depression. Ketamine protocols and sequencing of ketamine/psychotherapy treatment varied substantially between studies. Outcomes were largely positive for the addition of psychotherapy to ketamine treatment. Conclusion The combination of psychotherapy and ketamine offers promise for the treatment of psychiatric disorders, but study heterogeneity prevents definitive recommendations for their integration. Larger randomised controlled trials using manualised psychotherapies and standardised ketamine protocols are recommended to clarify the extent to which the addition of psychotherapy to ketamine improves outcomes over ketamine treatment alone.

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Section: Discussionmentioning

confidence: 99%

Ketamine and psychotherapy for the treatment of psychiatric disorders: systematic review

et al. 2023

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“…This is otherwise known as ketamine-assisted psychotherapy (KAP). As a prototypical psychoplastogen, ketamine has been shown to rapidly promote structural and functional neuroplasticity, which may enhance (or be enhanced by) the effects of psychotherapy to maximize treatment outcomes (Joneborg et al, 2022;Olson, 2018). The formation of new neural connections, restructuring of thought patterns, and promotion of emotional learning are potential mechanisms of behavior change within this context (Drozdz et al, 2022;Hasler, 2020).…”

Section: Discussionmentioning

confidence: 99%

Registered clinical trials investigating ketamine and esketamine for treatment-resistant depression: A systematic review

Brendle

Ragnhildstveit

Slayton

et al. 2023

JPS

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Background and AimsKetamine and esketamine have garnered interest in both psychiatric research and clinical practice for treatment-resistant depression (TRD). In this review, we examined registered trials investigating the therapeutic use of ketamine or esketamine for TRD, with the aim of characterizing emerging trends and knowledge gaps.MethodsThe ClinicalTrials.gov electronic registry and results database was queried from inception to February 5, 2022, adhering to elements of the PRISMA guideline, we evaluated trial eligibility in the qualitative synthesis. Data regarding study design, drug regimens, and measures were subsequently abstracted and descriptively analyzed.ResultsThe search returned 86 records, of which 56 trials were included in the final review. The number of trials investigating ketamine and esketamine for TRD increased since 2008, with higher peaks observed in 2015 (n = 9) and 2021 (n = 9). Most trials were Phase 2 (13, 23.2%) or Phase 3 (11, 19.6%), gathering preliminary data on efficacy and/or further data on safety and efficacy with variant dosing and pharmacological approaches. By and large, trials examined ketamine and esketamine as individual versus combination treatments (45% and 25%, respectively). The Montgomery-Asberg Depression Rating Scale (MADRS) was most commonly used to assess clinical outcomes (75%).ConclusionsThere are increasingly large-scale and late-phase trials of esketamine over ketamine for TRD, coupled with efforts to centralize evidence on these medications. Yet several trials do not assess patient characteristics that may affect treatment response, such as age, sex, and race. By understanding these design limitations, scientists and clinicians can avoid research waste and funding bodies can judiciously direct support towards high priority research.

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“…However, in the context of ketamine-assisted psychotherapy (KAP), clinicians interact with patients who are receiving low-dose ketamine ( 51 – 54 ). In this context, the psychedelic properties of ketamine (i.e., increased receptivity to new ideas, ego dissolution, time-out from ordinary consciousness) represent clinically useful tools, as opposed to problematic side effects ( 53 , 55 ).…”

Section: Introductionmentioning

confidence: 99%

Case report: Medical student types journals during ketamine infusions for suicidal ideation, treatment-resistant depression, post-traumatic stress disorder, and generalized anxiety disorder

Willms

McCauley²,

Kerr³

et al. 2022

Front. Psychiatry

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Suicide is the most common cause of death in male resident physicians and the second most common cause of death in resident physicians overall. Physicians also experience high rates of major depressive disorder (MDD), post-traumatic stress disorder (PTSD), and burnout. These conditions frequently develop during medical school, and threaten not only physicians but the patients they care for. A 30-year-old medical student presented to our clinic with a history of treatment-resistant depression (TRD), generalized anxiety disorder (GAD), PTSD, and 5 years of daily suicidal ideation. Previous treatments included therapy, lifestyle modifications, and various combinations of six antidepressants. These interventions had little effect on the patient’s mental health. The patient was treated at our clinic with an 8-month regimen of IV ketamine infusions and ketamine-assisted psychotherapy (KAP). The patient achieved remission from suicidality and PTSD within 1 month; and TRD and GAD within 7 months. The patient’s Patient Health Questionnaire (PHQ-9) score decreased from 25 (severe depression) to 1 (not depressed). These findings suggest that ketamine and KAP may represent effective interventions for mental health applications in healthcare professionals. The patient made the unique decision to attempt to type narrative journals during four of his ketamine infusions (doses ranged from 1.8 to 2.1 mg/kg/h IV). The patient successfully typed detailed journals throughout each 1-h ketamine infusion. To our knowledge, these journals represent the first independently typed, first-person, real-time narratives of ketamine-induced non ordinary states of consciousness. The transcripts of these journals may provide useful insights for clinicians, particularly in the context of KAP.

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Active mechanisms of ketamine-assisted psychotherapy: A systematic review

Cited by 25 publications

References 22 publications

Ketamine and psychotherapy for the treatment of psychiatric disorders: systematic review

Ketamine and psychotherapy for the treatment of psychiatric disorders: systematic review

Registered clinical trials investigating ketamine and esketamine for treatment-resistant depression: A systematic review

Case report: Medical student types journals during ketamine infusions for suicidal ideation, treatment-resistant depression, post-traumatic stress disorder, and generalized anxiety disorder

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