Skip to content

Anhedonia Behavioural Activation and Ketamine Therapy (AAKT): Shaping a Proposal With Patient and Public Involvement

Anna Borissova, Allan H. Young, Mitul A. Mehta, Tim Dalgleish, Camilla L. Nord

BJPsych Open June 1, 2025 DOI: 10.1192/bjo.2025.10791 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Qualitative study (PPI interviews) and description of a planned feasibility parallel-group randomized controlled trial Peer reviewed
Sample size 7
Population Participants from a previous study of ketamine in treatment-resistant depression
Topics Depression Ketamine Esketamine
Keywords Anhedonia Feeling Depression economics Clinical psychology Viewpoints Randomized controlled trial Placebo Alternative medicine Schizophrenia object-oriented programming Cognition
Key findings Participants supported combining ketamine with psychotherapy and provided recommendations for improving study procedures, including clearer communication about the temporary nature of mood changes and the addition of audiovisual preparation materials.

Abstract

Aims: Ketamine and behavioural activation (BA) reduce levels of anhedonia in major depressive disorder (MDD), though neither resolves anhedonia. Combining these treatments could yield additive or even multiplicative benefits. This poster summarises the development of a PhD fellowship proposal, discussing: (1) the initial patient and public involvement (PPI) interviews, exploring views on participation in ketamine research; (2) the resulting proposal, assessing the feasibility of a trial augmenting BA with IV ketamine for MDD and anhedonia.

Methods: 1. One-to-one PPI interviews were conducted with seven participants from a previous study of ketamine in treatment-resistant depression. Questions addressed (a) volunteering reasons, (b) positives to retain and areas to improve and (c) research objectives opinions. 2. Participants with MDD and anhedonia will be recruited from the community and local primary care services (GP and NHS Talking Therapies). A planned feasibility parallel-group randomised controlled trial will compare IV ketamine with BA (n=20), against midazolam with BA (n=20). Participants will attend eight visits (including one-month follow-up) over 10–12 weeks, receiving 3 ketamine or midazolam infusions in between 6 BA sessions. Feasibility of study procedures and collection of outcome measures will be assessed.

Results: A key motivator for participants to volunteer was hope that ketamine would improve depression symptoms. Some were curious about ketamine’s effects. They wished to support research into depression treatments. Most participants experienced a stark difference between ketamine and midazolam (placebo). They described feeling more open, malleable and involved in the world after ketamine. Participants suggested future studies retain a focus on treating participants as individuals rather than a ‘number’ and allowing unrushed sessions. They thought clinician-led interviews helped reflect on symptom changes. Participants found the consent process thorough. However, some suggested it should be clearer that mood changes from ketamine may not last. They recommended providing audiovisual materials on the ketamine experience/infusion room to support preparation. They suggested a check-in between infusion sessions and a final session to discuss onward referrals, medication advice and signposting to low-cost counselling and integration groups. Most thought ketamine could enable better use of therapy time and that therapy could help make sense of thinking changes post-ketamine. Other suggestions for research included duration of symptom relief post-ketamine, treatment accessibility including in primary care, and medication side effects.

Conclusion: PPI interviews supported combining ketamine with psychotherapy. They provided key insights on improving study procedures to support research into augmenting primary care therapies for depression treatment.

Comparable studies

Other randomized controlled trials on ketamine for depression, most cited first.

Study Year Design Participants
Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode 2013 Randomized controlled trial n = 73
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68

Explore topics

By condition and practice