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BMJ open

ISSN 2044-6055

13 papers in the library · 13 citations · publishing 2024-2026

Papers

Protocol for a randomised controlled trial of ketamine versus ketamine and behavioural activation therapy for adults with treatment-resistant depression in the community.

BMJ open May 1, 2024 Ben Beaglehole, Richard Porter, Katie Douglas et al. 5 citations

A randomized controlled trial will test the feasibility of adding behavioral activation therapy (BAT) to oral ketamine for treatment-resistant major depressive disorder. The study aims to recruit 60 adults aged 18–65 years, randomizing them to eight weeks of oral ketamine with BAT or oral ketamine alone. Feasibility will be measured by attendance, acceptability, and retention. The primary efficacy outcome is the Montgomery-Asberg Depression Rating Scale, assessed weekly during treatment and fortnightly during 12 weeks of follow-up. For a definitive trial to be recommended, the study must meet recruitment targets and show a greater than 20% reduction in relapse rates favoring the combined treatment arm.

S-ketamine versus placebo for cortical spreading depolarisation in severe acute brain injury (KETA-BID): protocol for a pilot, randomised, blinded clinical trial.

BMJ open July 28, 2025 Trine Hjorslev Andreasen, Markus Harboe Olsen, Christian Gluud et al. 2 citations

Cortical spreading depolarisation (SD) is a pathological wave of brain cell activity that occurs frequently after severe acute brain injury and can worsen damage by reducing blood flow and increasing energy demand. Ketamine appears to inhibit SDs in laboratory and patient studies. The KETA-BID trial is a randomized, blinded feasibility and pilot study testing S-ketamine for SDs in adults undergoing surgery for traumatic brain injury, aneurysmal subarachnoid hemorrhage, or spontaneous intracerebral hemorrhage. Participants who develop SD clusters receive either continuous S-ketamine or placebo, with dosing adjusted based on SD occurrence. The primary outcome is SDs per hour after randomization. The trial will provide insight into SD and ketamine's clinical effects, potentially offering a new treatment.

Intravenous ketamine for emergency department treatment of suicidal ideation in a paediatric population: protocol for a double-blind, randomised, placebo-controlled, parallel-arm pilot trial (KSI study).

BMJ open July 5, 2024 Michael Schlegelmilch, Amy C Plint, Nicholas Barrowman et al. 2 citations

A single intravenous dose of ketamine may rapidly reduce suicidal ideation in adults, but it has not been tested in adolescents. This pilot trial aims to determine whether studying ketamine for suicidal ideation in a pediatric emergency department is feasible. Twenty adolescents will be randomly assigned to receive either 0.5 mg/kg of intravenous ketamine or a saline placebo over 40 minutes. Suicidal ideation severity will be measured at several time points up to seven days. The main feasibility outcome is the proportion of eligible patients who complete the study protocol. The trial will also pilot three suicidal ideation severity tools and explore the intervention's efficacy, safety, and tolerability.

Online mindfulness interventions in the care of people with physical and mental health conditions: a scoping review.

BMJ open July 18, 2025 Vjura Senthilnathan, Susan Zahir, Robert Simpson et al. 1 citation

Online mindfulness programs are increasingly used to manage health conditions. This scoping review of 84 studies found that online mindfulness-based interventions have been studied for many physical and mental health conditions, with 63 studies focused on physical health. Mindfulness-based cognitive therapy was the most common type, assessed in 33 studies. Interventions typically lasted 8 weeks, were led by therapists or instructors, and delivered via web or videoconferencing. Content generally followed standard mindfulness programs, sometimes adding psychoeducation or disease management. Many studies did not report tailoring interventions to participants, and reporting of intervention details was inconsistent. The review suggests some evidence for online mindfulness programs but notes that intervention components remain unclear.

Protocol of an open-label safety and feasibility pilot study of ketamine-assisted psychotherapy for methamphetamine use disorder (the KAPPA trial).

BMJ open February 10, 2025 Kathryn Fletcher, Nadine Ezard, Krista J Siefried et al. 1 citation

A pilot study will test the safety and feasibility of combining subanaesthetic ketamine with cognitive behavioural therapy for adults with methamphetamine use disorder. Twenty participants seeking to reduce or stop methamphetamine use will receive three subcutaneous ketamine doses (0.75 to 0.9 mg/kg) at weekly intervals and four therapy sessions over four weeks. The study will measure recruitment time, eligibility rates, treatment completion, retention, and acceptability over eight weeks, and explore changes in methamphetamine use, cravings, withdrawal, quality of life, and treatment satisfaction over 24 weeks. No pharmacological treatments currently exist for this condition, and psychotherapy alone is only moderately effective.

Efficacy and safety of esketamine hydrochloride adjunct to sufentanil in non-surgical patients under mechanical ventilation in the ICU (SENSATION trial): protocol for a multicentre, single-blind, randomised controlled trial.

BMJ open September 25, 2024 Yi Long, Donghuang Hong, Haibin Ni et al. 1 citation

Esketamine as an adjunct to sufentanil may reduce opioid consumption in non-surgical patients receiving mechanical ventilation in the ICU. This ongoing multicenter, single-blind, randomized controlled trial in six ICUs in China will assign 132 patients to either standard care (sufentanil alone) or an esketamine infusion at 0.2 mg/kg/hour plus sufentanil. The primary outcome is mean hourly sufentanil consumption. The trial aims to provide evidence for esketamine's efficacy and safety, addressing a gap in knowledge for this patient population.

Comparative effect of different mindfulness-based intervention types and deliveries on depression in patients with breast cancer: a protocol for a systematic review and network meta-analysis.

BMJ open August 7, 2024 Deqi Zhang, Wenxin Zhao, Lin Yuan et al. 1 citation

Breast cancer is now the most common cancer worldwide. Mindfulness-based interventions, such as mindfulness-based cognitive therapy and mindfulness-based stress reduction, have been used in various delivery methods, including face-to-face and internet-delivered, to help patients with breast cancer reduce depression. No study has yet compared the effectiveness of all these types and deliveries. This protocol describes a planned systematic review and network meta-analysis to assess their effectiveness. The review will search seven electronic databases for randomized controlled trials from inception to December 2023. Two reviewers will assess risk of bias. The results will be published in peer-reviewed journals.

Acceptability and safety of two sequential doses of psilocybin in bipolar II depression: protocol for an open-label single-arm feasibility study.

BMJ open July 13, 2026 Thomas D Meyer, Lauren N Vale, Maya Ibrahim et al.

A protocol describes an upcoming feasibility study testing psilocybin-assisted therapy in 10 outpatients with bipolar II disorder who have mild to moderate passive suicidal thoughts. Participants may receive two oral doses of 25 mg psilocybin about four weeks apart, combined with a structured mindfulness-based cognitive-behavioral therapy protocol. The study aims to assess the acceptability and safety of this approach, measuring changes in suicidality and depressive symptoms, and to gather preliminary data for a future randomized trial. Individuals with bipolar disorder and suicidality have typically been excluded from psilocybin trials due to safety concerns.

Development of the MDMA-Assisted Psychotherapy Side Effects Tool (M-SET): a Delphi study.

BMJ open May 11, 2026 Julia Colcott, Alexandre A Guerin, Olivia Carter et al.

A new tool, the MDMA-Assisted Psychotherapy Side Effects Tool (M-SET), was developed to systematically capture side effects during MDMA-assisted psychotherapy. Experts in MDMA-AP and neuropsychopharmacology participated in a two-round online Delphi process to refine a list of 165 items across four questionnaires covering screening, baseline, medication session days, and follow-up. The tool aims to improve safety monitoring and build a more robust evidence base on the tolerability of MDMA-AP for research and clinical use.

Digital Intervention for Psychedelic Preparation (DIPP): protocol for a randomised controlled feasibility trial comparing meditation- and music-based programmes in healthy volunteers.

BMJ open March 12, 2026 Rosalind McAlpine, Magdalena Jaglinska, Krisztina Jedlovszky et al.

A 21-day mobile-accessible programme called the Digital Intervention for Psychedelic Preparation (DIPP) is being tested for feasibility and preliminary efficacy in a randomised controlled trial. The study will recruit 40 non-treatment-seeking adults without a clinical diagnosis, randomly assigning them to either a guided meditation with music condition or a music-only condition. After the digital intervention, all participants will attend an in-person supervised psilocybin session with a standardised 25 mg dose. Primary outcomes include recruitment efficiency, retention, and adherence; secondary outcomes assess preparedness, quality of the psychedelic experience, and wellbeing, with follow-ups up to 9 months. The trial is registered as NCT06815653.

Effects of low-dose esketamine on hypoxaemia during thoracoscopic non-tracheal intubation anaesthesia: protocol for a double-blind, randomised controlled trial.

BMJ open January 27, 2026 Jing Tian, Mengchao Xu, Songjie Li et al.

Low-dose esketamine may reduce the incidence of intraoperative hypoxaemia during non-intubation thoracoscopic surgery. This randomized controlled trial will assign patients to receive either esketamine or a placebo (normal saline). The main outcomes are the occurrence of hypoxaemia (oxygen saturation ≤90% for at least 10 seconds) and the time until it appears. Secondary outcomes include hypercapnia, inflammatory markers, pain scores, recovery times, and complications. The trial is registered and approved by an ethics committee.

Effect of aerobic exercise combined with meditation on cognitive frailty: study protocol for a parallel group randomised controlled trial.

BMJ open June 27, 2025 Sijia Xia, Feng Chen, Wenju Wang et al.

This registered clinical trial protocol describes a four-arm, assessor-blind randomized controlled trial that will test whether combining aerobic exercise with meditation produces greater improvements in physical and cognitive function for people with cognitive frailty than either practice alone. Cognitive frailty is the simultaneous presence of physical frailty and cognitive impairment without dementia. One hundred forty qualified participants will be randomly assigned to aerobic exercise, meditation, combined aerobic exercise and meditation, or a health education control group for 12 weeks. Primary outcome is the Edmonton Frailty Scale; secondary outcomes include cognitive tests, physical performance, subjective experiences, brain MRI measures, and blood biomarkers. Assessments occur at baseline and after the intervention.

Efficacy of a single low dose of esketamine for patients with irritable bowel syndrome: study protocol for a randomised controlled trial.

BMJ open June 23, 2025 Zhe Sun, Lei Jiang, Yan Xing et al.

Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction involving recurrent abdominal pain and altered bowel habits. Conventional treatments are often unsatisfactory. This trial hypothesizes that a single low dose of esketamine, which has rapid antidepressant effects, may alleviate IBS symptoms. The study is a single-centre, randomized, double-blind, placebo-controlled trial enrolling 92 patients per group across three severity levels. The primary outcome is the IBS Severity Scoring System measured at baseline and up to six weeks after colonoscopy. Secondary outcomes include quality of life, stool form, anxiety, depression, and somatic symptoms. The protocol is approved and registered.