Ketamine Treatment -- RCT (2).pdf

Randomized controlled trial Funded for $250,000 by the PSI Foundation: Psychotherapy for Ketamine's Enhanced Durability in Chronic Neuropathic Pain ¨ ¨ ¨ Chronic pain remains among the most prominent causes of disability worldwide, with the Canadian Pain Task Force indicating that 8 million Canadian...

Randomized controlled trial Funded for $250,000 by the PSI Foundation: Psychotherapy for Ketamine's Enhanced Durability in Chronic Neuropathic Pain ¨ ¨ ¨ Chronic pain remains among the most prominent causes of disability worldwide, with the Canadian Pain Task Force indicating that 8 million Canadians are disabled with major implications for physical and mental health. Despite the prevalence and impact, chronic pain therapies are limited by their short durability, adverse side effects, and variable efficacy. Ketamine, which is becoming increasingly used in Canada for the management of chronic pain, has not demonstrated any long-lasting analgesic effect in a number of randomized clinical trials. Despite its potent short-term benefits, the need for repeated and ongoing therapy is increasingly burdensome on patients, clinicians, and our healthcare system ¨ Biological and neurocognitive factors suggest that concurrent pharmacotherapy and psychotherapy can result in more durable and effective analgesic responses than either intervention alone.a \ ¨ To the investigators' knowledge, this will be the first study of its kind to explore the potential synergisms/additivity between psychotherapy and ketamine in a chronic neuropathic pain population. Four study goals 1. Test and inform hypotheses: K + Psychotherapy is better than K – alone or Psychotherapy - alone 2. Determine feasibility – can we ‘do’ the study? 3. Improve KAP delivery – Learn more about doing it effectively 4. Secure funding for the larger definitive trial. Week 1 - CBT + K - phone session 1 Preparation for the Trial – Gate Theory as related to CBT ¨ Week 2 – CBT + K - phone session 2 Combining CBT with Mindfulness – Meditation ¨ Week 3 - CBT + K - phone session 3 Befriending Yourself with Exercise ¨ Week 4 - CBT + K - phone session 4 Befriending with Nutrition ¨ Week 5 - CBT + K - phone session 5 Overcoming Chronic Pain Stigma ¨ ¨ ¨ ¨ ¨ ¨ ¨ ¨ ¨ ¨ Week 6 - CBT + K - phone session 6 Living by Your Truths - CBT Week 7 – CBT + K - Infusion…phone session 7 Body image… Week 8 - CBT + K - phone session 8 Intimacy Week 9 - CBT + K - phone session 9 Bravery Every Day Week 10 – CBT + K - phone session 10 Forgiveness ¨ ¨ ¨ ¨ ¨ ¨ Week 11 - CBT + K - session 11.. Loss, Grief and Resilience Week 12 – CBT + K - session 12.. Infusion 3 Relationships Week 13 - CBT + K - session 13.. Sleep Week 14 - CBT + K - session 14.. Overcoming ‘Shoulds’ Week 15 – CBT + K - session 15.. Inspiration Week 16 – CBT + K - session 16 Compassion as Analgesic and Antidepressant Ketamine Pharmacology ¨ NMDA receptor antagonist ⇢ rapid analgesia? (within ‘minutes’) ¨ Large reductions (25-40%) vs. controls in research literature ¨ But…Ketamine has limited treatment durability 2 eek…can they be extended with concurrent psychotherapy? Ketamine-assisted psychotherapy (KAP) M-CBT Cognitive-emotional change Ketamine Dissociative / Transpersonal experiences Integration of insights Ketamine-assisted psychotherapy (KAP) M-CBT Cognitive-emotional change Less Pain Better Health Ketamine Dissociative / Transpersonal experiences Integration of insights ¨ ¨ ¨ ¨ ¨ ¨ ¨ ¨ ¨ ¨ Appreciation of infusion effects & team support Sensitive transition from hospital to home Much sleep after infusion Phone contact difficulties (linked to scheduling) Platform use learning Sustained pain reduction & reduced carpal tunnel symptoms Peak contact – listened to audios & discussed CBT ‘The fall’ – in his apartment, rib injuries, flu onset Less contact & none-by-phone – audio SMS is positive Meeting with primary care physician ¨ ¨ ¨ ¨ ¨ ¨ Sensitive transition from hospital to home Much sleep following infusion Resolve phone challenges early (scheduling) Platform use learning Peak contacts – and sustained contacts – briefer, more frequent phone calls Audio SMS – effective at UCSD.. for shorter attention spans Text Message ‘Send’…and ‘Receipt’ December 10th…2:30 pm Text Message ‘Send’…and ‘Receipt’ December 11…10:20 pm Synergies between ketamine response, CBT & mindfulness ? Ketamine and psychoactive effects ¡ Similar to psychedelic effects? ¡ If mystical experiences ⇢ are outcomes better? ¡ If ketamine-induced anxiety ⇢ are positive effects reduced? CBT - Mindfulness training ¡ Acceptance ⇢ Reduces negative reactivity during infusion ¡ Cognitive Flexibility ⇢ Enhances cognitive-behavioral learning ¡ Pain-gate Closure ⇢ Increases in positive & neutral thinking ¡ Mindfulness training ⇢ healing/resilient experiences during & after infusion ¨ N = 30 (n = 10 per arm) ¨ Recruited from St. Michael’s Hospital’s (SMH) chronic pain clinic (Queen St.) ¨ Age: 18 years and older ¨ Moderate-to-severe NeP ¡ Clinical diagnosis ¡ > 3 on the ID Pain questionnaire (1- to - 5 scale) in the 7 days preceding inclusion Exclusions: ¨ ¨ ¨ Pregnancy Psychiatric disorders: ¡ Dissociative and psychotic disorders ¡ Borderline disorder and bipolar disorder ¡ Substance use disorder Poorly managed hypertension or high-risk heartdisease ¨ Severe liver dysfunction ¨ Elevated intracranial or intraocular pressure St. Michael’s Institutional Infusion Protocol ¨ Ketamine hydrochloride ¨ Intravenous doses 1mg/kg over 2 hrs ¨ Weeks 2, 7, and 12 MBCT Protocol ¨ NexJ Connected Wellness ¨ Internet workbooks + Instructional videos ¨ Phone-based mental-health counselling (16 hrs in 16 weeks) ¨ Text messaging support Feasibility Measures 1. Recruitment rate 2. Intervention adherence 3. Patient withdrawal/retention 4. Missing data or loss to follow-up 5. Rate of adverse events 1. Pain intensity ¡ 2. Physical functioning ¡ 3. ¡ ¡ Patient Health Questionnaire-9 (PHQ-9) Generalized Anxiety Disorder 7-item (GAD-7) Pain catastrophizing scale (PCS) Participant perception of global improvement ¡ 5. PROMIS Pain Interference – Short Form v1.1 6a Emotional functioning ¡ 4. PROMIS Numeric Rating Scale v.1.0 – Pain Intensity 1a Patient Global Impression of Change (PGIC) Scale Adverse events ¡ ¡ Monitored per Health Canada regulations Toronto Side Effects Scale Feasibility-related question ¨ Experiences with adherence ¨ Side effects and acceptability Core-domain questions ¨ Experiences related to pain + physical & emotional functioning ¨ Perceptions of Pain improvement/non-improvement ¡ Therapeutic impact ¡ Treatment-related processes ¡ Inductive Probes: Quality of life ¨ Canada’s first KAP trial for NeP ¨ Results will determine feasibility ¨ Clarify mechanisms of change ¨ Addresses Canada’s need for multidisciplinary pain management © 2018 NexJ Health Inc. Confidential and Proprietary. Standard psychiatric care available at CAMH vs. standard-care + online CBT – MM intervention. BDI-2 from baseline to 6 months (95% CI & p-value) N Change CI.low CI.high p-value 20 -15.6 -20.2 -11.1