Geke A H van den Elsen1, Amir I A Ahmed2, Robbert-Jan Verkes3, Ton Feuth4, Marjolein A van der Marck5, Marcel G M Olde Rikkert5. 1. Radboud Alzheimer Centre and Department of Geriatric Medicine, Radboud university medical center, Nijmegen, the Netherlands. Electronic address: Geke.vandenElsen@radboudumc.nl. 2. Radboud Alzheimer Centre and Department of Geriatric Medicine, Radboud university medical center, Nijmegen, the Netherlands; Department of Pharmacology and Toxicology, Radboud university medical center, Nijmegen, the Netherlands; Department of Elderly, Vincent van Gogh Institute, Venray, the Netherlands. 3. Department of Psychiatry, Radboud university medical center, Nijmegen, the Netherlands. 4. Department for Health Evidence, Radboud university medical center, Nijmegen, the Netherlands. 5. Radboud Alzheimer Centre and Department of Geriatric Medicine, Radboud university medical center, Nijmegen, the Netherlands.
Abstract
OBJECTIVES:Neuropsychiatric symptoms (NPS) are highly prevalent in dementia, but effective pharmacotherapy without important side effects is lacking. This study aims to assess the efficacy and safety of oral tetrahydrocannabinol (THC) in the treatment of NPS in dementia. DESIGN: Randomized, double-blind, placebo-controlled, repeated crossover trial, consisting of six treatment blocks of 2 weeks each. SETTING:Two hospital sites in The Netherlands, September 2011 to December 2013. PARTICIPANTS: Patients with dementia and clinically relevant NPS. INTERVENTION: Within each block THC (0.75 mg twice daily in blocks 1-3 and 1.5 mg twice daily in blocks 4-6) and placebo were administered in random order for 3 consecutive days, followed by a 4-day washout. MEASUREMENTS: Primary outcome was change in Neuropsychiatric Inventory (NPI) score. Analyses were performed intention-to-treat. Data from all subjects were used without imputation. Sample size required for a power of 80% was 20 patients, because of repeated crossover. RESULTS:22 patients (15 men, mean age 76.4 [5.3] years) were included, of whom 20 (91%) completed the trial. THC did not reduce NPI compared to placebo (blocks 1-3: 1.8, 97.5% CI: -2.1 to 5.8; blocks 4-6: -2.8, 97.5% CI: -7.4 to 1.8). THC was well tolerated, as assessed by adverse event monitoring, vital signs, and mobility. The incidence of adverse events was similar between treatment groups. Four non-related serious adverse events occurred. CONCLUSIONS: This is the largest randomized controlled trial studying the efficacy of THC for NPS, to date. Oral THC did not reduce NPS in dementia, but was well tolerated by these vulnerable patients, supporting future higher dosing studies.
RCT Entities:
OBJECTIVES:Neuropsychiatric symptoms (NPS) are highly prevalent in dementia, but effective pharmacotherapy without important side effects is lacking. This study aims to assess the efficacy and safety of oral tetrahydrocannabinol (THC) in the treatment of NPS in dementia. DESIGN: Randomized, double-blind, placebo-controlled, repeated crossover trial, consisting of six treatment blocks of 2 weeks each. SETTING: Two hospital sites in The Netherlands, September 2011 to December 2013. PARTICIPANTS: Patients with dementia and clinically relevant NPS. INTERVENTION: Within each block THC (0.75 mg twice daily in blocks 1-3 and 1.5 mg twice daily in blocks 4-6) and placebo were administered in random order for 3 consecutive days, followed by a 4-day washout. MEASUREMENTS: Primary outcome was change in Neuropsychiatric Inventory (NPI) score. Analyses were performed intention-to-treat. Data from all subjects were used without imputation. Sample size required for a power of 80% was 20 patients, because of repeated crossover. RESULTS: 22 patients (15 men, mean age 76.4 [5.3] years) were included, of whom 20 (91%) completed the trial. THC did not reduce NPI compared to placebo (blocks 1-3: 1.8, 97.5% CI: -2.1 to 5.8; blocks 4-6: -2.8, 97.5% CI: -7.4 to 1.8). THC was well tolerated, as assessed by adverse event monitoring, vital signs, and mobility. The incidence of adverse events was similar between treatment groups. Four non-related serious adverse events occurred. CONCLUSIONS: This is the largest randomized controlled trial studying the efficacy of THC for NPS, to date. Oral THC did not reduce NPS in dementia, but was well tolerated by these vulnerable patients, supporting future higher dosing studies.
Authors: Stuart M Brierley; Beverley Greenwood-Van Meerveld; Giovanni Sarnelli; Keith A Sharkey; Martin Storr; Jan Tack Journal: Nat Rev Gastroenterol Hepatol Date: 2022-09-27 Impact factor: 73.082
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