Randomized Placebo-Controlled Trial of Nabilone for Agitation in Alzheimers Disease.
To investigate the efficacy and safety of nabilone for agitation in patients with moderate-to-severe Alzheimers disease (AD). This 14-week randomized double-blind crossover trial compared nabilone to placebo (6 weeks each) with a 1-week washout between phases. Patients were recruited from a long-term care facility and geriatric psychiatry clinics. Patients had AD (standardized Mini-Mental State Examination sMMSE ≤24) and agitation (Neuropsychiatric Inventory-Nursing Home version NPI-NH-agitationaggression subscore ≥3). Nabilone (target 1-2 mg) versus placebo. The primary outcome was agitation (Cohen Mansfield Agitation Inventory CMAI). Secondary outcomes included NPI-NH total, NPI-NH caregiver distress, cognition (sMMSE and Severe Impairment Battery SIB or Alzheimers Disease Assessment Scale of Cognition), global impression (Clinicians Global Impression of Change CGIC), and adverse events. Thirty-nine patients (mean ± SD age 87 ± 10, sMMSE 6.5 ± 6.8, CMAI 67.9 ± 17.6, NPI-NH total 34.3 ± 15.8, 77% male, nabilone dose 1.6 ± 0.5 mg) were randomized. There were no crossover or treatment-order effects. Using a linear mixed model, treatment differences (95% CI) in CMAI (b -4.0 -6.5 to -1.5, t(30.2) -3.3, p 0.003), NPI-NH total (b -4.6 -7.5 to -1.6, t(32.9) -3.1, p 0.004), NPI-NH caregiver distress (b -1.7 -3.4 to -0.07, t(33.7) -2.1, p 0.041), and sMMSE (b 1.1 0.1-2.0, t(22.6) 2.4, p 0.026) all favored nabilone. However, in those who completed the SIB (n 25) treatment differences favored placebo (b -4.6 -7.3 to -1.8, t(20.7) -4.8, p 0.003). CGIC improvement during nabilone (47%) and placebo (23%) was not significantly different (McNemars test, exact p 0.09). There was more sedation during nabilone (45%) compared to placebo (16%) phases (McNemars test, exact p 0.02), but treatment-limiting sedation was not significantly different (McNemars test, exact p 0.22). Nabilone may be an effective treatment for agitation. However, sedation and cognition should be closely monitored.