Randomized Placebo-Controlled Trial of Nabilone for Agitation in Alzheimer's Disease
Herrmann et al.·The American Journal of Geriatric PsychiatryImpact 1.1
MixedGRADEModerate164 citations
Samplen = 39 Pat.
Duration14 weeks
ControlPlacebo over 6 weeks
EndpointCMAI
Blindingdoppelblind
DesignRCT
Cannabinoidthc
Max. dose2.0 mg
Routeoral
”Key finding
Nabilone showed significant improvement in agitation (CMAI) and neuropsychiatric symptoms, but worsening in one cognition test (SIB) and increased sedation.
Summary
n=39 Alzheimer's patients (moderate to severe, sMMSE=6.5±6.8) with agitation, randomized crossover study nabilone (1–2 mg) vs. placebo over 6 weeks each. Significant reduction in CMAI (b=-4.0, 95% CI -6.5 to -1.5, p=0.003), NPI-NH total (b=-4.6, p=0.004), caregiver distress (b=-1.7, p=0.041); sMMSE improvement (b=1.1, p=0.026), however SIB worsening in completers (b=-4.6, p=0.003). Sedation more frequent under nabilone (45% vs. 16%, p=0.02).
P
PopulationAdults with moderate to severe Alzheimer's dementia and agitation (NPI-NH Agitation/Aggression ≥3, sMMSE ≤24), long-term care facility and geriatric-psychiatric clinic, n=39, mean age 87 years
I
InterventionNabilone (target dose 1–2 mg oral, mean dose 1,6 mg) over 6 weeks
C
ControlPlacebo over 6 weeks (crossover with 1-week washout phase)
O
OutcomeAgitation (CMAI) significantly reduced under nabilone vs. placebo (b=−4,0; 95% CI −6,5 to −1,5; p=0,003); NPI-NH total (p=0,004) and caregiver distress (p=0,041) also favored nabilone; sMMSE favored nabilone (p=0,026); SIB cognition in n=25 however favored placebo (p=0,003); more sedation under nabilone (45% vs. 16%, p=0,02)
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
Objective: To investigate the efficacy and safety of nabilone for agitation in patients with moderate-to-severe Alzheimer's disease (AD).
Design: This 14-week randomized double-blind crossover trial compared nabilone to placebo (6 weeks each) with a 1-week washout between phases.
Setting: Patients were recruited from a long-term care facility and geriatric psychiatry clinics.
Participants: Patients had AD (standardized Mini-Mental State Examination [sMMSE </=24]) and agitation (Neuropsychiatric Inventory-Nursing Home version [NPI-NH]-agitation/aggression subscore >/=3).
Intervention: Nabilone (target 1-2 mg) versus placebo.
Measurements: 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 Alzheimer's Disease Assessment Scale of Cognition), global impression (Clinician's Global Impression of Change [CGIC]), and adverse events.
Results: 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 (McNemar's test, exact p = 0.09). There was more sedation during nabilone (45%) compared to placebo (16%) phases (McNemar's test, exact p = 0.02), but treatment-limiting sedation was not significantly different (McNemar's test, exact p = 0.22).
Conclusions: Nabilone may be an effective treatment for agitation. However, sedation and cognition should be closely monitored.