Randomized Placebo-Controlled Trial of Nabilone for Agitation in Alzheimer's Disease
Herrmann et al.·The American Journal of Geriatric PsychiatryImpact 1.1
GemischtGRADEModerat164 Zitate
Stichproben = 39 Pat.
Dauer14 Wochen
KontrollePlacebo über 6 Wochen
EndpunktCMAI
Verblindungdoppelblind
DesignRCT
Cannabinoidthc
Max. Dosis2.0 mg
Applikationoral
”Kernaussage
Nabilone zeigte signifikante Verbesserung bei Agitation (CMAI) und Neuropsychiatrischen Symptomen, aber Verschlechterung in einem Kognitions-Test (SIB) und erhöhte Sedation.
Zusammenfassung
n=39 Alzheimer-Patienten (mittelschwer bis schwer, sMMSE=6.5±6.8) mit Agitation, randomisierte Crossover-Studie Nabilon (1–2 mg) vs. Placebo über je 6 Wochen. Signifikante Reduktion CMAI (b=-4.0, 95% CI -6.5 bis -1.5, p=0.003), NPI-NH total (b=-4.6, p=0.004), Caregiver-Distress (b=-1.7, p=0.041); sMMSE-Verbesserung (b=1.1, p=0.026), jedoch SIB-Verschlechterung bei Completers (b=-4.6, p=0.003). Sedierung häufiger unter Nabilon (45% vs. 16%, p=0.02).
P
PopulationErwachsene mit moderater bis schwerer Alzheimer-Demenz und Agitation (NPI-NH Agitation/Aggression ≥3, sMMSE ≤24), Langzeitpflegeeinrichtung und geriatrisch-psychiatrische Klinik, n=39, mittleres Alter 87 Jahre
KontrollePlacebo über 6 Wochen (Crossover mit 1-wöchiger Auswaschphase)
O
OutcomeAgitation (CMAI) signifikant reduziert unter Nabilone vs. Placebo (b=−4,0; 95%-KI −6,5 bis −1,5; p=0,003); NPI-NH Gesamt (p=0,004) und Caregiver-Distress (p=0,041) ebenfalls zugunsten Nabilone; sMMSE zugunsten Nabilone (p=0,026); SIB-Kognition bei n=25 jedoch zugunsten Placebo (p=0,003); mehr Sedierung unter Nabilone (45% vs. 16%, p=0,02)
Vertrauen in die Evidenz
Sehr niedrigNiedrigModeratHoch
Moderat
Dritte von vier GRADE-Stufen, die Effektschätzung ist wahrscheinlich verlässlich.
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.