A placebo-controlled trial of valproate for agitation and aggression in Alzheimer's disease.
OBJECTIVE
To assess the efficacy and tolerability of valproate for the treatment of agitation and aggression in moderate-to-severe Alzheimer's disease (AD).


METHODS
This was a randomized, double-blind, placebo-controlled crossover trial of valproate in institutionalized AD patients. Patients were assessed with the Neuropsychiatric Inventory (NPI) and Cohen-Mansfield Agitation Inventory at baseline and after 6 weeks of treatment with valproate and placebo, with 2 weeks between phases to allow for placebo washout and tapering.


RESULTS
Fourteen patients (8 male/6 female) aged 85.6 +/- 4.5 years with baseline Mini Mental State Examination scores of 4.5 +/- 4.6 and NPI agitation/aggression scores of 6.4 +/- 3.5 were randomized to treatment. NPI agitation/aggression treatment change scores significantly worsened during valproate treatment compared with placebo (Z = -2.03, p = 0.04). Tolerability of valproate was also poor, with patients experiencing a significantly greater mean number of adverse events during valproate therapy compared to placebo (Z = -2.82, p = 0.005).


CONCLUSIONS
Valproate is not effective for the management of agitation in moderate-to-severe AD, and may be poorly tolerated in this population.
Herrmann
Nathan
N
Neuropharmacology Research Program, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. nathan.herrmann@sunnybrook.ca
Lanctôt
Krista L
KL
Rothenburg
Lana S
LS
Eryavec
Goran
G
D000368:Aged; D000369:Aged, 80 and over; D000374:Aggression / Q000523:psychology*; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000534:rehabilitation*; D000927:Anticonvulsants / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007326:Institutionalization; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011595:Psychomotor Agitation / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D012720:Severity of Illness Index; D014635:Valproic Acid / Q000627:therapeutic use*
D000927:Anticonvulsants; D014635:Valproic Acid