Strategies for Optimizing Antiepileptic Drug Therapy in Elderly People

Thomas E. Lackner, Pharm.D., FASCP


Pharmacotherapy. 2002;22(3) 

In This Article

Agitation and Aggression of Dementia

Although not FDA approved, evidence from a few controlled studies and several open studies, retrospective analyses, and case reports suggests that valproate, carbamazepine, and possibly other AEDs may diminish symptoms of agitation and aggressive behavior in elderly patients with dementia ( Table 7 ).[108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136] These are appealing options since many elderly patients do not improve adequately or experience intolerable adverse effects with traditional therapy with antipsychotic drugs (e.g., tardive dyskinesia) and benzodiazepines (e.g., falls, fractures).[137,138]

Short-term studies and several case reports suggest that carbamazepine, alone and in combination with other psychotropic agents, may be effective in decreasing agitation in elderly patients with dementia as first-line therapy or in those refractory to neuroleptic agents.[120,121,122,123,124,125,126,127,128,129,130] The pooled results of these studies indicate that carbamazepine decreases agitated behavior in approximately 31% more patients than placebo, similar to antipsychotic agents.[137,138] Decreased agitation generally is achieved with mean carbamazepine SDCs of 5-8 µg/ml, albeit some patients required SDCs up to 12 µg/ml. The dosage associated with good control approxi-mates 300-600 mg/day but up to 1000 mg/day (divided doses) may be necessary.[120,121,122,123,124,125,126,127,128,129,130]

Valproate appears to be effective in decreasing agitation associated with dementia in elderly people when given alone and in combination with antipsychotic agents.[108,109,110,111,112,113,114,115,116,117,118,119] Like carbama-zepine, the optimal dosage and concentration of valproate for alleviating agitation and aggression are not established. Efficacy rates approximate 50% when valproate is given alone and 70% when combined with an antipsychotic agent.[108,109,110,111,112,113,114,115,116,117,118,119] The starting dosage is 125 mg twice/day and increased by increments of 125 mg once or twice/day every 3-7 days depending on aggression severity and patient tolerance. The usual effective maintenance dosage approximates 375-1000 mg/day or a valproate SDC of 45-90 µg/ml.

Symptoms that most often improve with valproate and carbamazepine are physical aggression and restlessness; verbally aggressive behavior and psychosis are less responsive or unresponsive.[111,130] The response rate with valproate appears to be somewhat greater than that reported with carbamazepine; however, no controlled studies directly compared the agents. Some patients respond to SDCs far below the usual concentration range for seizures for either drug, and others require higher concentrations. Therefore, gradual valproate dosage escalation from the lowest recommended level is recom-mended. Both AEDs appear to provide benefit to some patients with agitation, but valproate may be somewhat more effective than carbamazepine and has a lower risk of ataxia and confusion, fewer significant drug-drug interactions, and a more convenient dosing schedule. Preliminary information suggests that other AEDs such as gabapentin and zonisamide may be effective in treating agitated behavior[131,132,133,134,135,136]; however, controlled studies are lacking.