Which drugs are best when aggressive Alzheimer’s patients need medication?

When compared with placebo, 480 mg daily of sodium valproate for 8 weeks showed no differences in controlling aggressive behavior.¹¹ In an open-label follow-up study, aggressive behavior improved from 10.52 on the Social Dysfunction and Aggression Scale to 6.31 (P<.001), but no improvement was observed using the Clinical Global Impression Scale for aggressive behavior. Seven deaths that authors couldn’t attribute to the drug occurred. Three patients experienced drowsiness. No other adverse events were noted.¹²

A very small, double-blind crossover RCT (N=14) evaluated 250 to 1500 mg sodium valproate daily for 6 weeks compared with placebo. A 2-week period separated the valproate and placebo regimens. Neuropsychiatric Inventory agitation and aggression scores worsened significantly with valproate (increase of 1.43 points compared with a decrease of 2.08 points with placebo; P=.04). Adverse events related to valproate included falls, sedation, loss of appetite, thrombocytopenia, and loose stools (NNH=3).¹³

Recommendations

The Expert Consensus Guideline for the Treatment of Agitation in Older Persons with Dementia¹⁴ and treatment guidelines for Alzheimer’s disease and other dementias from the American Psychiatric Association (APA)¹⁵ offer different recommendations for first-line treatment.

The Expert Consensus Guideline recommends divalproate, risperidone, and conventional high-potency antipsychotics for patients with severe anger and physical aggression. Alternative treatments include olanzapine, carbamazepine, trazodone, and SSRIs.¹⁴

The APA recommends antipsychotics to treat agitation based on available evidence. If treatment fails, consider anticonvulsants, lithium, or beta-blockers. The APA notes that although evidence for SSRIs is limited, they may be appropriate for agitated nonpsychotic patients.¹⁵