A randomized, double-blind study has examined the risk of relapse in AD patients with psychosis or agitation/aggression when the atypical antipsychotic risperidone was withdrawn (Devanand et al. N Engl J Med 2012;367:1497-1507).

Subjects received open-label risperidone (mean dose 0.97 mg/day) for 16 weeks. During the open-label phase, the response rate was 62%. A total of 110 responders were then randomized to continue risperidone for an additional 32 weeks, risperidone for 16 weeks followed by placebo for 16 weeks, or placebo for 32 weeks.

In the first 16 weeks, the relapse rate was significantly higher in the group receiving placebo compared to risperidone (60% vs. 33%, hazard ratio 1.94). Similarly, during the second 16-week period, a higher proportion of patients switched to placebo experienced a relapse compared to those continuing on active treatment (48% vs. 15%, HR 4.88).

Comment
Dr. Yves Bacher: Antipsychotics has serious side effects and limited efficacy in managing psychosis, agitation and aggressivity in patients suffering from dementia. It is suggested to remove these medications as soon as possible and many patients on long-term antipsychotics has been discontinued without any problem (Thapa et al. J Am Geriatr Soc 1994;42:280-286). The main interest of this study is despite limited clinical efficacy and tolerability, when the medication is effective  and stopped after a treatment duration of 16 or 32 weeks, the relapse rate was significantly higher than if the medication was continued.

We should be careful when risperidone is titrated or discontinued and should follow carefully any reappearance of behavioural or psychological symptoms of dementia.