Antipsychotic medications have been shown to be efficacious in the treatment of patients with Alzheimer s disease who have psychotic symptoms or behavioral dyscontrol (called behavioral complications here). However, these medications have a variety of short and long-term side effects. Although their prolonged effects in AD patients are not established, Federal (OBRA) regulations have mandated periodic discontinuation of antipsychotic medications in nursing homes. Surprisingly, there is little empirical evidence to support or refute this approach in nursing homes or in outpatients. In an NIMH-funded study (R01 MH55735) at the NYSPl/Columbia site, AD outpatients with behavioral complications receive open treatment with haloperidol for 20 weeks. Responders are randomized, double-blind, to continuation haloperidol or placebo. Patients on placebo have shown a significantly higher relapse rate (80%) than patients who continue on haloperidol (44.4% relapse in intent-to-treat analyses, and 22.2% relapse using a restricted definition of relapse). The study's limitations are the small number of subjects (19 responders randomized) and the use of haloperidol, a conventional antipsychotic that commonly causes extra pyramidal signs (EPS), and is associated with a high risk of tardive dyskinesia (TD) with prolonged use. The proposed multicenter study (four academic sites; nursing homes and outpatients) will address these limitations by studying a relatively large number of AD patients using an atypical antipsychotic, risperidone, which has less neurological side effects than haloperidol. Other reasons for studying extended treatment with an atypical antipsychotic include the risk of medication toxicity and the expense of taking these medications. The study design has two phases. In Phase 1, 200 AD patients with behavioral complications will receive open treatment with risperidone for 16 weeks. Responders will be randomized, double-blind, to one of three arms in Phase 2:(1) continuation risperidone for the next 32 weeks, (2) risperidone for the next 16 weeks followed by placebo for 16 weeks, or (3) placebo for the next 32 weeks. We hypothesize that in Phase 2, during the first 16 weeks, the time to relapse will be significantly shorter on placebo than on risperidone, and that the relapse rate on placebo will be significantly greater than the relapse rate on risperidone. This design will provide useful data on the efficacy and side effects of longer-term treatment with risperidone, and provide critical information about the likelihood and time to relapse, as well as predictors of relapse, in patients switched from risperidone to placebo. This information is essential to guide the clinician toward optimal use of such medications in one of the most challenging types of patients: the AD patient with psychosis or behavioral dyscontrol. The results will be of considerable value to the practicing clinician and have substantial implications for the regulatory oversight of elder care.
| Patel, Anjali N; Lee, Seonjoo; Andrews, Howard F et al. (2017) Prediction of Relapse After Discontinuation of Antipsychotic Treatment in Alzheimer's Disease: The Role of Hallucinations. Am J Psychiatry 174:362-369 |
| Devanand, D P; Mintzer, Jacobo; Schultz, Susan K et al. (2012) Relapse risk after discontinuation of risperidone in Alzheimer's disease. N Engl J Med 367:1497-507 |
| Devanand, D P; Mintzer, Jacobo; Schultz, Susan et al. (2012) The antipsychotic discontinuation in Alzheimer disease trial: clinical rationale and study design. Am J Geriatr Psychiatry 20:362-73 |
