On The Move
Discontinuation of Antipsychotic Treatment Poses Significant Risk of Relapse in Alzheimer’s Patients with Psychosis or Agitation
Oct 23, 2012
CHARLESTON, SC - October 23, 2012 - Discontinuing antipsychotic treatment is associated with a high risk for relapse in Alzheimer’s disease patients with psychosis and agitation or aggression, according to a new study in the October 18th issue of the New England Journal of Medicine. The study was led by D.P. Devanand, M.D. and co-authored by MUSC Alzheimer’s Research Program’s Principal Investigator, Jacobo Mintzer, M.D. The study shows that after clinical response to the antipsychotic medication risperidone, there was an increased risk of recurrence (relapse) of patients’ problematic symptoms of psychosis and agitation or aggression after risperidone was discontinued in patients who had maintained improvement for four to eight months.
These findings are significant, because current federal regulations strongly urge nursing homes to discontinue antipsychotic medications three to six months after initiating treatment. And until now, evidence from controlled studies in support of these long-standing regulations has been very limited.
Approximately 5.4 million Americans suffer from Alzheimer’s disease, and during the course of the illness a large proportion develop psychosis and agitation or aggression. These symptoms are associated with distress on the patient, an increased burden on the caregiver, a more rapid decline, and increased healthcare costs. Additionally, these symptoms become difficult to manage at home and often lead to nursing home admission and increased risk of dying from the disease.
This antipsychotic treatment study was conducted across eight U.S. centers to evaluate the risk of recurrence of symptoms after discontinuation of the antipsychotic medication risperidone in outpatients and nursing home patients with Alzheimer’s disease whose symptoms of psychosis and agitation or aggression had initially responded to treatment with risperidone. The study recruited 180 patients ranging in age from 50 to 95 years from memory clinics and nursing homes, as well as from Veterans Affairs medical centers and physicians’ offices. All the patients received risperidone for 16 weeks in the first phase of the study. In the second phase, 110 patients who had responded positively to risperidone were randomly assigned in a double-blind fashion (neither the patient nor the doctor knew if the treatment was risperidone or placebo) to one of three treatment groups: (1) continued treatment with risperidone for 32 weeks, (2) risperidone for 16 weeks followed by placebo for 16 weeks or (3) placebo for 32 weeks.
In the first 16 weeks after treatment with risperidone, those patients that switched from risperidone to placebo showed nearly double the risk of relapse compared to those who continued risperidone (60% versus 33%). In the second 16 weeks after treatment with risperidone, 48% of patients who were switched from risperidone to placebo relapsed, compared to 15% of those who continued risperidone. Importantly, serious adverse events did not differ significantly among the groups.
Dr. Mintzer notes that, “An independent analysis of all available data, has linked the use of antipsychotics to an increased risk of death which is approximately 1.6 times greater when compared to placebo. Because of these findings, the FDA imposed a black-box warning on these compounds several years ago. This regulation encourages clinicians to limit the use of typical antipsychotics for the treatment of demented patients. Even when these treatments are provided, clinicians are encouraged to discontinue use after a few months of exposure,” said Dr. Mintzer. “However, our recent research findings provide new scientific evidence of the value of this compound for a selected group of patients that show positive response to treatment. Further, these findings should help to inform regulators and scientists on how to better provide ongoing care to patients suffering from this devastating disease.”
Janssen Pharmaceuticals provided the active drug medication as well as placebo for this research study but was otherwise uninvolved in the research. Funding for the study was provided by the National Institutes of Health and the Department of Veterans Affairs.