Authors: Paul Parcon, M.D., Ph.D.; C. Heath Gauss, M.S.; Kalpana Padala, M.D.; Prasad Padala, M.D.
Abstract
Background: Apathy in Alzheimer’s disease (AD) is increasingly being recognized as a separate and distinct clinical syndrome from depression and has an out-sized effect on caregiver burden and quality of life. Evidence shows methylphenidate is an effective treatment for this condition, but fears regarding cardiovascular effects of methylphenidate (MPH) in the elderly have limited its widespread use. This project sought to assess the differences in EKG time variables and interpretation collected from an RCT for apathy in mild AD, comparing methylphenidate to placebo.
Methods: We used data from cohort of 59 community-dwelling patients with mild AD (30 from MPH arm, 29 from placebo arm) obtained from a randomized controlled trial. EKG data collected at baseline, 4 weeks, and 12 weeks was analyzed for changes from baseline for PR interval, QRS interval, and QT/QTc interval via repeated measures mixed model analyses of covariance. The predictor variables in each model were arm, time, the interaction between arm and time, and the baseline value of the EKG time variable of interest. The two arms were compared with respect to changes from baseline to 4 weeks and to 12 weeks using model-based t tests. Also, EKG interpretations were assessed in the analyses.
Results: No statistical difference was found between the two arms regarding changes from baseline to 4 weeks for any of the EKG time intervals considered. For changes from baseline to 12 weeks, no statistical difference was found except for P (+11.7 MPH vs. placebo, p=0.0492) and T (+15.4, p=0.0437). Although no cardiovascular adverse events were reported by patients, in terms of the changes in EKG interpretations, 3 patients in the MPH arm showed EKG changes, while 7 were seen in the placebo arm. Two patients in the MPH arm demonstrated new septal infarcts, and one showed QT prolongation at 4 weeks (but not at 12 weeks). Of the 7 changes in the placebo arm, there was one new inferior infarct, 2 new LBBBs, one new RBBB, and one possible anterior infarct. Also in the placebo arm, there was one change from possible infarct to confirmed, and one instance of QT Prolongation at 4 weeks (but not at 12 weeks).
Conclusions: Our results demonstrate that over the trial period, no statistical difference was found in the EKG time intervals of patients randomized either to MPH or placebo group. Further, the changes in the EKG interpretations favored the MPH over the placebo group. These results may bolster the data on safety of MPH in apathetic elders, and hopefully will lead to more widespread use.
Conference/Symposium/Course name, dates and location where the work was supposed to be presented:
American Association for Geriatric Psychiatry
March 14-16
San Antonio, TX