P4-404: Safety, tolerability & clinical impression of high dose rivastigmine treatment for patients with Alzheimer’s disease

Abstract

To investigate the safety, tolerability and clinical impression of high dose rivastigmine treatment for Alzheimer's disease (AD) patients. Patients receiving 12 mg/day of rivastigmine were included in the study. All met the DSM–IV and NINCDS–ADRDA criteria for possible AD. Enrolled patients were treated with 12 mg/day of rivastigmine for at least three months prior to study participation. Enrolled patients had no documented adverse events during previous treatment. Prior to study participation, all patients showed a subjective cognitive decline as described by caregivers. Folstein Mini Mental Status Examination (MMSE) scores further supported cognitive decline. Those with renal or hepatic disease were excluded from the study. At baseline, each patient was treated with rivastigmine 6 mg, 30 minutes after breakfast & dinner. An additional 1.5 mg was added after lunch. If no reported adverse events, dose was increased by 1.5 mg monthly, to a maximum of 6 mg after lunch. Patients were expected to reach 6 mg of rivastigmine 3 times daily, 30 minutes post meals, after a 4–month titration period. If a patient was unable to tolerate titration pattern, the dose was reduced to the previous tolerated level. Another titration was attempted after 4 weeks. Caregiver impressions and MMSE scores were obtained as part of the facility's routine for subsequent office visits. Thirty–nine patients were evaluated. Average length of previous treatment with rivastigmine 12 mg/day was 4.2 months. Average age was 83.8 & average baseline MMSE was 19.4 (range 13–24). Nine patients reached maximum doses of 15 & 16.5 mg/day due to poor compliance in office visits & availability of medication. Thirty patients reached the target dose of 18 mg/day. No adverse events were reported. Average MMSE for those who reached maximum dose and completed four months of treatment was 22.2 (range 14–27). Caregivers reported no cognitive deterioration. High dose rivastigmine at 18 mg/day, in 3 divided doses, was well tolerated in AD patients previously taking 12 mg/day, with no adverse events for at least 3 months. Cognitive benefits were documented by MMSE scores and subjective caregiver feedback.