Peer to Peer Behavioral Activation for Elderly Depressed Senior Center Clients

Abstract

Change (PGI-C), Quality of Life-Alzheimer’s disease (QOL-AD), ADCS-Activities of Daily Living (ADL), Caregiver Strain Index (CSI), MMSE, and Cornell Scale for Depression in Dementia (CSDD). Standard safety and tolerability outcomes were assessed. Stage 1 and stage 2 results were also analyzed separately. Results: 220 patients were enrolled and 194 (88%) completed the study. In stage 1, 218 patients were included in the modified intent-to-treat (mITT) efficacy population [AVP-923 (n1⁄493); placebo (n1⁄4125)]. In stage 2, 202 patients comprised the mITT: 83 patients from the stage 1 AVP-923 group continued on AVP-923; 89 placebo nonresponders were re-randomized [AVP-923 (n1⁄444); placebo (n1⁄445)], and 30 placebo responders were re-randomized [AVP-923 (n1⁄415); placebo (n1⁄415)]. The primary endpoint was significant for AVP-923 vs placebo (P 0.001). The mean (SD) baseline NPI agitation/aggression domain scores were 7.1 (2.6) for AVP-923 vs. 7.0 (2.4) for placebo, and showed significant improvement for AVP-923 vs placebo both at week 5 (stage 1, mean [SD] change from baseline -3.3 [2.98] vs -1.7 [3.10]; (P 0.001) and at week 10 (stage 2, mean [SD] change from baseline -2.0 [3.19] vs -0.8 [3.59]; P1⁄40.02). ADCS-CGIC agitation improved significantly with AVP-923 vs placebo on the primary analysis (P 0.001), as did PGI-C. Significant improvement for AVP-923 vs. placebo was also seen for secondary endpoints including: NPI total score, NPI-4D, NPI-4A, NPI Caregiver Distress Score, CSDD, and CSI. Treatment-emergent adverse events (TEAEs) occurred in 61.2% of patients taking AVP-923 and 43.3% of patients taking placebo and were considered to be at least possibly related to treatment in 16.4% and 10.2%, respectively. Adverse events led to discontinuation in 5.3% on AVP-923 and 3.1% on placebo. Serious AEs (SAEs) occurred in 7.9% and 4.7% of patients, respectively; no SAEs were considered treatment-related. No deaths occurred during the study. Falls were reported as an AE in 8.6% of patients on AVP-923 and 3.9% on placebo; however, history of falls was more common in the AVP-923 group at baseline (20.4% vs. 12.8%). Other AEs occurring in 5% of patients were diarrhea 5.9% vs. 3.1%, and urinary tract infection 5.3% vs. 3.9%. Conclusions: AVP-923 (dextromethorphan/quinidine) was associated with significant improvement in agitation in patients with AD as seen on the primary, and on the majority of secondary endpoints. These improvements were deemed clinically meaningful by patients/caregivers and physicians (as assessed by PGI-C and ADCS-CGIC ratings), and were associated with reduction in caregiver burden. AVP-923 was generally well tolerated over this 10 week trial.