Pharmacologic Augmentation of Computerized Auditory Training in Chronic Psychosis: Preliminary Findings From a Single-Site, Double-Blind Study

Background Computerized auditory training (AT) modestly improves symptoms, cognition, and functioning in schizophrenia. We assessed whether d-amphetamine (AMPH) or memantine (MEM) can enhance gains from 30-h of AT. Methods Antipsychotic-medicated individuals with chronic psychosis (n = 68; mean age 47.03y; M:F = 39:29) completed up to 30 AT sessions (2-3/week; n = 50 completed 30 sessions) in 3 groups: “AMPH group” (AMPH (5 mg po) 1-h before each AT session); “MEM group” (titrated to 10 mg MEM bid and maintained that dose throughout training); “PBO group” (PBO dosed identically to either AMPH or MEM). Primary (PANSS total, MCCB Composite, WHODAS) and secondary (PANSS positive, PANSS negative, YMRS, PHQ-9, PSYRATS) outcome measures were acquired at baseline, after 10, 20, and 30 AT sessions, and 12 weeks post-training. Pill identity (active/PBO) was blind to subjects and staff. Results Marginally significant between-group gains for AMPH vs PBO were detected for one of three primary outcomes (WHODAS, P =.050; but not PANSS total or MCCB Composite), and for 3 of 5 secondary clinical outcomes (PANSS positive, YMRS, PSYRATS, P’s≤.027–.049). Within-subject gains over time were detected for primary and secondary clinical measures for AMPH (P’s≤.014–.004) and MEM (P’s≤.02–.001) groups; some of these would not survive conservative correction for multiple comparisons. No measures detected symptom worsening; treatment satisfaction exceeded subjects’ expectations. Conclusions Results are mixed; drug-associated gains in several measures vs PBO suggest that these regimens may augment AT-induced functional and clinical improvement in psychosis patients, independent of changes in neurocognition. Assessment in larger samples seems warranted.