Journal Article

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

Din, Jenny Min, Joshi, Yash B, Thomas, Michael L, Ing, Kevin, Swerdlow, Neal R, Li, Francesca, Talledo, Jo, Nordberg, Bethany, Light, Gregory A, Molina, Juan L, Sprock, Joyce, Minhas, Jessica

2025

Overview

Abstract 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.

• Publisher: Oxford University Press
• Subject: Adult / Antipsychotic Agents / Central Nervous System Stimulants - administration & dosage / Central Nervous System Stimulants - pharmacology / Chronic Disease / Cognitive Remediation - methods / Combined Modality Therapy / Dextroamphetamine - administration & dosage / Dextroamphetamine - pharmacology / Dopamine Agents - administration & dosage / Dopamine Agents - pharmacology / Double-Blind Method / Female / Humans / Male / Memantine - administration & dosage / Memantine - pharmacology / Middle Aged / Outcome Assessment, Health Care / Psychosis / Psychotic Disorders - drug therapy / Psychotic Disorders - rehabilitation / Psychotic Disorders - therapy / Regular / Schizophrenia - drug therapy / Schizophrenia - rehabilitation / Schizophrenia - therapy / Therapy, Computer-Assisted - methods