IMPORTANCE: Auditory hallucinations (AHs) are a hallmark characteristic of schizophrenia spectrum disorders (SSDs) and are often associated with severe distress. Previous research lacks comprehensive evidence on the overall efficacy of approaches targeting AHs in SSDs.

OBJECTIVE: To evaluate the efficacy and acceptability of all available psychological and psychosocial interventions targeting AHs in SSDs.

DATA SOURCES: Embase, MEDLINE, PsycArticles, PsycInfo, PSYNDEX, and the Cochrane library were searched for eligible studies published until August 18, 2025.

STUDY SELECTION: Randomized clinical trials that analyzed psychological interventions targeting AHs compared to controls in adults with SSDs.

DATA EXTRACTION AND SYNTHESIS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two independent reviewers screened publications, extracted data, and assessed risk of bias. A random-effects meta-analysis was performed (Hedges g).

MAIN OUTCOMES AND MEASURES: The main outcomes were between-group differences in AHs and clinical characteristics at posttreatment and follow-up, measured with validated rating scales. Additional number-needed-to-treat (NNT) analyses and rating of evidence certainty (GRADE approach) were conducted.

RESULTS: A total of 23 studies with 2016 participants were included, with 1081 in the intervention groups across 5 different therapeutic approaches and 935 in the control groups. At posttreatment, targeted interventions reduced the severity of AHs compared with control groups (standardized mean difference [SMD], -0.18; 95% CI, -0.31 to -0.05; P = .007; NNT, 16; GRADE, low evidence). This effect was also observed for numerous secondary outcomes, comprising frequency and distress of AHs, total symptoms, positive symptoms, delusions, depression, and anxiety. Subgroup analysis showed that avatar therapy reduced the severity of AHs with the largest effect size (SMD, -0.37; 95% CI, -0.51 to -0.22; P < .001). Sensitivity analyses indicated robustness of results. Dropout rates and reports on adverse events indicated high tolerability and acceptability of treatments.

CONCLUSION AND RELEVANCE: Although targeted psychological and psychosocial interventions for AHs in SSDs were found to be effective in reducing the severity and other characteristics of AHs, with effect sizes ranging from small to medium, substantial differences were observed between approaches. In particular, avatar therapy seems to be effective at addressing AH symptoms. These findings could influence future studies and clinical care by advancing the development of targeted, novel approaches for AHs that address relevant treatment characteristics.