["Addiction, Volume 121, Issue 6, Page 1483-1494, June 2026. ", "\nAbstract\n\nBackground and aims\nMethamphetamine use disorder (MUD) is a major public health concern, often complicated by co‐occurring psychological distress (PD). Evidence suggests gender differences in both the prevalence of PD and its impact on treatment outcomes. This study examined impacts of PD on MUD treatment outcomes, focusing on gender differences.\n\n\nDesign\nSecondary analysis of pooled data from five randomized controlled trials of pharmacotherapy for MUD available on the NIDA DataShare site (accessed 19 October 2024). Individual participant data meta‐analysis methods were used, adjusting for sociodemographic factors and accounting for heterogeneity across trials. Regression analyses were conducted for total sample and stratified by gender.\n\n\nSetting\nTreatment facilities in the US.\n\n\nParticipants\nAdults seeking MUD treatment (n = 866).\n\n\nMeasurements\nPD was assessed using the Addiction Severity Index psychiatric domain (≥24.6 cutoff). Outcomes included reductions in methamphetamine use and positive urine tests for methamphetamine and other drugs.\n\n\nFindings\nPD was found in 39.9% of participants. PD was more common among women than men [odds ratio (OR) = 1.56, 95% confidence interval (CI) = 1.15–2.12], and among individuals who were younger (ages 35–45 vs. <35: OR = 0.72, 95% CI = 0.61–0.85; >45 vs. < 35: OR = 0.62, 95% CI = 0.44–0.88), had lower education (OR = 1.38, 95% CI = 1.16–1.65), chronic medical conditions (OR = 1.60, 95% CI = 1.16–2.20), history of injection drug use (OR = 1.47, 95% CI = 1.13–1.91) and prior treatment for alcohol use disorder (OR = 2.52, 95% CI = 1.64–3.84). PD was associated with lower odds of reduced use [adjusted OR (aOR) = 0.74, 95% CI = 0.66–0.82] and higher odds of positive methamphetamine urine tests (aOR = 1.27, 95% CI = 1.08–1.49). Stratified analyses revealed a stronger association among women between PD and lower odds of reduced use (aOR = 0.41, 95% CI = 0.23–0.75) and higher odds of positive urine tests for methamphetamine (aOR = 2.18, 95% CI = 1.25–3.81) and other drugs (aOR = 3.16, 95% CI = 1.53–6.47), whereas men showed no statistically significant impact of PD on treatment outcomes. A statistically significant interaction between treatment, gender and PD (P < 0.001) indicated that women without PD benefited more from treatment than those with PD, a pattern not mirrored in men.\n\n\nConclusion\nPsychological distress appears to negatively impact outcomes for MUD and the effects of MUD treatment, particularly among women. Integrated psychological interventions, tailored by gender, may enhance treatment efficacy for individuals with co‐occurring MUD and psychological distress.\n\n"]