Magnitude and Abstinence Trajectories of Neurocognitive Deficits in Methamphetamine Use Disorder: A Systematic Review and Meta-analysis.

Abstract

The magnitude and clinical profile of cognitive deficits in methamphetamine use disorder (MUD) remain debated. Prior syntheses treated same-sample cognitive outcomes as independent and did not model continuous abstinence-cognition associations. This multilevel meta-analysis quantified deficits across 13 cognitive domains, evaluated moderation by comorbidity and sex, and tested remission trajectories across abstinence. We synthesized 242 effect sizes from 68 independent studies (n=9045; 5244 MUD, 3801 controls) using three-level robust-variance models. Restricted cubic spline meta-regression modeled abstinence associations in 7 eligible domains. MUD showed a medium-to-large overall deficit (g=-0.68, 95% CI [-0.77, -0.58], P<0.001) across all 13 domains (g range: -0.42 to -1.09). Comorbidity did not moderate impairment (P=0.26). A higher male proportion predicted attenuated deficits in adjusted meta-regression (β=0.518, P=0.03). Primary spline models showed no remission in inhibitory control or self-reported impulsivity (all P>0.40) within abstinence windows up to 280 days. Among 5 exploratory domains, 4 replicated this flat trajectory, while only decision-making showed a nonlinear trajectory in analyses not adjusted for multiple comparisons. No publication bias was detected (Egger P=0.32). GRADE certainty was very low across all domains, reflecting cross-sectional study designs. Cognitive deficits in MUD are pervasive, stable across the observed abstinence window, and unmoderated by comorbidity profile. The potential sex vulnerability signal and the uncorrected decision-making remission trajectory warrant prospective confirmation. Routine cognitive assessment should be initiated during early treatment.