The role of Iowa gambling task performance in response to citalopram treatment for cocaine use disorder.

Abstract

Background: Cocaine use disorder (CUD) is associated with executive functioning impairments linked to serotonergic function. Previous studies reported efficacy with the selective serotonin reuptake inhibitor citalopram in reducing cocaine use.Objectives: The current study explored moderation and mediation of citalopram effects on cocaine use by performance across executive function domains.Methods: We conducted a secondary analysis of a double-blind, placebo-controlled, randomized Bayesian adaptive trial investigating citalopram efficacy in CUD treatment-seeking adults. At baseline and mid-treatment, participants completed assessments of decision-making (Iowa Gambling Task; IGT), attention, response inhibition, and cognitive flexibility. Outcomes were longest duration of abstinence (LDA; count of consecutive cocaine-negative urine tests) and Treatment Effectiveness Score (TES; count of cocaine-negative urine tests from study midpoint to endpoint). Bayesian models estimated independent moderation and mediation effects of cognitive ability on the association between treatment (citalopram 40 mg vs. placebo) and LDA/TES.Results: Of the four assessments, only the IGT demonstrated concurrent moderation and mediation in the sample (N = 80; 82% males). Treatment effects on LDA (IRR = 1.02) and TES (IRR = 1.03) were strongest in participants with higher baseline IGT scores, which indicate less risky decision-making (posterior probabilities >93%). Models supported a positive indirect effect of treatment on TES (IRR = 1.12, posterior probability = 81.6%), with 52.3% of the total effect mediated by changes in IGT scores from baseline to mid-treatment.Conclusion: We found evidence for IGT as a moderator and mediator of citalopram's effects on cocaine use. Decision-making ability may play a role in predicting who responds to citalopram and how.