The effects of combination levodopa-ropinirole on cognitive improvement and treatment outcome in individuals with cocaine use disorder: A bayesian mediation analysis

Abstract Background Chronic cocaine users show impairments in cognitive processes associated with dopamine (DA) circuitry. Medications aimed at bolstering cognitive functions via DA modulation might enhance treatment outcome. Methods The trial used a double-blind, double-dummy, parallel-group design with four treatment arms comparing placebo (PLC) to levodopa/carbidopa 800 mg/200 mg alone (LR0), levodopa plus extended release (XR) ropinirole 2 mg (LR2) or XR ropinirole 4 mg (LR4). Adults (n = 110) with cocaine use disorder attended thrice weekly clinic visits for 10 weeks. Potential cognitive mediators assessed at week 5 consisted of measures of decision-making (Iowa Gambling Task, Risky Decision-Making Task), attention/impulsivity (Immediate Memory Task), motivation (Progressive Ratio task), and cognitive control (Cocaine Stoop task). The primary outcome measure was the treatment effectiveness score (TES) calculated as the number of cocaine-negative urines collected from weeks 6–10. Results Bayesian mediation examined indirect and total effects of the relationships between each active treatment (compared to PLC) and TES. Total (direct) effects were supported for LR0 and LR2, but not for LR4. Indirect effects were tested for each mediator. Notably, 22.3 % and 35.4 % of the total effects of LR0 and LR2 on TES were mediated by changes in attention/impulsivity. Conclusions The hypothesized mediation effect was strongest for levodopa plus 2 mg ropinirole, indicating that this DA medication combination predicted change (improvement) in attention/impulsivity, which in turn predicted change (reduction) in cocaine use. This finding provides modest support for cognitive enhancement as a target for medications to treat cocaine use disorder.