Levodopa pharmacotherapy for cocaine dependence: Choosing the optimal behavioral therapy platform

Abstract

Background: The dopamine precursor levodopa has shown some, albeit relatively weak, promise in treating cocaine dependence. This study sought to identify the most appropriate behavioral therapy platform for levodopa pharmacotherapy by evaluating its effect when administered in combination with behavioral platforms of varying intensities. Method:A total of 161 treatment-seeking cocaine dependent subjects received sustained release levodopa/carbidopa (400/100 mg bid, Sinemet) or placebo delivered in combination with Clinical Management (ClinMan); ClinMan+Cognitive Behavioral Therapy (CBT); or ClinMan+CBT +Voucher-Based Reinforcement Therapy (VBRT) in a 12-week randomized, placebo-controlled, double-blind (for medication condition) trial. Medication compliance was monitored with riboflavin (100 mg/capsule) and the Medication Event Monitoring System. Protocol compliance was addressed in weekly, 10-minute nurse-delivered ClinMan sessions. Weekly, 1-hour CBT sessions focused on coping skills training. VBRT (with escalating reinforcer value) provided cash-valued vouchers contingent on cocaine-negative urine toxicology results. Urine benzoylecgonine assays collected thrice-weekly were analyzed by intention-to-treat criteria using generalized linear mixed models.Results: Levodopa main effects were found on all outcome measures of cocaine use. Contrasts testing the levodopa-placebo difference within each behavioral platform found reliable effects, favoring levodopa, only in the VBRT platform. Levodopa treatment with vouchers produced higher proportions of cocaine-negative urines and longer periods of consecutive abstinence compared to other treatment combinations.Conclusion: This is the first study to find a significant treatment effect for levodopa and, in doing so, to demonstrate that the magnitude of this effect is dependent upon conditions of the behavioral therapy platform. The data support use of levodopa with abstinence-based reinforcement therapy as one efficacious combination in cocaine dependence disorder treatment.

Psychostimulants

“…The effects of L-DOPA (plus carbidopa) were tested in combination with clinical management (CM), cognitive behavioral therapy (CBT), or CM + CBT + voucher-based reinforcement therapy (VBRT) in treatment-seeking cocaine-dependent individuals in a 12-week randomized, placebo-controlled, double-blind trial. L-DOPA showed beneficial effects on the number of cocaine-negative urine samples, but only in combination with CM + CBT + VBRT, suggesting that L-DOPA pharmacotherapy may be an option for cocaine dependence when combined with behavioral therapies (Schmitz et al, 2008). Ropinirole acted as, albeit a weak, reinforcer in nonhuman primates (Freeman, Heal, McCreary, & Woolverton, 2012), which partly supports clinical data, suggesting that ropinirole marginally reduced craving in humans (Meini et al, 2012) and reduced the subjective intensity for the "cocaine rush" (Maremmani et al, 2011).…”

Enduring effects of tacrine on cocaine-reinforced behavior: Analysis by conditioned-place preference, temporal separation from drug reward, and reinstatement

“…Within the first three months of initiating treatment for cocaine dependence, most patients will relapse to drug abuse (Schmitz et al, 2008). This persistence is paralleled by observations from animal models.…”

Pharmacotherapeutics for substance-use disorders: a focus on dopaminergic medications

“…A more elaborate clinical trial compared levodopa–carbidopa alone, and in combination with either cognitive behavioral therapy (CBT) alone, or CBT and CM (negative urine results). Only levodopa–carbidopa combined with both CBT and CM decreased cocaine-use [111]. Schmitz and colleagues subsequently included CBT in all groups and compared levodopa–carbidopa in combination with CM targeting clinic attendance, medication compliance or negative urine results.…”