Galantamine and Computerized Cognitive Behavioral Therapy for Cocaine Dependence: A Randomized Clinical Trial.

Abstract

To examine whether galantamine, a cognitive-enhancing medication that is both acetylcholinesterase inhibitor and agonist at nicotinic acetylcholine receptors, is effective at improving cocaine use outcomes and cognitive functioning, alone and in combination with computerized cognitive behavioral therapy (CBT). A 12-week, randomized 2 × 2, factorial trial was conducted to evaluate galantamine versus placebo (double-blind) and computerized CBT plus standard methadone treatment versus standard methadone treatment alone in a community-based methadone maintenance program (September 2009-April 2015). One hundred twenty individuals diagnosed with DSM-IV cocaine use disorder were randomly assigned to the following conditions: (1) galantamine (8 mg/d) plus standard methadone maintenance treatment (treatment as usual [TAU]), (2) placebo plus TAU, (3) galantamine plus computerized CBT plus TAU, or (4) placebo plus computerized CBT plus TAU; medication administration was supervised at the time of daily methadone dosing. The primary cocaine use outcome was change in percent days of abstinence over time. Number of cocaine-negative urine toxicology screens submitted and cognitive function were secondary outcomes. Random effect regression analysis indicated significant reductions in frequency of cocaine use over time, with significant treatment-by-time effects for both galantamine over placebo (F = 5.3, P = .02, d = 0.34) and computerized CBT over standard methadone treatment (F = 4.2, P = .04, d = 0.30) but no evidence of significant benefit of the combination over either treatment alone. Pretreatment to posttreatment comparisons of multiple indices of cognitive functioning, including sustained attention, indicated no benefit of galantamine over placebo. Findings suggest benefits of galantamine and computerized CBT for reducing cocaine use in this sample. Although galantamine did not improve measures of cognitive function in this sample, multiple measures of cognitive function were associated with cocaine use outcomes, underlining the significance of cognitive function in cocaine treatment outcomes. ClinicalTrials.gov identifier: NCT00809835.