Extended release mixed amphetamine salts and topiramate for cocaine dependence: A randomized clinical replication trial with frequent users

Abstract

Background-Cocaine use disorder (CUD) remains a substantial public health problem with no clearly effective pharmacotherapy available. In a prior trial, combined amphetamine and topiramate treatment significantly reduced cocaine use among individuals demonstrating the most frequent use at baseline. This trial targeted such frequent users.Methods-A double-blind, randomized placebo-controlled trial, testing the combination of mixed amphetamine salts extended-release (MAS-ER) and topiramate or placebo over a 12-week medication phase was conducted. The two-site outpatient trial included 127 adults (96 males

An adaptive clinical trial design for cocaine use disorder: Extended-release amphetamine salts for early behavioral intervention non-responders

“…all randomized participants) and dropouts will be accounted for by examining the primary outcome variables using longitudinal mixed effects models. Previous randomized trials of psychostimulants for CUD have reported that approximately one-third of participants drop out before the end of the maintenance treatment phase [31,32].…”

Continuing Increase in Stimulant Dependence – Time to Implement Medical Treatment

“…Studies suggest PSUD patients who are frequent stimulant users benefit most from the agonist treatment 24 and, therefore, the initial studies should include patients with an active and severe form of the disorder (e.g., daily use, large amounts, and intravenous use), based on thorough “treatment qualification” assessment. Treatment may be particularly impactful in this group which is less likely to respond to non-pharmacological interventions, 25 with benefits likely outweighing risks.…”

Pharmacotherapeutic strategies for treating cocaine use disorder—what do we have to offer?

“…Heavier cocaine users may benefit from MAS-ER/topiramate combination [56,127] Comorbid substance use disorders Comorbid alcohol use disorder may interfere with the benefits of modafinil [27,29] and disulfiram [46] treatment, while topiramate [41] or combination treatment with disulfiram/naltrexone [55] seem well-suited for the treatment of CUD patients who are alcohol-dependent. Topiramate [43] and galantamine [51] seem to be viable options for the treatment of patients with comorbid CUD and OUD Co-occurring attention deficit hyperactivity disorder (ADHD)…”

“…Exploratory post‐hoc analyses revealed that MAS‐ER/topiramate was more effective for participants who had a greater frequency of cocaine use at baseline. A larger follow‐up investigation of MAS‐ER/topiramate in heavy, frequent cocaine users showed even greater differences between treatment versus control groups for cocaine abstinence both during the trial (21.9 versus 6%) and ≥ 3 consecutive weeks at the end of the trial (14 versus 0%) [127].…”