Extended release mixed amphetamine salts and topiramate for cocaine dependence: A randomized clinical replication trial with frequent users.
Amphetamines
/ adverse effects
Cocaine-Related Disorders
/ therapy
Delayed-Action Preparations
/ adverse effects
Double-Blind Method
Drug Therapy, Combination
Female
Humans
Male
Medication Adherence
/ statistics & numerical data
Middle Aged
Salts
/ therapeutic use
Topiramate
/ adverse effects
Treatment Outcome
Amphetamines
Clinical trial
Cocaine dependence
Substance dependence
Topiramate
Treatment
Journal
Drug and alcohol dependence
ISSN: 1879-0046
Titre abrégé: Drug Alcohol Depend
Pays: Ireland
ID NLM: 7513587
Informations de publication
Date de publication:
01 01 2020
01 01 2020
Historique:
received:
02
07
2019
revised:
24
10
2019
accepted:
25
10
2019
pubmed:
23
11
2019
medline:
11
11
2020
entrez:
23
11
2019
Statut:
ppublish
Résumé
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. 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) with CUD using at least 9 days in the prior month. MAS-ER was titrated to a maximum dose of 60 mg/day and topiramate to a maximum dose of 100 mg twice/day. The primary outcome was the proportion of individuals who achieved three consecutive abstinent weeks at the end of the study (EOS) as measured by urine toxicology and self-report. The proportion of participants achieving three abstinent weeks at the EOS was significantly (P = .03) larger in the treatment (14.1%) compared to the placebo group (0.0%), while controlling for baseline cocaine use, sex, current alcohol use disorder, and site. Of note, due to conservative cardiac safety-parameters a considerable number of individuals in the treatment group were discontinued from study medication (20.3%). While these findings provide further evidence that the combination of MAS-ER and topiramate is efficacious in promoting abstinence in CUD adults with frequent use it remains possible that the combination treatment is no more effective than either treatment alone. Despite this, the study provides a valuable "proof of concept."
Sections du résumé
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) with CUD using at least 9 days in the prior month. MAS-ER was titrated to a maximum dose of 60 mg/day and topiramate to a maximum dose of 100 mg twice/day. The primary outcome was the proportion of individuals who achieved three consecutive abstinent weeks at the end of the study (EOS) as measured by urine toxicology and self-report.
RESULTS
The proportion of participants achieving three abstinent weeks at the EOS was significantly (P = .03) larger in the treatment (14.1%) compared to the placebo group (0.0%), while controlling for baseline cocaine use, sex, current alcohol use disorder, and site. Of note, due to conservative cardiac safety-parameters a considerable number of individuals in the treatment group were discontinued from study medication (20.3%).
CONCLUSIONS
While these findings provide further evidence that the combination of MAS-ER and topiramate is efficacious in promoting abstinence in CUD adults with frequent use it remains possible that the combination treatment is no more effective than either treatment alone. Despite this, the study provides a valuable "proof of concept."
Identifiants
pubmed: 31753736
pii: S0376-8716(19)30477-6
doi: 10.1016/j.drugalcdep.2019.107700
pmc: PMC6980777
mid: NIHMS1544654
pii:
doi:
Substances chimiques
Amphetamines
0
Delayed-Action Preparations
0
Salts
0
Topiramate
0H73WJJ391
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
107700Subventions
Organisme : NIDA NIH HHS
ID : K24 DA029647
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA033310
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA033368
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.
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