Abstract
Background
Cocaine dependence is a major public health problem that is characterised by recidivism and a host of medical and psychosocial complications. Although effective pharmacotherapy is available for alcohol and heroin dependence, none is currently available for cocaine dependence, despite two decades of clinical trials primarily involving antidepressant, anticonvulsivant and dopaminergic medications. Extensive consideration has been given to optimal pharmacological approaches to the treatment of individuals with cocaine dependence, and both dopamine antagonists and agonists have been considered. Anticonvulsants have been candidates for use in the treatment of addiction based on the hypothesis that seizure kindling-like mechanisms contribute to addiction.
Objectives
To evaluate the efficacy and safety of anticonvulsants for individuals with cocaine dependence.
Search methods
We searched the Cochrane Drugs and Alcohol Group Trials Register (June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6), MEDLINE (1966 to June 2014), EMBASE (1988 to June 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to June 2014), Web of Science (1991 to June 2014) and the reference lists of eligible articles.
Selection criteria
All randomised controlled trials and controlled clinical trials that focus on the use of anticonvulsant medications to treat individuals with cocaine dependence.
Data collection and analysis
We used the standard methodological procedures expected by The Cochrane Collaboration.
Main results
We included a total of 20 studies with 2068 participants. We studied the anticonvulsant drugs carbamazepine, gabapentin, lamotrigine, phenytoin, tiagabine, topiramate and vigabatrin. All studies compared anticonvulsants versus placebo. Only one study had one arm by which the anticonvulsant was compared with the antidepressant desipramine. Upon comparison of anticonvulsant versus placebo, we found no significant differences for any of the efficacy and safety measures. Dropouts: risk ratio (RR) 0.95, 95% confidence interval (CI) 0.86 to 1.05, 17 studies, 20 arms, 1695 participants, moderate quality of evidence. Use of cocaine: RR 0.92, 95% CI 0.84 to 1.02, nine studies, 11 arms, 867 participants, moderate quality of evidence; side effects: RR 1.39, 95% CI 1.01 to 1.90, eight studies, 775 participants; craving: standardised mean difference (SMD) -0.25, 95% CI -0.59 to 0.09, seven studies, eight arms, 428 participants, low quality of evidence.
Authors’ conclusions
Although caution is needed when results from a limited number of small clinical trials are assessed, no current evidence supports the clinical use of anticonvulsant medications in the treatment of patients with cocaine dependence. Although the findings of new trials will improve the quality of study results, especially in relation to specific medications, anticonvulsants as a category cannot be considered first-, second- or third-line treatment for cocaine dependence.
Plain language summary
Anticonvulsants for cocaine dependence
Background
Cocaine is an illicit drug available as a powder for intranasal or intravenous use or smoked as crack. Short- and long-term use of this drug results in the spread of infectious diseases (for example, AIDS, hepatitis, tuberculosis), crime, violence and prenatal drug exposure. Cocaine dependence is associated with medical and psychosocial complications and is a major public health problem. No proven pharmacological treatment for cocaine dependence is known. Antidepressant, anticonvulsant and dopaminergic medications have all been studied. The present review looked at the efficacy and safety of anticonvulsant drugs for treating cocaine dependence, both as a class and individually.
Study characteristics
The review authors searched scientific databases and Internet resources to identify randomised controlled trials (in which participants were allocated at random to any anticonvulsant drug or placebo or another type of drug or non-pharmacological intervention intended to reduce,the use of cocaine). We assessed also dropout from treatment and frequency of side effects .We included people of any gender, age or ethnicity.
Key results
The review authors identified 20 studies with 2068 participants, 77% male, with a mean age of 36 years. The mean duration of the trials was 11.8 weeks (range eight to 24 weeks). All but two of the trials were conducted in the USA, all with outpatients. The anticonvulsant drugs studied were carbamazepine, gabapentin, lamotrigine, phenytoin, tiagabine, topiramate and vigabatrin. All studies compared anticonvulsants versus placebo. No significant differences were found between placebo and any anticonvulsant in reducing the number of dropouts from treatment, use of cocaine, craving and severity of dependence, depression or anxiety. Side effects were slightly more frequent in the anticonvulsant groups. No current evidence supports the clinical use of anticonvulsant medications for the treatment of cocaine dependence.
Quality of the evidence
The quality of the evidence was moderate for the outcomes dropout and use of cocaine, and was low for the outcomes side effects and craving. The major limitation of the trials was incomplete reporting of the methods used to protect against selection bias, randomly allocate participants to groups and conceal allocation. The evidence is current to June 2014.
