Cocaine, particularly in its base form ('crack'), has become one of the drugs of most concern in many countries, being associated with a wide range of medical, psychiatric and social problems for the individual, and with significant public order consequences for society [1
]. In the Netherlands (16.7 million inhabitants), annual cocaine-related addiction treatment demand increased from 8,490 patients in 1994 to 17,270 in 2008, and approximately half of this treatment demand in 2008 concerned users of crack [4
]. Although the number of treatment seeking cocaine users slightly decreased in more recent years, the number of cocaine dependent patients that repeatedly returned to addiction treatment increased [5
]. Despite its status as one of the most problematic addictions, reliable prevalence estimates of cocaine dependence in the Netherlands are lacking. In 2005, 32,000 current cocaine users were identified in the Netherlands [4
], but this is likely to be a serious underestimation given the fact that the data were obtained in a population survey. Moreover, the survey did not allow a separate estimate of the prevalence of crack cocaine use.
Psychosocial treatments for cocaine dependence, which include cognitive behavioural therapy, counselling and relapse prevention, have generally produced modest results [6
], and both study data and practice-based experiences indicate that poor compliance is a major complicating factor in these treatments. One of the more promising psychosocial treatments for cocaine dependence to date is contingency management, which has shown positive results in terms of improved treatment retention and reduction of substance use in a series of studies [7
], and is therefore currently being investigated in the Netherlands in the context of a controlled study in heroin addicts with concurrent cocaine use. However, dissemination of contingency management has been problematic because of low acceptance and limited experience of therapists with this intervention [12
] and because contingency management is politically controversial because communities are often not willing to just pay for a change in health behaviour [13
The modest results of psychosocial treatments and the increasing knowledge about the neurobiology of cocaine dependence have led to an increasing number of studies searching for effective pharmacological agents that influence the neurochemistry of cocaine, including antipsychotics, anticonvulsants, antidepressants, psychostimulants and (other) dopamine agonists [14
]. Despite the considerable efforts in this field, however, there are no proven effective pharmacotherapies for cocaine dependence to date, and the testing of new medications for cocaine dependence should continue to be high on the research agenda. Basically, the research efforts are focused on two pharmacological strategies [23
]: one directed at abstinence from - or at least substantial reduction of - cocaine use and the other directed at minimizing cocaine-related harm by replacing short-acting, illicit cocaine by a long acting, legal stimulant that can be taken orally [24
Concerning the first strategy, from the wide range of medications tested, topiramate and modafinil are examples of new medications that are currently only registered for indications other than cocaine dependence, but have shown promise in several studies in cocaine dependent populations in terms of abstinence or stimulant use reduction [16
Topiramate was originally marketed as an anticonvulsant. Through its effects on the GABA- and the glutamate-system, it attenuates dopamine neurotransmission. In the alcohol field, various randomised controlled trials have shown that topiramate was more effective than placebo in treating alcohol dependence [29
], and was at least as effective as naltrexone [29
]. Concerning cocaine, topiramate was more effective in promoting abstinence and sustained abstinence in (crack-) cocaine users in a double-blind placebo-controlled pilot trial of Kampman and colleagues [32
], and cocaine craving significantly decreased after the administration of topiramate in an open label trial [33
]. A second promising treatment option is the use of the alpha-adrenergic/glutamate agonist modafinil, which is generally prescribed for the treatment of narcolepsy, obstructive sleep apnoea/hypopnoea and shift work sleep disorder. In addition, modafinil showed effectiveness in terms of duration of abstinence in the treatment of cocaine dependence in two randomised controlled trials [34
], and in the reduction of craving in cocaine dependent patients without comorbid alcohol dependence [36
]. More recently, modafinil was investigated in methamphetamine dependence with improved treatment retention and decreased methamphetamine use as a result [37
With respect to the second strategy, harm reduction or drug use reduction oriented treatment, a growing number of pre-clinical and human studies suggest that the monoamine releaser dexamphetamine, used for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy, is an important candidate for replacement therapy [18
]. The basic rationale for substitution treatment for cocaine dependence is similar to that for other addictions (nicotine replacement therapy in nicotine dependence, methadone and buprenorphine in opioid dependence): it aims to replace uncontrolled and harmful drug use with regulated and safer use, in terms of dose, route of administration and adverse effects, and to facilitate engagement with health care services by attracting and retaining addicted individuals in treatment [41
]. In addition, the regular supervised prescription regimen may by itself help patients to structure their daily life. In cocaine dependent patients several controlled studies have shown significant improvements associated with the administration of sustained-release (SR) dexamphetamine, without serious adverse events (including no serious cardiovascular complications). Shearer and colleagues [43
] reported positive results of dexamphetamine SR in a placebo-controlled study of cocaine dependent injectors in terms of reduced cocaine use, craving, severity of dependence and delinquent behaviour, and dexamphetamine SR was found to attenuate cocaine use and improve treatment retention in combined cocaine and heroin dependent patients in controlled studies of Greenwald et al. [44
] and Grabowski et al. [45
In sum, cocaine dependency is characterized by its chronic and relapsing nature and by high treatment dropout rates. A wide range of pharmacological agents has been tested for efficacy in cocaine dependence, but generally with disappointing or, at best, equivocal results. From the investigated candidate medications, topiramate, modafinil and dexamphetamine SR have shown the most promising results. The vast majority of these studies were conducted in the US, however, and therefore these study findings need to be confirmed in research outside the US.
The overall objective of the current study is to investigate topiramate, modafinil, and dexamphetamine SR for their acceptability and effectiveness in the treatment of cocaine dependent patients in The Netherlands. Dependent on the results, this study will also yield candidate medications for further investigation in a large-scale confirmatory trial. More specifically, we aim to evaluate in three separate randomised controlled, open-label, parallel-group feasibility trials in crack-cocaine dependent patients the response to each of these three medications, as an add-on to psychosocial treatment with cognitive behavioural therapy (CBT), compared to CBT alone, in terms of acceptance, treatment retention and compliance, efficacy, safety, and patient satisfaction. As in any medication study, our primary focus is on the balance between (potential) benefit and harm associated with the medications, taking into consideration the personal and societal damage linked to continued illicit use of cocaine, in a situation without effective pharmacological treatment options.
Because of the aim of the study - investigating treatment effectiveness with both abstinence and harm minimisation as treatment strategies for cocaine dependent patients - the study is named CATCH: Cocaine Addiction Treatments to improve Control and reduce Harm.