Commentary on Singh et al. (2016): Still searching for the answer.

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Pharmacotherapy trials for psychostimulant dependence have a long history, and no proven, effective drug has emerged. With attention turning to anticonvulsants, the work by Singh et al. is cautionary in that, again, the drug in question did not emerge as clearly effective. In their Introduction, Singh and colleagues note that cocaine dependence is a world-wide clinical and public health problem 1. Indeed, this has been the case for a considerable time, with the first cocaine ‘epidemic’ being seen in during the 1920s. The lack of progress in finding effective pharmacotherapies over this period is remarkable. Drugs trialled have included antidepressants, antipsychotics, dopamine agonists and other psychostimulants 1-4. To date, no drug has shown unequivocal efficacy in reducing use and craving. In recent years there has been interest in anticonvulsants as a treatment option. Singh et al.'s 1 review of the anticonvulsant topiramate continues this long-standing pattern, with the results indicating that the drug did not improve treatment retention but may, possibly, improve abstinence in the short term. There was certainly no compelling evidence that this was the pharmacological solution so desperately sought. This is a problem for the treatment of psychostimulants more broadly. As with cocaine, there is no proven pharmacological agent for the treatment of methamphetamine dependence 2, 5. Indeed, the psychostimulants stand in stark contrast to the treatment of opioids and nicotine, where effective pharmacological treatments have long been available 3. In terms of the search for agonists, we have argued recently that such a drug may never be found, due to the characteristics and harms of psychostimulants 3. Whether this is true for other types of pharmacological agents remains to be seen. The track record, however, is not encouraging. The work by Singh et al. 1 is an important contribution. It is only by analyses of this kind, taking stock across a number of studies, that the true picture emerges. Consistent with the long line of research preceding it the results were equivocal, although, as with previous drugs trialled, providing some hint of encouragement. Psychostimulants present a particularly difficult treatment problem. Given all that has preceded this work, it is open to question as to whether such an effective drug treatment actually exists. None.