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

Abstract

Background Cocaine use contines to be a significant public health problem world‐wide. However, despite substantial research efforts, no pharmacotherapies are approved for the treatment of cocaine use disorder (CUD). Argument Studies have identified positive signals for a range of medications for treating CUD. These include long‐acting amphetamine formulations, modafinil, topiramate, doxazosin and combined topiramate and mixed amphetamine salts extended‐release (MAS‐ER). However, valid conclusions about a medication's clinical efficacy require nuanced approaches that take into account behavioural phenotypes of the target population (frequency of use, co‐abuse of cocaine and other substances, genetic subgroups, psychiatric comorbidity), variables related to the medication (dose, short‐/long‐acting formulations, titration speed, medication adherence) and other factors that may affect treatment outcomes. Meta‐analyses frequently do not account for these co‐varying factors, which contributes to a somewhat nihilistic view on pharmacotherapeutic options for CUD. In addition, the predominant focus on abstinence, which is difficult for most patients to achieve, may overshadow more nuanced therapeutic signals. Conclusion While there is an emphasis on finding new medications with novel mechanisms of action for treating CUD, currently available medications deserve further investigation based on the existing literature. Evaluating refined metrics of treatment success in well‐defined subgroups of patients, and further exploring combination therapies and their synergy with behavioural/psychosocial interventions, are promising avenues to establishing effective therapies for CUD.

‘Resurgent’, ‘twin’ or ‘silent’ epidemic? A select data overview and observations on increasing psycho-stimulant use and harms in North America

“…A very recent RCT utilizing injectable naltrexone combined with bupropion for methamphetamine use disorder found a relatively higher response rate for the treatment intervention compared to placebo controls, yet a low overall treatment effect (11.1%) [99]. A few select medications (e.g., n-acetyl-cysteine, methylphenidate, modafinil, dexamphetamine) have shown some 'promise' for psycho-stimulant dependence treatment, or 'maintenance'-type interventions, yet require further rigorous investigation and substantially improved evidence for clearer assessment; while some observers are more optimistic regarding the therapeutic potential or prospects of medications-based treatment for psychostimulants, others do not expect major advances on the horizon of psycho-stimulant treatment in the foreseeable future [100][101][102]. The current standard of care for psycho-stimulant dependence treatment primarily involves on psycho-social interventions; however, their effectiveness is limited and commonly does not produce better outcomes than usual care [47,103,104].…”

If there were an effective pharmacotherapy for cocaine use disorder, what would it do?

“…Thirty years of outcomes using this strategy suggest only modest success. Brandt et al [1] highlights the call for a highrisk/high-reward strategy to engineer new compounds. To this end, we require mechanisms and partnerships for addiction scientists and medicinal chemists to meet and to consider building new molecules to help people not only to use less cocaine, but also to use treatment to build their lives with function-socially, psychologically, and productively.…”

Will hope triumph over experience in pharmacotherapy research on cocaine use disorder?

“…In the intervening decades, meta-analytical reviews of cocaine use disorder pharmacotherapy effectiveness have drawn disappointing conclusions regarding anticonvulsants [1][2][3], antidepressants [4], antipsychotics [5][6][7], disulfiram [8], dopamine agonists [9], opioids [10] and psychostimulants [11][12][13]. Today, some intelligent, well-intended, hard-working people [14] assure me that the future is much brighter than it looks. The younger me believed such arguments and was hopeful; the older me is skeptical, and not a little discouraged.…”