Combination pharmacotherapies for stimulant use disorder: a review of clinical findings and recommendations for future research

Abstract

Despite concerted efforts to identify a pharmacotherapy for managing stimulant use disorders, no widely effective medications have been approved. Innovative strategies are necessary to develop successful pharmacotherapies for stimulant use disorders. This manuscript reviews human laboratory studies and clinical trials to determine whether one such strategy, use of combination pharmacotherapies, holds promise. The extant literature shows that combination pharmacotherapy produced results that were better than placebo treatment, especially with medications shown to have efficacy as monotherapies. However, many studies did not compare individual constituents to the combination treatment, making it impossible to determine whether combination treatment is more effective than monotherapy. Future research should systematically compare combined treatments with individual agents using medications showing some efficacy when tested alone.

Keywords::

• amphetamine
• clinical trial
• cocaine
• human laboratory study
• pharmacotherapy

Acknowledgements

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Financial & competing interests disclosure

Preparation of this manuscript was supported by grants from the National Institute on Drug Abuse (R01DA032254 and R01DA033394 to CRR). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Effective pharmacotherapies for stimulant use disorders remain to be identified.

• Use of innovative strategies, like combination treatment, is necessary to develop successful medications to manage cocaine or amphetamine use disorder.

• Combination treatment is a viable strategy for a number of reasons including the use of lower doses of individual constituents to minimize side effects, the possibility of achieving additive or synergistic effects with combinations and targeting the diverse neurotransmitter systems impacted by stimulant drugs.

• Superior efficacy of combined treatments relative to placebo has been demonstrated for a wide range of outcomes including objective and self-reported drug abstinence.

• A number of methodological concerns including not systematically testing putative combinations from the human laboratory to the clinic and not evaluating individual constituents, make more definitive conclusions about the promise of this strategy impossible.

• Future research should more systematically evaluate drug combinations and include individual constituents that have at least some efficacy when tested alone to overcome these methodological limitations.