Pharmacotherapeutic strategies for methamphetamine use disorder: mind the subgroups

ABSTRACT

Introduction: Drug use related deaths are increasing and the lack of effective treatment for psychostimulants can be largely held responsible. Particularly, no pharmacotherapy is approved for methamphetamine (METH) use disorder despite decades of research. Only psychosocial interventions are clinically used, with limited long-term recovery and relapse.

Areas covered: This review aims to select and describe the most relevant findings to date. Selected clinical trials were found in PubMed using the following keywords (‘methamphetamine’) and (‘addiction’ OR ‘withdrawal’ OR ‘treatment’ OR ‘pharmacotherapy’). Randomized placebo-controlled trials enrolling treatment-seeking METH-dependent subjects and inherent secondary analysis were included.

Expert opinion: Overall, end-of-treatment abstinence, reduced METH use or lower relapse rates were seen on METH dependent subgroups or attained significance only following post hoc analysis, irrespective of the medication tested. For example, light and heavy METH users seem to respond differently to pharmacotherapy. This together with the heterogeneous nature of the METH dependent population strongly suggests that some drugs herein described (e.g. mirtazapine, methylphenidate) should be further tested in clinical trials focused on subgroups. Lastly, objective measures, such as urinalysis, are mandatory to include in clinical trials and early treatment response and/or medication compliance should be carefully monitored and considered as predictors of success/failure.

KEYWORDS:

• Drug use disorder
• clinical trials
• methamphetamine
• pharmacotherapy
• subgroups

Article Highlights

• Mirtazapine and methylphenidate have modest effect for methamphetamine use disorder.

• Most pharmacotherapies improve withdrawal symptoms, dependence degree/severity and craving.

• Methamphetamine dependent subjects’ heterogeneity hinders trial results generalization.

• Medication compliant, male or light/abstinent at baseline methamphetamine dependent patients are better treatment responders.

• Early exhaustive methamphetamine use characterization is the best treatment predictor.

This box summarizes key points contained in the article.

Declaration of interest

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This work was supported by Fundação para a Ciência e Tecnologia (FCT, Portugal), by the Speed, crash and run: exersomes boost neuroenergetics and mood in mice on speed project (MOOD EXERsomes, POCI-01-0145-FEDER-030786), Strategic Projects (UID/NEU/04539/2013 and UID/NEU/04539/2019), and COMPETE-FEDER (POCI-01-0145-FEDER-007440) and Centro 2020 Regional Operational Programmes (CENTRO-01-0145-FEDER-000012: HealthyAging2020 and CENTRO-01-0145-FEDER- 000008: BrainHealth 2020).