title: Pharmacotherapy of amphetamine-type stimulant dependence: an update.
abstract: OBJECTIVE
  Methamphetamine- or amphetamine-type stimulants are the second most frequently used illicit drug worldwide, second only to cannabis. Behavioural treatments are efficacious, but their impact is limited underscoring the need for other treatment options, notably, pharmacotherapy.
  
  
  METHODS
  A review of randomised controlled trials of pharmacotherapies for methamphetamine- or amphetamine-type stimulants was performed using PubMed and Google Scholar databases. Evidence for efficacy of medications is reported.
  
  
  RESULTS
  Clinical trials have yielded no broadly effective pharmacotherapy. Promising signals have been observed for methylphenidate, naltrexone, bupropion and mirtazapine in subgroups of patients in reducing stimulant use (e.g. patients with less severe dependence at baseline and men who have sex with men), though none has produced an unambiguous, replicable signal of efficacy.
  
  
  CONCLUSIONS
  Problems in Phase II trials, including high dropout rates, missing data and a lack of agreement on outcomes, complicate efforts to find a broadly effective pharmacotherapy for amphetamine-type stimulant disorders. Efforts to address these problems include calls for better validation of pharmacological target exposure, receptor binding and functional modulation. As well, there is a need for agreement in using findings from preclinical and early phases of the medication development process for selecting better pharmacotherapy candidates.
  
  
  CONCLUSIONS
  After over 20 years of efforts worldwide to develop a broadly effective medication for dependence on methamphetamine- or amphetamine-type stimulants, no candidate has emerged. This highlights the need for new compounds, consistent and stringent research methods, better integration between preclinical and clinical stages of medication development, and improved collaboration between government, industry and researchers.
authors.affiliation: Department of Family Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Brensilver
authors.forename: Keith G
authors.initials: KG
authors.lastname: Heinzerling
authors.forename: Steven
authors.initials: S
authors.lastname: Shoptaw
mesh_terms: D000661:Amphetamine; D019969:Amphetamine-Related Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D000818:Animals; D016642:Bupropion / Q000627:therapeutic use; D000697:Central Nervous System Stimulants; D006801:Humans; D008774:Methylphenidate / Q000627:therapeutic use; D009271:Naltrexone / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000379:methods
chemical_list: D000697:Central Nervous System Stimulants; D016642:Bupropion; D008774:Methylphenidate; D009271:Naltrexone; D000661:Amphetamine
keywords: agonist; amphetamine; methamphetamine; pharmacogenetics; pharmacotherapy