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Therapeutic Drug Monitoring for Drugs Used in the Treatment of Substance-Related Disorders: Literature Review Using a Therapeutic Drug Monitoring Appropriateness Rating Scale

Brünen, Sonja MSc*; Vincent, Philippe D MSc; Baumann, Pierre PhD; Hiemke, Christoph PhD*; Havemann-Reinecke, Ursula MD, PhD§

doi: 10.1097/FTD.0b013e31822fbf7c
Review Article
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Background: The efficacy of drugs for the treatment of substance-related disorders is moderate at best. Therapeutic drug monitoring (TDM) could be an instrument to improve outcomes. Because TDM for most of those drugs is not established, the authors reviewed the literature and built a rating scale to detect the potential added value of TDM for these pharmacologic agents.

Methods: A literature search was performed for acamprosate, bupropion, buprenorphine, clomethiazole, disulfiram, methadone, naltrexone, and varenicline. The rating scale included 22 items and was divided in five categories: efficacy, toxicity, pharmacokinetics, patient characteristics, and cost-effectiveness. Three reference substances with established TDM were similarly assessed for comparison: clozapine, lithium, and nortriptyline. The three reference substances achieved scores of 15, 12, and 14 points, respectively.

Results: Drugs for treatment of substance-related disorders achieved 3 to 17 points, 17 for methadone, 11 for buprenorphine, 10 for disulfiram, also 10 for naltrexone for the indication opioid-dependence and 9 for the indication alcohol dependence as well as bupropion, 7 points for acamprosate, 6 points for clomethiazole, and 3 for varenicline.

Conclusions: It is concluded that systematic evaluation of drug- and patient-related variables with the new rating scale can estimate the appropriateness of TDM. Because their rating revealed similar scores as the three reference drugs, it is proposed that TDM should be established for bupropion, buprenorphine, disulfiram or a metabolite, methadone, and naltrexone. An objective rating of drug- and patient-related characteristics could help laboratories focus their method development on the most likely drugs to require TDM along with a thorough drug use evaluation.

From the *Department of Psychiatry and Psychotherapy, University Medical Center of Mainz, Mainz, Germany; †Faculte´ de Pharmacie, Universite´ de Montre´al, and De´partement de Pharmacie, Hôpital Louis-H. Lafontaine, Montre´al, Canada; ‡Department of Psychiatry, University of Lausanne, Prilly-Lausanne, Switzerland; and §Department of Psychiatry and Psychotherapy, University of Göttingen, Göttingen, Germany.

Received for publication March 14, 2011; accepted July 18, 2011

S.B. and P.D.V. share first authorship.

The authors declare no conflicts of interest.

Correspondence: Christoph Hiemke, PhD, Department of Psychiatry, University Medical Center of Mainz, Untere Zahlbacher Str. 8, D-55131 Mainz, Germany (e-mail: hiemke@uni-mainz.de).

© 2011 Lippincott Williams & Wilkins, Inc.