Clonazepam is long-acting benzodiazepine agonist used in short-acting benzodiazepine withdrawal; however, recent observations suggest the existence of its abuse.
We demonstrate a 40-year-old man with a 20-year history of psychiatric care with recently benzodiazepine dependence (daily intake of ∼60 mg of clonazepam and 10 mg of alprazolam). High serum levels of both drugs were analyzed 3 weeks before admission to hospitalization (clonazepam 543.9 ng/mL, alprazolam 110 ng/mL) and at the time of admission (clonazepam 286.2 ng/mL, alprazolam 140 ng/mL) without any signs of benzodiazepine intoxication. Gradual withdrawal of clonazepam with monitoring of its serum levels and increase of gabapentin dose were used to minimize physical signs and symptoms of clonazepam withdrawal. Alprazolam was discontinued promptly. Clinical consequences of the treatment were controllable tension, intermittent headache, and rarely insomia.
It is the first case report showing utilization of therapeutic drug monitoring during withdrawal period in the patient with extreme toleration to severe benzodiazepine dependence.
From the Department of Clinical Pharmacology (IK, MG, HB), Faculty of Medicine, University of Ostrava; Department of Clinical Pharmacology (IK, HB), Department of Laboratory Diagnostics; and Department of Psychiatry (PS), University Hospital Ostrava, Czech Republic.
Correspondence: Milan Grundmann, Department of Clinical Pharmacology, Faculty of Medicine, University of Ostrava, Syllabova, Ostrava, Czech Republic (e-mail: firstname.lastname@example.org;email@example.com).
Abbreviations: C = concentration, Cl = clearance, Cmax = maximal concentration, CYP = cytochrome P450, GABA = γ-aminobutyric acid, HPLC = high-performance liquid chromatography, t1/2 = elimination half-life, TDM = therapeutic drug monitoring, Vd = volume of distribution.
Disclosure: authors certify that the manuscript has not been previously published, except in abstract form, and that it is not simultaneously under consideration by any other journal, and, if accepted, it will not be published elsewhere in the same form, in English or in any other language, including electronically without the written consent of the copyright-holder. Authors acknowledge that the publication is approved by all authors and by the responsible authorities where the work was carried out. Authors advise that there are not any actual or potential financial or other conflict of interest related to the submitted manuscript (ownership, equity position, stock ownership, stock options, consulting fees, expert testimony, employment, consultancies, honoraria, patent rights, corporate affiliations, grants received and pending, patents received and pending, royalties, and in-kind contributions) associated with any drug, product, process, or commercial laboratory mentioned in the submitted material.
Author contributions: KI—first author, wrote manuscript, analyzed data, literature search, TDM recommendations.
GM—corresponding author, wrote manuscript, designed research, final approval, analyzed data.
SP—attending physician of patient, performed research.
This is an open access article distributed under the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0
Received December 28, 2015
Received in revised form January 27, 2016
Accepted January 27, 2016