title: Interaction of valproic acid and amitriptyline: analysis of therapeutic drug monitoring data under naturalistic conditions.
abstract: Amitriptyline (AMI) and valproic acid (VPA) are common psychotropic drugs which are frequently used in psychiatry and also administered in neurology or anesthesia in the absence of a psychiatric indication. On the basis of the case of a 73-year-old man with therapy-resistant major depressive episode who experienced anticholinergic delirium after adding VPA to AMI, we retrospectively analyzed therapeutic drug monitoring data of the years 2008 to 2010. We assessed cases receiving a combination of AMI and VPA, and obtained a control sample of AMI patients without VPA which were matched for sex, age, daily dose, and comedication. Both samples were compared regarding the serum levels of AMI and nortriptyline (NOR) as well as the ratio of NOR and AMI with the Mann-Whitney U test. The combination of AMI and VPA led to a remarkable increase of AMI and NOR serum levels. When comparing 33 patients who received comedication with VPA versus 33 matched controls, the total concentration by combining mean AMI and NOR serum levels (237.1 [119.9] vs 126.4 [52.8] ng/mL) and NOR/AMI ratio (1.300 [0.905] vs 0.865 [0.455]) was significantly higher. Both AMI and VPA are widely prescribed drugs. A combination of both is common for psychiatric or neurologic patients. A cautious dosing of AMI with VPA comedication is advisable, and therapeutic drug monitoring should be performed because this combination may lead to a remarkable increase of AMI and NOR serum levels.
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Germany. Unterecker_S@klinik.uni-wuerzburg.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Unterecker
authors.forename: Rainer
authors.initials: R
authors.lastname: Burger
authors.forename: Amelie
authors.initials: A
authors.lastname: Hohage
authors.forename: Jürgen
authors.initials: J
authors.lastname: Deckert
authors.forename: Bruno
authors.initials: B
authors.lastname: Pfuhlmann
mesh_terms: D000328:Adult; D000368:Aged; D000639:Amitriptyline / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D016009:Chi-Square Distribution; D003693:Delirium / Q000097:blood / Q000139:chemically induced; D061218:Depressive Disorder, Treatment-Resistant / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D054796:Drug Dosage Calculations; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014635:Valproic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D000639:Amitriptyline; D014635:Valproic Acid