+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Interaction of valproic acid and amitriptyline: analysis of therapeutic drug monitoring data under naturalistic conditions



Interaction of valproic acid and amitriptyline: analysis of therapeutic drug monitoring data under naturalistic conditions



Journal of Clinical Psychopharmacology 33(4): 561-564



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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 053905523

Download citation: RISBibTeXText

PMID: 23775047

DOI: 10.1097/jcp.0b013e3182905d42


Related references

Interaction of valproic acid and the antidepressant drugs doxepin and venlafaxine: analysis of therapeutic drug monitoring data under naturalistic conditions. International Clinical Psychopharmacology 29(4): 206-211, 2014

Impact of age, gender and CYP2C9/2C19 genotypes on dose-adjusted steady-state serum concentrations of valproic acid-a large-scale study based on naturalistic therapeutic drug monitoring data. European Journal of Clinical Pharmacology 72(9): 1099-1104, 2016

The influence of old age and enzyme inducing comedication on the pharmacokinetics of valproic acid at steady-state: A case-matched evaluation based on therapeutic drug monitoring data. Epilepsy Research 70(2-3): 153-160, 2006

The use of therapeutic drug monitoring data to document kinetic drug interactions: an example with amitriptyline and nortriptyline. Therapeutic Drug Monitoring 16(1): 1-12, 1994

The Influence of Plasma Albumin Concentration on the Analysis Methodology of Free Valproic Acid by Ultrafiltration and Its Application to Therapeutic Drug Monitoring. Therapeutic Drug Monitoring 37(6): 776-782, 2015

Therapeutic drug monitoring of the amitriptyline perphenazine interaction in depressed patients. Clinical Chemistry 31(6): 939-940, 1985

Assessment of tear concentrations on therapeutic drug monitoring. II. Pharmacokinetic analysis of valproic acid in guinea pig serum, cerebrospinal fluid, and tears. Pharmaceutical Research (New York) 18(4): 500-509, 2001

Therapeutic drug monitoring of valproic acid. Nihon Rinsho. Japanese Journal of Clinical Medicine 48 Suppl: 1130-1133, 1990

Therapeutic drug monitoring of valproic acid. Pakistan Journal of Pharmaceutical Sciences 31(4(Special)): 1773-1776, 2018

Therapeutic drug monitoring data on olanzapine and its N-demethyl metabolite in the naturalistic clinical setting. Therapeutic Drug Monitoring 24(4): 518-526, 2002

A LC-MS/MS method for therapeutic drug monitoring of carbamazepine, lamotrigine and valproic acid in DBS. Bioanalysis 7(16): 2031-2039, 2015

Valproic acid-amitriptyline interaction in man. Therapeutic Drug Monitoring 8(3): 382-383, 1986

Does valproic acid warrant therapeutic drug monitoring in bipolar affective disorder?. Therapeutic Drug Monitoring 32(1): 19-29, 2010

Therapeutic drug monitoring of free fraction valproic acid in patients with hypoalbuminaemia. Netherlands Journal of Medicine 70(7): 329, 2012

Therapeutic drug monitoring of teicoplanin using an LC-MS/MS method: Analysis of 421 measurements in a naturalistic clinical setting. Journal of Pharmaceutical and Biomedical Analysis 167: 161-165, 2019