liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Therapeutic drug monitoring of racemic citalopram: a 5-year experience in Sweden, 1992-1997
Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.ORCID iD: 0000-0002-6041-0744
Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
2003 (English)In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 25, no 2, 183-191 p.Article in journal (Refereed) Published
Abstract [en]

Racemic citalopram (CIT) was introduced in Sweden in 1992 for management of major depression. During a 5-year period, 1992 to 1997, serum samples of CIT and desmethylcitalopram (DCIT) were collected for therapeutic drug monitoring (TDM) from patients from all over Sweden. These samples were accompanied by clinical information on a specially designed TDM request form. They represented men and women of various ages (11-94 years) usually on multiple concomitant medications and treated in a naturalistic setting. The TDM samples eligible for evaluation (n = 749), all trough values at steady state, were studied with respect to inter- and intraindividual pharmacokinetic variability. Extensive, interindividual serum concentration variability was seen on all dose levels. For dose-corrected concentrations (C/D) and for clearance (C1) we found the coefficient of variation (CV) to be approximately 55% for all variables (C/D CIT, C/D DCIT, the ratio DCIT to CIT, and for C1 CIT). The intraindividual variations over time for the same parameters were 30% to 35%. On a population level, signs of a possible saturation of CYP2D6 associated with increasing DCIT-to-CIT ratios with increasing daily doses was observed. Age and gender affected the pharmacokinetics of CIT and DCIT. Women showed significantly higher C/D CIT and C/D DCIT and lower C1 CIT values compared with men, and patients aged more than 65 years had higher C/D CIT and C/D DCIT and lower C1 CIT values compared with younger patients. Finally, concomitant medication affected the outcome of serum concentrations by a general increase in C/D CIT and C/D DCIT but without alteration in the DCIT-to-CIT ratio. Thus, this tendency of changes in the CIT disposition when multiple drugs are used (and multiple diseases are prevailing?) seems more general in character than specific for a certain drug or type of drugs.

Place, publisher, year, edition, pages
2003. Vol. 25, no 2, 183-191 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-26797DOI: 10.1097/00007691-200304000-00007Local ID: 11405OAI: diva2:247347
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2013-10-28Bibliographically approved
In thesis
1. Pharmacokinetics of antidepressant drugs: naturalistic and clinical trials
Open this publication in new window or tab >>Pharmacokinetics of antidepressant drugs: naturalistic and clinical trials
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Depression is a major public health problem and it is predicted to be the second leading cause of disease burden by the year 2020. The pharmacological treatment period for major depressive disorder (MDD) is relatively long and sometimes prophylactic over many years. Despite the many drugs introduced on this indication in recent years, details in the drug kinetics linked to the many possible clinical scenarios arising in phase-IV have not been adequately assessed.

The main objective of this thesis was therefore to focus on the posology of the frequently prescribed antidepressant drugs citalopram (CIT), sertraline (SERT), paroxetine (PAR) and venlafaxine (VEN) in terms of trough level serum concentrations of the parent compound and metabolite(s) under steady state conditions. Therapeutic Drug Monitoring (TDM)-based bioanalytical data were to be linked to clinical information obtained on patients in naturalistic or controlled clinical trial phase-IV settings for evaluation of the inter- as well as intraindividual PK (pharmacokinetic) variance. Specific aims were to identifY and analyze subgroups with possibly deviating PK such as adolescents, elderly patients, and the differences between the sexes. From a controlled trial setting during a six months period a possible serum concentration-effect relationship should be searched for, as well as testing the applicability of a novel type ofTDM procedure based on the metabolite/parent compound ratio to explore both total and partial pharmacological noncompliance.

Studies I-III were applied on the naturalistic TDM-based trial design. In brief, study I contained 44 adolescents treated with CIT. Study II evaluated trough values in steady state in 749 patients treated with CIT, and study III describes the same parameters for 187 patients treated with VEN. Results revealed that interindividual PK-variations were pronounced for all compounds on all dose levels, but the intraindividual variations were low. Adolescents seemed to have CIT values similar to adults, but old age was correlated with higher dose-corrected serum concentrations of both CIT and VEN. All studied compounds displayed differences between the sexes. Polypharmacy affected the metabolism of CIT and VEN as did smoking.

Study IV contained 353 patients treated with SERT or PAR in a prospective, randomized multi-center trial with up to eight serum samples each over six months. In study V the TDM-based "compliance method" was tested on the SERT population from the study cohort. Results revealed that no serum concentration - clinical effect relationship could be found for either PAR or SERT. It was observed that the TDM compliance method seemed to detect not only total but also significant partial non-compliance.

In conclusion, the present thesis describes the possibility for making further PK-assessments on antidepressant drugs commonly prescribed. Thus, by building up drug specific TDM databases in naturalistic clinical phase IV-trials, combined with a structured data analysis a detailed retrospective follow up on the PK of the drugs coming into play in real life emerged. Taken together with the PK-data obtained from a prospective, randomized trial, the overall significance of this thesis may be to forward a new strategy for TDM -related postmarketing surveillance studies. This strategy may also be of interest to explore for other psychoactive drugs as well as for other new drugs commonly used on lager patient groups on chronic medications but outside psychiatric indications.

Place, publisher, year, edition, pages
Lund: Bloms i Lund Tryckeri AB, 2003. 70 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 783
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-24799 (URN)7063 (Local ID)91-7373-543-4 (ISBN)7063 (Archive number)7063 (OAI)
Public defence
2003-04-25, Berzeliussalen, Hälsouniversitet, Linköping, 09:00 (Swedish)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2013-10-28Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Reis, MargaretaLundmark, JönsBengtsson, Finn
By organisation
PsychiatryClinical PharmacologyFaculty of Health Sciences
In the same journal
Therapeutic Drug Monitoring
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 48 hits
ReferencesLink to record
Permanent link

Direct link