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The effect of paroxetine on cerebrospinal fluid concentrations of neurotransmitter metabolites in depressed patients
Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences.
University Hospital, Lund, Sweden.
Novo Nordisk A/S, Copenhagen, Denmark.
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1994 (English)In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 4, no 1, 1-6 p.Article in journal (Refereed) Published
Abstract [en]

This paper describes the effect of the selective serotonin reuptake inhibiting drug (SSRI), paroxetine, on cerebrospinal fluid concentrations of neurotransmitter metabolites in depressed patients. 5-Hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were measured at baseline and after 3 weeks of treatment with 30 mg paroxetine daily. In line with similar studies on other SSRIs, influence on both the serotonin and noradrenaline metabolite was found. The mechanism behind the action of paroxetine on both 5-HIAA and MHPG is assumed to be an expression of the linkage between the serotonergic and noradrenergic systems in the brain. A frequently reported correlation between 5-HIAA and HVA was also found. The analysis of paroxetine in CSF proves the transportation of the drug into the central nervous system.

Place, publisher, year, edition, pages
1994. Vol. 4, no 1, 1-6 p.
Keyword [en]
Cerebrospinal fluid, Serotonin, Selective serotonin reuptake inhibitors, Paroxetine, Major depression
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-79926DOI: 10.1016/0924-977X(94)90308-5PubMedID: 7515737OAI: oai:DiVA.org:liu-79926DiVA: diva2:544663
Available from: 2012-08-15 Created: 2012-08-15 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Clinical and Pharmacological Aspects of Selective Serotonin Reuptake Inhibitors in the Treatment of Depression in Old Age
Open this publication in new window or tab >>Clinical and Pharmacological Aspects of Selective Serotonin Reuptake Inhibitors in the Treatment of Depression in Old Age
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Objective: The aim of the present thesis is to examine the pharmacokinetic and biochemical effects of the selective serotonin reuptake inhibitors (SSRIs) in the elderly.

Background: Symptoms of depression are found in up to 15% of the elderly and the prevalence of major depression is reported to be about 3%. At present SSRIs are the pharmacological tools most frequently used for the treatment of depression. Patients in old age account for a relatively higher proportion of SSRI expenditures, although the elderly are seriously underrepresented in pharmacological studies and are increasingly susceptible to adverse drug events.

Subjects and Methods: Serum concentrations of the SSRis fluoxetine, paroxetine, and sertraline in the elderly were compared to those in younger patients. Effects of paroxetine on cerebrospinal fiuid (CSF) monoamine concentrations were investigated. Influences of therapeutic drug monitoring (TDM) of citalopram, paroxetine, and sertraline on clinical dosing strategies and antidepressant drug costs during a 6-9-month follow-up were studied in depressed elderly patients. Various individual factors, including age, which may influence serum concentrations of fluoxetine and sertraline were evaluated using population TOM data.

Results: lnterindividual serum concentration variations were pronounced irrespective of age. Compared to the variability between subjects, the intraindividual variability of fiuoxetine and sertraline serum concentrations was found to be low. In the elderly, fiuoxetine, paroxetine, and sertraline serum concentrations were higher than in younger patients. In the case of fluoxetine, gross obesity influenced serum concentrations and sertraline serum concentrations were lower in smokers than in non-smokers. In the case of paroxetine, nonlinear pharmacokinetics were observed in some subjects and paroxetine treatment influenced both serotonergic and noradrenergic neurotransmission, as indicated by 5-HIAA and MHPG concentrations in the CSF. TDM-supported SSRI clinical dosing was found to reduce the doses used and efficacy was sustained when observed during an open follow-up.

Conclusions: The results reported in the present thesis emphasize the importance of conducting clinical and pharmacological research in the elderly in different phases of drug development. In the postmarketing phase, TOM databases provide important tools for the collection of new pharmacokinetic data from clinical populations and data important for the interpretation of population SS RI serum concentrations. TDM of the SSRis may support individual dose optimization, including assessments of drug compliance.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2000. 94 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 650
Keyword
Serum concentrations, cerebrospinal fluid, pharmacokinetics, selective serotonin reuptake inhibitors, therapeutic drug monitoring, elderly, depression, pharmaceutical economics
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-28058 (URN)12821 (Local ID)91-7219-751-X (ISBN)12821 (Archive number)12821 (OAI)
Public defence
2000-11-24, Berzeliussalen, Universitetssjukhuset, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-08-15Bibliographically approved

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Lundmark, JönsWålinder, Jan

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