Background: In analogy to tricyclic antidepressants, serum concentrations of selective serotonin
reuptake inhibitors (SSRIs) are frequently measured in order to optimize treatment
results. However, clinical evidence for this approach is sparse. Methods: Forty patients with major depression were treated with paroxetine 20 mg/day for 14
days and with 40 mg/day for further 49 days. Treatment response measured by Hamilton
depression rating scales (HAMD) was correlated with paroxetine plasma concentrations.
Results: There was a significant difference between paroxetine plasma levels at 20 and 40
mg/day, respectively [20 mg/d: median 24 (range 4-358); 40 mg/d: 92 (30-398)]. However,
the interindividual variance was very large. 18 out of 40 patients responded to paroxetine
treatment. Conclusions: Receiver operated characteristic (ROC) analysis suggested no upper or lower limit
of response. Responder had significantly higher paroxetine levels at day 7 [responder:
33 (4-107); non-responder: 13 (3-77)] but not at the end of the study [responder 93
(30-361); non-responder: 94 (59-398)]. Furthermore, plasma levels were not related
to adverse events, age, body weight or severity of depression. These findings do not
support any need for a routine screening of paroxetine plasma concentrations in clinical
practice.
References
- 1
Alvan G, Bechtel P, Iselius L, Gundert-Remy U.
Hydroxylation polymorphisms of debrisoquine and mephenytoin in European populations.
Eur J Clin Pharmacol.
1990;
39
533-537
- 2
Bolo N R, Hode Y, Nedelec J F, Laine E, Wagner G, Macher J P.
Brain pharmacokinetics and tissue distribution in vivo of fluvoxamine and fluoxetine
by flourine magnetic resonance spectroscopy.
Neuropsychopharmacology.
2000;
23
428-438
- 3
Danish University Antidepressant G roup.
Paroxetine: A selective serotonin reuptake inhibitor showing better tolerance, but
weaker antidepressant effect than clomipramine in a controlled multicenter study.
J Affect Disord.
1990;
18
289-299
- 4
Karson C N, Newton J E, Livingston R, Jolly J B, Cooper T, Spring J, Komoroski R A.
Human brain fluoxetine concentrations.
J Neuropsychiatry Clin Neurosci.
1993;
5
322-329
- 5
Kaye C M, Haddock R E, Langley P F, Mellows G, Tasker T C, Zussman B D, Greb W H.
A review of the metabolism and pharmacokinetics of paroxetine in man.
Acta Psychiatr Scand.
1989;
350
60-75
- 6
Kuhs H, Schlake H P, Rolf L H, Rudolf G A.
Relationship between parameters of serotonin transport and antidepressant plasma levels
or therapeutic response in depressive patients treated with paroxetine and amitriptyline.
Acta Psychiatr Scand.
1992;
85
364-369
- 7
Laursen A L, Mikkelsen P L, Rasmussen S, le-Fevre H P.
Paroxetine in the treatment of depression - a randomized comparison with amitriptyline.
Acta Psychiatr Scand.
1985;
71
249-255
- 8
Mossman D, Somoza E.
ROC curves, test accuracy, and the description of diagnostic tests.
J Neuropsychiatry Clin Neurosci.
1991;
3
330-333
- 9
Müller M J, Dragicevic A, Fric M, Gaertner I, Grasmader K, Hartter S, Hermann E, Kuss H J,
Laux G, Oehl W, Rao M L, Rollmann N, Weigmann H, Weber-Labonte M, Hiemke C.
Therapeutic drug monitoring of tricyclic antidepressants: how does it work under clinical
conditions?.
Pharmacopsychiatry.
2003;
36
98-104
- 10
Normann C, Hummel B, Schärer L O, Hörn M, Grunze H, Walden J.
Lamotrigine as adjunct to paroxetine in acute depression: a placebo-controlled, double
blind study.
J Clin Psychiatry.
2002;
63
337-344
- 11
Rasmussen B B, Brosen K.
Is therapeutic drug monitoring a case for optimizing clinical outcome and avoiding
interactions of selective serotonin reuptake inhibitors.
Ther Drug Monit.
2000;
22
143-154
- 12
Sindrup S H, Brosen K, Gram L F.
Pharmacokinetics of the selective serotonin reuptake inhibitor paroxetine: nonlinearity
and relation to the spartein oxidation polymorphism.
Clin Pharmacol Ther.
1992;
51
288-295
- 13
Tasker T C, Kaye C M, Zussman B D, Link C G.
Paroxetine plasma levels: lack of correlation with efficacy or adverse events.
Acta Psychiatr Scand.
1989;
350(suppl)
152-155
Dr. C. Normann
Department of Psychiatry and Psychotherapy
University of Freiburg
Hauptstrasse 5
79104 Freiburg
Germany
Email: claus_normann@psyallg.ukl.uni-freiburg.de
