Paroxetine Serum Concentrations in Depressed Patients and Response to Treatment

Introduction: There is no established relationship between the serum concentration of selective serotonin reuptake inhibitors (SSRIs) and clinical response in depressed patients. Methods: We analyzed paroxetine concentrations in serum of 46 depressed patients during treatment with a fixed dosage of 40 mg paroxetine. Results: After 5 weeks 29 patients responded to treatment, while 17 did not. Analysis of variance with repeated measures (ANOVA-rm) revealed a significant effect of ”response” with responders having lower serum concentrations throughout the treatment period, when compared to non-responders. After 2, 3, and 4 weeks of treatment, we could define an upper threshold of paroxetine serum concentrations (week 1 : 22.7 ng/mL; week 2 : 43 ng/mL; week 3 : 53.4 ng/mL; week 4 : 39.1 ng/mL) above which response to treatment was unlikely. Conclusion: We conclude that - in contrast to other pharmacological approaches - high rather than low drug serum concentrations may be associated with non-response in paroxetine treatment of depressed patients.

References

• 1 Deuschle M, Hamann B, Meichel C, Krumm B, Lederbogen B, Kniest A, Colla M, Heuser I. Antidepressive treatment with amitriptyline and paroxetine: effects upon saliva cortisol concentrations.  J Clin Psychopharmacol. 2003;  23 201-205
• 2 de la Torre B R, Dreher J, Malevany I, Bagli M, Kolbinger M, Omran H, Lüderitz B, Rao M L. Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients.  Ther Drug Monit. 2001;  23 435-440
• 3 Feighner P. Klinische Wirkungen von Serotonin-Wiederaufnahmehemmern - eine Übersicht.  Fortschr Neurol Psychiat. 1994;  62 (suppl 1) 9-15
• 4 Franke L, Schewe H J, Uebelhack R, Müller-Oerlinghausen B. Predictors of therapeutic effects in amitriptyline treatment-1. Plasma drug levels.  Pharmacopsychiatry.. 2003;  36 34-142
• 5 Frieboes R M, Sonntag A, Yassouridis A, Eap C B, Baumann P, Steiger A. Clinical outcome after trimipramine in patients with delusional depression - a pilot study.  Pharmacopsychiatry.. 2003;  36 12-17
• 6 Gerstenberg G, Aoshima T, Fukasawa T, Yoshido K, Takahashi H, Higuchi H. et al . Relationship between clinical effects of fluvoxamine and the steady-state serum concentrations of fluvoxamine and its major metabolite fluvoxamino acid in Japanese depressed patients.  Psychopharmacology. 2003;  167 443-448
• 7 Grözinger M, Dragicevic A, Hiemke C, Shams M, Muller M J, Härtter S. Melperone is an inhibitor of the CYP2D6 catalyzed O-demethylation of venlafaxine.  Pharmacopsychiatry. 2003;  36 3-6
• 8 Härtter S, Hermes B, Szegedi A, Hiemke C. Automated deterimination of paroxetine and its main metabolite by column switching and on-line high-performance liquid chromatography.  Ther Drug Monit. 1994;  16 400-406
• 9 Härtter S, Wetzel H, Hammes E, Torkzadeh M, Hiemke C. Serum concentrations of fluvoxamine and clinical effects.  Pharmacopsychiatry. 1998;  31 199-200
• 10 Kasper S, Dötsch M, Kick H, Vieira A, Möller H J. Plasma concentrations of fluvoxamine and maprotiline in major depression: implications on therapeutic efficacy and side effects.  Eur Neuropsychopharmacol. 1993;  3 13 - 21
• 11 Lundmark J, Bengtsson F, Nordin C, Reis M, Walinder J. Therapeutic drug monitoring of selective serotonin reuptake inhibitors influences clinical dosing strategies and reduces drug costs in depressed elderly patients.  Acta Psychiatr Scand. 2000;  101 354-359
• 12 Mauri M C, Laini V, Bitetto A, Boscati L, Scalvini M, Mapelli L, Budelli R. Long-term efficacy of paroxetine in major depression: a study with plasma levels.  Int J Psychiatry Clin Pract. 1999;  3 115-119
• 13 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
• 14 Normann C, Hörn M, Hummel B, Grunze H, Walden J. Paroxetine in Major Depression: correlating plasma concentrations and clinical response.  Pharmacopsychiatry. 2004;  37 123-126
• 15 Sandmann J, Lörch B, Bandelow B, Härtter S, Winter P, Hiemke C, Benkert O. Fluvoxamine or placebo in the treatment of panic disorder and relationship to blood concentrations of fluvoxamine.  Pharmacopsychiatry. 1998;  31 17-121
• 16 Sindrup S H, Grodum E, Gram L F, Beck-Nielsen H. Concentration-response relationship in paroxetine treatment of diabetic neuropathy symptoms: a patient-blinded dose-escalation study.  Ther Drug. Monit 1991;  13 408-14
• 17 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 Suppl. 1989;  350 152-155