Introduction: The aim of this study was to relate drug concentrations in serum and clinical effects in patients treated with the new antidepressant duloxetine.
Methods: Data were obtained from a newly established therapeutic drug monitoring (TDM) survey. Duloxetine was measured using HPLC with UV detection and clinical effects by the clinical global impressions (CGI) scale for improvement.
Results: The study included 103 depressed inpatients (69% female). Patients under duloxetine monotherapy who were very much improved according to CGI had significantly (p<0.05) higher serum levels than patients with moderate, minimal or lacking improvement (mean±SD and range, 93±53 ng/mL and 30–182 ng/mL and 47±39 ng/mL and 5–178 ng/mL, respectively). Daily doses were similar in the two groups (76±27 vs. 83±27 mg/d). Receiver operating characteristics (ROC) curve analysis revealed significant predictive properties of duloxetine serum levels (p=0.011) for improvement with a lower threshold concentration of duloxetine of 58 ng/mL.
Discussion: The findings indicate that therapeutic drug monitoring of duloxetine and titration to steady state serum concentrations above 58 ng/mL is useful for treatment optimization.
References
1
Adli M, Pilhatsch M, Bauer M. et al .
Safety of high-intensity treatment with irreversible monoamine oxidase inhibitor tranylcypromine in patients with treatment-resistant depression.
Pharmacopsychiatry.
2008;
41
252-257
2
Anderson IM.
Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability.
J Affect Disord.
2000;
58
19-36
3
Baumann P, Hiemke C, Ulrich S. et al .
The AGNP-TDM expert group consensus guidelines: therapeutic drug monitoring in psychiatry.
Pharmacopsychiatry.
2004;
37
243-265
4
Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG. et al .
Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors.
Neuropsychopharmacology.
2002;
25
871-880
6
Detke MJ, Lu Y, Goldstein DJ. et al .
Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial.
J Clin Psychiatry.
2002;
63
308-315
7
Detke MJ, Wiltse CG, Mallinckrodt CH. et al .
Duloxetine in the acute and long-term treatment of major depressive isorder: a placebo- and paroxetine- controlled trial.
Eur Neuropsychopharmacol.
2004;
4
457-470
9
Fava M, Mallinckrodt CH, Detke MJ. et al .
The effect of duloxetine on painful physical symptoms in depressed patients: do improvements in these symptoms result in higher remission rates?.
J Clin Psychiatry.
2004;
65
521-530
12
Goldstein DJ, Lu Y, Detke MJ. et al .
Duloxetine in the treatment of depression. A double-blind placebo-controlled comparison with paroxetine.
J Clin Psychiatry.
2004;
24
389-399
13 Guy W. Early Clinical Drug Evaluation Unit (ECDEU) assessment manual for psychopharmacology. Revised. NIMH publication (DHEW publ No ADM 76-338). Bethesda MD: National Institute of Mental Health 1976: p 217-222
15
Hansen RA, Gartlehner G, Lohr KN. et al .
Efficacy and safety of second-generation antidepressant in the treatment of major depressive disorder.
Ann Intern Med.
2005;
143
415-426
18
Lantz RJ, Gillespie TA, Rash TJ. et al .
Metabolism, excretion, and pharmacokinetics of duloxetine in healthy human subjects.
Drug Metab Dispos.
2003;
31
1142-1150
21
Lingjaerde O, Ahlfors UG, Bech P. et al .
The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients.
Acta Psychiatr Scand Suppl.
1987;
334
1-100
22
Lobo ED, Bergstrom RF, Reddy S. et al .
In vitro and in vivo evaluations of cytochrome P450 1A2 interactions with duloxetine.
Clin Pharmacokinet.
2008;
47
191-202
23
Lopez AD, Mathers CD, Ezzati M. et al .
Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data.
Lancet.
2006;
367
1747-1757
24
Lopez-Munoz F, Alamo C, Rubio G. et al .
Reboxetine combination in treatment-resistant depression to selective serotonin reuptake inhibitors.
Pharmacopsychiatry.
2007;
40
14-19
25
Mace S, Taylor D.
Selective Serotonin reuptake inhibitors: a review of efficacy and tolerability in depression.
Expert Opin Pharmacother.
2000;
1
917-933
26
MacGillivray S, Arroll B, Hatcher S. et al .
Efficacy and tolerability of selective serotonin reuptake inhibitors compared with tricyclic antidepressants in depression treated in primary care: systematic review and meta analysis.
BMJ.
2003;
326
1014
27
Mann K, Hiemke C, Schmidt LG. et al .
Appropriateness of therapeutic drug monitoring for antidepressants in routine psychiatric inpatient care.
Ther Drug Monit.
2006;
28
83-88
28
Montgomery SA, Baldwin DS, Blier P. et al .
Which antidepressants have demonstrated superior efficacy? A review of the evidence.
Int Clin Psychopharmacol.
2007;
22
323-329
29
Müller MJ, Dragicevic A, Fric M. et al .
Therapeutic Drug Monitoring of tricyclic antidepressants: how does it work under clinical conditions.
Pharmacopsychiatry.
2003;
36
98-104
30
Nierenberg AA.
The treatment of severe depression: is there an efficacy gap between SSRI and TCA antidepressant generation?.
J Clin Psychiatry.
1994;
55
((Suppl A))
55-59
, discussion 60–61, 98–100
33
Papakostas GI, Homberger CH, Fava M.
A meta-analysis of clinical trial comparing mirtazapine with selective serotonin reuptake inhibitors for the treatment of major depressive disorder.
J Psychopharmacol.
2008;
, Feb 28. [Epub ahead of print]
34
Pjrek E, Willeit M, Praschak-Rieder N. et al .
Treatment of seasonal affective disorder with duloxetine: an open-label study.
Pharmacopsychiatry.
2008;
41
100-105
35
Preskorn SH, Greenblatt DJ, Flockhardt D. et al .
Comparison of duloxetine, escitalopram and sertraline effects on cytochrome P450 2D6 function in healthy volunteers.
J Clin Psychopharmacol.
2007;
27
28-34
36
Raskin J, Goldstein DJ, Mallinckrodt CH. et al .
Duloxetine in the long-term treatment of major depression disorder.
J Clin Psychiatry.
2003;
64
1237-1244
37
Skinner MH, Kuan HY, Pan A. et al .
Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers.
Clin Pharmacol Ther.
2003;
73
170-177
39
Ulrich S, Hiemke C, Laux G. et al .
Value and actuality of the prescription information for therapeutic drug monitoring of psychopharmaceuticals: a comparison with the medico-scientific evidence.
Pharmacopsychiatry.
2007;
40
121-127
40
Waldschmitt C, Vogel F, Maurer C. et al .
Measurement of duloxetine in blood using high-performance liquid chromatography with spectrophotometric detection and column switching.
Ther Drug Monit.
2007;
29
767-772
