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Duloxetine in the treatment of major depressive disorder: a placebo- and paroxetine-controlled trial

Published online by Cambridge University Press:  16 April 2020

D.G.S. Perahia ,
F. Wang ,
C.H. Mallinckrodt ,
D.J. Walker  and
M.J. Detke
D.G.S. Perahia*
Affiliation:
Lilly Research Center, Erl Wood, Sunninghill Road, Windlesham, SurreyGU20 6PH, UK The Gordon Hospital, London, UK
F. Wang
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA
C.H. Mallinckrodt
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA
D.J. Walker
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA
M.J. Detke
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA Indiana University School of Medicine, Indianapolis, IN, USA Harvard Medical School, Boston, MA, USA
*
*Corresponding author. E-mail address: [email protected] (D.G.S. Perahia).
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Abstract

Objective:

Duloxetine doses of 80 and 120 mg/day were assessed for efficacy and safety in the treatment of major depressive disorder (MDD).

Methods:

In this randomized, double-blind trial, patients age ≥ 18 meeting DSM-IV criteria for MDD were randomized to placebo (N = 99), duloxetine 80 mg/day (N = 93), duloxetine 120 mg/day (N = 103), or paroxetine 20 mg/day (N = 97). The primary outcome measure was mean change from baseline in the 17-item Hamilton rating scale for depression (HAMD17) total score after 8 weeks of treatment; a number of secondary efficacy measures also were assessed. Safety and tolerability were assessed via collection and analysis of treatment–emergent adverse events (TEAEs), vital signs, and weight. The Arizona sexual experiences scale was used to assess sexual functioning. Patients who had a ≥ 30% reduction from baseline in the HAMD17 total score at the end of the acute phase entered a 6-month continuation phase where they remained on the same treatment as they had taken during the acute phase; efficacy and safety/tolerability outcomes were assessed during continuation treatment.

Results:

More than 87% of patients completed the acute phase in each treatment group. Duloxetine-treated patients (both doses) showed significantly greater improvement (P < 0.05) in the HAMD17 total score at week 8 compared with placebo. Paroxetine was not significantly different from placebo (P = 0.089) on mean change on the HAMD17. Duloxetine 120 mg/day also showed significant improvement on most secondary efficacy measures (six of nine) compared with placebo while duloxetine 80 mg/day (three of nine) and paroxetine (three of nine) were significantly superior to placebo on fewer secondary measures. HAMD17 mean change data from this study and an identical sister study were pooled as defined a priori for the purposes of performing a non-inferiority test versus paroxetine. Both duloxetine doses met statistical criteria for non-inferiority to paroxetine. TEAE reporting rates were low in all treatment groups and no deaths occurred in the acute or continuation phases.

Conclusions:

The efficacy of duloxetine at doses of 80 and 120 mg/day in the treatment of MDD was demonstrated. Tolerability, as measured by TEAEs, and safety were similar to paroxetine 20 mg/day and consistent with previous published data on duloxetine in the treatment of MDD.

Keywords

DuloxetineMajor depressive disorderPlaceboParoxetine
Type
Original article
Information
European Psychiatry , Volume 21 , Issue 6 , September 2006 , pp. 367 - 378
Copyright
Copyright © Elsevier SAS 2006

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References

Nemeroff, C.B., Schatzberg, A.F., Goldstein, D.J., Detke, M.J., Mallinckrodt, C.H., Lu, Y.et al.Duloxetine for the treatment of major depressive disorder Psychopharmacol Bull. 2002; 36:106–132.Google ScholarPubMed
Detke, M.J., Lu, Y., Goldstein, D.J., Hayes, J.R., Demitrack, M.A.Duloxetine, 60 mg once daily, for major depressive disorder: A randomized double-blind placebo-controlled trial J Clin Psychiatry 2002; 63:308–315.CrossRefGoogle ScholarPubMed
Detke, M.J., Lu, Y., Goldstein, D.J., McNamara, R.K., Demitrack, M.A.et al.Duloxetine 60 mg once daily dosing versus placebo in the acute treatment of major depression J. Psychiatr. Res. 2002; 36:383–390.CrossRefGoogle ScholarPubMed
Detke, M.J., Wiltse, C.G., Mallinckrodt, C.H., McNamara, R.K., Demitrack, M.A., Bitter, I.Duloxetine in the acute and long-term treatment of major depressive disorder: a placebo- and paroxetine-controlled trial Eur. Neuropsychopharmacol 2004; 14:457–470.CrossRefGoogle ScholarPubMed
Goldstein, D.J., Mallinckrodt, C., Lu, Y., Demitrack, M.A.Duloxetine in the treatment of major depressive disorder: A double-blind clinical trial Journal of Clinical Psychiatry 2002; 63:225–231.CrossRefGoogle ScholarPubMed
Goldstein, D.J., Lu, Y., Detke, M., Wiltse, C., Mallinckrodt, C., Demitrack, M.A.Duloxetine in the treatment of depression: A double-blind placebo-controlled comparison with paroxetine J. Clin. Psychopharmacol 2004; 24:389–399.CrossRefGoogle ScholarPubMed
Perahia, D.G., Gilaberte, I., Wang, F., Wiltse, C.G., Huckins, S.A., Clemens, J.W.et al.Duloxetine in the prevention of relapse of major depressive disorder: a double-blind, placebo-controlled study Br. J. Psychiatry 2006; 188:346–353.CrossRefGoogle Scholar
Khan, A., Schwartz, K.Study designs and outcomes in antidepressant clinical trials Essent Psychopharmacol 2005; 6:221–226.Google ScholarPubMed
Hamilton, M.A rating scale for depression J. Neurol. Neurosurg Psychiatry 1960; 23:56–62.CrossRefGoogle ScholarPubMed
Sheehan, D.V., Lecrubier, Y., Sheehan, K.H., Amorim, P., Janavs, J., Weiller, E.et al.The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10 J. Clin. Psychiatry 59(Suppl 20)1998 22–33.Google ScholarPubMed
Maier, W., Philipp, M.Improving the assessment of severity of depressive states: a reduction of the Hamilton Depression Scale Pharmacopsychiatry 1985; 18:114–115.CrossRefGoogle Scholar
Faries, D., Herrera, J., Rayamajhi, J., DeBrota, D., Demitrack, M., Potter, W.Z.The responsiveness of the Hamilton Depression Rating Scale J. Psychiatr. Res. 2000; 34:3–10.CrossRefGoogle ScholarPubMed
Tollefson, G.D., Holman, S.L.Analysis of the Hamilton Depression Rating Scale factors from a double-blind, placebo-controlled trial of fluoxetine in geriatric major depression Int. Clin. Psychopharmacol 1993; 8:253–259.CrossRefGoogle ScholarPubMed
Montgomery, S.A., Asberg, M.A new depression scale designed to be sensitive to change Br. J. Psychiatry 1979; 134:382–389.CrossRefGoogle ScholarPubMed
Hamilton, M.The assessment of anxiety states by rating Br. J. Med. Psychol. 1959; 32:50–55.CrossRefGoogle ScholarPubMed
Guy, W. ECDEU. Assessment Manual for Psychopharmacology, Revised. US Department of Health, Education, and Welfare publication (ADM) Rockville MD: National Institute of Mental Health; 1976.Google Scholar
Sheehan, D.V., Harnett-Sheehan, K., Raj, B.A.The measurement of disability Int. Clin. Psychopharmacol 11(Suppl 3)1996 89–95.CrossRefGoogle ScholarPubMed
DeLoach, L.J., Higgins, M.S., Caplan, A.B., Stiff, J.L.The visual analog scale in the immediate postoperative period: intrasubject variability and correlation with a numeric scale Anesth. Analg. 1998; 86:102–106.Google ScholarPubMed
Barsky, A.J., Wyshak, G., Klerman, G.L.et al.Hypochondriasis. An evaluation of the DSM-III criteria in medical outpatients Arch. Gen. Psychiatry 1986; 43:493–500.CrossRefGoogle ScholarPubMed
McGahuey, C.A., Gelenberg, A.J., Laukes, C.A., Moreno, F.A., Delgado, P.L., McKnight, K.M.et al.The Arizona Sexual Experience Scale (ASEX): reliability and validity J. Sex. Marital. Ther. 2000; 26:25–40.Google ScholarPubMed
Mallinckrodt, C.H., Clark, W.S., David, S.R.Accounting for dropout bias using mixed-effects models J. Biopharm. Stat. 2001; 11:9–21.CrossRefGoogle ScholarPubMed
Mallinckrodt, C.H., Clark, W.S., David, S.R.Type I error rates from mixed-effects model repeated measures compared with fixed-effects ANOVA with missing values imputed via LOCF Drug. Inf. J. 2001; 35:1215–1225.CrossRefGoogle Scholar
Lieberman, J.A., Greenhouse, J., Hamer, R.M., Krishnan, K.R., Nemeroff, C.B., Sheehan, D.V.et al.Comparing the effects of antidepressants: consensus guidelines for evaluating quantitative reviews of antidepressant efficacy Neuropsychopharmacol 2005; 30:445–460.CrossRefGoogle ScholarPubMed
Leon, A.C.Measuring onset of antidepressant action in clinical trials: an overview of definitions and methodology J. Clin. Psychiatry 62(Suppl 4)2001 12–16.Google ScholarPubMed
Thompson, W., Brunelle, R., Enas, G.et al.Routine laboratory tests in clinical trials Eli Lilly and Company, Indianapolis, IN 1990 1–63.Google Scholar
Khan, A., Detke, M.J., Khan, S.R.F., Mallinckrodt, C.Placebo Response and Antidepressant Clinical Trial Outcome J. Nerv. Ment. Dis. 2003; 19:211–218.CrossRefGoogle Scholar
Delgado, P.L., Brannan, S.K., Mallinckrodt, C.H., Tran, P.V., McNamara, R.K., Wang, F.et al.Sexual functioning assessed in 4 double-blind placebo- and paroxetine-controlled trials of duloxetine for major depressive disorder J. Clin. Psychiatry 2005; 66:686–692.CrossRefGoogle ScholarPubMed
Dunner, D.L., Dunbar, G.C.et al.Optimal dose regimen for paroxetine J. Clin. Psychiatry 53(Suppl)1992 21–26.Google ScholarPubMed
Benkert, O., Szegedi, A., Wetzel, H., Staab, H.J., Meister, W., Philipp, M.Dose escalation vs. continued dose of paroxetine and maptroline: a prospective study in depressed outpatients with inadequate treatment response Acta. Psychiatr. Scand. 1997; 95:288–296.CrossRefGoogle Scholar
Jenner, P.N.Paroxetine: an overview of dosage, tolerability, and safety Int. Clin. Psychopharmacol. 6(Suppl 4)1992 69–80.CrossRefGoogle ScholarPubMed
Wernicke, J.F., Faries, D., Milton, D., Weyrauch, K.Detecting treatment emergent adverse events in clinical trials: a comparison of spontaneously reported and solicited collection methods Drug Safety 2005; 28:1057–1063.CrossRefGoogle ScholarPubMed
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