Duloxetine in the treatment of major depressive disorder: an open-label study

James I Hudson, David G Perahia, Inmaculada Gilaberte, Fujun Wang, John G Watkin, Michael J Detke, James I Hudson, David G Perahia, Inmaculada Gilaberte, Fujun Wang, John G Watkin, Michael J Detke

Abstract

Background: Major depressive disorder (MDD) is a chronic and highly disabling condition. Existing pharmacotherapies produce full remission in only 30% to 40% of treated patients. Antidepressants exhibiting dual reuptake inhibition of both serotonin (5-HT) and norepinephrine (NE) may achieve higher rates of remission compared with those acting upon a single neurotransmitter. In this study, the safety and efficacy of duloxetine, a potent dual reuptake inhibitor of 5-HT and NE, were examined.

Methods: Patients (N = 533) meeting DSM-IV criteria for MDD received open-label duloxetine (60 mg once a day [QD]) for 12 weeks during the initial phase of a relapse prevention trial. Patients were required to have a 17-item Hamilton Rating Scale for Depression (HAMD17) total score >or=18 and a Clinical Global Impression of Severity (CGI-S) score >or=4 at baseline. Efficacy measures included the HAMD17 total score, HAMD17 subscales, the CGI-S, the Patient Global Impression of Improvement (PGI-I) scale, Visual Analog Scales (VAS) for pain, and the Symptom Questionnaire, Somatic Subscale (SQ-SS). Quality of life was assessed using the Sheehan Disability Scale (SDS) and the Quality of Life in Depression Scale (QLDS). Safety was evaluated by recording spontaneously-reported treatment-emergent adverse events, changes in vital signs and laboratory analytes, and the Patient Global Impression of Sexual Function (PGI-SF) scale.

Results: The rate of discontinuation due to adverse events was 11.3%. Treatment-emergent adverse events reported by >or=10% duloxetine-treated patients were nausea, headache, dry mouth, somnolence, insomnia, and dizziness. Following 12 weeks of open-label duloxetine therapy, significant improvements were observed in all assessed efficacy and quality of life measures. In assessments of depression severity (HAMD17, CGI-S) the magnitude of symptom improvement continued to increase at each study visit, while for painful physical symptoms the onset of improvement was rapid and reached a maximum after 2 to 3 weeks of treatment.

Conclusion: In this open-label phase of a relapse prevention study, duloxetine (60 mg QD) was shown to be safe and effective in the treatment of MDD.

Trial registration: ClinicalTrials.gov NCT00036309.

Figures

Figure 1
Figure 1
Visitwise plot of mean change in HAMD17 total score for patients receiving duloxetine (60 mg QD, n = 511). MMRM analysis. * p < .001 from t-test for LS mean change = 0.
Figure 2
Figure 2
Visitwise plot of mean change in VAS pain severity scores for patients receiving duloxetine (60 mg QD). MMRM analysis. p

References

    1. Greden JF. The burden of recurrent depression: causes, consequences, and future prospects. J Clin Psychiatry. 2001;62:5–9.
    1. Wells KB, Stewart A, Hays RD, Burnam MA, Rogers W, Daniels M, Berry S, Greenfield S, Ware J. The functioning and well-being of depressed patients. Results from the Medical Outcomes Study. JAMA. 1989;262:914–919. doi: 10.1001/jama.262.7.914.
    1. Anderson IM, Tomenson BM. Treatment discontinuation with selective serotonin reuptake inhibitors compared with tricyclic antidepressants: a meta-analysis. BMJ. 1995;310:1433–1438.
    1. Steffens DC, Krishnan KR, Helms MJ. Are SSRIs better than TCAs? Comparison of SSRIs and TCAs: a meta-analysis. Depress Anxiety. 1997;6:10–18. doi: 10.1002/(SICI)1520-6394(1997)6:1<10::AID-DA2>;2-9.
    1. Anderson IM. Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability. J Affect Disord. 2000;58:19–36. doi: 10.1016/S0165-0327(99)00092-0.
    1. Corey-Lisle PK, Nash R, Stang P, Swindle R. Response, partial response, and nonresponse in primary care treatment of depression. Arch Intern Med. 2004;164:1197–1204. doi: 10.1001/archinte.164.11.1197.
    1. Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, Shaw JL, Thompson L, Nelson DL, Hemrick-Luecke SK, Wong DT. 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. 2001;25:871–880. doi: 10.1016/S0893-133X(01)00298-6.
    1. Wong DT, Bymaster FP. Dual serotonin and noradrenaline uptake inhibitor class of antidepressants potential for greater efficacy or just hype? Prog Drug Res. 2002;58:169–222.
    1. Detke MJ, Lu Y, Goldstein DJ, Hayes JR, Demitrack MA. Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. J Clin Psychiatry. 2002;63:308–315.
    1. Detke MJ, Lu Y, Goldstein DJ, McNamara RK, Demitrack MA. Duloxetine 60 mg once daily dosing versus placebo in the acute treatment of major depression. J Psychiatr Res. 2002;36:383. doi: 10.1016/S0022-3956(02)00060-2.
    1. Goldstein DJ, Mallinckrodt C, Lu Y, Demitrack MA. Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial. J Clin Psychiatry. 2002;63:225–231.
    1. Goldstein DJ, Lu Y, Detke MJ, Wiltse C, Mallinckrodt C, Demitrack MA. Duloxetine in the treatment of depression: a double-blind placebo-controlled comparison with paroxetine. J Clin Psychopharmacol. 2004;24:389–399. doi: 10.1097/01.jcp.0000132448.65972.d9.
    1. Mallinckrodt CH, Goldstein DJ, Detke MJ, Lu Y, Watkin JG, Tran PV. Duloxetine: a new treatment for the emotional and physical symptoms of depression. Prim Care Companion J Clin Psychiatry. 2003;5:19–28.
    1. Nemeroff CB, Schatzberg AF, Goldstein DJ, Detke MJ, Mallinckrodt C, Lu Y, Tran PV. Duloxetine for the treatment of major depressive disorder. Psychopharmacol Bull. 2002;36:106–132.
    1. Perahia DG, Gilaberte I, Wang F, Wiltse CG, Huckins SA, Clemens JW, Montgomery SA, Montejo AL, Detke MJ. Duloxetine in the prevention of relapse of major depressive disorder. Br J Psychiatry. 2006;188:346–353. doi: 10.1192/bjp.188.4.346.
    1. American Psychiatric Association . Diagnostic and statistical manual of mental disorders. 4. Washington, DC: American Psychiatric Association; 1994.
    1. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC. 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. 1998;59:22–33.
    1. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56–62.
    1. Guy W. ECDEU assessment manual for psychopharmacology, revised 1976. Rockville, MD: National Institutes of Mental Health; 1976.
    1. JNC The sixth report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. 1997. NIH Publication No. 98-4080.
    1. Michelson D, Schmidt M, Lee J, Tepner R. Changes in sexual function during acute and six-month fluoxetine therapy: a prospective assessment. J Sex Marital Ther. 2001;27:289–302. doi: 10.1080/009262301750257146.
    1. DeLoach LJ, Higgins MS, Caplan AB, Stiff JL. The visual analog scale in the immediate postoperative period: intrasubject variability and correlation with a numeric scale. Anesth Analg. 1998;86:102–106. doi: 10.1097/00000539-199801000-00020.
    1. Kellner R. A symptom questionnaire. J Clin Psychiatry. 1987;48:268–274.
    1. Hunt SM, McKenna SP. The QLDS: a scale for the measurement of quality of life in depression. Health Policy. 1992;22:307–319. doi: 10.1016/0168-8510(92)90004-U.
    1. Sheehan DV, Harnett-Sheehan K, Raj BA. The measurement of disability. Int Clin Psychopharmacol. 1996;11:89–95. doi: 10.1097/00004850-199606003-00015.
    1. Mallinckrodt CH, Sanger TM, Dube S, DeBrota DJ, Molenberghs G, Carroll RJ, Potter WZ, Tollefson GD. Assessing and interpreting treatment effects in longitudinal clinical trials with missing data. Biol Psychiatry. 2003;53:754–760. doi: 10.1016/S0006-3223(02)01867-X.
    1. Mallinckrodt CH, Clark SW, Carroll RJ, Molenbergh G. Assessing response profiles from incomplete longitudinal clinical trial data under regulatory considerations. J Biopharm Stat. 2003;13:179–190. doi: 10.1081/BIP-120019265.
    1. Lexapro full prescribing information. [ , revision September 2006, accessed 8JAN2007].
    1. Paxil-CR full prescribing information. [ , revision July 2006, accessed 8JAN2007].
    1. Effexor-XR full prescribing information. [ , revision August 2006, accessed 8JAN2007].
    1. Delgado PL, Brannan SK, Mallinckrodt CH, Tran PV, McNamara RK, Wang F, Watkin JG, Detke MJ. 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.
    1. Hudson JI, Wohlreich MM, Kajdasz DK, Mallinckrodt CH, Watkin JG, Martynov OV. Safety and tolerability of duloxetine in the treatment of major depressive disorder: analysis of pooled data from eight placebo-controlled clinical trials. Hum Psychopharmacol. 2005;20:327–341. doi: 10.1002/hup.696.
    1. Agelink MW, Ullrich H, Baumann B, Strum S, Majewski T. Effects of reboxetine, a selective norepinephrine reuptake inhibitor, on sympathetic and parasympathetic outflow to the heart: preliminary data. Psychopharmacology (Berl) 2002;163:151–156. doi: 10.1007/s00213-002-1146-7.
    1. Bielski RJ, Ventura D, Chang CC. A double-blind comparison of escitalopram and venlafaxine extended release in the treatment of major depressive disorder. J Clin Psychiatry. 2004;65:1190–1196.
    1. Raskin J, Goldstein DJ, Mallinckrodt CH, Ferguson MB. Duloxetine in the long-term treatment of major depressive disorder. J Clin Psychiatry. 2003;64:1237–1244.
    1. Eli Lilly & Company Data on file and Cymbalta full prescribing information. [ , revision September 20, 2006]
    1. Jones SL. Descending noradrenergic influences on pain. Prog Brain Res. 1991;88:381–394.
    1. Richardson BP. Serotonin and nociception. Ann NY Acad Sci. 1990;600:511–519. doi: 10.1111/j.1749-6632.1990.tb16906.x.
    1. Willis WD, Westlund KN. Neuroanatomy of the pain system and of the pathways that modulate pain. J Clin Neurophysiol. 1997;14:2–31. doi: 10.1097/00004691-199701000-00002.
    1. Goldstein DJ, Lu Y, Detke MJ, Hudson J, Iyengar S, Demitrack MA. Effects of duloxetine on painful physical symptoms associated with depression. Psychosomatics. 2004;45:17–28. doi: 10.1176/appi.psy.45.1.17.
    1. Fava M, Mallinckrodt CH, Detke MJ, Watkin JG, Wohlreich MM. 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.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi