Duloxetine in the treatment of Major Depressive Disorder: a comparison of efficacy in patients with and without melancholic features

Craig H Mallinckrodt, John G Watkin, Chaofeng Liu, Madelaine M Wohlreich, Joel Raskin, Craig H Mallinckrodt, John G Watkin, Chaofeng Liu, Madelaine M Wohlreich, Joel Raskin

Abstract

Background: The most prominent feature of melancholic depression is a near-total loss of the capacity to derive pleasure from activities or other positive stimuli. Additional symptoms can include psychomotor disturbances, anorexia, excessive guilt, and early awakening from sleep. Melancholic patients may exhibit treatment responses and outcomes that differ from those of non-melancholic patients. Pooled data from double-blind, placebo-controlled studies were utilized to compare the efficacy of duloxetine in depressed patients with and without melancholic features.

Methods: Efficacy data were pooled from 8 double-blind, placebo-controlled clinical trials of duloxetine. The presence of melancholic features (DSM-IV criteria) was determined using results from the Mini International Neuropsychiatric Interview (MINI). Patients (aged >or= 18 years) meeting DSM-IV criteria for major depressive disorder (MDD) received duloxetine (40-120 mg/d; melancholic, N = 759; non-melancholic, N = 379) or placebo (melancholic, N = 519; non-melancholic, N = 256) for up to 9 weeks. Efficacy measures included the 17-item Hamilton Rating Scale for Depression (HAMD17) total score, HAMD17 subscales (Maier, anxiety, retardation, sleep), the Clinical Global Impression of Severity (CGI-S) and Patient Global Impression of Improvement (PGI-I) scales, and Visual Analog Scales (VAS) for pain.

Results: In data from all 8 studies, duloxetine's advantage over placebo did not differ significantly between melancholic and non-melancholic patients (treatment-by-melancholic status interactions were not statistically significant). Duloxetine demonstrated significantly greater improvement in depressive symptom severity, compared with placebo, within both melancholic and non-melancholic cohorts (p <or= .001 for HAMD17 total score, CGI-S and PGI-I). When analyzed by gender, the magnitude of improvement in efficacy outcomes did not differ significantly between duloxetine-treated male and female melancholic patients. In the two studies that assessed duloxetine 60 mg once-daily dosing, duloxetine-treated melancholic patients had significantly greater improvement compared with placebo on HAMD17 total score, CGI-S, PGI-I, 3 of 4 subscales of the HAMD17, and VAS overall pain severity (p < .01). Estimated probabilities of response and remission were significantly greater for melancholic patients receiving duloxetine 60 mg QD compared with placebo (response 74.7% vs. 42.2%, respectively, p < .001; remission 44.4% vs. 24.7%, respectively, p = .002.

Conclusions: In this analysis of pooled data, the efficacy of duloxetine in patients with melancholic features did not differ significantly from that observed in non-melancholic patients.

Figures

Figure 1
Figure 1
Mean changes in HAMD17 Maier subscale for melancholic patients receiving duloxetine (60 mg QD) or placebo. ** p < .005 vs. placebo.
Figure 2
Figure 2
Mean changes in VAS overall pain severity for melancholic patients receiving duloxetine (60 mg QD) or placebo. ** p

References

    1. Jackson SW. Melancholia and depression: from Hippocratic times to modern times. New Haven, CT: Yale University Press; 1986.
    1. American Psychiatric Association . Diagnostic and statistical manual of mental disorders. 4th. Washington, DC: American Psychiatric Association; 1994.
    1. Tedlow J, Smith M, Neault N, Polania L, Alpert J, Nierenberg A, Fava M. Melancholia and axis II comorbidity. Compr Psychiatry. 2002;43:331–335. doi: 10.1053/comp.2002.34631.
    1. Parker G, Roussos J, Austin MP, Hadzi-Pavlovic D, Wilhelm K, Mitchell P. Disordered personality style: higher rates in non-melancholic compared to melancholic depression. J Affect Disord. 1998;47:131–140. doi: 10.1016/S0165-0327(97)00133-X.
    1. Lafer B, Nierenberg AA, Rosenbaum JF, Fava M. Outpatients with DSM-III-R versus DSM-IV melancholic depression. Compr Psychiatry. 1996;37:37–39. doi: 10.1016/S0010-440X(96)90048-6.
    1. Hildebrandt MG, Stage KB, Kragh-Soerensen P. Gender differences in severity, symptomatology and distribution of melancholia in major depression. Psychopathology. 2003;36:204–212. doi: 10.1159/000072791.
    1. Wilhelm K, Roy K, Mitchell P, Brownhill S, Parker G. Gender differences in depression risk and coping factors in a clinical sample. Acta Psychiatr Scand. 2002;106:45–53. doi: 10.1034/j.1600-0447.2002.02094.x.
    1. Zimmerman M, Black DW, Coryell W. Diagnostic criteria for melancholia. The comparative validity of DSM-III and DSM-III-R. Arch Gen Psychiatry. 1989;46:361–368.
    1. Kendler KS. The diagnostic validity of melancholic major depression in a population-based sample of female twins. Arch Gen Psychiatry. 1997;54:299–304.
    1. Hansen PE, Wang AG, Stage KB, Kragh-Sorensen P. Comorbid personality disorder predicts suicide after major depression: a 10-year follow-up. Acta Psychiatr Scand. 2003;107:436–440. doi: 10.1034/j.1600-0447.2003.02048.x.
    1. Nemeroff CB. The corticotropin-releasing factor (CRF) hypothesis of depression: new findings and new directions. Mol Psychiatry. 1996;1:336–342.
    1. Wong ML, Kling MA, Munson PJ, Listwak S, Licinio J, Prolo P, Karp B, McCutcheon IE, Geracioti TD, Jr, DeBellis MD, Rice KC, Goldstein DS, Veldhuis JD, Chrousos GP, Oldfield EH, McCann SM, Gold PW. Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: relation to hypercortisolism and corticotropin-releasing hormone. Proc Natl Acad Sci U S A. 2000;97:325–330. doi: 10.1073/pnas.97.1.325.
    1. Amsterdam JD. Selective serotonin reuptake inhibitor efficacy in severe and melancholic depression. J Psychopharmacol. 1998;12:S99–111.
    1. Gold PW, Chrousos GP. Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Mol Psychiatry. 2002;7:254–275. doi: 10.1038/sj.mp.4001032.
    1. Brown R, Kocsis JH, Caroff S, Amsterdam J, Winokur A, Stokes PE, Frazer A. Differences in nocturnal melatonin secretion between melancholic depressed patients and control subjects. Am J Psychiatry. 1985;142:811–816.
    1. Perez V, Bel N, Celada P, Ortiz J, Alvarez E, Artigas F. Relationship between blood serotonergic variables, melancholic traits, and response to antidepressant treatments. J Clin Psychopharmacol. 1998;18:222–230. doi: 10.1097/00004714-199806000-00007.
    1. Sarrias MJ, Artigas F, Martinez E, Gelpi E, Alvarez E, Udina C, Casas M. Decreased plasma serotonin in melancholic patients: a study with clomipramine. Biol Psychiatry. 1987;22:1429–1438. doi: 10.1016/0006-3223(87)90100-4.
    1. Hickie I, Hickie C, Lloyd A, Silove D, Wakefield D. Impaired in vivo immune responses in patients with melancholia. Br J Psychiatry. 1993;162:651–657.
    1. Rothermundt M, Arolt V, Peters M, Gutbrodt H, Fenker J, Kersting A, Kirchner H. Inflammatory markers in major depression and melancholia. J Affect Disord. 2001;63:93–102. doi: 10.1016/S0165-0327(00)00157-9.
    1. Parker G, Hadzi-Pavlovic D, Brodaty H, Boyce P, Mitchell P, Wilhelm K, Hickie I. Predicting the course of melancholic and nonmelancholic depression. A naturalistic comparison study. J Nerv Ment Dis. 1992;180:693–702.
    1. Thase ME, Friedman ES. Is psychotherapy an effective treatment for melancholia and other severe depressive states? J Affect Disord. 1999;54:1–19. doi: 10.1016/S0165-0327(99)00033-6.
    1. Prusoff BA, Weissman MM, Klerman GL, Rounsaville BJ. Research diagnostic criteria subtypes of depression. Their role as predictors of differential response to psychotherapy and drug treatment. Arch Gen Psychiatry. 1980;37:796–801.
    1. Raskin A, Crook TH. The endogenous – neurotic distinction as a predictor of response to antidepressant drugs. Psychol Med. 1976;6:59–70.
    1. Fairchild CJ, Rush AJ, Vasavada N, Giles DE, Khatami M. Which depressions respond to placebo? Psychiatry Res. 1986;18:217–226. doi: 10.1016/0165-1781(86)90109-5.
    1. Stewart JW, McGrath PJ, Liebowitz MR, Harrison W, Quitkin F, Rabkin JG. Treatment outcome validation of DSM-III depressive subtypes. Clinical usefulness in outpatients with mild to moderate depression. Arch Gen Psychiatry. 1985;42:1148–1153.
    1. Peselow ED, Sanfilipo MP, Difiglia C, Fieve RR. Melancholic/endogenous depression and response to somatic treatment and placebo. Am J Psychiatry. 1992;149:1324–1334.
    1. Nelson JC, Mazure CM, Jatlow PI. Does melancholia predict response in major depression? J Affect Disord. 1990;18:157–165. doi: 10.1016/0165-0327(90)90032-4.
    1. Heiligenstein JH, Tollefson GD, Faries DE. Response patterns of depressed outpatients with and without melancholia: a double-blind, placebo-controlled trial of fluoxetine versus placebo. J Affect Disord. 1994;30:163–173. doi: 10.1016/0165-0327(94)90077-9.
    1. Perry PJ. Pharmacotherapy for major depression with melancholic features: relative efficacy of tricyclic versus selective serotonin reuptake inhibitor antidepressants. J Affect Disord. 1996;39:1–6. doi: 10.1016/0165-0327(96)00014-6.
    1. Roose SP, Glassman AH, Attia E, Woodring S. Comparative efficacy of selective serotonin reuptake inhibitors and tricyclics in the treatment of melancholia. Am J Psychiatry. 1994;151:1735–1739.
    1. Citalopram: clinical effect profile in comparison with clomipramine. A controlled multicenter study. Danish University Antidepressant Group. Psychopharmacology (Berl) 1986;90:131–138.
    1. Paroxetine: a selective serotonin reuptake inhibitor showing better tolerance, but weaker antidepressant effect than clomipramine in a controlled multicenter study. Danish University Antidepressant Group. J Affect Disord. 1990;18:289–299. doi: 10.1016/0165-0327(90)90081-I.
    1. Stuppaeck CH, Geretsegger C, Whitworth AB, Schubert H, Platz T, Konig P, Hinterhuber H, Fleischhacker WW. A multicenter double-blind trial of paroxetine versus amitriptyline in depressed inpatients. J Clin Psychopharmacol. 1994;14:241–246.
    1. Feighner JP, Boyer WF, Meredith CH, Hendrickson GG. A placebo-controlled inpatient comparison of fluvoxamine maleate and imipramine in major depression. Int Clin Psychopharmacol. 1989;4:239–244.
    1. Reimherr FW, Chouinard G, Cohn CK, Cole JO, Itil TM, LaPierre YD, Masco HL, Mendels J. Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression. J Clin Psychiatry. 1990;51:18–27.
    1. Hirschfeld RM. Efficacy of SSRIs and newer antidepressants in severe depression: comparison with TCAs. J Clin Psychiatry. 1999;60:326–335.
    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. 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. 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 CH, 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. 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;36:383–390. doi: 10.1016/S0022-3956(02)00060-2.
    1. American Psychiatric Association . Diagnostic and statistical manual of mental disorders. 4. Washington, DC: APA; 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. 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. Bech P, Gjerris A, Andersen J, Bojholm S, Kramp P, Bolwig TG, Kastrup M, Clemmesen L, Rafaelsen OJ. The Melancholia Scale and the Newcastle Scales. Item-combinations and inter-observer reliability. Br J Psychiatry. 1983;143:58–63.
    1. Parker G, Hadzi-Pavlovic D, Austin MP, Mitchell P, Wilhelm K, Hickie I, Boyce P, Eyers K. Sub-typing depression, I. Is psychomotor disturbance necessary and sufficient to the definition of melancholia? Psychol Med. 1995;25:815–823.
    1. Joyce PR, Mulder RT, Luty SE, McKenzie JM, Sullivan PF, Abbott RM, Stevens IF. Melancholia: definitions, risk factors, personality, neuroendocrine markers and differential antidepressant response. Aust N Z J Psychiatry. 2002;36:376–383. doi: 10.1046/j.1440-1614.2001.01025.x.
    1. Zimmerman M, Coryell W, Pfohl B. Melancholic subtyping: a qualitative or quantitative distinction? Am J Psychiatry. 1986;143:98–100.
    1. Schotte CK, Maes M, Cluydts R, Cosyns P. Cluster analytic validation of the DSM melancholic depression. The threshold model: integration of quantitative and qualitative distinctions between unipolar depressive subtypes. Psychiatry Res. 1997;71:181–195. doi: 10.1016/S0165-1781(97)00051-6.
    1. Berlin I, Lavergne F. Relationship between body-mass index and depressive symptoms in patients with major depression. Eur Psychiatry. 2003;18:85–88. doi: 10.1016/S0924-9338(03)00007-5.
    1. Fabre LF. Buspirone in the management of major depression: a placebo-controlled comparison. J Clin Psychiatry. 1990;51:55–61.
    1. Robinson DS, Rickels K, Feighner J, Fabre LF, Jr, Gammans RE, Shrotriya RC, Alms DR, Andary JJ, Messina ME. Clinical effects of the 5-HT1A partial agonists in depression: a composite analysis of buspirone in the treatment of depression. J Clin Psychopharmacol. 1990;10:67S–76S.
    1. Parker G, Mitchell P, Wilhelm K, Menkes D, Snowdon J, Schweitzer I, Grounds D, Skerritt P, Roy K, Hadzi-Pavlovic D. Are the newer antidepressant drugs as effective as established physical treatments? Results from an Australasian clinical panel review. Aust N Z J Psychiatry. 1999;33:874–881. doi: 10.1046/j.1440-1614.1999.00648.x.
    1. Kasper S, Moller HJ, Montgomery SA, Zondag E. Antidepressant efficacy in relation to item analysis and severity of depression: a placebo-controlled trial of fluvoxamine versus imipramine. Int Clin Psychopharmacol. 1995;9:3–12.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren