The safety and tolerability of duloxetine in depressed elderly patients with and without medical comorbidity

T N Wise, C G Wiltse, D V Iosifescu, M Sheridan, J Y Xu, J Raskin, T N Wise, C G Wiltse, D V Iosifescu, M Sheridan, J Y Xu, J Raskin

Abstract

Aim and methods: The impact of medical comorbidity on the efficacy and tolerability of duloxetine in elderly patients with major depressive disorder (MDD) was investigated in this study. Data were obtained from a multicentre, randomised, double-blind, placebo-controlled study in 311 patients with MDD aged 65-89. The primary outcome measure was a prespecified composite cognitive score based on four cognitive tests: (i) Verbal Learning and Recall Test; (ii) Symbol Digit Substitution Test; (iii) 2-Digit Cancellation Test and (iv) Letter-Number Sequencing Test. Secondary measures included the Geriatric Depression Scale (GDS), 17-Item Hamilton Depression Scale (HAMD17), Clinical Global Impression-Severity (CGI-S) Scale, Visual Analogue Scale (VAS) for pain and 36-Item Short Form Health Survey (SF-36). Tolerability measures included adverse events reported as the reason for discontinuation and treatment-emergent adverse events (TEAEs). The consistency of the effect of duloxetine vs. placebo comparing patients with and without medical comorbidity (vascular disease, diabetes, arthritis or any of these) was investigated.

Results: Overall, duloxetine 60 mg/day demonstrated significantly greater improvement compared with placebo for the composite cognitive score, GDS and HAMD17 total scores, CGI-Severity, HAMD17 response and remission rates, and some of the SF-36 and VAS measures. There were few significant treatment-by-comorbidity subgroup interactions for these efficacy variables, or for adverse events reported as the reason for discontinuation and common TEAEs.

Conclusions: The present analyses suggested that the efficacy of duloxetine on cognition and depression in elderly patients, and its tolerability, were not largely affected by the comorbidity status. These results further support the use of duloxetine in elderly patients with MDD.

Trial registration: ClinicalTrials.gov NCT00062673.

Figures

Figure 1
Figure 1
Effects of duloxetine compared with placebo on composite cognitive score: mean change analysis in all randomised patients and in baseline comorbidity subgroups
Figure 2
Figure 2
(A) Effects of duloxetine compared with placebo on GDS total score: mean change analysis in all randomised patients and in baseline comorbidity subgroups. (B) Effects of duloxetine compared with placebo on HAMD17 total score: mean change analysis in all randomised patients and in baseline comorbidity subgroups
Figure 3
Figure 3
Effects of duloxetine compared with placebo on SF-36 Physical Component Summary: mean change analysis in all randomised patients and in baseline comorbidity subgroups

References

    1. NIH consensus conference. Diagnosis and treatment of depression in late life. JAMA. 1992;268:1018–24.
    1. Steffens DC, Skoog I, Norton MC, et al. Prevalence of depression and its treatment in an elderly population: the Cache County study. Arch Gen Psychiatry. 2000;57:601–7.
    1. Conwell Y, Duberstein PR, Cox C, Herrmann JH, Forbes NT, Caine ED. Relationships of age and axis I diagnoses in victims of completed suicide: a psychological autopsy study. Am J Psychiatry. 1996;153:1001–8.
    1. Palsson S, Skoog I. The epidemiology of affective disorders in the elderly: a review. Int Clin Psychopharmacol. 1997;12(Suppl. 7):S3–13.
    1. Unutzer J, Patrick DL, Simon G, et al. Depressive symptoms and the cost of health services in HMO patients aged 65 years and older. A 4-year prospective study. JAMA. 1997;277:1618–23.
    1. Ziegelstein RC. Depression in patients recovering from a myocardial infarction. JAMA. 2001;286:1621–7.
    1. Anderson RJ, Freedland KE, Clouse RE, Lustman PJ. The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care. 2001;24:1069–78.
    1. Dickens C, McGowan L, Clark-Carter D, Creed F. Depression in rheumatoid arthritis: a systematic review of the literature with meta-analysis. Psychosom Med. 2002;64:52–60.
    1. Frasure-Smith N, Lesperance F, Talajic M. Depression following myocardial infarction. Impact on 6-month survival. JAMA. 1993;270:1819–25.
    1. Frasure-Smith N, Lesperance F, Talajic M. Depression and 18-month prognosis after myocardial infarction. Circulation. 1995;91:999–1005.
    1. Ickovics JR, Hamburger ME, Vlahov D, et al. Mortality, CD4 cell count decline, and depressive symptoms among HIV-seropositive women: longitudinal analysis from the HIV Epidemiology Research Study. JAMA. 2001;285:1466–74.
    1. Wassertheil-Smoller S, Applegate WB, Berge K, et al. Change in depression as a precursor of cardiovascular events. SHEP Cooperative Research Group (Systoloc Hypertension in the elderly) Arch Intern Med. 1996;156:553–61.
    1. Ciechanowski PS, Katon WJ, Russo JE. Depression and diabetes: impact of depressive symptoms on adherence, function, and costs. Arch Intern Med. 2000;160:3278–85.
    1. Katon W, Ciechanowski P. Impact of major depression on chronic medical illness. J Psychosom Res. 2002;53:859–63.
    1. 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. 2001;25:871–80.
    1. Ressler KJ, Nemeroff CB. Role of norepinephrine in the pathophysiology of neuropsychiatric disorders. CNS Spectr. 2001;6:670.
    1. Reneman L, Lavalaye J, Schmand B, et al. Cortical serotonin transporter density and verbal memory in individuals who stopped using 3,4-methylenedioxymethamphetamine (MDMA or ‘ecstasy’): preliminary findings. Arch Gen Psychiatry. 2001;58:901–6.
    1. Nelson JC, Wohlreich MM, Mallinckrodt CH, Detke MJ, Watkin JG, Kennedy JS. Duloxetine for the treatment of major depressive disorder in older patients. Am J Geriatr Psychiatry. 2005;13:227–35.
    1. Raskin J, Wilse CG, Siegal A, et al. Efficacy of duloxetine on cognition, depression, and pain in elderly patients with major depressive disorder: an 8-week, double-blind, placebo-controlled trial. Am J Psychiatry. 2007;164:900–9.
    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, 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. 1998;59(Suppl. 20):22–33.
    1. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56–62.
    1. Folstein MF, Folstein SE, McHugh PR. ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–98.
    1. Thompson WL, Brunelle RL, Enas GG, Simpson PJ. Routine laboratory tests in clinical trials: interpretation of results. J Clin Res Drug Dev. 1987;1:95–119.
    1. Lezak M. Neuropsychological Assessment. New York: Oxford; 1995. pp. 438–45.
    1. REY A. L'examen psychologique dans les cas d'encephalopathie traumatique [French] Arch Psychol. 1941;28:286–340.
    1. Burt DB, Zembar MJ, Niederehe G. Depression and memory impairment: a meta-analysis of the association, its pattern, and specificity. Psychol Bull. 1995;117:285–305.
    1. Cohen RM, Weingartner H, Smallberg SA, Pickar D, Murphy DL. Effort and cognition in depression. Arch Gen Psychiatry. 1982;39:593–7.
    1. Yesavage JA, Brink TL, Rose TL, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982;17:37–49.
    1. Sheikh JI, Yesavage JA. Geriatric Depression Scale (GDS): Recent evidence and development of a shorter version. Clinical Gerontology: A Guide to Assessment and Intervention. New York: The Haworth Press; 1986. pp. 165–73.
    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;86:102–6.
    1. Butters MA, Becker JT, Nebes RD, et al. Changes in cognitive functioning following treatment of late-life depression. Am J Psychiatry. 2000;157:1949–54.
    1. Nebes RD, Pollock BG, Houck PR, et al. Persistence of cognitive impairment in geriatric patients following antidepressant treatment: a randomized, double-blind clinical trial with nortriptyline and paroxetine. J Psychiatr Res. 2003;37:99–108.
    1. O'Brien J, Ames D, Chiu E, Schweitzer I, Desmond P, Tress B. Severe deep white matter lesions and outcome in elderly patients with major depressive disorder: follow up study. BMJ. 1998;317:982–4.
    1. Sternberg DE, Jarvik ME. Memory functions in depression. Arch Gen Psychiatry. 1976;33:219–24.
    1. Andersson HI, Ejlertsson G, Leden I, Rosenberg C. Chronic pain in a geographically defined general population: studies of differences in age, gender, social class, and pain localization. Clin J Pain. 1993;9:174–82.
    1. Turk DC, Okifuji A, Scharff L. Chronic pain and depression: role of perceived impact and perceived control in different age cohorts. Pain. 1995;61:93–101.
    1. Raskin J, Pritchett YL, Wang F, et al. A double-blind, randomized multicenter trial comparing duloxetine with placebo in the management of diabetic peripheral neuropathic pain. Pain Med. 2005;6:346–56.
    1. Wernicke JF, Pritchett YL, D'Souza DN, et al. A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain. Neurology. 2006;24:1411–20.
    1. Brannan SK, Mallinckrodt CH, Brown EB, Wohlreich MM, Watkin JG, Schatzberg AF. Duloxetine 60 mg once-daily in the treatment of painful physical symptoms in patients with major depressive disorder. J Psychiatr Res. 2005;39:43–53.
    1. Sheikh JI, Cassidy EL, Doraiswamy PM, et al. Efficacy, safety, and tolerability of sertraline in patients with late-life depression and comorbid medical illness. J Am Geriatr Soc. 2004;52:86–92.
    1. Gill D, Hatcher S. A systematic review of the treatment of depression with antidepressant drugs in patients who also have a physical illness. J Psychosom Res. 1999;47:131–43.
    1. Evans M, Hammond M, Wilson K, Lye M, Copeland J. Treatment of depression in the elderly: effect of physical illness on response. Int J Geriatr Psychiatry. 1997;12:1189–94.
    1. Krishnan KR, Doraiswamy PM, Clary CM. Clinical and treatment response characteristics of late-life depression associated with vascular disease: a pooled analysis of two multicenter trials with sertraline. Prog Neuropsychopharmacol Biol Psychiatry. 2001;25:347–61.
    1. Small GW, Birkett M, Meyers BS, Koran LM, Bystritsky A, Nemeroff CB. Impact of physical illness on quality of life and antidepressant response in geriatric major depression. Fluoxetine Collaborative Study Group. J Am Geriatr Soc. 1996;44:1220–5.
    1. Walsh BT, Sysko R. Placebo control groups in trials of major depressive disorder among older patients. J Clin Psychopharmacol. 2005;25(4 Suppl. 1):S29–33.
    1. Schatzberg A, Roose S. A double-blind, placebo-controlled study of venlafaxine and fluoxetine in geriatric outpatients with major depression. Am J Geriatr Psychiatry. 2006;14:361–70.
    1. Roose SP, Sackeim HA, Krishnan KR, et al. Antidepressant pharmacotherapy in the treatment of depression in the very old: a randomized, placebo-controlled trial. Am J Psychiatry. 2004;161:2050–9.
    1. Tollefson GD, Bosomworth JC, Heiligenstein JH, Potvin JH, Holman S. A double-blind, placebo-controlled clinical trial of fluoxetine in geriatric patients with major depression. The Fluoxetine Collaborative Study Group. Int Psychogeriatr. 1995;7:89–104.
    1. Goldstein DJ, Lu Y, Detke MJ, Hudson JI, Demitrack MA. Effects of duloxetine on painful physical symptoms associated with depression. Psychosomatics. 2004;45:17–28.
    1. Roose SP, Sackeim HA. Clinical trials in late-life depression: revisited. Am J Geriatr Psychiatry. 2002;10:503–5.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe