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depression severity is a confounder in the relation between anxiety and treatment response
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Rob M. Kok, psychiatrist Altrecht Institute of Mental Health Care, Utrecht, The Netherlands, Willem A. Nolen, Thea J. Heeren
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r.kok{at}altrecht.nl Rob M. Kok, et al.
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The recent paper of Andeescu et al (2007) presents valuable information on the negative effect of comorbid anxiety on response to acute treatment of late-life depression and on rates of recurrence. The first finding is in concordance with many papers cited by the authors. However, it should also be noted that others (not or wrongly cited by the authors) found that anxious and nonanxious depressed elderly did not differ in terms of response rates and time to response (Small et al,1995; Lenze et al, 2003). In a review of prognosis of depression in elderly community and primary care populations of which the majority was not treated at all, Cole et al (1999) found no studies with an association between anxiety and prognosis. Another, and perhaps more important, issue is that greater anxiety may reflect a more severe depression, and the latter is an important predictor of nonresponse (Cole et al, 1999). Many of the studies cited by Andreescu to illustrate the negative effect of anxiety on the outcome of depression, have not corrected for severity of depression as a confounder of this association. We recently finished a double-blind, randomised trial in which venlafaxine was compared with nortriptyline in 81 elderly inpatients with major depressive disorder according to DSM-IV (Kok et al, 2007). Patients were assessed with the Montgomery Åsberg Depression Rating Scale (MADRS) and the 17-item Hamilton Rating Scale for Depression (HRSD), the latter was also used by Andreescu et al. All participating patients were assessed again at 6, 9, 12, 24 and 36 months after starting with the trial. We have reanalysed our data with the same definition of response, assessment of anxiety and dichotomising the anxiety scores as Andreescu et al to be able to compare the results of both studies. In addition, we also analysed the score on the anxiety item of the MADRS (item 3). We found no association between higher pre-treatment anxiety scores on the HRSD or MADRS and the percentage of patients achieving a response (χ2=0.694, d.f.=1, P=0.434 and χ2=3.324, d.f.=1, P=0.101, respectively). We could also not demonstrate an association between anxiety according to the HRSD and time-to-response using Cox proportional hazards model, corrected for the severity of the depression (Wald 0.745, d.f.=1, P=0.388). The same results were obtained using the MADRS anxiety item or dichotomising anxiety according to both the HRSD and the MADRS. In all these analyses, adding depression severity as a confounder resulted in a significant (> 10%) change of the regression coefficient B for anxiety, suggesting that depression severity is indeed a confounder. We could not demonstrate an association between higher pre-treatment anxiety according to the HRSD or MADRS-items and risk of recurrence (χ2=1.679, d.f.=1, P=0.195 and χ2=0.716, d.f.=1, P=0.397, respectively). Using Cox proportional hazard model with correction for depression severity, also no significant association was found between anxiety and time-to-recurrence (all p-values > 0.10). Despite our different results, we fully agree with Andreescu et al that there is a need for improved identification and management of anxiety symptoms in late-life depression. However, whether this is needed to achieve a better response or stable recovery of late-life depression, needs to be addressed in further studies before conclusions can be drawn. Andreescu, C., Lenze, E.J., Dew, M.A., et al (2007) Effect of comorbid anxiety on treatment response and relapse risk in late-life depression: controlled study. British Journal of Psychiatry, 190, 344-349. Cole, M.G., Bellavance, F. & Mansour, A. (1999) Prognosis of depression in elderly community and primary care populations : a systematic review and meta-analysis. American Journal of Psychiatry, 156, 1182-1189. Kok, R.M., Nolen, W.A. & Heeren T.J. (2007) Venlafaxine versus nortriptyline in the treatment of elderly depressed inpatients. A randomised, double-blind, controlled trial. International Journal of Geriatric Psychiatry, 22. (In Press) Small, G.W., Hamilton, S.H., Bystritsky, A. et al (1995) Clinical response predictors in a double-blind, placebo-controlled trial of fluoxetine for geriatric major depression. International Psychogeriatrics, 7, suppl., 41-53. Rob M. Kok, Department of Old Age Psychiatry, Altrecht Institute of Mental Health Care, Jutfaseweg 205, 3522 HR Utrecht, The Netherlands, tel +31-30-2297600, fax. +31-30-2297501; Willem A. Nolen, Department of Psychiatry, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; Thea J. Heeren, Symfora Group Centres of Mental Health Care, Utrechtseweg 266 3818 EW, Amersfoort, The Netherlands. Declaration of interests R.K. has received a research grant by Wyeth and Lundbeck and has received speaker’s honoraria from GlaxoSmithKline, Lundbeck, Pfizer and Wyeth. W.N. has received research grants from the Netherlands Organisation for Health Research and Development, Netherlands Organisation for Scientific Research, Stanley Medical Research Institute, Astra Zeneca, Eli Lilly, GlaxoSmithKline, Wyeth; has served as consultant for Astra Zeneca, Cyberonics, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Pfizer, Servier, and had received speaker’s honoraria from Astra Zeneca, Eli Lilly, Johnson & Johnson, Pfizer, Servier, Wyeth. T.H. has received speaker’s honoraria from Eli Lilly and Lundbeck. |
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