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Effect of comorbid anxiety on treatment response and relapse risk in late-life depression: controlled study

  • Carmen Andreescu (a1), Eric J. Lenze (a1), Mary Amanda Dew (a1), Amy E. Begley (a1), Benoit H. Mulsant (a2), Alexandre Y. Dombrovski (a3), Bruce G. Pollock (a4), Jacqueline Stack (a1), Mark D. Miller (a1) and Charles F. Reynolds (a1)...

Abstract

Background

Comorbid anxiety is common in depressive disorders in both middle and late life, and it affects response to antidepressant treatment.

Aims

To examine whether anxiety symptoms predict acute and maintenance (2 years) treatment response in late-life depression.

Method

Data were drawn from a randomised double-blind study of pharmacotherapy and interpersonal psychotherapy for patients age 70 years and over with major depression. Anxiety symptoms were measured using the Brief Symptom Inventory. Survival analysis tested the effect of pre-treatment anxiety on response and recurrence.

Results

Patients with greater pre-treatment anxiety took longer to respond to treatment and had higher rates of recurrence. Actuarial recurrence rates were 29% (pharmacotherapy, lower anxiety), 58% (pharmacotherapy, higher anxiety), 54% (placebo, lower anxiety) and 81% (placebo, higher anxiety).

Conclusions

Improved identification and management of anxiety in late-life depression are needed to achieve response and stabilise recovery.

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Copyright

Corresponding author

Dr Eric Lenze, Western Psychiatric Institute and Clinic, 3811 O'Hara Street, Room E 823, Pittsburgh, PA 15213, USA. Tel:+ 1412 246 6007; fax:+1412 246 6260; email: Lenzee@upmc.edu

Footnotes

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Declaration of interest

E.J.L., B.H.M., B.G.P., M.D.M. and C.F.R. have received support and/or consult for (one ormore of): Forest Laboratories, Pfizer Inc., Johnson & Johnson Co., Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Lundbeck, Janssen Pharmaceutica, and Sepracor (detailsin Acknowledgements).

Footnotes

References

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Effect of comorbid anxiety on treatment response and relapse risk in late-life depression: controlled study

  • Carmen Andreescu (a1), Eric J. Lenze (a1), Mary Amanda Dew (a1), Amy E. Begley (a1), Benoit H. Mulsant (a2), Alexandre Y. Dombrovski (a3), Bruce G. Pollock (a4), Jacqueline Stack (a1), Mark D. Miller (a1) and Charles F. Reynolds (a1)...
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eLetters

depression severity is a confounder in the relation between anxiety and treatment response

Rob M. Kok, psychiatrist
29 May 2007

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 predictorof 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 assessedagain at 6, 9, 12, 24 and 36 months after starting with the trial. We havereanalysed our data with the same definition of response, assessment of anxiety and dichotomising the anxiety scores as Andreescu et al to be ableto 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 resultswere 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 anxietysymptoms 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 2663818 EW, Amersfoort, The Netherlands.

Declaration of interestsR.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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Conflict of interest: None Declared

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