Maintenance Treatment of Depression in Old Age
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Reynolds et al. (March 16 issue)1 demonstrate that pharmacotherapy is effective at preventing the recurrence of major depression in elderly patients. However, the more specific conclusion that "maintenance treatment with paroxetine is effective" cannot be supported without additional data. Nearly one third of the patients in the study required augmented pharmacotherapy before randomization, and all pharmacotherapy was discontinued in the placebo group. The need for augmentation was associated with a higher risk of recurrence. Bupropion, one of the agents used for augmentation, has been shown to decrease the risk of relapse.2 Patients requiring augmentation probably had more severe depression, which is associated with a greater risk of recurrence.3,4 Thus, in this high-risk subgroup, the treatment benefit may have been due to agents other than paroxetine. Before concluding that maintenance therapy with paroxetine is appropriate for the entire study population, it is important to know whether a benefit was observed in patients who did not require augmentation.
Jonathan L. Edwards, M.D.
Barberton Citizens Hospital
Barberton, OH 44203
jedwards@barbhosp.com
References
Reynolds CF III, Dew MA, Pollock BG, et al. Maintenance treatment of major depression in old age. N Engl J Med 2006;354:1130-1138.
Weihs KL, Houser TL, Batey SR, et al. Continuation phase treatment with bupropion SR effectively decreases the risk for relapse of depression. Biol Psychiatry 2002;51:753-761.
Melartin TK, Rytsala HJ, Leskela US, Lestela-Mielonen PS, Sokero TP, Isometsa ET. Severity and comorbidity predict episode duration and recurrence of DSM-IV major depressive disorder. J Clin Psychiatry 2004;65:810-819.
Kessing LV. Severity of depressive episodes according to ICD-10: prediction of risk of relapse and suicide. Br J Psychiatry 2004;184:153-156.
To the Editor: The study by Reynolds et al. should be subjected to two additional analyses. First, the authors state that recurrence rates were higher in the group that received augmented pharmacotherapy (74 percent) than in the group that did not receive such therapy (29 percent). It would be interesting to know whether these two groups had differences in demographic and clinical variables. Measures such as the severity of the previous depressive episode and the amount of residual symptoms are of particular interest, since these two variables are known to be putative predictors of the recurrence of a depressive episode.1,2
Second, the duration of the episode of depression varied markedly among the treatment groups (e.g., 57 weeks in the group that received paroxetine plus psychotherapy, as compared with 26 weeks in the group that received paroxetine plus clinical management). Since previous studies reported an influence of the duration of the episode on recurrence rates among patients with depression,2 the authors should report the effect of this variable on recurrence rates.
Malek Bajbouj, M.D.
Heidi Danker-Hopfe, Ph.D.
Charité Universit?tsmedizin Berlin, Campus Benjamin Franklin
14050 Berlin, Germany
malek.bajbouj@charite.de
References
Keller MB. Past, present, and future directions for defining optimal treatment outcome in depression: remission and beyond. JAMA 2003;289:3152-3160.
Brugha TS, Bebbington PE, Stretch DD, MacCarthy B, Wykes T. Predicting the short-term outcome of first episodes and recurrences of clinical depression: a prospective study of life events, difficulties, and social support networks. J Clin Psychiatry 1997;58:298-306.
The authors reply: Dr. Edwards and Drs. Bajbouj and Danker-Hopfe are correct to surmise that patients requiring augmentation were more severely ill. As compared with those not requiring augmentation, these patients were more likely to have recurrent depression (P=0.02), an earlier age at onset (P=0.04), more severe symptoms of depression before treatment (P<0.001), and higher levels of residual symptoms at the time they were randomly assigned to a maintenance treatment (P<0.004), including the symptom of greater anxiety (P=0.04). In addition, as we noted in our article, these patients had higher rates of recurrence during maintenance treatment (74 percent) than did those who did not require augmentation (29 percent, P<0.001). Thus, one may view the need for augmentation as a proxy for having more severe illness. However, additional analyses revealed that the effect of paroxetine in the prevention of recurrence was independent of the need for augmentation. Specifically, recurrence rates remained significantly different among the four groups, even after we controlled for augmentation (P=0.03). The pattern of these differences was the same as we originally reported in our article. Finally, although the duration of the current episode of depression was indeed the longest in the combined-treatment group, additional analyses indicated that the duration had no significant effect on the time to recurrence in the Cox regression analysis (P=0.66).
Mary Amanda Dew, Ph.D.
Patricia R. Houck, M.S.H.
Charles F. Reynolds III, M.D.
University of Pittsburgh School of Medicine
Pittsburgh, PA 15213
reynoldscf@upmc.edu
Jonathan L. Edwards, M.D.
Barberton Citizens Hospital
Barberton, OH 44203
jedwards@barbhosp.com
References
Reynolds CF III, Dew MA, Pollock BG, et al. Maintenance treatment of major depression in old age. N Engl J Med 2006;354:1130-1138.
Weihs KL, Houser TL, Batey SR, et al. Continuation phase treatment with bupropion SR effectively decreases the risk for relapse of depression. Biol Psychiatry 2002;51:753-761.
Melartin TK, Rytsala HJ, Leskela US, Lestela-Mielonen PS, Sokero TP, Isometsa ET. Severity and comorbidity predict episode duration and recurrence of DSM-IV major depressive disorder. J Clin Psychiatry 2004;65:810-819.
Kessing LV. Severity of depressive episodes according to ICD-10: prediction of risk of relapse and suicide. Br J Psychiatry 2004;184:153-156.
To the Editor: The study by Reynolds et al. should be subjected to two additional analyses. First, the authors state that recurrence rates were higher in the group that received augmented pharmacotherapy (74 percent) than in the group that did not receive such therapy (29 percent). It would be interesting to know whether these two groups had differences in demographic and clinical variables. Measures such as the severity of the previous depressive episode and the amount of residual symptoms are of particular interest, since these two variables are known to be putative predictors of the recurrence of a depressive episode.1,2
Second, the duration of the episode of depression varied markedly among the treatment groups (e.g., 57 weeks in the group that received paroxetine plus psychotherapy, as compared with 26 weeks in the group that received paroxetine plus clinical management). Since previous studies reported an influence of the duration of the episode on recurrence rates among patients with depression,2 the authors should report the effect of this variable on recurrence rates.
Malek Bajbouj, M.D.
Heidi Danker-Hopfe, Ph.D.
Charité Universit?tsmedizin Berlin, Campus Benjamin Franklin
14050 Berlin, Germany
malek.bajbouj@charite.de
References
Keller MB. Past, present, and future directions for defining optimal treatment outcome in depression: remission and beyond. JAMA 2003;289:3152-3160.
Brugha TS, Bebbington PE, Stretch DD, MacCarthy B, Wykes T. Predicting the short-term outcome of first episodes and recurrences of clinical depression: a prospective study of life events, difficulties, and social support networks. J Clin Psychiatry 1997;58:298-306.
The authors reply: Dr. Edwards and Drs. Bajbouj and Danker-Hopfe are correct to surmise that patients requiring augmentation were more severely ill. As compared with those not requiring augmentation, these patients were more likely to have recurrent depression (P=0.02), an earlier age at onset (P=0.04), more severe symptoms of depression before treatment (P<0.001), and higher levels of residual symptoms at the time they were randomly assigned to a maintenance treatment (P<0.004), including the symptom of greater anxiety (P=0.04). In addition, as we noted in our article, these patients had higher rates of recurrence during maintenance treatment (74 percent) than did those who did not require augmentation (29 percent, P<0.001). Thus, one may view the need for augmentation as a proxy for having more severe illness. However, additional analyses revealed that the effect of paroxetine in the prevention of recurrence was independent of the need for augmentation. Specifically, recurrence rates remained significantly different among the four groups, even after we controlled for augmentation (P=0.03). The pattern of these differences was the same as we originally reported in our article. Finally, although the duration of the current episode of depression was indeed the longest in the combined-treatment group, additional analyses indicated that the duration had no significant effect on the time to recurrence in the Cox regression analysis (P=0.66).
Mary Amanda Dew, Ph.D.
Patricia R. Houck, M.S.H.
Charles F. Reynolds III, M.D.
University of Pittsburgh School of Medicine
Pittsburgh, PA 15213
reynoldscf@upmc.edu