Time course of response to antidepressants in late-life major depression: therapeutic implications

Drugs Aging. 2004;21(8):531-54. doi: 10.2165/00002512-200421080-00004.


In the treatment of depression, there is considerable interest in the time course of response and, in particular, the speed with which individuals recover from depressive episodes. Examination of the time course and speed of response is critical for assessing the usefulness of specific treatments. However, while this issue has received attention in mid-life adult populations, it has received little consideration in the context of late-life major depression. The synthesis of empirical reports indicates that, while older adults with depression seem to respond with the same speed as mid-life adults, several factors have consistently been associated with reduced speed of response to antidepressant treatment, including greater severity of depressive symptoms and co-occurring anxiety symptoms. Limited evidence suggests that sleep impairment and genetic factors (e.g. presence of the s allele of the serotonin transporter gene promoter region) may also be associated with reduced speed of response. Some factors have consistently been found to be unrelated to speed of response (demographic characteristics, nonpsychiatric physical illnesses) whereas other factors have only mixed evidence supporting any effect (psychosocial and other clinical factors). While there is little work available to date, some evidence suggests that time course and speed of response affect longer-term outcomes of depression pharmacotherapy; thus, older adults with more rapid versus slower patterns of response may differ in the types of maintenance treatment needed to avert additional depressive episodes. None of potential strategies for accelerating speed of response have been clearly shown to be effective in late-life depression. Future treatment studies for late-life depression should routinely consider not only overall efficacy of a given pharmacotherapy (i.e. total rate of response), but time course and speed of response. To this end, new investigations must be designed to overcome the methodological limitations of prior studies that have examined time course and they should include a range of potential covariates and outcomes of between-patient differences in speed of response. Better understanding of factors related to such differences may suggest new intervention strategies to accelerate response.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Aged
  • Antidepressive Agents / administration & dosage*
  • Antidepressive Agents / therapeutic use*
  • Clinical Trials as Topic
  • Depressive Disorder, Major / classification
  • Depressive Disorder, Major / drug therapy*
  • Drug Administration Schedule
  • Humans
  • Psychiatric Status Rating Scales
  • Time Factors
  • Treatment Outcome


  • Antidepressive Agents