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How long to wait for an antidepressant to ‘work’

Several recent studies demonstrate a real, drug-based response in many patients as early as the first week of treatment.

Vol. 6, No. 6 / June 2007

Prevailing wisdom says it takes 3 to 4 weeks for an antidepressant to show clinical effect. Historically, patients who improve in the first 2 weeks have been labeled “placebo responders.”1 Several recent studies, however, demonstrate a real, drug-based response in many patients as early as the first week of treatment, depending on the medication (Table).2-5 In practical terms, these studies raise the question of how long you should wait for an antidepressant to “work.”


Variables in antidepressant response

It is not surprising that onset of antidepressant response in some patients varies. The new data—derived mainly from meta-analyses of studies using the Hamilton Depression Rating Scale (HAM-D)—do not tease out sources of variability in the studies, including:

  • heterogeneity within the construct of ‘major depressive episode’
  • limitations of the HAM-D total score as a measure of response
  • wide variability in drug pharmacodynamics and bioavailability
  • individual differences in neuronal sensitivity to antidepressants
  • variability in patients’ psychosocial support

Early indications. Here are some tips for gauging antidepressant response, depending on what you see in the first 2 to 4 weeks:

  • Obtain a pretreatment score on the Beck Depression Inventory or other depression rating scale, and repeat the assessment at least once between days 7 and 10 of treatment. If there is little or no improvement, consider a modest dosage increase.
  • Don’t assume that a patient who responds to an antidepressant during the first 2 weeks is experiencing a placebo effect. It may be a drug-mediated response. Some patients will retain and build on this early response, whereas others’ response may wane over subsequent weeks.
  • No response to an antidepressant during weeks 1 through 4 does not bode well for most patients,5,6 although the data do not support giving up on an antidepressant after 1 to 2 weeks of nonresponse. Responses will “accumulate” during weeks 3 to 5 of treatment.7
  • Patients who show little response during the first 2 weeks of treatment but experience some improvement during weeks 3 and 4 may be late responders. However, if the patient shows no improvement by week 3 or 4, consider switching to a different antidepressant, perhaps one from a different chemical class.8
  • Different neurovegetative signs and symptoms of depression may improve at different rates, with some requiring >8 weeks of treatment. Insight, for example, may not improve until the second month of treatment.9
  • Individualize treatment. Many treatment-refractory depressed patients—who failed to respond to 1 or more adequate drug trials—may require longer and more intensive treatment (>3 months) beffore showing a robust response.10
  • “Onset of response” does not equal “clinical recovery,” nor is an improved Hamilton Depression Scale score a proxy for “high quality of life.” Patients may need ≥2 months for clinically significant improvement in interpersonal, social, and vocational function.11


The author expresses his appreciation to Michael Posternak, MD, Andrew Nierenberg, MD, and Alex J. Mitchell, MD, for their helpful comments on an early draft of this article.


1. Quitkin FM, McGrath PJ, Rabkin JG, et al. Different types of placebo response in patients receiving antidepressants. Am J Psychiatry 1991;148:197-203.

2. Posternak MA, Zimmerman M. Is there a delay in the antidepressant effect? A meta-analysis. J Clin Psychiatry 2005;66:148-58.

3. Taylor MJ, Freemantle N, Geddes JR, et al. Early onset of selective serotonin reuptake inhibitor antidepressant action. Arch Gen Psychiatry 2006;63:1217-23.

4. Mitchell AJ. Two week delay in onset of action of antidepressants: new evidence. Br J Psychiatry 2006;188:105-6.

5. Katz MM, Bowden CL, Berman N, et al. Resolving the onset of antidepressants’ clinical actions. J Clin Psychopharmacol 2006;26:549-53.

6. Nierenberg AA, Farabaugh AH, Alpert JE, et al. Timing of onset of antidepressant response with fluoxetine. Am J Psychiatry 2000;157:1423-8.

7. Stassen HH, Angst J, Delini-Stula A. Delayed onset of action of antidepressant drugs: fact or fiction? CNS Drugs 1998;3:177-84.

8. Trivedi MH, Morris DW, Grannemann BD, et al. Symptom clusters as predictors of late response to antidepressant treatment. J Clin Psychiatry 2005;66:1064-70.

9. Hirschfeld RM, Mallinckrodt C, Lee TC, et al. Time course of depression-symptom improvement during treatment with duloxetine. Depress Anxiety 2005;21(4):170-7.

10. Tew JD, Jr, Mulsant BH, Houck PR, et al. Impact of prior treatment exposure on response to antidepressant treatment in late life. Am J Geriatr Psychiatry 2006 Nov;14(11):957-65.

11. Dubini A, Bosc M, Polin V. Noradrenaline-selective versus serotonin-selective antidepressant therapy: differential effects on social functioning. J Psychopharmacol 1997;11(suppl 4):S17-S23.

Dr. Pies is clinical professor of psychiatry, Tufts University School of Medicine, Boston, MA.

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