• image.alt
  • With Mayo Clinic psychiatrist

    Daniel K. Hall-Flavin, M.D.

    read biography
The Mayo Clinic Diet Book, learn more

Free

E-newsletter

Subscribe to Housecall

Our weekly general interest
e-newsletter keeps you up to date on a wide variety of health topics.

Sign up now

Question

Antidepressants: Can they stop working?

I've taken fluoxetine (Prozac) for several years. But recently, the medication doesn't seem to be having the same effect. Can antidepressants lose effectiveness?

Answer

Managing Depression

Subscribe to our Managing Depression e-newsletter to stay up to date on depression topics.

Sign up now
from Daniel K. Hall-Flavin, M.D.

When depression symptoms improve after starting an antidepressant, most people need to continue taking medication long term to prevent symptoms from returning. However, treatment may seem to stop working over time. This can happen for a number of reasons. These include:

  • Worsening depression. It's common for depression symptoms to return or worsen at some point, despite treatment. Called breakthrough depression, symptoms may be triggered by stress or may appear with no apparent cause. The current dose of medication you're taking may not be enough to prevent your symptoms when depression gets worse.
  • Another medical condition. Underlying health problems, such as hypothyroidism, can cause or worsen depression.
  • A new medication. Some medications for unrelated conditions can interfere with the way your body breaks down and uses antidepressants, decreasing their effectiveness.
  • Undiagnosed bipolar disorder. Bipolar disorder, also called manic-depressive disorder, causes periodic mood swings. While an antidepressant is sometimes used to treat bipolar disorder, a mood-stabilizing or antipsychotic medication is generally needed along with an antidepressant to keep emotional highs and lows in check.
  • Age. In some people, depression gets worse with age. As you get older, you may have changes in your brain and thinking (neurological changes) that affect your mood. In addition, the manner in which your body processes medications may be less efficient. You're also likely to be taking more medications. All of these factors can play a role in depression.
  • Loss of drug effectiveness. In some people, a particular antidepressant may simply stop working over time. Doctors don't fully understand what causes the so-called "poop-out" effect — known as tachyphylaxis — or why it occurs in some people and not in others.

In most cases, depression symptoms get better with adjustments to medication. Your doctor may recommend that you change the dose of your current antidepressant, change to another antidepressant or add another antidepressant or other type of medication to your existing treatment. Psychological counseling (psychotherapy) also may help.

Because there are so many reasons depression treatment can stop working, you may need to see a medical doctor who specializes in diagnosing and treating mental illness (psychiatrist) to figure out the best course of action.

Next question
Antidepressants and alcohol: What is the concern?
References
  1. Zimmerman M, et al. How often do SSRIs and other new-generation antidepressants lose their effect during continuation treatment? Evidence suggesting the rate of true tachyphylaxis during continuation treatment is low. Journal of Clinical Psychiatry. 2007;68:1271.
  2. Amsterdam J, et al. Does tachyphylaxis occur after repeated antidepressant exposure in patients with Bipolar II major depressive episode? Journal of Affective Disorders. 2009;115:234.
  3. Raja M. Delayed loss of efficacy and depressogenic action of antidepressants. Journal of Clinical Psychopharmacology. 2009;29:612.
  4. Katon W, et al. Treatment of resistant depression in adults. http://www.uptodate.com/index. Accessed March 29, 2012.
  5. Frye MA. Bipolar disorder — A focus on depression. New England Journal of Medicine. 2011;364:51.
  6. Kung S (expert opinion). Mayo Clinic, Rochester, Minn. April 5, 2012.
AN01312 May 1, 2012

© 1998-2013 Mayo Foundation for Medical Education and Research (MFMER). All rights reserved. A single copy of these materials may be reprinted for noncommercial personal use only. "Mayo," "Mayo Clinic," "MayoClinic.com," "EmbodyHealth," "Enhance your life," and the triple-shield Mayo Clinic logo are trademarks of Mayo Foundation for Medical Education and Research.

  • Reprints
  • Print
  • Share on:

  • Email

Advertisement


Text Size: smaller largerlarger