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    Daniel K. Hall-Flavin, M.D.

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Question

Antidepressants: Can they stop working?

Can antidepressants lose effectiveness? I've taken fluoxetine (Prozac) for several years. But recently, I've noticed the medication doesn't seem to be having the same effect, and I feel more depressed. Can you explain this?

Answer

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 medication is also 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, 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) may also 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
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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.
AN01312 March 18, 2010

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