What Is "Prozac Poop-out"?

Prozac Poop-Out
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Question: What is "Prozac poop-out"?

Answer:  When we talk about the phenomenon of Prozac poop-out, what we mean is that the patient's antidepressant has simply stopped working as well as it once did, causing a relapse of a person's depression symptoms.

Although this phenomenon is most commonly referred to as "Prozac poop-out," it can actually occur with any SSRI.  An SSRI, or Selective Serotonin Reuptake Inhibitor, is a type of antidepressant medication which is able to prevent nerve cells from taking back up a mood-regulating neurotransmitter called serotonin.

  This allows more serotonin to be available in the spaces between nerve cells where it can be used, possibly helping depression.

According to Jonathan E. Alpert, MD, PhD, chief of clinical psychiatry at Massachusetts General Hospital in Boston, about 30% of antidepressant users will experience depression relapse over a one-year period.

While there is no definitive answer as to why this happens, it may be a case of the patient developing tolerance to the drug as the brain's receptors become less sensitive to its effects.

A variety of other factors may also potentially cause depression relapse, including:

  • Worsening depression
  • Another health problem, such as hypothyroidism
  • Medication side effects
  • Bipolar disorder misdiagnosed as depression
  • Aging
  • Not taking one's antidepressant as prescribed

It is not clear what percentage of antidepressant users might experience relapse due to developing a tolerance to their antidepressant medication versus those who may experience returning depression symptoms for other reasons.

Some of the strategies used to deal with Prozac poop-out include augmentation with a second drug (such as buspirone, a mood stabilizer or an antipsychotic), raising the dose, lowering the dose or going on a drug holiday  or switching to another drug entirely (the patient can switch to either another SSRI or a drug from a different class of antidepressants).

Another strategy that has been reported to be effective involves keeping a regular schedule of rotating between the SSRIs. Once the patient cycles through all the SSRIs, they can then start through them again. It appears that being off any particular SSRI for a period of time will restore its effectiveness.

Any changes to your treatment plan should be made only after consulting with your doctor for advice.


Allen, Arthur.  "The Ups and Downs of Depression Treatment:  The Journey From Depression Rarely Follows a Straight Line."  WebMD.  WebMD, LLC.  Last reviewed:  By Brunilda Nazario, MD on April 29, 2011.  Accessed:  January 13, 2016.

Hall-Flavin, Daniel K., M.D.  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?    Mayo Clinic.  Mayo Foundation for Medical Education and Research.  Last updated:  May 13, 2015.  Accessed:  January 13, 2016.

Targum, Steven D.  "Identification and Treatment of Antidepressant Tachyphylaxis."  Innovations in Clinical Neuroscience.  11.3-4 (March-April 2014):  24-28.  Published online:  March-April 2014.

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