What To Do When Your Prozac Stops Working

Reasons This Can Happen and Simple Strategies To Deal With It

tired man taking pills
What is Prozac poop out, what causes it, and how can you deal with it?. David Burton/Getty Images

You've been taking Prozac (fluoxetine) for ages, but lately, it's not working very well. Your depression symptoms seem to be coming back and you feel you're on the verge of a total relapse. What do you now? Double your dose? Switch to another medication? Here's some guidance.

What Happened?

This phenomenon can occur with any selective serotonin reuptake inhibitor (SSRI) used to treat depression. If you aren't sure if the medication you take is an SSRI, besides Prozac here are the ones most often prescribed:

  • Zoloft (sertraline)
  • Paxil (paroxetine)
  • Celexa (citalopram)
  • Lexapro (escitalopram)

When a medication no longer works as well for someone as it did when they first started taking it, that person is said to have developed a tolerance for the drug. The medical term for decreased effectiveness of a medication is tachyphylaxis. Note that this refers only to a drug that once worked well but is no longer as effective—not a drug that never worked at all. Experts don't know how often someone taking an SSRI will develop a tolerance for it, but some studies suggest that 25 to 30 percent of people will notice a decrease in effectiveness over time.

It's also not clear why certain medications lose their effectiveness over time. One theory why this happens with SSRIs is that receptors in the brain become less sensitive to the medication. Sometimes, however, other factors can play a part in what seems like a loss of effectiveness of an antidepressant. These include:

  • Worsening illness
  • Added stress 
  • A secondary health problem that can independently cause depression, such as diabetes
  • Cigarette smoking or drinking alcohol, which both can interfere with the way antidepressants are metabolized in the body 
  • Other medications—for example, certain antibiotics may interact with antidepressants
  • Bipolar disorder misdiagnosed as depression. This is important to consider because the seeming loss of effectiveness of an antidepressant may actually be due to the cyclic change in mood that's characteristic of bipolar disorder.
  • Aging
  • Not taking the antidepressant as prescribed

Steps To Take

Schedule an appointment with the professional who prescribes your medication, whether it's your internist, a psychiatrist, or a special nurse practitioner. She'll want to know if there's anything happening in your life that could be causing additional stress, or if another doctor has prescribed a drug for you that might interfere with your SSRI.

The doctor also will want to know how often you drink or smoke cigarettes. Be honest about this. Again, both of these habits can affect how well your medication works. She also may want you to be tested for hypothyroidism, a common cause of worsening depression. If you have any symptoms of mania or hypomania, it's important to talk to your doctor and perhaps undergo testing to see if you may have bipolar disorder rather than clinical depression.

Once you and your doctor work out why your antidepressant has stopped working as well as in the past, she may suggest one or more of the following changes to your treatment regimen:

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