What to Do If Your Antidepressant Has Stopped Working

Antidepressant Stopped Working
Dean Mitchell/Getty Images

According to Dr. Jonathan E. Alpert, chief of clinical psychiatry at Massachusetts General Hospital, the rate of relapse while using an antidepressant is about 30 percent during a one-year period.  Depression relapse basically means that a patient is experiencing a return of his depression symptoms even though he was previously responding to his medication. 

The Return of Depression Symptoms

During a depression relapse, a person might experience a return of or worsening of the following symptoms:

  • Feeling sad or empty
  • Losing pleasure in things which are usually enjoyable to him
  • Feeling irritable
  • Having problems with sleep
  • Feeling tired or lacking in energy
  • Having changes in weight or appetite
  • Feeling anxious or restless
  • Speaking or moving very slowly
  • Having problems with memory, thought and concentration
  • Feeling guilty or worthless
  • Feeling hopeless
  • Thinking frequently about death and suicide
  • Experiencing unexplained physical pain

Why Do Antidepressants Become Less Effective?

The potential reasons that an antidepressant might become less effective for you over time are several:

  • Certain medications, such as antibiotics or steroids, can interact with an antidepressant, causing it to become less effective.  In addition, steroids can have a direct effect on destabilizing mood.  Drinking alcohol and smoking heavily can also interfere with an antidepressant's effectiveness.
  • You could have another medical condition which is making your depression worse, such as hypothyroidism.
  • Increased stress in your life can cause chemistry in your brain which counteracts some of the benefits of your antidepressant.
  • The effects of aging could be making your body process medications in a less efficient manner.
  • You might have undiagnosed bipolar disorder and need a mood stabilizer or antipsychotic medication in addition to your antidepressant in order to best control your moods.
  • It is possible that your brain's receptors have built up a tolerance to the effects of your antidepressant, although it is poorly understood how or why this might occur.

Generally, if you begin to experience a return of your depression symptoms, your doctor will deal with this by either increasing your dose, adding an additional medication or changing you to a different medication.  If there is an underlying cause for your returning depression symptoms, such as a medical condition, he will take steps to treat it.  He may also opt to refer you for psychotherapy or counseling to help you deal with any new sources of stress in your life.  If it is determined that you might be suffering from bipolar disorder, your treatment plan could be altered to include appropriate medications for this condition as well.


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.  

"CME:  Treating Depressive Disorder:  Relapse and Recurrence."  CANMAT.  Canadian Network for Mood and Anxiety Treatments.  

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.  

Mayo Clinic Staff.  "Major Depression Disorder:  Symptoms."  Mayo Clinic.  Mayo Foundation for Medical Education and Research.  Last updated:  July 22, 2015. 

Continue Reading