Antidepressants: Can they lose effectiveness over time?

Q: Can antidepressants lose effectiveness over time? 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?

Mary / Minnesota

You describe a phenomenon that affects approximately 20 percent of people who take antidepressants — the so-called "poop-out" effect. In such cases, the medications simply stop being effective. Doctors don't fully understand what causes this. But factors that you and your doctor may want to consider include:

• Relapse or worsening of depression. For most people, depression is a disease that will recur at least once — if not more frequently — after the first episode. Sometimes depression worsens for no apparent reason or due to added stress that overrides the effects of the medication.
• Underlying medical condition. Some conditions, such as hypothyroidism, can cause depressive symptoms. It is important to rule out such conditions as a cause of worsening depression.
• Aging. Sometimes depression can get worse as you get older.
• A new medication. Some medications for unrelated conditions can interfere with the way your body metabolizes and uses antidepressants, decreasing their effectiveness.
• Reassessment of original diagnosis. For example, it is possible that an illness previously diagnosed as depression may actually be bipolar disorder, in which depression is a prominent feature.

The good news is that adjusting the dosage, changing medications or adding other medications is usually effective in countering the poop-out effect. Psychotherapy also can help.

For all these reasons, it is important to have a psychiatrist trained in the use of antidepressant medications review all of the possible causes and interventions that may be helpful when an antidepressant seems to lose its effectiveness.