What To Do If Your SSRI Stops Working

In our latest question and answer, the pharmacist discusses what to do if your SSRI antidepressant medications stops working.

What To Do If Your SSRI Stops Working
Jun 09, 2018

Mark asked

I am writing a research paper and would like your assistance regarding antidepressants. If a SSRI stops working and the patient can no longer increase the dosage or does not wish to add another type of drug, is it necessary to switch to a different class of antidepressants (for example, SSRI to SNRI)? Can staying in the same class be just as effective (for example, going from Lexapro to Zoloft)? Thank you in advance for your help.


Antidepressant pill facesIt is not uncommon for your first SSRI (selective serotonin re-uptake inhibitor) to stop working after a period of time, or not achieve remission at all. In fact, one 2017 study published in JAMA states that less than one-third of patients achieve remission during their first course of antidepressant therapy.

Commonly used SSRI medications include:

  • Celexa (citalopram)
  • Lexapro (escitalopram)
  • Prozac (fluoxetine)
  • Luvox (fluvoxamine)
  • Paxil (paroxetine)
  • Zoloft (sertraline)

If you are not receiving adequate results with your SSRI medication, it is important to try optimize your dose (i.e. increasing to effect) first. However, if dose optimization is unsuccessful or your cannot tolerate effective doses, switching antidepressants may be your best option.

How To Switch Antidepressants

Most studies, such as this article from the New England Journal of Medicine, report that individuals may respond better to a drug in a different class but are equally as likely to respond to another medication in the same class. Therefore, if your SSRI isn't working well, it may be a good idea to try and simply switch to another SSRI and assess the effects.

Once someone has failed 2 drugs from one class (e.g. SSRIs), the Practice Guidelines For The Treatment of Patients With Major Depressive Disorder recommends to try a drug from a different class.

Direct Switching

If an individual is trying to switch from one SSRI to another, in most cases, they can:

  • Simply stop the SSRI they are taking
  • Start taking the new SSRI (at a low dose) and increase over time to an effective dose.

As an example, if you were taking Zoloft, and wanted to switch to Lexapro, you stop Zoloft and start Lexapro the next day at a low dose.

One caveat to this is if you were initially taking Prozac (fluoxetine). Prozac has a very long half-life and lasts in the body for a long time. Many sources recommend to start a new SSRI only after a seven-day washout period to avoid additive side effects.


When switching between classes of antidepressants, it may be a good idea to "cross-taper", meaning that you will gradually reduce the dose of your old drug while simultaneously increasing the dose of the new one. It is important to note that when discontinuing your old drug, tapering should typically be done over at least 4 weeks to minimize withdrawal symptoms.

Other commonly used antidepressant medications (aside from SSRIs) include:

  • SNRIs (e.g. Effexor, Cymbalta)
  • Mirtazapine
  • Wellbutrin (bupropion)
  • Viibryd (vilazodone)
  • Trintellix (vortioxetine)

Additional Information

It is always important to speak with your doctor regarding the best method for adjusting antidepressant therapy. Everyone's medical situation is different and many factors need to be taken into account when choosing antidepressants or when coming up with dose optimization/switching strategies.

Ready for a more personal experience with your meds?