Safe Pain Medications To Use With Zoloft (Sertraline)

In our latest question and answer, the pharmacist discusses why Tylenol (acetaminophen) is a safer analgesic choice than Advil or Aleve when taking Zoloft (sertraline).


I was recently prescribed Zoloft and an inhaler, I asked the pharmacist if I was allowed to take Tylenol, Aleve, and Advil, and they said only Tylenol. My dad and brother have Zoloft as well but take other pain relievers. I wanted to verify if other over the counter pain relievers are still safe to take. Also how crucial is it to take Zoloft at the same time every day? Thank you

Asked by Kaitlynn On Jul 31, 2018

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Aug 01, 2018

In most cases, it is recommended that you use pain relievers other than ibuprofen (Advil) or naproxen (Aleve) when taking sertraline (Zoloft), to avoid potential interactions and side effects. Tylenol is typically the preferred option.

Tylenol is in a different class of pain reliever than the non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen and it does not work to relieve pain in the same way. Due to the different mechanism of action, Tylenol does not interact with selective serotonin reuptake inhibitors (SSRIs) like sertraline.

An analysis of several studies shows there is a significant increase in the risk of bleeding (mostly stomach bleeds) when NSAIDs (like Aleve and Advil) and SSRIs are taken together. In fact, SSRIs and NSAIDs alone have been shown to cause a risk for bleeding. Adding them together only increases the risk.

When taking NSAIDs and SSRIs in combination, studies have shown anywhere from a 2.8-fold to 15.6-fold increase in stomach bleeds. If taking a combination of NSAIDs and SSRIs, it is recommended to monitor for signs and symptoms of bleeding.

When To Take Zoloft

Generally, it is recommended to take medication around the same time of day so there is consistency. This can help people to remember to take their medication every day. It is also important for medications like Zoloft to be taken around the same time of day to keep the levels of the drug consistent in the body since it is altering serotonin levels. Taking it at the same time each day will help it be fully effective.

Although rare, some patients may start to experience symptoms such as:

  • Irritability
  • Agitation
  • Dizziness
  • Anxiety
  • Confusion
  • Headache
  • Lethargy
  • Insomnia

These symptoms may be experienced more if the Zoloft is stopped abruptly, which is why it is important to be weaned off if stopping. If missing a dose, it is recommended to take the dose as soon as you remember unless it is close to the timing of the next one. It is not recommended to take two doses at the same time.

It is up to you regarding what time of day to take the Zoloft. Many people base this on potential side effects, mainly either drowsiness or restlessness. It is recommended to take it in the morning if it makes you feel restless. It is recommended to take it at night if it makes you feel drowsy. This depends on how it affects you and when you feel it would be best for you to take and when you feel you will remember best.

Alternative Pain Relivers

Aside from Tylenol, you can feel safe using most topical pain relievers with Zoloft, like Tiger balm, Bengay and lidocaine patches. These will not interact with it.

About the Pharmacist

Dr. Anna Staudt Pharm.D

Dr. Anna Staudt graduated in 2017 with a Doctor of Pharmacy degree. She is completing a pharmacy fellowship focused on ambulatory care. Her current practice site is at a Federally Qualified Health Center (FQHC) where she deals with the underserved.

About Zoloft (Sertraline)

Zoloft (sertraline) (pronounced SER tra leen) is used to treat depression. It may also be used to treat obsessive compulsive disorder, panic disorder, post-trauma stress, premenstrual dysphoric disorder (PMDD) or social anxiety. It is classified as a SSRI, selective serotonin re-uptake inhibitor, which work by increasing the availability of serotonin in the brain as well as changing the balance of serotonin receptors over time. Zoloft may be taken without regard to meals in the morning or evening. Like many antidepressants, full effects of the drug may not be realized for 6-8 weeks.

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