6 Reasons To Avoid SSRIs

Selective Serotonin Reuptake Inhibitors are a mainstay in the management of depression and other mental health disorders. All SSRIs are not created equal and when I am reviewing a patient case, I make sure to look for specific things that may put a patient at risk for issues from specific SSRIs. Here are 6 specific reasons to avoid SSRIs.

QTC Prolongation

If your patient is at risk for QT prolongation or is taking other medications that could raise QT prolongation issues, you should generally avoid using citalopram. It is one of the worst as far as this issue is concerned and especially as we escalate dosages.

Anticholinergic Burden

Paroxetine is seldom used in geriatric patients and the reason this is true is that it has more anticholinergic activity than other SSRIs in the group. Avoiding this medication in elderly patients and those who may be taking other anticholinergic medications is important.


All SSRIs can cause GI adverse effects, but one tends to be worse than the others when it comes to diarrhea. In patients with gastrointestinal disorders that cause diarrhea, it would be best to avoid sertraline. This medication is often termed “Squirtraline” because of its propensity to cause loose stools. IBS, Crohn’s, and Ulcerative Colitis are common GI issues that can cause diarrhea symptoms and it would be advisable to consider another SSRI than sertraline.

Numerous Drug Interactions

Fluvoxamine is well known for drug interactions and this is the primary reason why you don’t see this medication used very often for major depression. It is critical to avoid this medication and this is especially true in our polypharmacy patients.

CYP2D6 Interactions

Fluoxetine and paroxetine are well known to impact CYP2D6. One of the most consequential drug interactions with these medications is tamoxifen. Adding fluoxetine or paroxetine to a patient’s regimen who is taking tamoxifen will reduce the effectiveness of tamoxifen.


Fluoxetine (and possibly sertraline) tend to be more activating. This can be advantageous in some patients who tend to feel sedated and sleep all day when they are experiencing depression symptoms. For those that have difficulty with sleeping, these drugs can worsen insomnia. If you see a patient who is taking a sleeper medication and are going to start an SSRI, you might want to avoid these two activating agents.

What other important considerations do you think about when it comes to reasons to avoid SSRIs?

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Written By Eric Christianson

December 5, 2021

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