What Is Bad About Paroxetine – 3 Strikes and You’re Out

Paroxetine is from the family of SSRIs (selective serotonin reuptake inhibitors. It has been around for a long time and is indicated for depression, anxiety, and many other psychiatric indications just like other SSRIs. It doesn’t get much love from healthcare professionals. In this article, I’ll discuss what is bad about paroxetine and why we don’t like to use it as much as other antidepressants.

Paroxetine in Pregnancy

Paroxetine should generally be avoided in pregnancy. The primary reason that it is avoided in pregnancy is that it has demonstrated fetal risks. Through the previous FDA rating system, it was considered an FDA pregnancy rating of D. Fifteen studies have found a statistically significant increase of major congenital malformations, specifically atrial and ventricular septal defects, in babies born to mothers taking it during the first trimester of pregnancy (Bérard et al., 2016). I have discussed this in-depth previously, but that is strike #1.

Paroxetine Use in the Elderly

In practice, paroxetine use in the elderly is discouraged. The primary reason for this is that it has more anticholinergic activity than other SSRIs. It can increase the risk of dry eyes, dry mouth, constipation, urinary retention, and other adverse effects. Increased confusion may also be a concern with paroxetine use in the elderly. The 2023 Beers criteria also raises the concern of orthostatic hypotension which can increase the risk of falls in our geriatric patients. The pregnancy and elderly concerns are good nuggets to remember if you are taking a board exam!

Paroxetine Pharmacokinetics

The final strike against paroxetine is probably slightly less consequential but can be problematic at times. There are two pharmacokinetic concerns with this medication that have impacted my patients. The first is paroxetine’s short half-life. When attempting a reduction or trial discontinuation, a patient may experience SSRI withdrawal syndrome. Because of the short half-life, those symptoms should develop within 2-4 days of stopping the medication. I outline the challenge of missed dosages in this previous post.

The other pharmacokinetic concern is that it inhibits CYP2D6. There are many medications that are metabolized by CYP2D6 or can even use this pathway for activation. Here’s a perfect case example of an interaction involving tamoxifen and paroxetine.

Patients will rightly have questions and concerns when this medication is being used. Hopefully, this post will help you have a good discussion with your patients about what is bad about paroxetine and why it is rarely used.

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