Dear Dr. Aiken: Your review of Paxil’s risks in the May issue failed to mention a benefit that’s unique to this drug. Isn’t it the best SSRI for anxiety?

Dr. Aiken: Paroxetine’s (Paxil’s) reputation as the anti-anxiety SSRI got off to a running start. It was first launched for panic disorder in 1996, two years before its approval for depression, and went on to gain approval in 4 other anxiety disorders. A rumor began to percolate that paroxetine was a better choice for anxious patients, and it continues to be spread. For example, Stephen Stahl highlights it on his website: “In clinical practice, many clinicians use [paroxetine] for patients with anxious depression.”

The data tells a different story. In head-to-head comparisons, paroxetine works as well as other serotonergic agents in anxiety disorders, and sometimes worse. That includes around a dozen large, head-to-head trials in generalized anxiety disorder, social anxiety disorder, panic disorder, and major depression with anxiety. It fared no better than sertraline, citalopram, venlafaxine, and clomipramine, and was consistently outperformed by escitalopram (Sanchez C et al, Int Clin Psychopharmacol 2014;29:185-196). Overall, paroxetine has only modest anxiolytic effects (effect size of 0.3), and anxiety does not predict whether a depressed patient will respond to it (Sugarman MA et al, PLoS One 2014;27(9):e106337).

Paroxetine does hold more FDA-approvals in anxiety disorders than most other antidepressants: panic disorder, generalized anxiety disorder, social anxiety disorder, PTSD, and OCD. Those approvals came with a license to market, and that marketing may be responsible for its clinical lore. Side effects may have also assisted in its reputation. Paroxetine causes more fatigue than other SSRIs, and sedative effects can be conflated with anxiolytic effects (Nevels RM et al, Psychopharmacol Bull 2016;46:77-104).

Paroxetine does stand out in a few ways that aren’t so desirable. It has higher rates of weight gain, sexual dysfunction, withdrawal problems, anticholinergic effects, congenital malformations, and CYP2D6 drug interactions than other SSRIs (Marks DM et al, Expert Opin Drug Saf 2008;7:783-794). Our May 2019 issue added another risk to that list: dementia. There may be patients who respond uniquely to paroxetine, but anxiety is not a reliable guide to finding them.