My focus on Paxil (an SSRI antidepressant medication) began with a question from a patient: "Have you had much success with helping patients withdraw from Paxil?"
"To be honest," I thought to myself, "frankly, no . . . "
I thought of all the patients who had ever tried to get off an SSRI in my practice and realized that although patients got off other SSRIs without much ado, Paxil was different. Patients had more difficulty tapering off of it.
Why?!!
I quickly found the answer on Wikipedia once I suspected that I was missing something important with Paxil withdrawal. Read on to discover the critical difference about Paxil that I learned.
Have a great week!
Critical Information on Effexor XR and Paxil Withdrawals
On SNRIs and the misclassification of Paxil
What is the difference between an SSRI and an SNRI?
An SSRI is a Selective Serotonin Reuptake Inhibitor, and an SNRI is both a serotonin and a norepinephrine reuptake inhibitor.
They are all antidepressants, but SNRIs affect two neurotransmitter pathways, while SSRIs affect just one.
Some medications classified as SSRIs are: Prozac, Paxil, Zoloft, Celexa, and Lexapro.
Some medications classified as SNRIs are: Effexor and Cymbalta.
The inhibitor constant, Ki, is an indication of how potent an inhibitor is. The smaller the number, the more potent the medication's effect on the receptors.
In the tables below:
SERT = Serotonin Reuptake Transporter
NET = Norepinephrine Transporter
DAT = Dopamine Transporter
Here's Effexor XR's Ki values:
Here’s Cymbalta’s Ki values:
Here’s Paxil’s Ki values:
And here’s a real SSRI’s Ki values (Lexapro):
Do you see the answer?
Lexapro's Ki value for NET is much larger than Effexor XR's, which means that it isn't nearly as potent at the NET receptor. This is the kind of Ki value that we expect to see from an SSRI.
On the other hand, Paxil's Ki values reflect a much stronger inhibitory effect on the norepinephrine transporter than Effexor XR. In fact, Paxil, which is classified as an SSRI, acts more like an SNRI than a "typical" SNRI.
Now that I found this out about Paxil, I looked at another SSRI—Zoloft. Here is its Ki values:
Although Zoloft doesn't inhibit the norepinephrine reuptake transporter as powerfully as Paxil, it is at least twice as potent as Effexor.
Bottom line: not all SSRIs only inhibit SERT receptors. They affect other receptors like the NET receptor, sometimes even more powerfully than a typical SNRI. When withdrawing from some SSRIs, the norepinephrine system also needs support.
I usually like to support the NET receptor withdrawal process with L-phenylalanine 500 mg capsules (not D-L phenylalanine, which can create more anxiety). I tend to avoid using L-tyrosine because it makes my patients too anxious.
Hope these insights help you to understand why some SSRI withdrawals are much more difficult than others.
Have a great week!
The Holistic Psychiatrist Podcast (Ep. 4):
Conversation with a Patient who
Successfully Withdrew from Effexor XR
I look forward to sharing the inspiring story of a patient’s amazing healing journey as he came off Effexor XR and how he faced two simultaneous, catastrophic challenges—his own cancer and the death of his mother from cancer—and overcame both without falling back into depression.
Click here for the full episode available on Wednesday.
Be sure to subscribe! Watch the teaser here!