Background Information
We have changed our suggested tapering options for some people taking a daily dose of over 90mg of duloxetine, also known as Cymbalta, and other generic brand names.
Recent research shows that serotonin transporter occupancy (SERT occupancy), a measure of the therapeutic effect of the drug, changes very little at doses above 60mg. “Occupancy” is a measure of the effectiveness of the medicine doing its work, preventing the re-uptake (absorption) of Serotonin or Norepinephrine.
In layman’s terms, “occupancy” means how much the serotonin receptors are blocked. When the serotonin receptors are blocked, circulating serotonin levels are increased in the brain and many other areas in the body. Prior theory was that this can reduce depression. That theory is now being questioned…
If the receptors are “occupied” they cannot absorb, that accomplishes the goal of SSRIs and SNRIs. Cymbalta is both an SSRI and an SNRI. The current research demonstrates the relationship between antidepressant dose and serotonin transporter occupancy. This is the primary biological effect of most all antidepressants.
We know that serotonin and norepinephrine occupancy also has a biological effect that may affect withdrawals during a taper.
Research article
In summary, the following research shows that Cymbalta becomes less effective at occupying the receptors as the dose increases. This is counter-intuitive, as our experience with most medicine is that the more you take, the MORE the effect.
Sørensen, A., Ruhé, H.G. & Munkholm, K. —
The relationship between dose and serotonin transporter occupancy of antidepressants—a systematic review.
Mol Psychiatry 27, 192–201 (2022)
This research explains why taking a higher dose often has no greater effect than taking 60mg. In fact, Eli Lilly, the inventor of Cymbalta, specifies a maximum dose for virtually all approved treatments. This does not indicate that it is safe to drop directly to 60mg, as some people experience withdrawals even at these high doses, regardless of the SERT occupancy.
SERT occupancy of duloxetine at various doses, approximate
5 mg: 44%
20 mg: 74%
40 mg: 81%
60 mg: 85%
Example: A person taking a 60mg dose of duloxetine may have SERT occupancy or blocked serotonin receptors of ~85% while a person taking a 5mg dose may have a SERT occupancy of ~44%. That shows that increasing the dose 12 times only increases the effectiveness 2 times!
This graph is from the 2022 Sørensen, Ruhé, and Munkholm article linked above:
This hyperbolic pattern of SERT occupancy means that withdrawal symptoms arise when the dose reduction is large enough to decrease the effects of the drug. This may not happen with every dose reduction.
Tapering Guidelines From More Than 90mg
Based on the above information and our experience with about 40,000 members over more than a decade, we suggest, if you are taking more than 90mg daily:
*IF* you meet all of the following criteria:
- Have “little or no history” of taking other psychotropic drugs such as antidepressants, benzodiazepines, prescription sleep aid drugs etc.
- Have not ever stopped duloxetine or other psychotropic drugs with large rapid drops or all at once (“cold turkey”)
- Have not frequently changed the dose
and you take more than 90mg of Cymbalta/duloxetine daily, drop immediately to 90mg.
If you do NOT meet all of the three criteria above, we suggest:
- Reduce immediately to 90mg. Hold that dose for 60 days. Retain your current prescription in case you need to adjust the dose upward in that time, and in general, throughout the entire taper process.
- If you are reducing from a dose greater than 120mg, reduce by 30mg every 60 days until you reach 90mg.
- If significant withdrawal symptoms arise, immediately post in the Facebook group Cymbalta Hurts Worse for suggestions. You may need to hold at that dose for some time or go back up in dose to some degree.
- Once at 90mg, if all goes well after holding for 60 days, start tapering by five percent or less of each previous dose every 14 days or longer as outlined in the standard tapering guide. Do not make large drops below 90mg.
- Keep a tapering journal of when you do your drops.
- We often speak of “listening to your body” when tapering. A tapering journal may reveal a pattern of withdrawals and help your entire taper. Your journal will help you and CHW learn and make needed adjustments to your taper.
- Note any issues, but to help yourself feel better, keep your general focus outward instead of on your symptoms.
If you try this new reduction method from greater than 90mg, please let us know how it goes for you. Do contact us if any issues arise.
***Caution***
These large reductions in dosing that we now suggest for some people based on SERT occupancy numbers may cause unpredicted withdrawal symptoms or have other unforeseen risks. It is essential for you to understand the science of SERT occupancy to plan a safe taper.
Because people react differently due to many factors, we do not recommend making large drops below 90mg.
We provide no guarantees when tapering off a psychotropic drug. Withdrawals are unpredictable, so these are merely suggestions based on Cymbalta Hurts Worse members’ “lived experiences” and the science of how the serotonin receptors are blocked in relation to the actual dose you are taking of duloxetine.
###