Psychiatrist at UC Irvine Medical Center
Joined May 2024
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New Substack Short: "Simtriyo: Not a Good Choice for ADHD" bryanshapiromd.substack.com/…
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Protracted Antidepressant Withdrawal Is (Usually) Central Sensitization open.substack.com/pub/bryans…
New Substack: A Point-by-Point Scientific Criticism of "The Top 10 Misleading Claims About Antidepressants" open.substack.com/pub/bryans…
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Substack: The Taper No One Can Agree On: Recommendations for Deprescribing a Nation on Antidepressants bryanshapiromd.substack.com/…
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Bryan Shapiro MD, MPH retweeted
A few weeks ago, @BShapiroMD posted a great high-level summary of our new paper: “The relationship between serotonin transporter occupancy and extracellular serotonin concentration is hyperbolic, not linear: implications for safely tapering antidepressants.” Now that we have an updated preprint out, I wanted to do a deeper dive into the underlying mechanism and modeling.
I’m very excited about this paper —it not only opens new avenues for future antidepressant tapering research, but also provides a deeper understanding of the mechanisms of serotonin reuptake inhibitors (SRIs) more broadly.
To avoid burying the lead, our central finding is this:
Extracellular serotonin rises substantially within the therapeutic dose range of serotonin reuptake inhibitors (SRIs)—exactly where SERT occupancy plateaus. Because current frameworks largely rely on SERT occupancy as a proxy for biological effect, they struggle to explain why withdrawal and other dose-response effects continue to occur within this range. Our model offers a potential mechanistic explanation.
Thread follows. Updated preprint is available on medRxiv here:
medrxiv.org/content/10.64898…
Theory: The prevalence of psychiatric drug use in a society will be proportional to its environmental divergence from the ancestral conditions to which human beings are evolutionarily adapted.
Bryan Shapiro MD, MPH retweeted
Some Predictions About the Future of “Withdrawal Studies”
What we talk about when we talk about antidepressant withdrawal
psychiatrymargins.com/p/some…
Bryan Shapiro MD, MPH retweeted
I have long espoused the same sentiment as @awaisaftab does here: that the variety of conditions, responses and outcomes currently referred to as “withdrawal” has become SO excessively broad, the lack of definition becomes harmful to productive discourse and a roadblock to addressing the many discrete issues falling into that categorical bucket
Unfortunately, over-broad categories are a defining feature of our modern mental health system, so it shouldn’t be surprising that colloquially-derived definitions end up being just as squishy and low-resolution as clinically-derived definitions.
Indeed, the even the term “mental health” itself lacks any singular, widely agreed-upon definition, let alone “depression” or “anxiety”
Update to the science of hyperbolic tapering:
The true hyperbolic curve for SSRIs/SNRIs is best reflected by the blue line, not the red line (prevailing model).
*Manuscript preprint with @DanielCohrsMD at end of thread*
And why side effects in the therapeutic dosage range (e.g. sexual side effects and emotional numbing) are dose-dependent despite minimal deltas in SERT occupancy.
Compared to current hyperbolic tapering, consider going slower at the beginning and faster towards the end, as tolerated. Proportional reductions in serotonin, not SERT occupancy, is biologically correct.
Preprint below:
papers.ssrn.com/sol3/papers.…
Bryan Shapiro MD, MPH retweeted
The full webinar 'How To Taper Off Cymbalta with Dr. Bryan Shapiro' is now available on YouTube.
Watch now: youtu.be/X8O0oxl95q4
#cymbalta #duloxetine #antidepressants #tapering #withdrawal #mentalhealth #medicaleducation #psychiatry #neuroscience #healthylifestyle
