Joshua Siegel
@realJoshSiegel
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Neuroscientist, Psychiatrist, Father, Human, Philomath. Good science is careful. Great science is playful.
St Louis, MO
Joined August 2017
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After a high dose of psilocybin, the brain desynchronizes at a massive scale, causing loss of our sense of self, time, and space. This may drive the burst of plasticity caused by psychedelics. The next day, brain activity has largely returned to normal, but an echo remains – a
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We tracked brain changes in healthy adults before, during, and for weeks after a large dose of psilocybin, and again 6+ months later.
Psilocybin caused profound and widespread desynchronization to brain activity, altering connections across cortical networks and subcortical
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Interestingly, when participants on psilocybin were asked to focus on a simple matching task, psilocybin’s disruptive effects decreased. This suggests a neurobiological basis for grounding - connecting with physical reality during psychedelic therapy.
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We saw these changes across association cortex, but strongest in the default mode network (DMN), which is connected to the anterior hippocampus and is thought to create our sense of self. The amount of change strongly predicted the intensity of the mystical experience.
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Brilliant title
@AndrewJacobsNYT
.
Bonus (if you made it this far) - a blog post I wrote describing our adventure doing this study:
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It appears the massive desynchronization on psilocybin jump starts plasticity in the hippocampus and cortex. This burst of plasticity (the neurotrophic cascade) seems to be necessary and sufficient for rapid antidepressant-like effects in animal models.
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Psilocybin caused a lasting decrease in connectivity between the anterior hippocampus and cortex (DMN in particular) which lasted for weeks afterwards.
Zheng et al., suggest that the anterior hippocampus-DMN circuits controls self-oriented thinking and memory. Some past studies
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This may provide a key link between the plasticity observed at the cellular level and the rapid antidepressant response observed in recent clinical trials.
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I am thrilled to announce that I start today as Asst. Prof. at
@nyulangone
Center for Psychedelic Medicine - world leader in clinical and translational psychedelics research. 🥳
I will be using precision imaging to study how rapid antidepressants target brain circuits - as I
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Nature’s cover is an Easter egg! Huxley‘s Doors of Perception described (effed?) the ineffable psychedelic experience.
I’m honored to have our study featured
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Psychedelics are becoming decriminalizing in the US by state legislation at a dizzying and accelerating rate. See our analysis of legislation out today in JAMA Psych:
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In 2022, the number of PubMed hits (articles) for "
#Psychedelics
" has passed the number of PubMed Hits for "
#SSRIs
". Truly astounding.
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Snuck my favorite bracelet into my NYU faculty profile pic 🌈
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That repeated scanning gives “an unprecedented view on how brain connectivity evolves after a dose of psilocybin,” says Alex Kwan.
Thanks
@kwanalexc
! Means a lot coming from a giant of neuroplasticity/psychedelics research.
Inside your skull, your brain hums along with its own unique pattern of activity, a neural fingerprint that’s yours and yours alone. A heavy dose of psilocybin temporarily wipes the prints clean.
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@giorgallidis
I clicked on this really looking forward to some answers backed with good scientific evidence.
Disappointed that all I got was conjectures.
Maybe these things matter, but frankly, there is more objective evidence behind the role of sugary drinks and sedentary lifestyle.
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Placebo response is a BIG problem in psychiatric clinical trials.
The corporatization of clinical trials has created perverse incentive to enroll participants who may not meet objective criteria for depression.
At SMPA, we used speech latencies as an OBJECTIVE measure of
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Even bigger thanks to all my co-authors, our brave research volunteers (who spent >20 HOURS in the scanner - some while on high doses of psilocybin), and everyone who helped with this study!
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Psychedelics stimulate plasticity. But why? And what does that MEAN in the human mind/brain?
We found that psilocybin changes your brain to a degree that is many fold larger than any other intervention we looked at (figure above). It is as large as the difference between people!
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I went from chopping fire wood in my backyard outside STL to doing 'wood chops' in my HIIT workout class in Manhattan. It's going to take a bit of time for me to adjust...
Jokes aside, moving my family from STL to NYC has been one of the biggest challenges of my life.
Doing my
I am thrilled to announce that I start today as Asst. Prof. at
@nyulangone
Center for Psychedelic Medicine - world leader in clinical and translational psychedelics research. 🥳
I will be using precision imaging to study how rapid antidepressants target brain circuits - as I
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This is a momentus paper. Can the organization of brain networks help us to understand serious mood disorder? OF COURSE THEY CAN! It just took us (neuroimagers) a while to figure it out... Congrats
@cl9681
,
@conorliston
, and the rest of your team. Well done.
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@ConnorMEwing
I feel like this is a problem with the title, not the student.
I mean, who ARE you an assistant to anyways?
I can easily think of 5 better titles for tenure track faculty than ‘assistant’
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How can fMRI be so GOOD at telling you what part of the brain does stuff, but so BAD at telling you how different brains differ?
Maybe answering that question has important implications for the endeavor of cognitive neuroscience.
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I had fun playing with cover ideas on Dall-E. This one is pretty sweet.
But Nature prefers to support real artists.
One of my favorite things is to have one of "my" papers on
@nature
's cover... and that's what happened this week! Check out our issue featuring
@realJoshSiegel
@ndosenbach
et al's work
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The largest change was in the
#DefaultNetwork
, which creates our sense of self.
But it wasn’t only in cortex! DMN-connected parts of the thalamus/BG/cerebellum/hippocampus showed changes as well.
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Best. Gift. Ever.
My daughters made me this little book. Love my brilliant, creative, and kind-hearted girls. ❤️🍄
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A project I have been working on for quite some time with
@smarek0502
and the brilliant folks in the
@DosenbachLab
: Spatial and Temporal Organization of the Individual Human Cerebellum
@SSRN
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Most importantly, participants came back 3x/wk for weeks after – we were looking for ‘persisting’ effects.
What did we find?
Connectivity between the
#hippocampus
and
#DefaultNetwork
is decreased for weeks (but returns to normal at 6+ months).
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Fun fact: the 'massive' effects of psilocybin got MUCH smaller when participants engaged in a grounding task!
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What does that mean??
@DosenbachLab
(Zheng et al., 2021) suggest that these anterior hippo-cortical circuits are controlling self-oriented processing. Past studies have linked hyperconnectivity of these circuits with depression.
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💊 Unveil new dimensions in psychopharmacology! Expert insights on managing psychiatric disorders, addiction, psychedelics await. Transform your care strategies.
#PsychPharm24
Explore:
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The change was a results of widespread desynchronization (nicely paralleling
@CarhartHarris
entropic brain hypothesis!).
This desynchronized replicated in a prior LSD dataset (thanks
@LeorRoseman
and
@CarhartHarris
for data sharing) and fit nicely with 5HT2A expression maps.
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WashU Neuroscience is recruiting tenure track faculty - the best neuroscience community in the world - also building a HUGE new neuroscience research facility FYI -
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@LFeldmanBarrett
@TrendsCognSci
We considered the implication of these very same principles on stroke and brain lesions!
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Wow, this is shocking - use of psychiatric medication increases by "40 percent by the fifth year compared to pre-PhD levels. After the fifth year, which represents the average duration of PhD studies in our sample, we observe a notable decrease in the utilization of psychiatric
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Excited to share my work with Nuri Farber and the
@HealthyMindLab
. A long ketamine infusion kick-starts the depressed brain from the limbic system on up. And the effects last for months. It's 100% changed the way I think about depression treatment.
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@DrBreaky
@RCarhartHarris
@GrattonCaterina
@MAPS
@ndosenbach
@HealthyMindLab
@WUSTLmed
It will!
We will release it with my paper AND we are working on a "Data Resource" paper which describes some interesting expected/unexpected advantages of the precision imaging 🧠 x 💊 design.
But if you can't wait and want it now, DM me! I'm happy to share.
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Hahaha well so much for participant anonymity.
JK, you already crushed an NPR interview.
Was great getting to know you during the study Scott. Hope you are well!
I took 25 mg psilocybin and for some reason my brain's functional connectivity change in the anterior hippocampus decreased afterward? Everyone else's went up. I apparently also have lower whole-brain entropy in general (higher brain synchronization)
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Had the privilege to go to Jefferson City with
@gingerenicol
to provide expert testimony to MO lawmakers re psychedelics reform. It was exciting and humbling. A reminder of the power of democracy and also that I am a Missourian.
@HealthyMindLab
@JeffSmithMO
@tonylovasco
‘Interesting times’ at Missouri Capitol, as lawmakers consider bill to legalize certain psychedelic drugs by
@GraceZokovitch
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I had a great chat with Alex Stipanovich on the Origins of Sentience Podcast.
Check it out:
After doing a couple podcasts, I actually feel like I'm getting better at expressing ideas without sounding like a bumbling fool! 🤓
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Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder via
@JAMAPsych
part of
@JAMANetwork
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Heard a talk on effect sizes in brain connectivity-behavior associations today by
@smarek0502
that has left me feeling rather... small
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@RCarhartHarris
@LeorRoseman
@_fernando_rosas
@PedroMediano
Yes! I was thrilled to see that the grounding effect replicates across fMRI and MEG! Great work
@PedroMediano
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@Chaos2Cured
@ndosenbach
@Nature
@DosenbachLab
@RCarhartHarris
@DrDamienFair
@gordonneuro
@Subha__S
25mg of psilocybin is roughly = 5 grams of psilocybe cubensis mushroom
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@GrattonCaterina
The Gratton 2018 model of individual stability was the key starting point for quantifying the magnitude of psilocybin effects. Thanks for your great work, Caterina!
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@IFLScience
Thanks for posting this great summary
@IFLScience
! Here is a thread outlining our findings:
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Cover of Door of Perception:
Thanks to Jasiek and the creative team at Nature
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I heard an interview with Lamar Johnson. Freed from prison after 30 years for wrongful conviction. He’s most looking forward to “holding a baby, waiting in line and feeling frustrated because it’s taking too long,” [and everything in between]. Goals: live every day like Lamar.
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What I’ve learned from rehab:
pain, no gain = ❌
No discomfort, no gain = ✅
2.Body & Mind.
When I feel great, then the pain is “not bad, it’s better than yesterday!” I when I feel grumpy, then the pain is “a pain in the a$$.”
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Thanks to
@TylerKjorvestad
and the rest of the
@psychedelic_org
crew for a fun conversation about ketamine, psychedelic, and my research plans with Ginger Nicol and the Healthy Mind Lab
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Progress towards medical psilocybin in MO!
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@RCarhartHarris
Wow - I hadn’t seen it! Just read the abstract but very excited to dig deeper… Will be citing this as I explore the desynchronization idea further
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Super interesting study.
I fit the trend I think.
Here's why its justifiable to me - recommending an antidepressant gives your patient PERMISSION to try it (info, rx). I can tell you, many patients will still decline.
So I err on the side of opening the door...
79% of psychiatrists recommend immediate treatment with an antidepressant to an outpatient with depression, but only 39% of psychiatrists would immediately take an antidepressant if they personally had depression, while 61% would prefer watchful waiting
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An interesting look at the psychedelic renaissance in Riverfront Times, featuring my research with Ginger Nicol and the
@HealthyMindLab
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@Lvsitanian_Ivan
This seems to be a common fear. But fear not! Steve Jobs spoke extensively about using LSD. He achieved something. The Beatles sang about them. They may have been hippies, but not whimpy, and pretty high achievers, I’d say. Kary Mullis credited using LSD with helping him invent
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Cover of Door of Perception:
Thanks to Jasiek and the creative team at Nature
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To the new interns, congratulations. And to the rest of you, be safe out there tonight. For tomorrow is the worst day of the year to go to the hospital.
@washupsychres
@BarnesJewish
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Spatial and Temporal Organization of the Individual Human Cerebellum
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Can someone with a subscription to National Geographic tell me if this headline is intentionally being ironic? I’m dying to know.
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So cool!! The latest smash hit in precision brain imaging. When you use a within subject design, effects of pregnancy on the brain are massive! Figure 1d is just… beautiful.
Two questions I am left with -
1) What does decreased cortical thickness during pregnancy mean??
2)
Pregnancy changes the brain, and new research reveals intriguing clues about how. Some areas shrink, while others appear to show temporarily improved communication, a new study of brain scans found.
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@cosmicrabbitt
@AndrewJacobsNYT
Our study was in healthy individuals with no psychiatric illness. In some states, psilocybin has been decriminalized, in others it has been made available in therapeutic settings only. but there is no evidence that psychedelics improve memory.
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For those interested in the science and history behind the
#psychedelicrenaissance
and where
#psychedelicmedicine
is going, here is a nice primer by
@CraigSPearson
, me, and
@drjessigold
.
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One parenting hack the doctors do want you to know about:
Drugs! Your kid won’t pay attention in class? Drugs! Trouble getting your kids to bed on time? Try Drugs. Trouble building a loving bond with your teen?
#Drugs
! (Not FDA approved, some restrictions in exclusions may apply)
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Heading to Chicago to give a lecture at Suncloud Health - “Psychedelics: Hope or Hype?” 11CST - I think it’s open to public -
Should I wear my lucky socks?
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@TheBorisLab
@DanRyskamp
@aminoacidhead
Congrats Boris, its a great study. We are also finding limited evidence that subjective experience has much impact on brain changes (by doing human brain imaging during multiple psilocybin doses).
BUT we must admit that persisting effects may be a different story...
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We are recruiting healthy adults for psilocybin research at WU. If you are and adult, have ever taken a psychedelic drug before, and want to take psilocybin for science, shoot me a message. Also, feel free to share. Here are the clinical trial details:
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Here comes my favorite part - Moses is about to inhale DMT from the burning acacia and hear the voice of god!
Happy Passover everyone!
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@tervoclemmensb
Thanks Brenden!
@ndosenbach
likes to say "if you want a reliable result, start with the biggest🔨 you can find." 🍄 turned out to be a good option!
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I am proud to share a review - 6 years in the making (maybe not proud of that part) - detailing how correlated neurological deficits arise from distributed brain networks (& how this discovery shapes our view of brain function).
@MauCorbetta
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After all my years of complaining, finally someone is listening.
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I was excited to see such a good deal on a hardcover Hermann Hesse novel on Amazon. Didn’t realize it was going to be quite so small…
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I have an intuition that my country is on a path to political collapse. But I admit I don’t have the historical knowledge to know if my intuition is valid.
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@LeorRoseman
@RCarhartHarris
@_fernando_rosas
@PedroMediano
Hadn’t seen your paper until now, it’s fantastic! I think they all fit together into a powerful theory about how to optimize the benefits of psychedelics.
Would love to collaborate to build out the idea empirically.
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Scientists of Twitter! The world needs more reminders that we're living, breathing human beings.
Quote tweet this with a picture of you doing not-science
Scientists of Twitter! The world needs more reminders that we're living, breathing human beings.
Quote tweet this with a picture of you doing not-science
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A cutoff was applied for baseline turn latencies to classify individuals into two groups: Speech Latencies Slow (SL-Slow) and Speech Latencies Normal (SL-Normal). At week 6, SL-Slow (N = 172)
At week 6, SL-Slow (N = 172) showed separation in MADRS scores between placebo and
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On psychiatry consults I see the darker side of the opioid crisis. And one provocative thought emerges - maybe it isn’t always right as a doctor (or as a parent) to make the pain go away.
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@therealRYC
This is fantastic! Although I have to point out, the heritability of depression is 30-40% (and 80-90% for SCZ)
The article you reference gives SNP-based heritability, which is not an ideal marker of actual heritability bc it doesnt account for additive genetic variance,
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In my Cognitive Computation and Systems Neuroscience class in 2013 each student had to build/train a neural network (MLP) to recognize handwritten numbers.
That blew my mind.
What are the students going to build in CCSN class in 2033? 2043?
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Check out a great conversation with
@drjessigold
and Ginger Nicol about healthcare worker burnout and efforts by WU psychiatry to take care of our teammates in the hospital -
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Sign up for a red cross donation - Get a FREE covid antibody test.
If you have covid antibody, donate covid antibody and save a life.
If you dont have covid antibody, donate blood/blood products and save a life.
win-win-win?!
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In case you don’t know me… I’m kind of a mushroom fan :).
For pizza, studying consciousness, spiritual cleansing, whatever.
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It is a strange world we live in.
Here, men are getting paid money to lift heavy things…
And there, men are paying money to lift heavy things…
And over there, people need help lifting heavy things, but they haven’t enough money to pay for help.
There must be a solution
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@RCarhartHarris
It is a stark contrast to pharma. In academia you are encouraged to differentiate from mentors and those around you - which is probably why we have 800 different ways of analyzing fMRI data and no one can agree. In pharma, you fill a narrow role in a larger enterprise, rigidly
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@foundmyfitness
This is not correct. Or at best very misleading. They passed an expanded access bill to allow physicians to prescribe it even though it isnt approved. The same thing actually exists in US but cant currently be done for psilocybin because it is DEA schedule 1.
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@RadoslawStupak
Psychiatrist here - I fit the trend I think.
Here's why its justifiable to me -
Recommending an antidepressant gives your patient PERMISSION to try it (info, rx). I can tell you, many patients will still decline/choose alternative strategies.
And thats fine.
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