Hyman & Nestler, 1996 Initiation & adaptation: a paradigm for understanding psychotropic drug action pubmed.ncbi.nlm.nih.gov/8561194/

"...describes a paradigm...to conceptualize the drug-induced neural plasticity that underlies the long-term actions of psychotropic drugs in the brain."
Hyman & Nestler, 1996 Initiation & adaptation: a paradigm for understanding psychotropic drug action pubmed.ncbi.nlm.nih.gov/8561194/

"Chronic perturbations can produce different types of adaptations in the brain. Many adaptations can be viewed as compensatory homeostatic responses...."
Hyman & Nestler, 1996 Initiation & adaptation: a paradigm for understanding psychotropic drug action pubmed.ncbi.nlm.nih.gov/8561194/

"Rather than conceptualizing receptor down-regulation as the mechanism of action of #antidepressant drugs,
...conceptualize...as a marker of adaptation."
Hyman & Nestler, 1996 Initiation & adaptation: a paradigm for understanding psychotropic drug action pubmed.ncbi.nlm.nih.gov/8561194/

"However, it is less clear how compensatory adaptations to a drug would result in a therapeutic response."
Hyman & Nestler, 1996 pubmed.ncbi.nlm.nih.gov/8561194/

"#antidepressants do not produce addictive behavior, presumably because they do not cause adaptations within brain reward pathways or, if they do, they are unlike the adaptations produced by cocaine or opiates."
Hyman & Nestler, 1996 pubmed.ncbi.nlm.nih.gov/8561194/

"Chronic administration of psychotropic drugs creates
perturbations in neurotransmitter function...In the case of #antidepressant & antipsychotic drugs...adaptations
are therapeutic; in...drugs of abuse, the result is addiction."
Hyman & Nestler, 1996 pubmed.ncbi.nlm.nih.gov/8561194/

"Compared with drugs of abuse, much less is known
about the mechanisms by which chronic administration
of antidepressants, antipsychotic drugs, & lithium al-
ters brain function....similar types of mechanisms are involved."
Hyman & Nestler, 1996 Initiation & adaptation: a paradigm for...psychotropic drug action pubmed.ncbi.nlm.nih.gov/8561194/

"Specific syndromes of dependence & withdrawal depend [on] which particular brain pathways undergo long-term adaptations in response to repeated exposure to a drug."

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More from @Altostrata

Apr 15, 2022
FACT: “Chemical imbalance” or "neurotransmitter deficiency theory" was deployed by pharmaceutical companies to advertise their #psychiatric psychotropics. Never been scientifically proven, debunked many years ago, still circulating as rumor 20+ years later.
See sources below. /1
Read 8 tweets
Mar 24, 2022
@_pem_pem Why this is nonsensical: "Jeffrey Lieberman, a professor of #psychiatry at Columbia University...“The problems that they’ve been criticized for have more to do [with] the way they’re used by doctors & the heterogeneity of the condition that they’re indicated for.” /1
@_pem_pem What Lieberman is saying is that if #antidepressants were prescribed to a population for which they are known to work well, they would have a much better track record. This is true, because it is a tautology. /2
@_pem_pem The reasoning is circular, if #antidepressants were prescribed for those people for whom the drugs worked, they would work. /3
Read 38 tweets
Jan 28, 2022
Monoamine hypothesis aka "chemical imbalance" & other synonyms, arose circa 1965, but was known to only #psychiatrists, who were unhappily prescribing TCAs and MAOIs to a niche market. Patients hated the many adverse effects of the drugs. /1
Until mid-1990s, monoamine hypothesis (aka "chemical imbalance", "serotonin deficiency" etc.) was not circulating as a "folk model", not in medicine or in the general public. 1990 is ~center of this chart, when #psychiatrists, many paid by pharma, started churning out papers. /2
As a meme or "folk model", monoamine hypothesis (aka "chemical imbalance", "serotonin deficiency", "neurohormone imbalance", etc.) was diligently planted by dozens of #psychiatrists -- not a few -- many paid by pharma. Not something that arose organically out of nowhere. /3
Read 15 tweets
Jan 1, 2022
Lewis, et al. respond to letters to the NEJM editor, demonstrating they do not understand basic concepts of #antidepressant withdrawal @ANTLERtrial

Maintenance or Discontinuation of Antidepressants in Primary Care | NEJM nejm.org/doi/full/10.10…
@ANTLERtrial Some in non-discontinuation group were taking their drugs inconsistently. Lewis, et al. missed potential withdrawal symptoms in that group: "but participants reported some new & worsening symptoms while continuing to take #antidepressants"
@ANTLERtrial Lewis, et al. claim "an increase in depressive symptoms might lead to an increase in “new & worsening” symptoms that are recorded as withdrawal symptoms" EXCEPT they also recorded physical withdrawal symptoms, failed to identify who had both, & did not exclude them from "relapse"
Read 4 tweets
Nov 4, 2021
@sanilrege @markhoro @SenadHasanagic1 Not at all, Sanil. Among my site members, many people come off #antidepressants & other drugs with slight or no withdrawal symptoms except an emotional anesthesia, which they may describe as depression, anhedonia, various kinds of malaise, even "relapse" but.... /1
@sanilrege @markhoro @SenadHasanagic1 ....it's a "relapse" unlike anything they've experienced before. While they may use #psychiatry's vocabulary, because that's all they've got, this emotional anesthesia is actually a result of long-term psychotropic exposure, not "relapse"..../2
@sanilrege @markhoro @SenadHasanagic1 Post-drug emotional anesthesia is well known among those who have gone off psychotropics classified as addictive & considered a feature of those protracted withdrawal syndromes. There is no reason to think chronic #psychiatric psychotropics are exempt..../3
Read 10 tweets
Oct 6, 2021
With all due respect to the fine @awaisaftab, these are the varieties of #antidepressant withdrawal syndrome:

1) WS with only physical, no emotional symptoms
2) WS with both physical & emotional symptoms
3) WS with only emotional symptoms
4) WS manifested as emotional anesthesia
@awaisaftab Of the above, types 1 & 2 are WS, not "relapse", even if "depression" is present. Emotions such as those that compose "depression" do not exist apart from experience. Emotional reaction to feeling neurobiologically out of control should not be diagnosed as "depression".
@awaisaftab Type 3 may include the waves of intense anxiety, fear, & "black holes" characteristic of WS. Characterized by intense sensations with interludes of relative calm. Typically, these very gradually abate over months.
Read 14 tweets

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