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Hyman, 1996 Initiation and adaptation: a paradigm for understanding psychotropic drug action.


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A description of how psychiatric drugs, as well as other psychotropics, perturb normal homeostasis, requiring a neurological adaptation that leads to physical dependency and withdrawal difficulties.


Am J Psychiatry. 1996 Feb;153(2):151-62.

Initiation and adaptation: a paradigm for understanding psychotropic drug action.

Hyman SE, Nestler EJ.


Department of Psychiatry, Massachusetts General Hospital, Charlestown 02129, USA.


Abstract at https://www.ncbi.nlm.nih.gov/pubmed/8561194



This article describes a paradigm--initiation and adaptation--within which to conceptualize the drug-induced neural plasticity that underlies the long-term actions of psychotropic drugs in the brain.




Recent advances in neurobiology are reviewed.




Recent developments in cellular and molecular neurobiology provide new conceptual and experimental tools for understanding the mechanisms by which psychotropic drugs produce long-lived alterations in brain function. Because of the availability of more robust animal models, the mechanisms by which drugs of abuse produce dependence are better understood than the mechanisms by which antidepressants, antipsychotics, and lithium produce their therapeutic effects. Nonetheless, the fundamental types of mechanisms appear to be similar: chronic drug administration drives the production of adaptations in postreceptor signaling pathways, including regulation of neural gene expression. Whether the results are deleterious or therapeutic depends on the precise neural systems targeted by a particular drug.




Biological investigation in psychiatry has often focused too narrowly on synaptic pharmacology, especially on neurotransmitter turnover and neurotransmitter receptors. This review focuses on molecular and cellular changes in neural function that are produced as adaptations to chronic administration of addictive drugs such as psychostimulants and therapeutic drugs such as antidepressants. To understand normal brain function, psychopathology, and the actions of psychiatric treatments, and to exploit the eventual findings of psychiatric genetics, psychiatric research must now extend its efforts beyond the synapse, to an understanding of cellular and molecular neurobiology (in particular, postreceptor signal transduction) as well as to a better understanding of the architecture and function of neural systems. A paradigm is presented to help understand the long-term effects of psychotropic drugs, including the latency in onset of their therapeutic actions.



According to Corinna West on her blog http://corinnawest.com/it-feels-so-great-to-be-off-psych-meds/


Steven Hyman [author of this paper, then director of the US NIMH] explained that all psychotropic medications, both illicit substances and prescribed medications, work by “causing perturbations in normal neurotransmitter functioning.” Robert Whitaker quoted this article [June 2011] in his keynote address at the National Empowerment Center’s conference where activists came together to figure out what to do about the over-prescription of psychiatric medications. This article says, “The immediate molecular targets of these drugs in the nervous system initiate perturbations that activate homeostatic mechanisms...until cellular signalling reaches an adapted state which may be qualitatively and quantitatively different from the normal state.” These adaptations are things like up-regulation of transmitters being blocked and down-regulation of transmitters being boosted. When the drug is withdrawn, these adaptions remain. Robert Whitaker said, “For the illicit drugs, we call this process addiction. For the prescribed medications, we call this process therapeutic.” This is why psychiatric medications are so hard to get off....


Thanks to Gianna Kali, the above also quoted on her blog http://beyondmeds.com/2011/06/15/greatoffmeds/


Edited by Altostrata

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

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From a presentation by Robert Whitaker http://contextualscience.org/files/Case%20Against.Whitaker.pdf.


Psychotropic Drugs


Stephen Hyman, former director of the NIMH, 1996:


• Psychiatric medications “create perturbations in neurotransmitter


• In response, the brain goes through a series of compensatory adaptations in order “to maintain their equilibrium in the face of alterations in the environment or changes in the internal milieu.”


• The “chronic administration” of the drugs then cause “substantial and long-lasting alterations in neural function.”


• After a few weeks, the person’s brain is now functioning in a manner that is “qualitatively as well as quantitatively different from the normal state.”


Source: Hyman, S. “Initiation and adaptation: A paradigm for understanding psychotropic drug action.” Am J

Psychiatry 153 (1996):151-61.

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

All postings © copyrighted.

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  • 3 years later...

Just stumbled upon this post while searching in google for this very thing.


Great post.

Cant believe that in 3 years no one has been appreciative of this post.

The Whitaker presentation link doesn't appear to work.


I checked out C Wests link .above...just loved the opening sentence, "I’m not anti-medication, but I am anti-bullsh*t."




Thought for the day: Lets stand up, and let’s speak out , together. G Olsen

We have until the 14th. Feb 2018. 

URGENT REQUEST Please consider submitting  for the petition on Prescribed Drug Dependence and Withdrawal currently awaiting its third consideration at the Scottish Parliament. You don't even have to be from Scotland. By clicking on the link below you can read some of the previous submissions but be warned many of them are quite harrowing.


Please tell them about your problems taking and withdrawing from antidepressants and/or benzos.

Send by email to petitions@parliament.scot and quote PE01651 in the subject heading. Keep to a maximum of 3 sides of A4 and you can't name for legal reasons any doctor you have consulted. Tell them if you wish to remain anonymous. We need the numbers to help convince the committee members we are not isolated cases. You have until mid February. Thank you

Recovering paxil addict

None of the published articles shed light on what ssri's ... actually do or what their hazards might be. Healy 2013. 

This is so true, with anything you get on these drugs, dependance, tapering, withdrawal symptoms, side effects, just silent. And if there is something mentioned then their is a serious disconnect between what is said and reality! 

  "Every time I read of a multi-person shooting, I always presume that person had just started a SSRI or had just stopped."  Dr Mosher. Me too! 

Over two decades later, the number of antidepressant prescriptions a year is slightly more than the number of people in the Western world. Most (nine out of 10) prescriptions are for patients who faced difficulties on stopping, equating to about a tenth of the population. These patients are often advised to continue treatment because their difficulties indicate they need ongoing treatment, just as a person with diabetes needs insulin. Healy 2015

I believe the ssri era will soon stand as one of the most shameful in the history of medicine. Healy 2015

Let people help people ... in a natural, kind, non-addictive (and non-big pharma) way. J Broadley 2017



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