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6/2/2020--Review Documents Severe Withdrawal Effects of Psychiatric Drugs


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Mad in America--Science, Psychiatry, and Social Justice

Review Documents Severe Withdrawal Effects of Psychiatric Drugs

 

"A new article in Psychotherapy and Psychosomatics reviews the current literature on withdrawal syndromes after the discontinuation or decreased dosage of several psychiatric drugs. The review included antidepressant, antipsychotic, and anti-anxiety drugs. The researchers found that even with the use of gradual discontinuation, known as slow tapering, withdrawal symptoms were present for all classes of drugs studied.

 

"The review was conducted by Fiammetta Cosci of the University of Florence and Guy Chouinard of Maastricht University. The authors found that, contrary to popular belief, selective serotonin reuptake inhibitors (SSRI antidepressants), antipsychotics, and serotonin noradrenaline reuptake inhibitors (SNRI antidepressants) showed more severe and long-lasting post-withdrawal syndromes than benzodiazepines. This evidence challenges the suggestions of clinicians and researchers who propose replacing the use of benzodiazepines for anxiety with antidepressants and antipsychotics."

 

https://www.madinamerica.com/2020/06/review-documents-short-long-term-withdrawal-effects-psychiatric-drugs/

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For interested readers, below is the citation and abstract for the journal article discussed in the Mad in America piece. Regrettably, I was unable to find the entire journal article online.

 

Cosci, F. & Chouinard, G. (2020). Acute and Persistent Withdrawal Syndromes Following Discontinuation of Psychotropic Medications. Psychotherapy and Psychosomatics, Published online first: April 7, 2020. DOI:10.1159/000506868.


 

Studies on psychotropic medications decrease, discontinuation, or switch have uncovered withdrawal syndromes. The present overview aimed at analyzing the literature to illustrate withdrawal after decrease, discontinuation, or switch of psychotropic medications based on the drug class (i.e., benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonists, antidepressants, ketamine, antipsychotics, lithium, mood stabilizers) according to the diagnostic criteria of Chouinard and Chouinard [Psychother Psychosom. 2015;84(2):63-71], which encompass new withdrawal symptoms, rebound symptoms, and persistent post-withdrawal disorders. All these drugs may induce withdrawal syndromes and rebound upon discontinuation, even with slow tapering. However, only selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors, and antipsychotics were consistently also associated with persistent post-withdrawal disorders and potential high severity of symptoms, including alterations of clinical course, whereas the distress associated with benzodiazepines discontinuation appears to be short-lived.  As a result, the common belief that benzodiazepines should be substituted by medications that cause less dependence such as antidepressants and antipsychotics runs counter the available literature. Ketamine, and probably its derivatives, may be classified as at high risk for dependence and addiction. Because of the lag phase that has taken place between the introduction of a drug into the market and the description of withdrawal symptoms, caution is needed with the use of newer antidepressants and antipsychotics. Within medication classes, alprazolam, lorazepam, triazolam, paroxetine, venlafaxine, fluphenazine, perphenazine, clozapine, and quetiapine are more likely to induce withdrawal. The likelihood of withdrawal manifestations that may be severe and persistent should thus be taken into account in clinical practice and also in children and adolescents.

 

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I was able to find the full article here on Sci Hub. There's a creepy graphic thing, though, with a woman waving at us. I have no idea what the heck it is or why it's there!

 

https://sci-hub.tw/https://www.ncbi.nlm.nih.gov/pubmed/32259826 

 

Please note that the Mad in America author got it wrong with regards to Dr. Guy Chouinard. He's associated with both McGill University and the University of Montreal, both of which are in Montreal, Quebec, Canada.

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Hello, Lapis2.  You are amazing!  Thank you for the link and the heads up re: the creepy graphic thing.  (Dark humor here but it makes me want to don a mask and gloves plus stand at least 6 feet away before I click the link. :laugh:)

 

I also appreciate your pointing out the error in the Mad in America article.  As you and I both know, reading primary sources versus “interpretations” of primary sources is a wise practice.  It’s also important to give credit where credit is due. McGill and University of Montreal are both top-notch institutions - go Canada!

 

Gratefully yours, Libertas

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Hello, Lapis2.  You are amazing!  Thank you for the link and the heads up re: the creepy graphic thing.  (Dark humor here but it makes me want to don a mask and gloves plus stand at least 6 feet away before I click the link. :laugh:)

 

I also appreciate your pointing out the error in the Mad in America article.  As you and I both know, reading primary sources versus “interpretations” of primary sources is a wise practice.  It’s also important to give credit where credit is due. McGill and University of Montreal are both top-notch institutions - go Canada!

 

Gratefully yours, Libertas

 

Oh, Libertas, you made me laugh, which is an incredible thing to do during what has been a very stressful time for me. I appreciate it so much! Sometimes I think I don't remember how to laugh. Anyhoo, I think was, indeed, wearing my mask as I watched that creepy graphic thing. I still feel slightly freaked out, but at least I'm protected from COVID while reading the article. I'll just put some sort of paper in front of that gal to block her out. Hayulp!

 

Thanks for the shout-out with regards to the Canadian universities. I've read some of Dr. Chouinard's work before and knew he was Canadian, so when I read that he was associated with Maastricht University, I said "Huh?!" I think it's sloppy journalism to get that wrong when it's so clearly noted at the top of the paper. And yes, I agree, it's always best to read the original paper rather than an article about it. I actually had that link in a handy spot since I'd planned to read it carefully a number of weeks ago. I just got completely bogged down with all the COVID reading I was doing at the time. Rather overwhelming.

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Thanks, Lapis2, for locating a free version of the full source document!!  :D

 

The pdf I found cost $39! 

 

   

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Thanks, Lapis2, for locating a free version of the full source document!!  :D

 

The pdf I found cost $39! 

 

 

 

Oh noooooo, Koko! That's insane! Always try Sci Hub first. It can't access everything, but it's always worth a try. I still don't have a clue why there's that weird graphic/video thing with the woman waving at us on this particular one (first time I've ever seen that!), but at least we can still read the actual study.

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Thanks, Lapis2, for locating a free version of the full source document!!  :D

 

The pdf I found cost $39! 

 

 

 

Oh noooooo, Koko! That's insane! Always try Sci Hub first. It can't access everything, but it's always worth a try. I still don't have a clue why there's that weird graphic/video thing with the woman waving at us on this particular one (first time I've ever seen that!), but at least we can still read the actual study.

 

Are you referring to Alexandra Elbakyan?

https://en.wikipedia.org/wiki/Alexandra_Elbakyan

&

https://www.google.com/search?rls=en&source=univ&tbm=isch&q=images+Alexandra+Elbakyan&client=safari&sa=X&ved=2ahUKEwjE1K_O1fjpAhVPTTABHbKGAd4Q7Al6BAgJECk&biw=647&bih=363&dpr=2

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Thanks, Lapis2, for locating a free version of the full source document!!  :D

 

The pdf I found cost $39! 

 

 

 

Oh noooooo, Koko! That's insane! Always try Sci Hub first. It can't access everything, but it's always worth a try. I still don't have a clue why there's that weird graphic/video thing with the woman waving at us on this particular one (first time I've ever seen that!), but at least we can still read the actual study.

 

Are you referring to Alexandra Elbakyan?

https://en.wikipedia.org/wiki/Alexandra_Elbakyan

&

https://www.google.com/search?rls=en&source=univ&tbm=isch&q=images+Alexandra+Elbakyan&client=safari&sa=X&ved=2ahUKEwjE1K_O1fjpAhVPTTABHbKGAd4Q7Al6BAgJECk&biw=647&bih=363&dpr=2

 

Thanks, Fi! I had no idea! I wonder why they don't identify her there rather than just put a creepy graphic/video thing in. I found it very off-putting and confusing.

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"If you analyse the situation with scientific publications, the real parasites are scientific publishers, and Sci-Hub, on the contrary, fights for equal access to scientific information."--Alexandra Elbakyan

 

LOL!  :thumbsup:

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For interested readers, below is the citation and abstract for the journal article discussed in the Mad in America piece. Regrettably, I was unable to find the entire journal article online.

 

Cosci, F. & Chouinard, G. (2020). Acute and Persistent Withdrawal Syndromes Following Discontinuation of Psychotropic Medications. Psychotherapy and Psychosomatics, Published online first: April 7, 2020. DOI:10.1159/000506868.


 

Studies on psychotropic medications decrease, discontinuation, or switch have uncovered withdrawal syndromes. The present overview aimed at analyzing the literature to illustrate withdrawal after decrease, discontinuation, or switch of psychotropic medications based on the drug class (i.e., benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonists, antidepressants, ketamine, antipsychotics, lithium, mood stabilizers) according to the diagnostic criteria of Chouinard and Chouinard [Psychother Psychosom. 2015;84(2):63-71], which encompass new withdrawal symptoms, rebound symptoms, and persistent post-withdrawal disorders. All these drugs may induce withdrawal syndromes and rebound upon discontinuation, even with slow tapering. However, only selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors, and antipsychotics were consistently also associated with persistent post-withdrawal disorders and potential high severity of symptoms, including alterations of clinical course, whereas the distress associated with benzodiazepines discontinuation appears to be short-lived.  As a result, the common belief that benzodiazepines should be substituted by medications that cause less dependence such as antidepressants and antipsychotics runs counter the available literature. Ketamine, and probably its derivatives, may be classified as at high risk for dependence and addiction. Because of the lag phase that has taken place between the introduction of a drug into the market and the description of withdrawal symptoms, caution is needed with the use of newer antidepressants and antipsychotics. Within medication classes, alprazolam, lorazepam, triazolam, paroxetine, venlafaxine, fluphenazine, perphenazine, clozapine, and quetiapine are more likely to induce withdrawal. The likelihood of withdrawal manifestations that may be severe and persistent should thus be taken into account in clinical practice and also in children and adolescents.

 

Hi Libertas,

I'm just coming back to this abstract now and, indeed, when I read it, I couldn't believe my eyes. The whole BB experience is negated by one of the lines you put in bold. According to the authors, benzodiazepine withdrawal is "short-lived". Well, I think the many, MANY people who have come to BB and found support while they endure varying lengths (from months to years) of withdrawal symptoms might disagree.

 

The thing is this: They can only base their statements on the available studies, and if there aren't many studies on this topic, then they don't have the full picture. I'm not sure if any BBs have taken part in studies. I haven't been made aware of any. But again, if people like us don't take part in studies, then our experiences aren't reflected in the studies. And it would be completely unethical to put people on benzos (for days, weeks, months or years) and then rip them off just for the purpose of a study.

 

I met a doctor here on BB awhile back, and we used to discuss this topic. As a doctor, she knew that certain types of studies on people taking benzos could not be done due to ethical issues. It leaves a hole in the literature. You would need to do multiple types of tests on people, then put them on benzos for a period of time, and then take them off -- possibly without even telling them when you were going to do that. And then you'd need to do more testing, and also follow them for extensive periods of time. There would be so many confounding factors, including, but not limited to, individual genetics. It's just not going to happen.

 

I took different kinds of medications -- three different benzos, an SNRI and an SSRI. I didn't take them all simultaneously, though. So, for me, the picture is muddy. Are my symptoms due to one, two, three or four of those meds? Was it the cumulative effects? Or the various combinations I took them in? What role did my genetics play? What about my changing hormones, which, for women, can play a significant role in health issues throughout ? Can you draw conclusions from my experience and extrapolate them to others?

 

So many questions.

 

I'm glad there's more literature coming out, but I think some questions may remain unanswered for quite some time.

 

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Hat tip to Ajusta for the following post. 

 

http://www.benzobuddies.org/forum/index.php?topic=204005.0

 

AN International Taskforce has been set up to look in to Benzos.

 

Their initial paper seems to say all is fine and dandy in benzo land.

 

https://www.karger.com/Article/FullText/489538

 

May I suggest that everyone who is remotely able to writes to the Corresponding Author explaining why their initial position may need revising

 

Corresponding Author

Richard Balon, MD

Department of Psychiatry

Wayne State University

Detroit, MI 48201 (USA)

E-Mail rbalon@wayne.edu

 

As this international I presume it doesn’t matter which country you are in but these people clearly need educating.

 

 

 

International Task Force on Benzodiazepines

Published online: May 22, 2018

 

This brief editorial is a statement to introduce a new working group on benzodiazepines, the International Task Force on Benzodiazepines, which comprises independent scientists, clinical researchers, and clinical psychopharmacologists. No references are included here as it would be beyond the scope and goal of this introduction, but a full review on benzodiazepines will be the topic of a number of papers and presentations in the near future.

 

Benzodiazepines have been with us since the dawn of modern psychopharmacology. Chlordiazepoxide, the first benzodiazepine, was discovered by Leo Sternbach in the late 1950s and was approved for use in the USA in 1960. Sternbach, a genial chemist, also discovered several other benzodiazepines, such as clonazepam, diazepam, flurazepam, flunitrazepam, and nitrazepam.

 

Benzodiazepines quickly became popular and widely used due to their versatility, tolerability, and ease of use. As they have anxiolytic, anticonvulsant, hypnotic, muscle relaxant, and sedative properties, they have been used widely and remain the most widely prescribed psychotropic medications among all medical specialties. Psychiatrists have been using benzodiazepines for the treatment of anxiety disorders, insomnia, alcohol withdrawal, and as adjunct therapy for many other indications since their discovery. The anxiolytic properties of benzodiazepines are still unsurpassed by other psychotropic medications, such as antidepressants and antipsychotics that are used in the treatment of anxiety disorders and anxiety symptoms in other mental disorders. Their adverse effect profile is relatively benign, with sedation and possible cognitive impairment being noted most frequently.

 

In spite of the unquestionable benefits of benzodiazepines and their popularity among physicians of various disciplines, we have witnessed a fairly negative campaign against benzodiazepines, which are often described as being readily abused (although their abuse liability is low and, if abuse occurs, it is in the context of other substance abuse). Interestingly, this campaign has intensified since the advent of selective serotonin reuptake inhibitors (SSRIs) in the mid-1990s. The SSRIs, originally approved for the treatment of depressive disorders, were quickly approved for various anxiety disorders despite the lack of sufficient evidence (i.e., comparison to the existing efficacious anxiolytic drugs, benzodiazepines), and they are now promoted as the first-line treatment for these disorders. In addition, the scientific literature has gradually and surreptitiously been flooded with more and more articles on “negative” properties of benzodiazepines. While many of these publications have either not been based on good science or been frankly biased, they easily achieved a common goal that negative propaganda frequently reaches: they aroused suspicion of benzodiazepines and suggested difficulties in using them, while overlooking their benefits. An “illusion of truth” effect then occurred as frequently repeated negative information and half-truths gradually became the truth as benzodiazepines were given a “bad” name and their reputation was damaged, especially in some scientific circles. Even prescribing these drugs has become a cumbersome procedure around the world.

 

The International Task Force on Benzodiazepines, as a group of investigators and clinical psychopharmacologists with long-standing clinical and scientific expertise, has been concerned about this excessively negative trend. We feel that benzodiazepines have not been given proper attention during the last 2–3 decades, they have not been adequately compared to other psychotropic medications in various indications, and their risks and side effects have been overemphasized. Some of us feel that benzodiazepines have been the subject of an unspoken “commercial war.”

 

This Task Force will be working on presenting various psychiatric and medical audiences with information about benzodiazepines which is evidence based, balanced, unbiased, and clinically relevant and useful. We believe that our colleagues deserve such information as it will encourage our common goal of treating our patients effectively, properly, and safely. We hope to preserve benzodiazepines as a valuable part of our armamentarium.

 

Disclosure Statement

Dr. Balon, Dr. Chouinard, Dr. Cosci, Dr. Fava, Dr. Freire, Dr. Greenblatt, Dr. Nardi, Dr. Rickels, Dr. Salzman, Dr. Shader, Dr. Silberman, Dr. Sonino, Dr. Starcevic, and Dr. Weintraub have no conflicts of interest.

 

Dr. Dubovsky received support from Janssen, Otsuka, Intracellular Therapies, Boehringer Ingelheim, Johnson & Johnson, and Patrick Lee Foundation.

 

Dr. Krystal reports the following support. Sources of research support: Department of Veterans Affairs, VA National Center for PTSD; Department of Veterans Affairs/Department of Defense, Consortium for Alleviation of PTSD; National Center for Advancing Translational Science, NIH; National Institute on Alcohol Abuse and Alcoholism, P50 (CTNA); National Institute of Mental Health, FAST-Psychosis Consortium. Paid editorial relationship: Biological Psychiatry (editor).

 

Scientific advisory boards: biOasis Technologies Inc., Biohaven Pharmaceuticals; Blackthorn Therapeutics Inc.; Broad Institute at MIT and Harvard; Lohocla Research Corporation; Luc Therapeutics Inc.; Pfizer Pharmaceuticals; TRImaran Pharma.

 

Stocks: ArNETT Neuroscience Inc.; Biohaven Medical Sciences; Blackthorn Therapeutics Inc.; Spring Care Inc.

 

Stock options: Biohaven Pharmaceuticals Medical Sciences; Luc Therapeutics Inc. Consulting relationships: AstraZeneca Pharmaceuticals; Biogen, Idec, MA; Biomedisyn Corporation; Janssen Research & Development; L.E.K. Consulting; Otsuka America Pharmaceuticals Inc.; Pragma Therapeutics; S K Life Science; Spring Care Inc.; Sunovion Pharmaceuticals Inc.; Takeda Industries; Taisho Pharmaceuticals Co. Ltd; Teva Branded Pharmaceutical Products R&D Inc.

 

Patents: Dopamine and Noradrenergic Reuptake Inhibitors in Treatment of Schizophrenia; Glutamate Modulating Agents in the Treatment of Mental Disorders; Intranasal Administration of Ketamine to Treat Depression; Methods of Treating Suicidal Ideation.

 

Provisional patents: Composition and Method to Treat Addiction; Treatment Selection for Major Depressive Disorder; Compounds Compositions and Methods for Treating or Preventing Depression and Other Diseases.

 

Speaker’s Bureau: None.

 

Dr. Roth has consulted for Merck, Pfizer, Novartis, Jazz, Purdue Eisai, SEQ, Avadel, GSK, Pernix, and Sanofi.

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Hello, Lapis2.  Why am I not surprised that you “get” why I bolded and underlined the text I did?  I agree with you.  I don’t know many BB members who would agree with the authors’ conclusion that the “distress associated with benzodiazepines discontinuation appears to be short-lived.”  However, you’ve made an important point—the authors reached this conclusion after reviewing the available research.  Regrettably, the quality of available research on benzodiazepine discontinuation is generally low or very low so it’s inappropriate to draw firm conclusions from it.  (To be fair, the authors did use conditional language “distress ... appears to be short-lived.”)

 

Forgive me if you’ve done so and I missed it but have you posted this paper as a separate entry to Benzos in the News using your usual format along with the link to the primary source you found?  Despite the above issue, the paper is worth reading plus, as you know, one can learn much from checking out the references.

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Hello, Lapis2.  Why am I not surprised that you “get” why I bolded and underlined the text I did?  I agree with you.  I don’t know many BB members who would agree with the authors’ conclusion that the “distress associated with benzodiazepines discontinuation appears to be short-lived.”  However, you’ve made an important point—the authors reached this conclusion after reviewing the available research.  Regrettably, the quality of available research on benzodiazepine discontinuation is generally low or very low so it’s inappropriate to draw firm conclusions from it.  (To be fair, the authors did use conditional language “distress ... appears to be short-lived.”)

 

Forgive me if you’ve done so and I missed it but have you posted this paper as a separate entry to Benzos in the News using your usual format along with the link to the primary source you found?  Despite the above issue, the paper is worth reading plus, as you know, one can learn much from checking out the references.

 

Hi Libertas,

I did post it back on April 25, 2020 -- both the abstract and the Sci Hub link to the full study. And I shared the Sci Hub link again on this thread (on the previous page). There were 117 (!) views of that first posting of the abstract and study, but no one replied. Granted, we're in the midst of a pandemic, so people may be quite preoccupied with other concerns. As well, studies aren't "light reading", and not everyone is in the mood or has the right frame of mind to read such literature in full -- pandemic or no pandemic.

 

Sometimes I ask someone to print these things out for me (I don't have a printer myself), since reading the fine print of a study on a computer screen isn't always easy. In this case, I was so caught up in the pandemic articles and videos that I never came back to this one. It's still on my "To Read Carefully" list. 

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Thank you, Lapis2.  I agree about people being preoccupied with other concerns.  I certainly have been. Libertas
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