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Henosis

Horowitz, 2019 Tapering of SSRI treatment to mitigate withdrawal symptoms

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Henosis
Posted (edited)

Published:March 05, 2019 The Lancet DOI:https://doi.org/10.1016/S2215-0366(19)30032-X

Tapering of SSRI treatment to mitigate withdrawal symptoms

Mark Abie Horowitz, PhD

Prof David Taylor, PhD

 

Summary at https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(19)30032-X/fulltext Full text requested.

 

All classes of drug that are prescribed to treat depression are associated with withdrawal syndromes. SSRI withdrawal syndrome occurs often and can be severe, and might compel patients to recommence their medication. Although the withdrawal syndrome can be differentiated from recurrence of the underlying disorder, it might also be mistaken for recurrence, leading to long-term unnecessary medication. Guidelines recommend short tapers, of between 2 weeks and 4 weeks, down to therapeutic minimum doses, or half-minimum doses, before complete cessation. Studies have shown that these tapers show minimal benefits over abrupt discontinuation, and are often not tolerated by patients. Tapers over a period of months and down to doses much lower than minimum therapeutic doses have shown greater success in reducing withdrawal symptoms. Other types of medication associated with withdrawal, such as benzodiazepenes, are tapered to reduce their biological effect at receptors by fixed amounts to minimise withdrawal symptoms. These dose reductions are done with exponential tapering programmes that reach very small doses. This method could have relevance for tapering of SSRIs. We examined the PET imaging data of serotonin transporter occupancy by SSRIs and found that hyperbolically reducing doses of SSRIs reduces their effect on serotonin transporter inhibition in a linear manner. We therefore suggest that SSRIs should be tapered hyperbolically and slowly to doses much lower than those of therapeutic minimums, in line with tapering regimens for other medications associated with withdrawal symptoms. Withdrawal symptoms will then be minimised.

Edited by Altostrata
Journals format

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Henosis

“We examined the PET imaging data of serotonin transporter occupancy by SSRIs and found that hyperbolically reducing doses of SSRIs reduces their effect on serotonin transporter inhibition in a linear manner. We therefore suggest that SSRIs should be tapered hyperbolically and slowly to doses much lower than those of therapeutic minimums”

 

How long have we all known this now? 😄

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Caspur
Posted (edited)

Hi All,

 

I wrote to [Dr. Horowitz] last week and he sent me a copy very quickly, which as nice of him. He is also looking for further funding to do more research in this area. I had to compress the pdf and zip it up to get within the limits allowed by the forum. If anyone wants a copy of the original, message me you're email address.

Cheers

Capsur

 

Edited by Altostrata
removed copyrighted material

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Caspur
Posted (edited)

There's also been some news coverage on this paper in the UK. Not sure I like the title of the article as it implies the drugs are not taken long enough!

 

https://www.thetimes.co.uk/article/depressed-patients-stop-pills-too-hastily-gps-told-20f7vtmsk?fbclid=IwAR2F_z42eQgvnFPyZjeDYBMSJptfM-90x8XpYAEZYCmdqsrhj-X8si7ilDE

 

Here's full text of TIMES articleincase you can't access it: Coming off antidepressants can take months and doctors must not rush patients into stopping, experts say.
Patients benefit from tapering off the drugs over nine months to avoid getting trapped on the medicines by debi
litating withdrawal symptoms, they argue.
Brain scans show that current methods of stopping can lead to abrupt changes that could be avoided with more gradual dose reductions, according to a review of research published in The Lancet Psychiatry.
More than seven million people in England are on antidepressants and the number has been rising. They have been shown to work for severe depression but many patients experience withdrawal symptoms. Critics of current methods say these are often mistaken for the return of depression, leading to people being put back on medication long term.
A review into the problem has been beset by rows and current guidelines recommend halving the dose for four weeks before stopping to avoid symptoms. However, David Taylor of King’s College London and Mark Horowitz, a training psychiatrist at the Prince of Wales Hospital in Sydney, argue that this is wrong. “When you halve the dose of your antidepressant once you don’t decrease the action of the drug very much at its target receptors. But when you reduce the drug to 0mg from half the dose you go down a huge amount in effect at receptors,” Dr Horowitz said.
“We suggest that this is why people get into trouble when they taper — they are going down too fast. We therefore suggest that patients should halve their dose a number of times before stopping, which will mean the drop in effect at receptors is much more gradual.”
He proposes halving doses six times over many months, arguing: “There is no downside to doing our technique. All we are saying is go slower.” Dr Horowitz, who struggled to come off antidepressants himself, added: “If I hadn’t had my own experience of this I wouldn’t have believed it either.”
Professor Taylor said: “Doctors and patients need better evidence on how to taper people off safely and carefully.”
James Davies of the Council for Evidence-based Psychiatry, a critic of current methods, said: “We have sufficient evidence to update our guidelines. . . for many people a 2-4 week taper is far, far too fast and very dangerous.”

Carmine Pariante of the Royal College of Psychiatrists said: “When withdrawal is properly managed, most patients can come off them with minimal side-effects or with side-effects that can be managed with the help of their doctor, by slowing or stopping over four weeks. However, we know this is not the case for all patients . . . While this paper is an important theoretical contribution, the recommended protocols will need to be tested to ensure they work.”

 

Cheers

Caspur

Edited by Caspur
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dcrmt

It made the New York Times
https://www.nytimes.com/2019/03/05/health/depression-withdrawal-drugs.html

 

Quote

But the brain-imaging studies found that inhibition of the transporter increases sharply with addition of the drug and, by extension, also drops sharply with any reduction in dosage. The standard medical advice, to reduce dosage by half — for instance, by taking a pill every other day — and end medication entirely after four weeks, does not take this into account, the two researchers argued.

“Doctors have in mind that these drugs act in a linear way, that when you reduce dosage by half, it reduces the effect in the brain by a half,” Dr. Horowitz said. “It doesn’t work that way. And as a result, there’s a huge load in terms of the effect on brain receptors, and patients are being advised to come off way too quickly.”


Discussion of this has been largely confined to forums like this one, even though people discovered they needed to taper to tiny fractions of the therapeutic dose to get off paxil more than a decade ago - now it's out there and it's finally being regarded as credible.

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Kittygiggles

Thank you @Henosis and @dcrmt.

 

The fact that it made the NYT is great. I loved this comment especially:

 

"Daniel Smith
Leverett, MA

March 8
Well it's about time. I went through this years ago, when it was still mostly unrecognized. I ran into an acquaintance who is an addiction counselor and, with trepidation, told him what I was experiencing. He said, without missing a beat, "Yeah, it's actually worse than heroin because it just goes on and on and on--everyone in my business knows that. And what makes it worse is that there's no socially acceptable narrative. If you get off heroin, everyone knows that's incredibly hard and that you've done something heroic. With this stuff, people think you're making it up, because it's supposed to be a  nice medicine that some smart doctor gave you." Those words helped me get through it and I'm glad people now can find more support. What I especially love is the last line of this article. Why in the world would a doctor believe the experience of patients when it's not in the textbooks?!" 

 

One day, perhaps it will become common knowledge that SSRI withdrawal is a condition that requires more support and help than probably any of the conditions for which these drugs are prescribed. I can vouch for that, anecdotally of course, having now recovered from OCD with CBT alone and I found it so much easier than SSRI withdrawal!

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Lakelander82

If the the lower doses of Drugs have the vast majority of receptors locked down, why bother  for instance tapering down from 50mg of Sertraline in 10percent steps when you could just go from 50mg to say 12mg directly and then taper down slowly from 12mg to 0mg. The advice does not stack up against the occupancy curves. 

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Altostrata
10 hours ago, Altostrata said:

It's likely that many people are taking dosages with excess capacity, i.e., they could reduce by 25% and still maintain full SERT saturation, then taper by 10% from there.

 

HOWEVER, we don't know what your individual curve looks like. It could be that a quarter of your dosage saturates your SERT receptors, or it could be that you need 90% for saturation, and a 25% reduction might throw you into acute withdrawal.

 

Admittedly -- we make this clear -- an initial 10% reduction is very cautious. But being that we only offer peer support over the Internet, we can't rescue you should you reduce by 25% and panic because you have severe symptoms. So we advise everyone to go the more cautious route of 10%, where if you do get withdrawal symptoms from tapering, they are less likely to be severe.

 

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Altostrata

Another commentary on this paper, this time in Neurology Today https://journals.lww.com/neurotodayonline/Fulltext/2019/04180/Avoiding_Withdrawal_Syndrome_for_SSRIs_Requires.4.aspx


 

Quote

 

Avoiding Withdrawal Syndrome for SSRIs Requires Months, Not Weeks, and a More Gradual Curve, Paper Concludes

....

“I have seen the withdrawal effect; it can go on for months,” said Richard B. Lipton, MD, FAAN, the Edwin S. Lowe Professor and vice chair of neurology at Albert Einstein College of Medicine, where he is also director of the Montefiore Headache Center. “I definitely agree with the authors of this paper on the need for more gradual tapering in some patients. I've certainly had certain patients buy pill cutters to cut an already low dose of an SSRI into quarters and take them daily, then take them every other day, to try to make the taper more comfortable.”

 

Dr. Lipton said he also agreed with the authors of the paper that current guidelines on tapering SSRIs should be reconsidered, and that randomized, controlled trials would be useful to more rigorously test the effects of a slower, more gradual tapering protocol.....

....

Expert Commentary

Mamatha Pasnoor, MD, associate professor of neurology at the University of Kansas, noted that the standard dose for duloxetine for the treatment of diabetic neuropathy is much lower, at 60 mg, than is typically used for depression, which can be up to 120 mg.

 

“If they're only on 60 milligrams, you're tapering them over just a few weeks,” Dr. Pasnoor said. “The maximum amount of time I've used is a month or so. I haven't seen any issues with my patients at tapering from that dose.”

 

Michael Polydefkis, MD, MHS, professor of neurology at Johns Hopkins School of Medicine, said he has become more conservative over the years in tapering antidepressants, including SNRIs and tricyclics, when treating neuropathy.

 

“Some people can taper quickly, others need to go very slowly, over several months,” he said. “It's very idiosyncratic. But it's certainly never taken a patient of mine a year to taper off completely.”

 

Rebecca C. Burch, MD, assistant professor of neurology at Harvard Medical School and a headache specialist at the John R. Graham Headache Center, recalled one patient who required two years to taper off an SNRI.

 

“But the vast majority of my patients can do it within three or four months,” she emphasized. “Most patients with migraine seem to be susceptible to acute changes in any of their medications. As a result, headache specialists have developed a practice of starting medications at relatively low doses and increasing slowly. Likewise, when we're in the process of discontinuing a medication, we taper down slowly too.”

 

She agreed with the paper's conclusion that tapering should be individualized based on the patient's response.

 

“Putting it in the patients' hands is the most important thing,” Dr. Burch said. “Some want to decrease as rapidly as every four days. Others choose to do so once a month.”

 

The new paper, she said, “starts to build a body of evidence that will help us understand how best to taper SSRIs, and possibly SNRIs, in the future. I don't think it's conclusive enough to warrant widespread changes for now, but as more studies come out, we hopefully will better understand how best to approach the use of these important medications.”

 

Dr. Lipton, who led the Chronic Migraine Epidemiology and Outcomes (CaMEO) study as well as the American Migraine Prevalence and Prevention (AMPP) study, noted that both studies showed that the frequency of migraines varies dramatically over time. As a result, he said, it's not surprising that patients' use of antidepressants, whether SNRIs or SSRIs, can wax and wane.

 

“I always tell people, if you're tapering an SSRI, you have to go by how you feel,” Dr. Lipton said. “It's not a race. You can always taper more slowly.”

Rather than taper over a single month, he said, “My usual taper is over two months. But if someone is tapering an SSRI and feels uncomfortable at that rate, it makes sense to go more slowly and keep the patient comfortable.”

 

While he has not studied the pharmacokinetics of tapering antidepressants, Dr. Lipton said, “I've come to my approach just by listening to what the patients were saying. It feels like common sense to say that tapering should be individualized and slowed down. I don't think it's rocket science. But I'm glad there's a paper in Lancet Psychiatry describing a phenomenon I've seen.”

 

 

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Linus
On 5/19/2019 at 9:16 PM, Lakelander82 said:

If the the lower doses of Drugs have the vast majority of receptors locked down, why bother  for instance tapering down from 50mg of Sertraline in 10percent steps when you could just go from 50mg to say 12mg directly and then taper down slowly from 12mg to 0mg. The advice does not stack up against the occupancy curves. 

 

 

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Altostrata

Do you have a question, @Linus?

 

Please note: Questions and remarks are more productive IF YOU READ THE PAPER FIRST before commenting.

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TriD

What you can try is look at the receptor occupancy vs dosage chart. Don’t use the x axis, instead use the y axis ie. occupancy %. Find your current dose, then on the y axis make 10% divisions and see what the corresponding dosage is on the x axis.

 

this dosage is your new dose every month. I think one will find that at the lower end the dose becomes microdosing to get the same 10% occupancy drop as with any exponential function or rather it’s a hyperbolic function. The dosage at low doses is compressed for the same 10% drop in receptor occupancy

 

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ChessieCat
On 6/2/2019 at 8:29 PM, TriD said:

this dosage is your new dose every month.

 

It's important to listen to your body and symptoms and not a calendar or a formula.

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TriD
On 6/9/2019 at 2:48 PM, ChessieCat said:

 

It's important to listen to your body and symptoms and not a calendar or a formula.

Yes i do this.. but i mean the formula as a guide and also go by how we feel at each dose in making the next decision.

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