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Antidepressant withdrawal: The hidden danger


David Lam


14/03/2024 4:26:35 PM

New benchmark guidelines highlight the dangers of antidepressant withdrawal and support GPs in safe deprescribing.

Zoomed in photo of several blister packs.
Currently, around one in seven Australian adults are taking antidepressants.

A dramatic shake up could be on the way for the deprescribing of antidepressants, thanks to the release of the new Maudsley Deprescribing Guidelines next week.
 
The landmark textbook is designed to be a practical guide on how to safely deprescribe psychotropic medication and minimise the effects of medication withdrawal.
 
Authored by the National Health Service’s Dr Mark Horowitz and Psychopharmacology Professor David Taylor, the book outlines a new approach to recognising potential withdrawal.
 
It also provides specific directions for weaning patients off antidepressants, benzodiazepines and gabapentinoids, accounting for different drugs within each class, and the duration of therapy before cessation.
 
According to the guidelines, antidepressants should not commonly be a lifelong therapy and both the prevalence and severity of antidepressant withdrawal in Australia are much higher than many believe.
 
The book aims to remedy a current lack of detailed Australian guidelines on the subject of antidepressant deprescribing.
 
Dr Horowitz told newsGP that GPs play a crucial role in deprescribing and hopes the resource will support them safely through the process.

‘The evidence-based handbook provides an overview of principles to be used in deprescribing … it is written for anyone interested in safe deprescribing of psychiatric medications including psychiatrists, GPs, pharmacists, nurses, medical trainees and interested members of the public,’ he said.
 
‘We took the word “psychiatry” out of the title because we think that GPs will be the primary reader.’
 
GPs are currently the most common prescribers for mental health conditions, with the most recent data from the Australian Institute of Health and Welfare revealing 4.7 million Australians fill scripts for psychotropic medication annually, with GPs prescribers in 85% of cases.
 
The vast majority of these medications are antidepressants, with the Organisation for Economic Co-operation and Development (OECD) reporting Australia has the second highest number of antidepressants per capita amongst OECD countries.
 
Currently, an estimated one in seven Australian adults are taking antidepressants, with most antidepressants taken long-term despite clinical guidelines usually recommending therapy for 6–12 months for a single episode of major depression.
 
Professor Katharine Wallis, Head of the Mayne Academy of General Practice at the University of Queensland, said the guidelines are timely and useful for both GPs and psychiatrists battling a worsening national health problem.
 
‘Antidepressant use in Australia is high and increasing, with much of [this] due to increasing long-term use, such as people failing to stop antidepressants,’ she told newsGP.
 
‘Many people may need help from their doctor if they are to stop antidepressants and avoid the risks and adverse effects associated with long-term use of these drugs.’

While antidepressants are important in the modern treatment of depression, they also have the potential for side effects and withdrawal symptoms, ranging from mild to severely debilitating.
 
Alarmingly, Dr Horowitz said severe withdrawal symptoms are far more common than previously thought.
 
He says the likelihood of having severe withdrawal increases the longer someone is on an antidepressant and that, unrecognised withdrawal often leads to a patient being unable to successfully come off their medication.
 
‘Two out of five Australians have unsuccessfully tried to get off antidepressants,’ Dr Horowitz said.
 
‘Of the three million Australians on an antidepressant, approximately half will have some trouble. How much trouble depends on which drug and for how long [they have been on it].’
 
Dr Horowitz argues both the dangers of unmonitored continuation of antidepressants and severe withdrawal are underestimated by the medical profession.
 
He said a previous lack of evidence-base has resulted in a lack of clinical guidelines and education on the subject.
 
‘Studies inform guidelines … this issue has been minimised in training and it’s pretty hard to see what you haven’t been taught to see. The drugs are much harder to come off than the textbooks ever said,’ Dr Horowitz said.
 
‘I wouldn’t have known [about withdrawal] if I hadn’t myself come off an antidepressant after twelve years and almost loss my life because of it … whenever I tried to come off I’d never been so sick in my life.
 
‘We are selling cars without breaks. Doctors prescribed these drugs; doctors should know how to deprescribe them.’
 
He also said most of the existing data comes from big pharmaceutical companies, casting doubt on findings.
 
‘There are roughly one thousand studies on starting antidepressants but less than a dozen on stopping them,’ Dr Horowitz said.
 
‘Ninety-seven per cent of these studies are conducted by the drug companies themselves and the drug companies have polluted the academia.’

Dr-Cathy-Andronis-article-1.jpg
Deprescribing of antidepressants can be ‘a confounding area of medicine’, says Dr Cathy Andronis, Chair of RACGP Specific Interests Psychological Medicine.
 
Chair of RACGP Specific Interests Psychological Medicine, Dr Cathy Andronis, told newsGP deprescribing of antidepressants can be a confounding area of medicine for clinicians.
 
‘Some patients stop using them completely, the “cold turkey approach", with little or no problems, and others have great difficulty due to physical withdrawal symptoms, emotional readjustment and relapse of underlying depression,’ she said.
 
‘I have seen many patients who have had no problem at all stopping some drugs quickly but have struggled with other drugs’ withdrawal.’

Dr Andronis maintains that a multi-faceted approach involving non-pharmacological treatments is key to the success of antidepressant deprescribing.

‘[Continuous] review and close monitoring by a patient’s GP is the best option but potentially costly in time and money for the patients,’ she said.
 
‘One patient may even see multiple GPs, one GP who for the [assumed] more complex problems and then another GP who will bulk bill them for a quick appointment, “just for another antidepressant script”.

‘Counselling is part of the deprescribing process, especially for patients who have often unwittingly relied on these drugs alone for years rather than regulating their stresses naturally [through] breathing, CBT, mindfulness, exercise activity scheduling and assertiveness.’

Professor Wallis, whose team at the University of Queensland is currently undertaking the ‘RELEASE: Redressing Long-tErm Antidepressant uSE in general practice’ study, advises a measured hyperbolic tapering approach.
 
‘Withdrawal symptoms can last for as long it takes for the brain to adjust, which can be weeks, months or even years,’ she said.
 
‘Hyperbolic tapering of antidepressant drug dose helps to minimise withdrawal symptoms … and is now recommended for discontinuing antidepressants. [This] means smaller decreases in drug dose at lower drug doses, such as using increasingly smaller step-downs in drug dose.’
 
‘The speed of tapering, and hence the time taken to wean off antidepressants, depends upon several factors including duration of therapy, the particular antidepressant drug, and individual variation.’
 
Dr Horowitz concluded that carefully measured weaning doses are essential owing to the non-linear pharmacological relationship between dosages and effects across common antidepressants.
 
The effort and cost involved in having smaller doses made at a compound pharmacist further can burden the patient.
 
However, Dr Horowitz said a patient feeling unheard when reporting symptoms of withdrawal can damage the therapeutic alliance between patients and doctors, and encourages his colleagues to be vigilant for antidepressant withdrawal.
 
‘I’d implore doctors to listen to their patients and urge them to take their patients’ complaints seriously,’ he said.
 
The Maudsley Deprescribing Guidelines will be available in Australian bookstores from 18 March.
 
Dr Horowitz, Dr Andronis and Professor Wallis will also speak at a free online public lecture on the topic on 19 March.
 
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Dr Christopher John Hazzard   15/03/2024 7:45:47 AM

I am surprised that there is a problem with deprescribing.
It has been self-evident to me since the '80s that one has to do so carefully and that there is a cohort who will need them for a lifetime -- usually patients with an element of bipolar in their condition.
Always have what I call non-pharmacological antidepressants in the mix. Eat well, exercise, make the bed, clean the house, and have a shower. My list goes on. Then, when we are ready to stop (for it is a collaborative effort), do so in small increments over a long time. Usually, I take six weeks between reductions because the recurrence of depression takes time.


Dr Vivienne Anne Tedeschi   15/03/2024 7:55:08 AM

I have a patient stuck on desvenlaxafine 100mg, seemingly forever. He us no longer depressed, but repeated attempts at slow withdrawal are aborted by severe discontinuation syndrome. This of course is complicated by the fact that this medication seems to only come in slow release forms with the minimal dose of 50mg. Any suggestions for gradual withdrawal and management of "brain zaps", confusion anxiety and insomnia?


Dr Raouf-Fareid George   15/03/2024 10:57:04 AM

IT IS A COMPLEX TOPIC AND EACH PATIENT IS DIFFERENT.EACH PATIENT NEEDS TO KNOW THE POTENTIAL OF WITHDROWAL SYMPTOMS AND WHAT TO DO.


Dr Peter James Strickland   15/03/2024 11:59:56 AM

I'm with Chris Hazzard (above). To de-prescribe successfully get the patient to use a pen and paper for their daily dosage written down each week. I suggest dose percentage drops to a clinically pragmatic dose for each patient as follows (daily) ---100%, 50% for a week (or over 2 - 3weeks) every 2 days, then 100%, 50%, 50% for a week every 3 days (over 2-3 weeks), i.e. until there is any definite reversal to depression, or not. Anti-depressives are stated to NOT be addictive, but they really are for those taking them long-term. To prevent confusion in dosages we at the RACGP could work out a pragmatic printed protocol for patients to use in withdrawal from antidepressives with advice from pharmaceutical experts, and reviews of our patients..


Dr Rodney Paul Jones   15/03/2024 6:02:42 PM

I am stuck with a client on long-haul escitalopram who has symptomatic hyponatremia. Does anyone know the estimated prevalence of this AE for this drug?
My AI bot says the spectrum of this side effect for SSRIs ranges from 0.5% to 32 %, but will not state where escitalopram stands upon this spectrum


A.Prof Christopher David Hogan   15/03/2024 6:10:21 PM

It is amazing how many psychoactive substances have withdrawal symptoms even some antihistamines.
While there are many withdrawal syndromes a common & unexpected one is the aggravation of the condition being treated. It can be very hard to detect, unless it is looked for.
A holistic approach to withdrawal- diet, exercise, sleep hygiene, routine & education is sensible. So sensible it should be part of the treatment from the start.
It is extremely rare to find that medication alone is adequate treatment.
Health Literacy in Australia is not good, regardeless of what 90% of the population think happens. 60% have have very poor knowledge, even if they have a single non medical degree.
Prescribers are compelled by circumstance to spend a lot of time helping patients understand their conditions & how to manage them.


A.Prof Christopher David Hogan   15/03/2024 6:26:37 PM

I take umbrage at the statement "Ninety-seven per cent of these studies are conducted by the drug companies themselves and the drug companies have polluted the academia."
Of course the studies are conducted by drug companies as our governments insist on that . Governments or non profit organisations will not pay for speculative experiments on unproven molecules !
As a member of academia, I do not consider myself to be polluted. At least when you read industry funded material, you can be assured that what is written is the truth, the only issue is whether it is the whole truth.
Bias is an instrinsic part of life & according to the Greek Philosophers no one can expect to be objective , the best we can do is to recognise our biases. It is easy to recognise drug company biases & adjust for them.
The bias of government funded studies is to seek their cheapest option.