Six weeks after my doctor advised me to stop taking the lowest dose of desvenlafaxine, an antidepressant I had used for seven years, I returned to my GP.
I was having huge mood swings: one minute I’d be so jittery and hyperactive I felt as if I could jump out of my skin, next I’d be sobbing hysterically, convinced that life was hopeless. My stomach churned with nausea and bright light burned my eyes. Worst of all were the “brain zaps”, a deeply unpleasant buzzing pulse that shot through my skull at random.
My doctor told me it was unlikely these symptoms were being caused by withdrawal from the drug, also known as Pristiq, because it was out of my system, and said I could either stick it out or go back on the medication. Neither felt like the outcome I wanted.
Antidepressants had played a vital role in restoring and maintaining good health for me for years. They are a critical intervention for millions of people experiencing the debilitation of depression, and can be life-saving. But, once the drugs have done their job, how well do we manage what comes next?
“Antidepressants are thought to work largely by the way they cause connections between nerve cells – synaptic connections – to change over time,” says psychiatrist Prof Ian Hickie, from the University of Sydney’s Brain and Mind Centre. “So six weeks is a short period of time in terms of the rearrangement of the circuits that happen as a consequence of taking the drug away.”
About one in seven Australian adults take antidepressants, the second-highest rate of all OECD countries. On average, Australians take the drug for about four years, and according to the Royal Australian College of GPs, half of these are longterm users. Royal Australian and New Zealand College of Psychiatrist guidelines state that generally, patients should stop the medicine after being in remission for about nine months to one year.
Historically, psychiatric bodies believed antidepressant withdrawal was mild and short and research into withdrawal was relatively limited. A 2021 Cochrane systematic review found over 1,000 studies looking at safely starting antidepressants, but just 33 randomised control trials on stopping them.
A 2019 major review of studies found that about half of those coming off the drugs will experience withdrawal symptoms, with half of those describing them as severe. The 2020 Royal Australian and New Zealand College of Psychiatrists (RANZCP) guidelines for mood disorders estimate that, based on “clinical experience, coupled with the published literature”, about 40% of patients may be affected and for some of those patients, “symptoms can persist for months rather than weeks”.
“We’ve learned in the last few years that [withdrawal] is much more common, more severe, and longer-lasting than it has been presented as in guidelines for many years,” says Dr Mark Horowitz, an Australian who is now a clinical research fellow in psychiatry at the National Health Service in England.
Horowitz experienced a prolonged antidepressant withdrawal in 2015 that caused intense panic attacks and, he says, even left him contemplating suicide. This personal experience has led the training psychiatrist to become an advocate for reforming antidepressant deprescribing.
In June 2022 the UK health regulator, Nice, amended its guidance on how to support people coming off antidepressants, acknowledging the severity and length of withdrawal symptoms can vary. Nice encourages slow, staggered tapering over many months, if needed.
In Australia, the RANZCP guidelines continue to recommend tapering by halving and quartering the lowest dose over about two to six weeks, and acknowledged that while slower tapering might sometimes be needed, it mostly isn’t possible in Australia “as current preparations of antidepressants do not allow for the dose to be reduced by such small decrements”.
It is currently reviewing its clinical guidelines and hopes to provide a recommendation to the board later this year.
The psychiatrist and former RANZCP president Prof Malcolm Hopwood says most people who taper off a standard antidepressant dose will be able to do so without major withdrawal symptoms.
For those who do experience withdrawal, common symptoms include flu-like symptoms, dizziness, nausea, brain zaps, insomnia, anxiety and mood swings.
“There’s a small group who really experience significant withdrawal symptoms that they really find very difficult to manage,” he says.
“Why some people have a particularly difficult time coming off antidepressants and others don’t – I don’t think we really know, if I’m honest.”
Dr Horowitz claims Australia in general is in the “dark ages” when it comes to providing adequate support for patients ceasing antidepressants, because beyond changes to the RANZCP guidelines in 2020, he argues little is being done to improve the support for patients struggling to reduce their medication.
“I get countless emails now from people in Australia who want help coming off antidepressants. The fact that they’re talking to some random research fellow in London for help and not their doctors, I think speaks volumes.”
The GP connection
GPs prescribe about 85% of all antidepressants in Australia. Dr Cathy Andronis, the chair of the Royal Australian College of General Practitioners (RACGP) Psychological Medicine group, says: “Despite the fact that the most opportune time to have these deprescribing conversations are in general practice, our government funding of nonprescription (ie counselling) services is grossly underfunded in the GP context.”
“Deprescribing needs to be sensitively tailored to individuals, and like most mental health consultations, requires valuing time over quick fixes,” she says.
There are multiple guidelines Australian prescribers can reference, including those from the RANZCP, Therapeutic Guidelines, the NSW Therapeutic Advisory Group guidelines and the now defunded NPS MedicineWise. All vary slightly in advice, and prescribers aren’t required to consult any particular one. Prof Katharine Wallis of the University of Queensland, who is also a general practitioner, says the problem goes beyond what is in each guideline as many GPs “do not perceive this to be an issue that they need guidance on”.
“There has been low awareness of how common and how severe withdrawal symptoms can be and the difficulties that people have stopping antidepressants, and low recognition of withdrawal symptoms,” she says.
A commentary led by Wallis on antidepressant prescribing, published in the Australian Journal of General Practice, said despite reviewing and stopping medication when it is no longer needed being an “essential part” of good practice, “in the time-pressured context of general practice it is sometimes overlooked”.
“Barriers for GPs include time constraints, reluctance to destabilise a stable situation and poor access to non-pharmaceutical alternatives; barriers for patients include an expectation that doctors would suggest stopping if it were warranted, fear of relapse and unpleasant withdrawal symptoms,” the commentary read.
Hickie says he would like to see more interdisciplinary teams working with GPs to help manage issues like antidepressant withdrawal.
“Quality mental healthcare is not GPs working on their own with complex problems.”
Hickie believes the issue of antidepressant withdrawal can sometimes be overstated, particularly relative to the benefits of the drugs. He cites a 2020 genetics of depression study he was involved in that surveyed 20,000 Australians and found two-thirds derived benefits from antidepressants.
“In the mental health area there’s a notion that the drugs are bad and psychology’s good and you’re not really well unless you’re off the drugs,” he says.
“I think [deprescribing is] a significant problem because it’s poorly managed, not because of the drug.”
‘I got better, almost instantly’
While some people are content to stay on antidepressants long term, others want to come off because they feel they’ve recovered, or due to side-effects. Tim has tried to get off antidepressants, on and off, over 12 years.
The 39-year-old Melbourne-based accountant was prescribed Escitalopram, also known as Lexapro, after struggling with low moods in his early 20s.
He found the medication helpful and recovered in a few years, but since 2011 has unsuccessfully tried coming off the medication three times under the supervision of different GPs in Australia and England. Each time Tim experienced acid reflux for a few weeks followed by anxiety that lasted months.
“I stopped sleeping and I just had that sort of constant thought and that adrenaline going through me.”
It’s not clear why people have such varying experiences, why some like Tim struggle and others can stop their medication without great issue. But Australian and New Zealand guidelines suggest people who have been on antidepressants for longer periods of time, on higher doses, as well as those on SNRIs may be more likely to struggle.
When Tim reported symptoms of insomnia and anxiety to his doctors, they encouraged him to go back on the medication, telling him he was experiencing a relapse of his initial mental health issues.
“But before I started taking this medication, I’d never had anxiety before, never had panic attacks before,” he says.
While relapse and withdrawal can be difficult to distinguish, Dr Horowitz says that withdrawal is more likely to differ from the initial mental health diagnosis and include a mix of physical and psychological symptoms which subside quickly after retaking the medication.
“The really obvious one for me was that when I reinstated the drug in a very small dose a month ago, I got better almost instantly, within an hour,” Tim says. For him, “then it was really apparent that it’s withdrawal”.
Tinkering with tapering
Like many patients in Australia, Tim was advised to come off his antidepressants over two to six weeks by breaking the dose into halves or quarters.
Dr Horowitz argues there is a better way to reduce antidepressant dosage. He has published research supporting hyperbolic tapering instead, which is slower and non-linear, with dose size reductions getting smaller and smaller the closer you get to zero. The UK changed its guidelines last year to recommend that doctors use this hyperbolic method of tapering and prescribe liquid forms if needed.
Dr Horowitz is currently working with the National Health Service in England to improve guidelines and education on antidepressant deprescribing, and is running a government-funded deprescribing clinic in London.
This kind of tapering is difficult to do in Australia, simply because of the nature of the kinds of pills sold. The majority of antidepressants in Australia are sold as pills that can only be halved or quartered, while a few cannot be divided at all. Compounding chemists can help patients create smaller, tapered doses, but this can be expensive. Only escitalopram is available in a liquid form, which makes slower tapering possible.
The Therapeutic Goods Administration said in a statement said: “The supply of products in Australia is a commercial decision for the sponsor, and the Australian government typically does not encourage medicine sponsors to import or supply certain medicines, except in cases of public health emergencies and critical medicine shortages.”
Wallis says a new trial into hyperbolic tapering will establish whether the method should be used more widely. The randomised controlled trial will compare a hyperbolic tapering regime with current deprescribing practices at 24 GP clinics in south-east Queensland.
“We are doing our best to develop evidence in this space, but until we have that [evidence on best deprescribing practices] we can’t roll out our intervention nationally,” she says.
After his third attempt to come off Lexapro, Tim started reading about withdrawal online. He recently went to the doctor asking for a prescription of the liquid version of the drug so he could try tapering more slowly.
He is now on the lowest dose he’s ever been on, and plans to continue tapering very slowly over the next 18 months.
“It’s now been a month and my anxiety’s zero, it’s completely gone. It’s given me a lot of hope.”