While I was writing up my PhD on antidepressants at the Institute of Psychiatry, Psychology and Neuroscience at King’s College London, I tried to come off an antidepressant that I had been on for 15 years. The process produced horrendous results: I became dizzy, had profound insomnia, agitation and panic, which lasted for months until I was forced to re-start the drug. These symptoms bore little resemblance to the Woody Allen-level neurosis that had led to me being on the medication in the first place.

We were not taught about withdrawal effects from antidepressants in my psychiatry training. Most of the literature and the guidelines described antidepressant ‘discontinuation symptoms’ as ‘mild and brief’ (Iacobucci, 2019), and recommended coming off the drugs in two to four weeks. Some academics went so far as to describe people complaining of trouble coming off antidepressants as malingering or motivated by a desire for legal payouts (Nutt et al., 2014).

This minimisation and denial was not helpful to me; instead I found the most useful advice on online peer support websites like Surviving Antidepressants (and on the Mental Elf). I did not find malingerers or people seeking a financial upside, but thousands of people who experienced severe and prolonged withdrawal effects, unable to get help from their doctors (White, Read and Julo, 2021).

Colleagues of mine (those who have not had experience coming off these drugs themselves; Stockmann, 2019) tend to regard such online groups with scientific scepticism – as I would have. Regarding antidepressants as mostly benign, I had not often seen withdrawal problems in my patients – although, admittedly, I rarely had tried to stop them. I would have wondered if people on these sites were mistaking relapse of their condition for withdrawal effects.

Given my experience, I do not think this explanation is credible. Many of the symptoms are quite distinct and some entirely novel. To doubt people’s accounts requires us to believe that these people are unable to distinguish their familiar mood states from novel ones that arise after stopping antidepressants – often accompanied by distinct physical and sensorial symptoms. This means having to believe that distinctive symptoms such as dizziness, and electric ‘zaps’ in the head are symptoms of depression/anxiety.

Instead we would be placing more faith in the account of an Eli Lilly consensus panel (the origin of the phrase ‘discontinuation symptoms are mild and brief’) over the reports of tens of thousands of patients, backed up by randomised controlled studies. Double-blind randomised controlled trials (Rosenbaum et al., 1998; Davies and Read, 2019) support patient accounts and find withdrawal symptoms from antidepressants are common, with argument centring over whether this affects half of people or just over a third. It is also true that many patients are unaware of withdrawal effects and have been taught to see any symptoms that occur on stopping medication as relapse.

It was only relatively recently (2019) that both the Royal College of Psychiatrists (RCPsych) and NICE recognised that antidepressant withdrawal can be “severe and long-lasting” in some people. Previous to this change it would be understandable to conclude that any symptoms that were severe and/or long lasting must signify relapse.

So, I find scepticism amongst my colleagues to this relatively recent shift in knowledge to be understandable. Equally, however, I also hope that they might be open-minded enough to learn from the experience gathered over the last few years from outside the Academy, as the College has.

Pearls from extensive experience of tapering antidepressants

Adele Framer, an information systems designer, was forced to become a lay expert on psychiatric drug withdrawal during her protracted experience of withdrawal effects from paroxetine. She has used this expertise to better inform people who are going through the process of withdrawal on her peer support site Surviving Antidepressants. The popular site receives 750,000 hits a month. Her expertise contributed to RCPsych’s thinking behind their guidance on Stopping Antidepressants, by the account of the then President of the College . I know of psychiatrists who send patients of theirs to her site for help; the site is cited in Continuing Medical Education courses about deprescribing.

“What I have learnt from helping thousands of people taper off antidepressants and other psychotropic medications” (Framer, 2021) represents a distillation of what Ms Framer has learnt from filling the void left by traditional experts in advising thousands of people how to taper off antidepressants (and other psychiatric drugs) over a decade. In addition to a glimpse of a supportive and eclectic online community united by shared experience, she offers a wealth of practical insight for prescribers who lack familiarity with this topic.

Physiological dependence: setting the scene for withdrawal

The paper re-iterates some basic neurobiology: psychotropic substances cause adaptation of the body and brain. This adaptation is usually called physiological dependence and predicts withdrawal when such substances are stopped. Physiological dependence is different from addiction which, as officially defined, requires craving, compulsion and a narrowing behavioural repertoire.

Consensus that antidepressants are not addictive (Jauhar et al., 2019) should not distract from recognition of their ability to cause physiological dependence and withdrawal (Lerner and Klein, 2019). Similarly, no one believes that caffeine causes worrisome addictive behaviour and yet we recognise the physiological dependence and withdrawal it can cause.

The conundrum: withdrawal or relapse

Thousands of patients on her site report mis-diagnosis of withdrawal for relapse by their doctors. Psychological symptoms (anxiety, low mood, poor sleep) instantly bring to clinician’s minds relapse (and often to patient’s minds too). However, there are often neurological and other physical symptoms that appear alongside these psychological symptoms (dizziness, electric sensations (often called ‘zaps’), nausea, profound insomnia).

Patients will often describe these physical and psychological symptoms as especially severe or completely novel. The refrain on her site again and again is: “I’ve never felt this before.” Doctors (and patients) are often confused as these withdrawal symptoms often do not come on as quickly as textbooks suggest but can be delayed by weeks (Fava et al., 2015).

The emotions of withdrawal

A complex array of emotions is experienced by people in antidepressant withdrawal – from anxiety to all forms of despair. The paper argues that these feelings are neurologically-induced by the biochemical process of withdrawal (hence ‘neuro-emotions’), a concept familiar from withdrawal from illicit psychotropic drugs. These effects can be long-lasting for months or more. Alternatively, some people experience profound emotional numbness or anhedonia in withdrawal, that some people have called ‘emotional anaesthesia’.

It seems, as with many withdrawal symptoms, to abate over time for most people. However, we really know so little about the nature or mechanisms of withdrawal effects or protracted withdrawal and legacy effects. They remain unpredictable in nature and this presents a huge gap in our knowledge of how to help and guide patients in this process.

Conclusions

The piece ends with a plea by the author to be retired from her role:

People should be able to rely on their doctors for tapering support rather than having to look for it on the Internet.

Her request is for doctors to recognise the issues that drive patients to her site:

• Carefully monitoring adverse effects of drugs;
• Carefully considering withdrawal effects to avoid mis-interpreting them as either relapse or onset of a new medical disorder (Guy et al., 2020);
• Carefully individualising tapers off antidepressants, which can take months or years – consistent with advice from RCPsych;
• Recognising the existence of protracted withdrawal symptoms from antidepressants.

This piece and other articulate pleas like it present prescribers with a choice. They might take the defensive position that reports of harm from psychiatric medications as evidence of an ideologically anti-psychiatry stance (rather peculiar anti-psychiatrists who sought out psychiatric treatments and used them diligently for years), or they can listen to the harm that patients have experienced with curiosity, and learn how to minimise these problems in the future. Osler famously said “listen to the patient, he is telling you the diagnosis”; we now have them telling us the appropriate management as well.

Limitations

There are several limitations to the paper that the author acknowledges. One would hope – as she does – that the cases on her website represent the severe end of the spectrum of withdrawal problems. The ideas presented are a thematic summary of years of experience and not the result of systematic study. On the hierarchy of evidence, in the absence of careful studies comparing tapering rates, an expert review is no bad place to start. Some might point to the lack of academic credentials of the author as a weakness, but being free of the ideological framing put forward by drug companies, propagated by the Academy, might be seen as a strength.

Implications for practice

When considering prescription

• Patients should be informed about the possibility of severe and/or prolonged withdrawal effects when an antidepressant is being considered (Royal College of Psychiatrists, 2019);
• Prescribers and patients should take into account the possibility of severe and/or prolonged withdrawal effects when weighing up the risks and benefits of prescribing an antidepressant;
• On prescribing, prescribers should outline to patients that a careful and often gradual approach to tapering is required to safely stop the medication.

On stopping

• Gradual dose reduction at an individualised pace is likely to minimise the risk of withdrawal symptoms;
• This pace may be as little as 10% a month of the most recent dose (so that doses become smaller and smaller as the total dosage gets lower);
• This process may take months or years for some patients and may require going down to doses less than 1mg for many antidepressants before stopping;
• A month is recommended in between reductions because it allows enough time for mild withdrawal symptoms to arise and resolve;
• If people experience withdrawal symptoms they should pause – or increase the dose – and thereafter withdraw more slowly – perhaps even slower than 10% a month.

Pitfalls in practice

• Protracted withdrawal syndrome (PWS) (Cosci and Chouinard, 2020): persistent, sometimes disabling, withdrawal symptoms that can last for months or years after stopping antidepressants, seemingly more likely in those who stop abruptly or very quickly (Hengartner et al., 2020). The phenomenon of protracted withdrawal syndrome from psychotropic substances, both prescribed and illicit is widely recognised (SAMHSA, 2010), including by the FDA (Lerner and Klein, 2019).
• Kindling: a phenomenon observed with illicit psychotropic medications may be relevant to antidepressants – whereby repeated rounds of trialling different medications, or stopping and starting medications makes withdrawal increasingly more difficult (Fava, 2020). (This may help explain why people who use a single antidepressant for a short period of time often do not experience difficulty in stopping, whereas those who have years of complex regimes often do.)
• “Never, ever, skip doses to taper.” The changes in plasma levels are too great and likely to cause severe withdrawal effects. (The one exception to this is fluoxetine because of its long half-life) .

Research implications

There are several lines of research suggested for this area:

• Study of people coming off antidepressants assessing severity and duration of withdrawal effects;
• Studies comparing the effect of differing tapering rates on withdrawal effects, successful stopping and long-term outcomes;
• Study on the long-term prognosis and methods of treating people with protracted withdrawal symptoms from antidepressants;
• Studies examining the long-term effects of antidepressants on the brain and how long-lasting these effects are and whether they are reversible.

Statement of interests

I was the guest editor for the paper discussed in this blog, as part of the collection on ‘Discontinuing Psychotropic Medication’ in Therapeutic Advances in Psychopharmacology.

Links

Primary paper

Framer A. What I have learnt from helping thousands of people taper off antidepressants and other psychotropic medications. Therapeutic Advances in Psychopharmacology. January 2021. doi:10.1177/2045125321991274

Other references

The Royal College of Psychiatry guidance on ‘Stopping Antidepressants’

The Royal College of Psychiatry’s position statement on Antidepressants

Surviving Antidepressants

Cosci, F. and Chouinard, G. (2020) ‘Acute and Persistent Withdrawal Syndromes Following Discontinuation of Psychotropic Medications’, Psychotherapy and Psychosomatics, 89(5), pp. 283–306. doi: 10.1159/000506868.

Davies, J. and Read, J. (2019) ‘A systematic review into the incidence, severity and duration of antidepressant withdrawal effects: Are guidelines evidence-based?’, Addictive Behaviors. Elsevier, 97(August), pp. 111–121. doi: 10.1016/j.addbeh.2018.08.027.

Fava, G. A. et al. (2015) ‘Withdrawal symptoms after selective serotonin reuptake inhibitor discontinuation: A systematic review’, Psychotherapy and Psychosomatics, 84(2), pp. 72–81. doi: 10.1159/000370338.

Fava, G. A. (2020) ‘May antidepressant drugs worsen the conditions they are supposed to treat? The clinical foundations of the oppositional model of tolerance’, Therapeutic Advances in Psychopharmacology. SAGE Publications Ltd STM, 10, p. 2045125320970325. doi: 10.1177/2045125320970325.

Guy, A. et al. (2020) ‘The “Patient Voice” – Patients who experience antidepressant withdrawal symptoms are often dismissed, or mis-diagnosed with relapse, or onset of a new medical condition’, Therapeutic Advances in Psychopharmacology.

Hengartner, M. P. et al. (2020) ‘Protracted withdrawal syndrome after stopping antidepressants: a descriptive quantitative analysis of consumer narratives from a large internet forum’, Therapeutic Advances in Psychopharmacology. SAGE Publications Ltd STM, 10, p. 2045125320980573. doi: 10.1177/2045125320980573.

Iacobucci, G. (2019) ‘NICE updates antidepressant guidelines to reflect severity and length of withdrawal symptoms’, BMJ (Clinical research ed.), 367(October), p. l6103. doi: 10.1136/bmj.l6103.

Jauhar, S. et al. (2019) ‘Antidepressants, withdrawal, and addiction; where are we now?’, Journal of Psychopharmacology, 33(6), pp. 655–659. doi: 10.1177/0269881119845799.

Lerner, A. and Klein, M. (2019) ‘Dependence, withdrawal and rebound of CNS drugs: an update and regulatory considerations for new drugs development’, Brain Communications. doi: 10.1093/braincomms/fcz025.

Nutt, D. J. et al. (2014) ‘Attacks on antidepressants: signs of deep-seated stigma?’, The lancet. Psychiatry. England, 1(2), pp. 102–104. doi: 10.1016/S2215-0366(14)70232-9.

Rosenbaum, J. F. et al. (1998) ‘Selective serotonin reuptake inhibitor discontinuation syndrome: A randomized clinical trial’, Biological Psychiatry, 44(2), pp. 77–87. doi: 10.1016/S0006-3223(98)00126-7.

Royal College of Psychiatrists (2019) Position statement on antidepressants and depression.

SAMHSA (2010) ‘Protracted Withdrawal Symptoms’, 9(1), pp. 1–8. Available at: www.samhsa.gov.

Stockmann, T. (2019) ‘What it was like to stop an antidepressant’, Therapeutic Advances in Psychopharmacology. SAGE Publications Ltd STM, 9, p. 2045125319884834. doi: 10.1177/2045125319884834.

White, E., Read, J. and Julo, S. (2021) ‘The role of Facebook groups in the management and raising of awareness of antidepressant withdrawal: is social media filling the void left by health services?’, Therapeutic Advances in Psychopharmacology. SAGE Publications Ltd STM, 11, p. 2045125320981174. doi: 10.1177/2045125320981174.

Photo credits

• Photo by Laurynas Mereckas on Unsplash
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