This is a transcription of a Radio New Zealand (RNZ), interview with Professor David Taylor, Director of Pharmacy and Pathology at the Maudsley Hospital in London. Professor Taylor is a co-author of the Maudsley Prescribing Guidelines
The interview took place on the 9th July 2019
RNZ Radio Presenter: “Now why some clinicians are starting to take more seriously potentially severe side-effects of antidepressant withdrawal and in some cases to recommend longer tapering. In a significant shift in position in the last few months, the Royal College of Psychiatrists in the UK now accepts that it has not paid enough attention to patients suffering from severe withdrawal symptoms when coming off antidepressants. The new stance follows a Lancet Psychiatry paper co-authored by our guest, David Taylor, a Professor of Psychopharmacology and the Director of Pharmacy and Pathology at the Maudsley Hospital in London who has himself experienced withdrawal. At the moment the standard advice in the UK recommends tapers of anything between weeks and months before complete cessation. But David Taylor’s paper argues for a withdrawal regime tapering off for months or even years, depending on the dose taken and the duration of treatment, and calls for more carefully conducted research to be done. In New Zealand, The Royal Australian and New Zealand College of Psychiatrists advises cessation of medication over an extended period of time because withdrawal symptoms may be experienced. Its clinical guidelines give general but not specific advice on the length of tapering regimes [I will refer to them in more detail later in the interview] But we welcome David Taylor from the UK. Hello David.
Professor David Taylor: “Yes, Good Morning”
RNZ Radio Presenter: “It’s a very interesting journey that you have been on, that began how?”
Professor David Taylor: “Well, em, I long had an interest in em psychiatry from my undergraduate years, but em, I had, em, the experience of taking and stopping antidepressants more than ten years ago now, and that brought home to me the difference what one might read in a book and how one might actually feel. Although the words em adequately express the symptoms they don’t really give a flavour of the severity of those symptoms or how one feels when one suffers all those symptoms in one go, often very suddenly. Em, so, I have long had a profound interest in the difference I suppose what the Medical profession is told and what patients’ experience. And the paper that I wrote with my colleague Mark Horowitz, an Australian psychiatrist, eh, was really to look at the disparity between what many patients say and what many authorities recommend.”
RNZ Radio Presenter: “Could you tell us a little of what the experience was like for you, and for how long?”
Professor David Taylor: “Well mine was em, fairly standard but fairly short-lived. Em, I was taking an antidepressant called Venlafaxine. I knew about the potential for withdrawal effects so I withdrew it in a manner which I thought was slowly, but em [and I’ll come to this in a bit] turns out it wasn’t. I experienced just em, about every experienced just about every symptom you might read about: dizziness, anxiety, mood changes, flu-like symptoms, insomnia, vivid dreams, em, and others beside, and oh, electric-shock-like sensations in my limbs, head-zaps. The whole gamete really of withdrawal symptoms”
RNZ Radio Presenter: “Can I ask if you were on very long and if that is relevant – have you been on the medication very long and if that’s relevant?”
Professor David Taylor: “Well, eh ah, I been on em, Venlafaxine for about six months. But the duration of treatment, em, is relevant. It is important. Generally speaking, the longer you have been on an antidepressant the higher the dosage that you have taken, the more likely you are to experience withdrawal symptoms and the more severe those withdrawal symptoms are likely to be. Having said that, em, not everybody eh gets withdrawal symptoms, even sometimes after very long periods of treatment.”
RNZ Radio Presenter: “Well it is very interesting to hear your story and it says something – it says something about something – is that, there had been this great resistance and great defence by the Royal College of Psychiatrists and others. The way you went about – having personally experienced this – the way you went about doing some research was two-fold – yes, you went and found some specific studies but you also went on-line and patient forums: what did you find there?”
Professor David Taylor: “Well, eh ah, I had another source as well, which is . . we used to run at our Department at the Maudlsey a patient help-line, so we received, received em over two-thousand calls on that line, em during its existence from people asking about withdrawal symptoms, as it turned out from every single marketed antidepressant. So, em you have already said that, em, the authorities, eh Royal Colleges etc recommend a slow decrease in the dose over weeks or months. Patient Groups on line often described people, em taking much longer than that. Our experience of speaking to people on the helpline: we often spoke to people who were still on a withdrawal schedule one or two years after initiating their cessation of an antidepressant. I must confess I was quite sceptical – this is perhaps ten years ago now – that those really were continued withdrawal symptoms, but I am more convinced now. And I think the nub of the problem is really that we haven’t appreciated the eh, scientific background to withdrawal symptoms and the nature of the relationship between the dose and the activity of the drug. In particular, although we have always known it, we hadn’t factored it into our recommendations: and what we have always known is that there isn’t a straight-line relationship between the dose and how active the drug is in the brain. Em, in fact, em, once you get past a certain dose you increase the activity by only a very small amount – so conversely when you start to decrease the dose, often if you halve the dose from the therapeutic dose you are taking, you reduce the activity by a very small amount indeed – it is only when you go down into much smaller doses that you take big chunks out of the activity of a drug and that s when the withdrawal symptoms become more evident and severe.”
RNZ Radio Presenter: “It is from studies, em, clinical studies that you have learned so much of this, so I guess the point I was making was the gap between what the advice was and the attitude was of the physicians and what you found people were doing themselves and advising each other to do – there was a massive gap – it was almost like eh, a sort of mini representative sample, that set you on this journey of further research. Is this part of the problem: there is actually not a lot of clinical research on withdrawal?”
Professor David Taylor: “That is certainly true. Em, the, the medications, antidepressants of course, em, were discovered, eh, eh, and tested by Pharmaceutical Manufacturers who undertake trials according to the demands of Regulatory authorities around the world, and those authorities usually ask that the Manufacturers test the safety and efficacy of the drug in trials often of six weeks, more recently they have demanded trials of up to a year. But, what they haven’t demanded, and therefore very few Manufacturers have examined, is that em, the condition of patients is monitored once the trial is finished and when they stop taking the antidepressant. So, em the proportion of information, em, on antidepressants that relates to withdrawal is miniscule: it is probably less than 5% of published papers”
RNZ Radio Presenter: “You did find some however. You were alluding to earlier that jut halving the dose doesn’t mean you are halving the impact of the medication on the brain. Could you explain a little more about that? What some – and again there are different types of drugs and I don’t want to be caught generalising too much here – but the Lancet paper refers em, to the fact that some drugs target serotonin transmittance, I think, and just explain a little more about what they are doing in order to try and extend the presence of serotonin in the brain – a feel good chemical – em, but how the tapering regime is particularly relevant. You can’t just say halve-the-dose half the effect.”
Professor David Taylor: “No you can’t. And and, you say you don’t want to generalise, but this is an instance actually where you can generalise because em, drugs act according to the law of ‘Mass Action’, which means effectively that the relationship between the amount of drug taken and what it does in the brain em, is a complex one, but effectively at very small doses the effect in the brain, the activity in the brain increases rapidly, and once you get to a certain dose above that you only get only very small changes in activity. It just so happens that the effective dose of antidepressants usually represents around 90% of the maximum activity of antidepressant. That activity is to stop, em the neurons, nerve cells, taking up serotonin. If they can’t take it up then they cannot issue it out so to speak. So it decrease, em, the amount of serotonin available em, for transmission. And em, as I say this activity is near maximum at therapeutic doses. If we take a common example, Fluoxetine, em Prozac, Fluoxetine. If you were to take 40mg of that em, you would be near the maximum activity, 90-100%. At 20mg you would be perhaps be at 80%. At 10mg you would go down to perhaps 65%. Now after 10mg, we haven’t got much space left, so you can imagine that the drop is going to be quite precipitous if you, reduce the dose again by say, 5mg. So, em it is at the end of the dose-reduction schedule that we have to be particularly careful with em, the dose reduction we are undertaking.”
RNZ Radio Presenter: “Again, even referring to the clinical practice guidelines, and I will if you don’t mind read them here from em, the Royal Australian and New Zealand College of Psychiatrists, these date from 2015. They make the point actually that they are about to update their clinical guidelines, which I imagine is across all practice, but, em, they do point this out to us in their statement to us, which will involve psychiatric experts in New Zealand and Australia. The current position on the discontinuation of antidepressants is addressed in Clinical Practice Guidelines for Mood Disorders. One page I have addresses the duration of discontinuation specifically, and I quote: ‘When patients have received maintenance antidepressant medication, cessation of medication should occur slowly with a taper over an extended period of time, because withdrawal symptoms may be experienced. Discontinuation symptoms may emerge following the cessation of all classes of antidepressants. The risk of discontinuation symptoms is greatest with higher doses of antidepressants and longer duration of treatment, however symptoms are usually transient and mild and resolve with antidepressant re-instatement. Therefore a slow taper of medication over a longer period of time is preferred in order to reduce the likelihood of discontinuation symptoms but may not impact the likelihood of early relapse. Further, when patients are withdrawn from medication a clear plan for monitoring for potential symptom re-emergence should be put in place. During medication withdrawal more frequent visits should be scheduled to ensure adequate monitoring and detection of early signs of depression recurrence.’ So it does acknowledge, the possibility of withdrawal symptoms, eh it does advise the slow tapering of medication over a longer period of time, but it is not specific. And, is this is where the Royal College of Psychiatrists in the UK is at this time? Are we about to see some more specific guidance?”
Professor David Taylor: Well, eh, I should say that the, the Guidance you have read out is pretty good. I would agree with most of it. Em, I think a particular problem is saying that the withdrawal symptoms are – I think what the, the Guidance said is ‘often mild and transient’ – em, you might also say that they are often not at all mild and not at all transient, although admittedly sometimes they are. So, em I think it is the recognition that in some people, and it by no means everybody, em, withdrawal symptoms are anything but mild, they can be quite severe, they can be very disturbing, and they can be long lasting. And they can in particular be long lasting if one doesn’t follow the guidance of the patient, which I will come to in a minute, but also the schedule that I outlined which is effectively halving or quartering the dose, so as to reduce the activity in equal amounts. But the individual person is all important here, because, em, it is that person who is experiencing the symptoms so it is up to them how quickly they reduce and how much of the dose is reduced each time. Very broadly speaking – and even this is more specific than you have in your Guidance – patients should be looking to have or quarter the dose and then wait for any symptoms that occur to subside completely before attempting the next decrease in dose. Now that may mean that some people em, get off antidepressants in a matter of weeks, it may mean that some people get off them only in a matter of months or even perhaps a year or two in rare cases”
RNZ Radio Presenter: “There is a little bit more specificity, just looking at the Guidelines themselves, it talks about discontinuation symptoms more likely with Venlafaxine and short acting SSRIs, especially Paroxetine, but less likely with Fluoxetine. Em, abrupt cessation may cause cholinergic rebound phenomena, Flu-like illness, myalgia and abdominal cramps. So, it is certainly indicative isn’t it, but to your point do you think it is specific enough? And even more importantly, is there a wider acknowledgement of what patients are experiencing? I did read some reaction that said, even hearing advice that, yes you can be having these withdrawal symptoms was a relief for people who were being told ‘No it’s got nothing to do with it’”
Professor David Taylor: “Yeh, yeh. Well I don’t think Guidance anywhere in the world really captures the breadth of peoples’ experience: which can be, em, not having any symptoms at all, to having very severe and disturbing symptoms over a long period. And as I said, I don’t think any Guidance captures the variety of peoples’ experience. I think it is worth bearing in mind that there are extremes, em of reactions, extremes of withdrawal reaction, from effectively nothing to, I note, there have been cases where people have presented at em, Emergency Departments with severe symptoms that they thought were signs of a severe physical illness. Em, so there is a huge range which Guidance doesn’t currently capture”
RNZ Radio Presenter: “Can we also be clear, this is disconnected from risk of relapse, that those Guidelines were talking about two different things with tapering: one, was [interviewer interrupted by Professor Taylor]
Professor David Taylor: “Well, well, I don’t think that is the case. Em, eh the Guidance that you read to me seem to imply that, em, the rate of withdrawal wasn’t important in respect to relapse from depression. We have to be clear about what we mean by that. When we stop suddenly an antidepressant and you get these withdrawal symptoms that isn’t relapse that is a withdrawal reaction. Relapse is, em the recurrence of depression having stopped the drug. Now, there is even less research on this but what there is says, uniformly the same thing, which is that if you stop suddenly an antidepressant the likelihood that you will relapse is twice as high, probably, possibly higher than that, than if you slowly reduce the antidepressant. So, slow reduction has two purposes: one, it mitigates, it reduces the severity, the likelihood of discontinuation symptoms, and secondly, slow reduction reduces the risk of relapse of depression.”
RNZ Radio Presenter: “Given what you have just said that everyone’s experience is different, what will good advice look like? And as you say there is a lack of actual clinical research into the impacts. Will good advice leave a big buffer zone and be guided by a good management by a professional of what your symptoms are? The regime that you have given us David is based on what? How did you reach that reduction schedule that you have outlined to us?
Professor David Taylor: “Because it follows what is known about the relationship between the dose and activity of the drug. You are perhaps alluding to, eh, perhaps a more important question, which is: is there any evidence that following this schedule that I have outlined actually reduces the severity and frequency of withdrawal reactions? The answer sadly is no. But what we do know, when we have tested different regimes for withdrawing antidepressants, the longer ones tend to do very much better than the shorter ones, even if they use linear dose reductions. So, em, we think people can do rather better with our schedule, alongside as having as long as they like to withdraw from the drug”
RNZ Radio Presenter: “What is the commitment that the Royal College of Psychiatrists in the UK has made now to look at its Guidelines on this?”
Professor David Taylor: “Well it is effectively to re-examine its Guidance to see if anything more specific can be recommended and, I think probably to try and capture the breadth of experience people who have stopped antidepressants, because, as I have said no Guidance in the world currently does that: they all say more or less the same thing: which is to withdraw over a period of weeks or months and they usually have the phrase in about ‘mild and transient symptoms’.
RNZ Radio Presenter: “Thank you David. Appreciate your time. David Taylor who is co-author of this article in the Lancet Psychiatry which has prompted a re-think on this by the Royal College of Psychiatrists in the UK.