Professor David Healy and citalopram (Also known as cipramil and Celexa)

 
This is a transcript of Professor Healy’s deposition at the inquest of Yvonne Woodley. 30/11/2010
 
Professor Healy.
 
 
 

 

 Take oath.

AC: Your full name and qualifications please.
 
 
 

 

DH: David Thomas Healy. MD degree, BCH, BAO and also scholar of the Royal College of Psychiatrists.

AC: When were you first qualified?
 
 
 

 

DH: 1979.

AC: And where are you based?
 
 
 

 

DH: North Wales, Bangor but I’m actually employed through Cardiff University.

AC: I’ve been deliberating on the best way to take us through your evidence. The easiest way seems for you to read through your report unless in your view from the evidence you’ve already heard that you’d like to add to this.
 
 
 

 

DH: I don’t need to add to this although there is one mistake I do need to point out. But I do think it would be quicker for me to go through the main points without me reading it word for word.

AC: Ok. Let’s see how we get on.
 
 
 

 

DH: The first point I’d like to make it that I prescribe the SSRI group of drugs including the drug mentioned in this case. This is a drug I use fairly routinely. I’ve got good a very good relationship with the pharmaceutical industry generally and the company that produces this drug. I know Dr Muldoon who you have as your next witness.

The issue of the antidepressant drugs causing people to become actively suicidal and to take their own lives is an old one and dates back to the late 1950s. The first of these drugs was produced in 1958 and in 1959 the first reports were there that the people put on these drugs could become suicidal. For the most part the antidepressant group of drugs at that point in time were reserved for people in hospital so that if things went wrong staff in the hospital could see the change in the patient and pick up the fact that this drug didn’t suit them. We use these drugs far more often now for people being treated in primary care and they aren’t under the kind of supervision where when things goes wrong this is picked up as easily.

AC: Can I stop you there. Can you give us an indication of how many people each year worldwide receive citalopram?
 
 
 

 

DH: If you’d asked me this question yesterday I’d have had the data to answer it. There are estimates that several 100 million people have received SSRI drugs of which this is one. This group of drug includes drugs like Prozac which you have heard of. They are the most commonly used drugs to treat people who are anxious or depressed in primary care in the UK and it is probably one of the most commonly used here in the UK. So several 100 thousand in the UK will be on the drug.

AC: What I want you to do is always stick to citalopram. I know your point of view is it’s like others but I’m not interested in others. I’m interested in what Yvonne had. She had citalopram. So several hundred thousands?
 
 
 

 

DH: Will have been on it or will be on it at this point in time, yes.

AC: And over what sort of period?
 
 
 

 

DH: The drug came on the market in 1996 in the UK. It came on the market elsewhere in the world earlier. So it’s been on the market approx 14 to 15 years here in the UK.

AC: We talking here about a million people.
 
 
 

 

DH: No there is a complex relationship between the number of people who go on it each year, which is a much smaller figure than that, and the number of people who remain on it each year. Of all the people who go on it each year, more than half of them stop within about 4 weeks or so often because the side effects of the drug can be uncomfortable for them or because they feel this drug isn’t actually suiting them or they don’t wish to have pills to treat the problems that they have. But of the people that get put on it there is a proportion that would remain on it at the end of the year. So during the life of a drug in the first few years that people go on a drug most of the people on the drug in any one year are people who have been put on it recently. When you get a drug that has been on the market for as long as this drug has been on most of the people on the drug have been on it for years, in that they are the people who have built up at the end of each year who remained on the drug through the year.

AC: And roughly how many people have you prescribed citalopram to? Sorry I know I didn’t ask you yesterday.
 
 
 

 

DH: Possibly several hundred people.

AC: Several hundred?
 
 
 

 

DH: Possibly yes.

AC: Sorry I interpreted you. Carry on.
 
 
 

 

DH: I did mention that this drug came on the market in 1996. The SSRI group of drugs as whole came on market from end of the 80s to early 90s. They were portrayed as being safer than the older group of antidepressants, in overdose in particular. Generally they are probably less effective in people who are severely depressed than the older pills were.

One of the areas in which they have not been safer than older drugs has been the area of causing people to become suicidal. From very early on these drugs came on the market, and this includes citalopram, there have been convincing case reports of people who have been put on these drugs who shortly after they go on the drug become suicidal; when the drug is stopped the problems clear up; if the person is put back on drug the problem reoccurs. The problem may often not be there when the dose is low but when the dose is put up the problem then appears. There are recognised antidotes to the problems that citalopram and the other drugs in group can cause and these include taking medications like diazepam or propranolol. Now you have noted that in terms of the things I have laid out that quite a few of the features that pharmaceutical companies use to work out whether their drug is causing the problems or not were present in Yvonne Woodley’s case. The problems appeared when the dose was low, increased when the dose was put up, she was put on a few of the antidotes that are routinely used to help the problems that this drug can cause and they seem to have been helpful to her but did not clear the problems up. Based on considerations like this I am absolutely certain were her case reported to the pharmaceutical company that makes this drug they would have said their drug has likely caused this problem.

Furthermore based on the volume of reports companies get into them on the range of problems that their drugs can cause they’re able to pick out signals of particular problems that their drug causes and in the case of this group of drugs including citalopram making people suicidal, again that signal has been picked up by all of the pharmaceutical companies in question and also by Lundbeck.

Finally, clinical trials are done which bring these drugs to the market. For a drug to come to the market these days they have to go through extensive clinical trials. In the course of the clinical trials that were done it was clear that there was an excessive number of people going on to commit suicide on the drug, on citalopram, and an excessive number of people going on to a suicidal act on this drug and the other drugs in the group. In all of the studies that have been done to look at this particular hazard in the antidepressant group of drug, in quite a few occasions you will get people representing the pharmaceutical company saying ‘look, the drug has not caused any problem at all’. What they mean by this is usually in the trials that have been done the problems haven’t been shown to be present to a statistically significant extent. But in all the trials that have been done there is an excess of people on the drug going on the commit suicide or going on to an act of suicide- they don’t actually complete the act but they do try to kill themselves.

AC: Am I right in thinking that many more people talk about taking their own lives than actually do it?
 
 
 

 

DH: You are, yes.

AC: Can I take it step by step or I’ll lose my train of thought. There are many people who report acts of attempted suicide? Like they say ‘I took 4 pills yesterday’ but they don’t actually ever go onto take their own lives. Is that right as well?
 
 
 

 

DH: Yes it is.

AC: So when you talk about someone becoming suicidal, how do you know until they’ve actually committed suicide? How can you say that someone has become suicidal if they don’t go on to do it?
 
 
 

 

DH: There are three things the drugs can do. Let me explain. The drug can do this in healthy volunteers also. They haven’t just been given to people who are depressed. They have been given to people who are anxious who don’t usually commit suicide; they have been given to healthy volunteers who don’t usually commit suicide; they have been given to a range of different people, who in the ordinary course of events, don’t go onto commit suicide.

The drugs can cause three different things. One is that they can make people report they have become suicidal. Now that could just be a report and they don’t intend to go onto harm themselves. The drugs can also lead to the person having an overdose, cutting their wrist or trying to hang themselves but actually failing. And then it could lead to people actually taking their own lives. If what you said was an important factor in this case I’d expect in the clinical trials that were done, there would be a far greater risk linked to the drug of people reporting they’d become suicidal than there was of people actually going onto a suicidal act or completed suicide. In fact it’s the other way around. When you compare the rates of people on the drug reporting to be suicidal compared with rates of people on placebo in the same trial reporting being suicidal, the risk from the drug isn’t as great as when you just look at the people who go onto a clear act, either one that is completed or not. So it appears to be just the other way around. Actually the drug does lead to people taking their own life or engaging in a significant act of self harm.

AC: And when you do that- When you do your studies and you deal with a suicide, does whoever is running the trial attend the inquest? Do they actually work out the difference between the act but not the intent or the intent without the final act? Do they actually go through the procedure we’re going through today?
 
 
 

 

DH: I don’t know. That’s an extraordinarily good question. I don’t know what the procedures are in the case of people who kill themselves during a clinical trial. I don’t know what the procedures are in that instance.

AC: Unless you have that information it seems to me that the basis of your hypothesis is at fault. So the government take every open verdict for statistics and call that a suicide. So coroners spend days trying to work whether it really is someone taking their own life, intending to die- and at the end they decide ‘no it isn’t’ and recall an open verdict. And in statistics the government simply ignore that and call it suicide. And it seems to me your trial is doing exactly the same thing?
 
 
 

 

DH: No. I possibly mislead you slightly in terms of wording. When I said that people go on to commit suicide I do not mean that people go on to intent to kill themselves in the way that people usually do when they aren’t on these drugs. What happens in the course of these trials is that people take their own lives. I’m going on the data simply of people who take their lives without any determination in an inquest as to whether this has actually been a suicide or not. From my point of view as I outlined in the report I believe the majority of deaths of people on this group of drugs should not be diagnosed as suicide. People cannot or do not form the intention to take their own life in the usual way that people not on these drugs might form an intention.

AC: Ok, that’s a bit difficult to prove, isn’t it?
 
 
 

 

DH: But there’s a series of convergent lines of evidence. There’s the clinical trial evidence; there’s the case reports where people including the pharmaceutical companies go in detail through particular cases where people have gone on the drug and the problems appear, stop drug and it clears up, go back on the drug and it reappears, when they put up the dose the problem gets worse and go onto commit to suicide. We have at this stage a gene which appears to make you much more likely to have an adverse effect on this drug. It looks at this stage, biologically, fairly solid. We also have a fairly good understanding of the mechanisms through which the drug causes a problem. It’s not looking simply at people on this drug all of a sudden out of the blue commit suicide. There’s usually a very clear fingerprint previously.

I would not be here today, having read Mrs Woodley’s notes if during the previous weeks everything appeared to be fine. It’s very clear from the medical records that things weren’t fine. While she was anxious before she went on the drug these appeared to get worse on the drug. They appeared to get worse when the dose was put up, appeared at times to be helped by the antidotes she was put on. So I think she does have the fingerprint that leads me to say yes the drug was likely to have played a part in this case. And I believe it would have lead the pharmaceutical company to much same conclusion. There’s a set of algorithms used both by pharmaceutical companies and by people like me when trying to look at these issue which guide us through what to look for. So it’s not just a personal view that this drug can cause a problem. This is a lady who was on a drug, and she had a problem. I’ve looked closely at the records to see if the fingerprint that ought to be there if the drug had actually caused a problem is there and I believe it is. For the most part when I’ve been asked to give reports or review cases like this I have usually said ‘no the drug hasn’t played a part’. So I’m here today in one of the less usual positions of saying I believe the drug likely has played a part.

AC: So from the history you’ve heard from her husband about the instance at the field with 100 paracetamol and photos of the children and family dog, do you count that as an attempt to take her own life?
 
 
 

 

DH: Without knowing the details of what had happened I believe at that point she had been on the drug for a period of time and she does appear to have become more distressed over a week or two prior to that while she was on the drug. And I believe she had quite likely begun to think about harming herself at that point in time in a way she hadn’t done before. I haven’t had the chance to interview her husband or family members but all the indications from the medical records are that this was a woman that no one thought was likely to commit suicide. It’s even a woman that when she went along to the doctor they viewed the condition that she had as being low risk. She wasn’t likely to commit suicide. But I think what wasn’t low risk was that she was clearly suffering the adverse effects of the drug at that point in time that you’ve mentioned and it was this that put her at high risk.

AC: The question was, do you count it as an attempt to take her own live?
 
 
 

 

DH: That sounds like either an episode of very clear thinking that she might take her own life or an early attempt to engage in the idea. It’s unclear to me how many pills she actually took. It isn’t clear that she put herself at significant risk on that day. But she does appear to have moved from a lady who wasn’t thinking about harming herself to one that was now actively thinking about.

AC: But I’m trying to find out whether you now count that as an attempt to take her own life.
 
 
 

 

DH: I would have to have a few more details of the actual incident in terms of how many pills it was agreed she took. If she took any pills at all you could regard it as an act of self harm.

AC: So as of this moment you are not counting it as an attempt to take her own life?
 
 
 

 

DH: The data are ambiguous at the moment. I think it’s quite likely that it was a first preparatory attempt to harm herself.

AC: So you do count it as an attempt to take her life? I’m trying to work out what you’re saying- yes or no?
 
 
 

 

DH: I’m leaning that way at the moment. It’s just that I’m aware that I haven’t got the full details of what actually happened on that day.

AC: So that’s the point your making – that you simply don’t have sufficient information for you to call that it was an attempt to take her own life? Do you agree with that?
 
 
 

 

DH: Yes I do.

AC: Despite the fact that you’ve got a lot more information now than you had when you wrote the report.
 
 
 

 

DH: I haven’t got a great deal more information now. I’m still not fully in possession of all the facts as to how many pills she had actually taken.

AC: But you’ve got the significant advantage from hearing from her husband who received the telephone call and went out to her.
 
 
 

 

DH: Yes. She was clearly on that day very distressed.

AC: But if she really wanted to take her own life on that day, if that was her real attempt to take her own life, surely she would have taken the tablets. Surely she wouldn’t, if she was intent on killing herself, ring her husband who had no idea where she was, tell him that not only was she intending to take her own life but to tell him where to go to stop her from doing it. That doesn’t sound like much of an attempt to me. That sounds like someone saying I want help – ‘come away from your job, come out to me to this field and for God sake help me’. It doesn’t sound to me like a real attempt to take her own life.
 
 
 

 

DH: Well, I would agree with you that it would appear that on that day that the odds of actually committing suicide weren’t that high. This is a woman who very early in the course in treatment had begun to have thoughts that she most probably hadn’t ever had before. She was a person who –

AC: Can I ask what evidence you base that on?
 
 
 

 

DH: I base it on the reports in the medical records that this was not a lady that neither doctors nor her family said was ever likely to commit suicide.

AC: Ok.
 
 
 

 

DH: Now I think what you need to appreciate is that when people are exposed to the adverse effects of these drugs they begin to have thoughts that they haven’t ever had before such as they might harm themselves or harm others, that they don’t instantly go from that to actually committing suicide or an act of aggression towards other. It can take a good deal of time ‘playing around’ with the issues as it were. And I don’t want to use the term ‘playing around’ in a sense that would trivialise that. They need to explore the issues to a degree. But I do think that marks a point where she had changed from the state that she had been in prior to going on the drug at all to ultimately the state where she did take her own life whether we regard it as an actual suicidal act or not is to some extent from my point of view less important.

AC: The only other evidence or suggestion that I’ve heard of, of an earlier attempt to take her own life is the fact that she told someone that she’d put some paracetamol in water but then didn’t like the taste so didn’t swallow it. Do you agree with me that that’s the only other attempt that we’ve heard anything at all about, if that was an attempt?
 
 
 

 

DH: That’s one of the only ones that’s clearly recorded in the medical notes. There may have been other ones but going from the medical notes that’s the only other one that I’ve picked up. I might add that it might be a mistake to view the issues as this was the case of the dynamics between this woman and her husband or it was a case of this pill playing a part, in that the two can interact malignantly with each other. The change to mental state she ends up with may be viewed in part as a feature by her husband as part of the interaction between him and her that is designed to achieve a particular end by her and he may view quite reasonably because prior to being on the pills and even while on the pills there may be other acts that she engages in that are to that purpose. Having said that you know that – when people on these drugs go onto to commit suicide it’s usually within context and you can’t ignore the context. What you get is a picture where yes the person was having difficulties, this is the reason they were on the pills, but the acts seems disproportionate to the context and you have to ask yourself well what is it that lead to the disproportionate action on the part of the person? I think that’s where the drug plays a role in it.

I think in Mrs Woodley’s case we have good data that the drug can cause a problem, regulators worldwide have said this group of drugs do cause people to commit suicide. There is black box warning on the drugs in the United States which is the highest level of warning there can be. Having said that there is then the question of saying well just because Mrs Woodley was on this drug and she did go onto to commit suicide did the drug play any part in that at all and it may not have played a part. But in her case in the medical records the mechanisms through which the drug can lead to people going on to commit suicide appear to be there.

One the things the drug can do and it’s well recognised to do – the pharmaceutical companies say our drug can cause- is ‘akathisia’, an unusual word. What it means is a state of mental turmoil or mental restlessness. Where if the drug is not suited to you, you become physically restless but also mentally restless and begin to entertain or have thoughts you wouldn’t normally have. Now all of that appears to be present in Mrs Woodley’s records. We’ve noted the issue regards how she wouldn’t have ever committed suicide with the children in the house in the way she did. One of the other things that the drugs can do is to reduce emotional reactivity – to cause a degree of emotional numbing so that the usual moral considerations you might have about the feelings of the other people who are going to find your body – particularly your children- seem not to play a role. So I regularly hear reports of people who have hung themselves in the house, when the children are there and likely to find them, which again is a feature of the kind of deaths that can happen on a drug like this.

AC: Can I ask when you refer to these cases, how many inquests you’ve attended?
 
 
 

 

DH: I’ve attended a number of inquests. I’ve prepared reports for 10-20 inquests. I’ve attended a number of court cases as well where the issues have been heavily contested by the pharmaceutical company for instance making the drug. I’ve attended a number of homicide trials as well so the drug has played a comparable role in the case of suicide and homicide. This is the 2nd inquest regarding this drug that I’ve attended in the last 4-5 months.

AC: And in the last 4-5 yrs how many
 
 
 

 

DH: I’ve prepared reports in 10-20 cases and attended

AC: If you answer the questions first then give the overall explanation last. It’s a simple question. If it’s so many you can remember say ‘I can’t remember’ but I’m betting it’s less than two.
 
 
 

 

DH: No its about 5.

AC: Five. So you’ve attended 5 inquests?
 
 
 

 

DH: Approximately, yes.

AC: Approximately. Right so when you talk about these other deaths and what the drug does you are relying on what?
 
 
 

 

DH: Sorry, can you repeat the question?

AC: When you refer to these other deaths you say people have committed suicide when they’ve been on Citalopram, what evidence are you relying on?
 
 
 

 

DH: Are you actually talking about the people I have put on the drug that have gone onto commit suicide? Or are you talking about people in clinical trials or are you talking about legal cases I have been involved in?

AC: Whichever you want. You are telling me that people on the drug have committed suicide. I’m trying to find out what you base that on. Is it the fact that someone’s written to you to tell you they did it? Have you been to the inquest and heard the coroner say ‘yes they took their own life’? Is it that someone has sent you a report or is it a newspaper report? Or what?
 
 
 

 

DH: No it’s usually based on my own scrutiny of the medical records that I have been asked to prepare a view on as to whether the drug in this case did actually lead to the person taking their own life or not. It isn’t ever by hearsay or third hand. I’m only talking about cases where I have been asked to prepare reports.

AC: Ok. Carry on.
 
 
 

 

DH: One of the other issues that I pick up in the report is the role of Mrs Woodley’s doctors and this is the issue that has concerned me in that it seems to me that primary care doctors and the mental health team involved did a very good job in the ordinary course of events. There isn’t anything there to particularly blame them. What I would want to say is that you need to appreciate that all doctors in the UK as regards these drugs, and as regards citalopram no less than any other of the drugs in the group, have been under significant constraint. In terms of the clinical trials that might show the hazards of these drugs, 50% of the trials in which the drug has failed to work or has caused real problems remain unpublished including studies done by Lundbeck on this drug. In the case of the trials that are published which often say that the drug works wonderfully well and they are free of risk, a significant proportion of those are ghost written and ghost written in a way so that while the actual data from the trial becomes available publicly (which is actually quite rare) shows that the drug didn’t work and posed significant risks, the published article in some of the best journals in the field will say it worked extraordinarily well and has no risks. So it’s against a climate like that doctors generally in UK, hearing lectures by experts so have felt fairly comfortable about the use of these drugs. While they are now in more recent years becoming more aware of the risks the drugs could pose and the case of doctors like Mrs Woodley’s doctors have made her aware that the drugs can make you feel uncomfortable for a period of time when you go on them first but that you need to hold on in there because it takes a while for the drugs to work.

What you need to appreciate is that the pharmaceutical company have regularly gone to doctors and said to them there is a thing called ‘serotonin pickup syndrome’ on this drug. That is if you just keep the person on the drug for a period of time and give them antidotes they’ll get through all this and everything will be ok – when in fact this isn’t the case.

I think what I see in the medical records has been Mrs Woodley’s doctors looking at her case and repeatedly noting that she’s at low risk and in terms of the diagnosis she had I’m sure they’re correct. What wasn’t at low risk though is that I believe, and her doctors probably agree, was suffering the side effects from the drug. They note in the medical records that she had become more anxious, fidgety, restless. They not that she had been talking about suicide in a way she hadn’t before. They see all this but don’t recognise it – they think that the risk she’s at in terms of the condition she has as opposed to stemming from the treatment that she is now on. And if the treatment was contributing to the risk then putting the dose up as they did was just the wrong thing to do.

It isn’t a thing I blame them for. It’s as I’ve tried to outline to you the culture that we’ve all had to work in, in recent years, with regards to the drug has made it extraordinarily difficult for doctors to recognise the risk that drugs pose. But if I turn this round slightly. These drugs have been given to healthy volunteers and they have become suicide and gone to suicide acts. Clearly healthy volunteers are at little or no risk from the condition they have, because they don’t have a condition that puts them at risk. It’s the drug that carries the risk. But in Mrs Woodley’s case I read in the medical records that her doctors got the condition right but missed the risk of what the drug was posing in her case.

There is one further thing to add and this is an ambiguity in the notes because it does make a difference to interpretation of things. The primary care notes do record a particular date where she appeared to have begun the antidepressants. The secondary care team seem to note a completely different date. They appear to have a picture where she’s been actively suicidal, she’s engaged in the incident you mentioned earlier, where she texted her husband that she was thinking about taking the pills. They appear to think she engaged in that before she went on the drug. But the primary care records seem to indicate that she engaged in that incident after she went on the antidepressant. That’s probably a thing that needs to be found out.

AC: That’s if your interpretation is right, that it was an actively suicidal act.
 
 
 

 

DH: An actively suicidal act and I believe that she had been on the antidepressant at that point in time. Can I make one more quick point in my report that needs to be corrected on page 9. The paragraph in the middle which start ‘the competing explanations are…’ in the middle of that paragraph ‘such cases are typically admitted to hospital but those treating Mrs Woodley-’ now that should read ‘did not think her so severely ill that she needed hospitalisation’.

AC: Ok if I were to write a letter under rule 43 I would send a copy of your whole report to any interested persons. Is there anything else in your report that you wish to amend or alter or are you content for it to be sent out as it is?
DH: Yes I am.
 
12:16:50
Mr Woodley and family questions:
Since we’re all different and made up differently can it be possible that certain chemicals react adversely with one person and helpful to another. Is that ever taken into consideration when these drugs are handed out like sweets?
 

 

DH: Absolutely. It’s not regularly taken into consideration. One of the senior people in one of the other companies making one of the other drugs in the group estimated that only 30-40% of the people put on their SSRI are actually suited to it. Close to 50% of people who go on any one of these drugs aren’t suited but of course the other half are suited. Clinically up until recently the only option we’ve had is to give the drug to people and say to them ‘Look this drug may not suit you please come back and let me know within a few days or even earlier if there are any hints that you are getting more anxious or more nervous please get in touch because there are all sorts of things we can do’. Not just change the drug we may just need to lower the dose of drug. Or there are other drugs which work in a completely different way or another approach we can take, that doesn’t involve drugs that may be helpful.

The companies however have taken the force out of doctors interest to do all that, in the sense that they said the drugs may not suit people but they haven’t conceded that the risk of remaining on the drug can be life threatening and I think that if doctors were aware earlier that it’s not just a case of the drug causing mild problems but can cause serious problems, it would have been standard clinical practice to warn people much earlier – to say come back to me if there is any hint of the drug not working right.

More recently but this hasn’t come into clinical practice yet, we now have good indications of genes that may dispose you of becoming suicidal. To pick you out as a person who oughtn’t to be put on this drug in first place. The only other thing we have at the moment we know that it’s more likely that anyone related genetically to a person who has had an adverse reaction to the drug in this way is at a much greater increase risk of having an adverse reaction themselves. So Mrs. Woodley’s children and other members of her family probably shouldn’t go on this group of drugs.

Are you able to comment to at what level of prescription of this particular drug you start to see the side effects that you’ve described?
 
 
 

 

DH: You can start to see the side effects at an extraordinary low dose- at 5mg of the dose or even less. One of the things that regulators will do in terms of letting a company bring a drug on the market or in terms of trying to work out does it cause a particular problem or not is to see if there is a change with the dose of the drug and if you put the dose up it gets worse its usual good evidence to the company and to the regulator and most people that the drug is causing a problem. If putting the dose up causes a problem what this means is that on average more people will have the problem than on lower dose. You will always get a small proportion of people even on a very low dose.

Further questions 12:21:22 – 12:44:00
 
12: 44
Chris Muldoon: How many of the inquests involved citalopram

DH: Three

 

They can be emotionally numb on the drugs

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