Zantac Lawsuit

Researching drug company and regulatory malfeasance for over 16 years
Humanist, humorist

Monday, February 18, 2019

Q&A with Carmine Pariante

Carmine Pariante FRCPsych is a professor of biological psychiatry at the Institute of Psychiatry at King's College, London, and consultant perinatal psychiatrist at the South London and Maudsley NHS Trust. He received his PhD from the University of London and his MD from Gemelli University, Rome (Source Wikipedia)

Toward the end of last year, I became increasingly concerned about the behaviour of some of the psychiatrists on Twitter, many of whom were (and still are) belittling patients harmed by brain pellets.

I was hoping to discuss this in person with Carmine Pariante but due to logistics and time restraints, this never happened. Instead, we both agreed on a Q&A.

Sadly, for me at least, communication between us (via email) came to an abrupt end.

My reasons for ceasing communication can be seen in the thread of emails below. I will leave it to readers of this blog to decide whether or not I made the correct decision in ending the conversation.

Carmine wanted the last word but because he opened the questioning and was given ample opportunity to express himself, I have denied this request. I did inform him, however, that he can leave a comment on here if he wishes or publish this Q&A with his additional comment on his own website.

As a side note, when I eventually retire from this often dark and depressing arena, I hope some of the newer advocates, of which there are plenty, take up the issue of clinical trial data that is withheld and ghostwritten literature. It's the single most important issue regarding brain pellets, any other debate is irrelevant until this issue has been tackled and resolved. We need to speak about this because it has been sidestepped for far too long.

Bob Fiddaman


Q&A with Carmine Pariante

** Some grammatical errors have been rectified

All medications have profound side effects: antibiotics, painkillers, or drugs for cardiovascular disorders. People suffer severe and life-threatening, unpredictable adverse effects taking many common medications. Do you think that antidepressants are simply like any other drugs: helpful and safe for a lot of people; ineffective, unsafe and intolerable in an important minority of patients; and tragically able to cause severe, unpredictable, life-threatening adverse effects in a small minority of patients? If not, how are they different from other medications?

First off, I'm happy you raised this issue as it seems to be the defence of many psychiatrists when the efficacy and dangerous issues of antidepressants are raised.

Yes, all medicines carry risks of adverse events but, in the main, those other medicines target specific areas or diseases. I wouldn't really class suicidality as an "adverse event", to do so plays it down and it becomes lumped together with headaches, nausea, dizziness etc, as do the issues of withdrawal, birth defects, sexual dysfunction.

Antidepressants can induce suicidal thinking and, in some cases, completion of suicide, I hope we can agree on that?

To take a gun and pull a trigger, to tie a noose and wrap it around your neck, to take a knife and stab yourself through the heart, to jump from a bridge to your death, all carry horrifying images but this is the stark reality of it for some people. These should never be classed merely as 'adverse events' - these are people, both young and old, who, because of antidepressants, killed themselves because of an inner restlessness (akathisia) caused by these drugs. Nobody in authority, except for a small handful, seems to want to address this issue, opting instead to deflect by wishing to talk about the adverse events of 'other drugs.' I have never seen any discussion by yourself or RCP that tackles this issue. It's almost as if its a taboo subject for you or something you, and your peers, are ignorant of?

Do I think antidepressants are safe and effective for a lot of people and not safe for a minority? - No. I think both prescriber and patient believe they are safe and effective when in actual fact this may just be the placebo effect at work. If, as you suggest, they do help people then I'd like to know how? Aspirin, for example, helps by targeting the pain and swelling - What do antidepressants target, why do people seem to do well on them (group A) when others don't (Group B)? What is it that group A has that group B doesn't? Also, one should not use the term 'safe and effective' when one knows that they cannot clearly state this because of the suicide link. Isn't it more important to say, these drugs could induce suicide but are safe and effective for others? What's more important to you given that you, or anyone else for that matter, have never seen the raw data that drug companies seem reluctant to release?

I think depression is over-diagnosed and, as a result, antidepressants are over-prescribed. If you see today's figures as a modern-day clinical trial then the results will, of course, favour their safety and efficacy - the more taking them actually masks the problems people face whilst on them, be it suicidal thoughts or withdrawal problems. If, for example, two in ten people suffer at the hands of antidepressants then prescribing more would eventually bring this figure down. In any event, the apparent safety and efficacy of these group of drugs are based on 8 to 12-week clinical trials. In the real world, people are taking them for much longer. In the real world, people aren't 'severely' depressed, as they are in clinical trials, they may just be going through a bad stage of their life because they may need help due to circumstances in their environment. A pill cannot magically pay bills, fix broken marriages, or help a child pass exams but, for some prescribers, this seems to be the reason why they prescribe them.

I feel the question you asked here is irrelevant when the focus should not be 'other meds cause problems' - the focus should be, 'we acknowledge that these drugs can make people self-harm, have suicidal thoughts or, at worst, kill themselves and/or others.' This is what needs to be addressed, along with a whole other multitude of dangerous adverse events associated with these drugs. Talking about it and referencing 'other drugs have adverse events' is shying away and playing down the risks.

If an airline company had a fleet of ten 737's and one of those planes was unsafe to fly in, I doubt very much if the airline CEO would say 'one of our planes, we don't know which one, is unsafe to fly in but the other 9 are safe'.

In the case of antidepressants, prescribers are, in essence, playing Russian Roulette when they prescribe them. It's an unfair advantage prescribers have as they never take turns in pulling the trigger.

I should probably start by stating one thing on which I am sure you and I both agree. I am, like you (and many others) very concerned that antidepressants (especially the selective serotonin reuptake inhibitors) may have more frequent negative effects than originally thought, in terms of reactions to both taking the antidepressants and to stopping them. The reasons behind this slow building of awareness within the medical and psychiatry communities are multiple.

Certainly, there has been a lack of transparency on such data from clinical trials conducted by pharmaceutical companies in the 90’s and early 2000’s , before current guideline and practice changed.

But there is also an objective difficulty, at times, to distinguish between these described negative effects of antidepressants (for example, the increased anxiety, physical agitation and suicidal ideation, which has been typically described in young patients) and the increased anxiety, physical agitation and suicidal ideation that are common symptoms during a depressive illness.

Withdrawal symptoms at the time of stopping these drugs (especially if stopped abruptly) have been well described and are recognizable, but distinguishing symptoms that develop weeks or months after stopping antidepressants from the relapse of the depressive illness  (which, in most patients, has a continuous, peak-and-trough natural course), is very difficult.

Of course, we do need to develop better clinical and research understanding of these negative effects.

There is one thing on which we obviously disagree: you believe that antidepressants are not helpful at all, to any patients, and thus, for you, any negative effect is an unjustified burden. I do not agree with you on this.

Most of the medical and psychiatric communities, and hundreds of studies conducted so far, clearly show that antidepressants do work in improving the core symptoms of depression – especially, the pervasive sadness and lack of hope and motivation that so many patients describe as unbearable, in their account of this serious condition.

We shall not forget that most people who commit suicide suffer from depression and that antidepressants, when you study a large population of patients taking antidepressants, do reduce suicides rates in adults and older people (although in young people, as I have said before, it might be different).

You say that antidepressants do not work, that they have only a “placebo effect” and thus that they are like “dummy” pills. But this is simply not correct: hundreds of studies have been conducted comparing antidepressants to a placebo (“dummy pills”), showing that antidepressants are better than placebo in improving the aforementioned core symptoms of depression – the pervasive sadness and lack of hope and motivation.

Moreover, there have been many studies who have examined other drugs that affect the brain (for example, opioids and benzodiazepines), which in theory should have a very strong placebo effect, yet they lack this specific antidepressant effect of improving the pervasive sadness and lack of hope and motivation.

Of course, you are right that antidepressants are not safe and effective for everybody, for 100% of patients who take them. In fact, only 50% of patients respond very well to an antidepressant, and probably only around 75% are somehow helped. And yes, some people suffer from severe negative effects, sometimes life-threatening.

I accept that it is possible that some patients might have died as a consequence of taking antidepressants, and my heart goes to them and to their families. But these, as tragic and sad as they are, are very rare events.

Many more patients do not die, do not take their own life, because they are on antidepressants.  Not only the scientific and clinical studies demonstrate this, but also the testimony of many such patients who have gone public with their positive, life-saving experience with antidepressants.

In response to one of your comments, I would like to stress that this is the same exact situation that afflicts all branches of medicine. People suffer from negative effects of medications, or even die, because they take drugs for pain, hypertension, infection, cardiac problems: all drugs have the potential to induce negative (and sometimes life-threatening) effects. Your example of the airline company applies to all of medicine.

Yet we take medications because we know that in general, we are more likely to benefit than to suffer from them; that many more people benefit from them than suffer from their negative consequences.

It is the same for antidepressants – although I acknowledge that, if you think that there is no benefit from taking antidepressants, you may only see the burden. But clinical and research evidence (and patients’ accounts) tell us that these drugs do help patients.

Of course, you are right that there is a risk that antidepressants may be prescribed too much, to people who do not need them – and, for these people, the negative effects would outweigh the benefits.

However, all the clinical guidelines are strongly preventing this from happening. Clinicians and psychiatrists are reminded over and over again that antidepressants should only be prescribed to people with ‘clinically-significant depression’, and not to people with a ‘bad stage in their life’, to use your words.

‘Clinically-significant depression’ means being so sad and hopeless and tired that we cannot go to work, or socialize with friends, for weeks and months; that our work and family life suffer; that we feel that life is no longer worth living; that we think about taking our own life, or that we plan to do so. These are the people that should be prescribed antidepressants.

Yes, more antidepressants are prescribed today than 10 years ago, but this may also mean that more people are seeking help because the stigma against depression has reduced. It does not need to be a bad thing if these drugs are taken only by the people who really need them.

Where do we go from here?

Personally, I am grateful to the ‘harmed’ patients community who, through social media and advocacy, has raised awareness of the fact that antidepressants may have more serious negative effects than we originally thought.

The question now is: how do we help these patients, and help the patients who may be suffering from such negative effects in the future, while also at the same time protecting the patients who are benefiting from taking antidepressants, and will continue to do so in the future?

How do we bring my community and your community together, since we both want the same things: help people who suffer from depression?

You and I will have to agree to disagree on the points you raise, Carmine, otherwise, we will get bogged down in missing the glaringly obvious. Before I answer your question, regarding the prescribing community and the prescribed harm community moving forward, I'd like for you to answer the following...

Do you think withholding clinical trial data is appropriate?

Do you think ghostwriting is acceptable?

Carmine added a personal note to this email suggesting that I was being discourteous. I have not added the personal note but it can be provided should the need arise

Let me first clarify that I can only express an opinion as a scientist. I have never been involved in conducting or participating to, a commercial clinical trial, or a trial for regulatory purposes, nor I have ever worked work for a regulatory agency; so I am not familiar in details with the process required by the FDA or equivalent regulatory bodies.

Having said that, as a scientist, let me say again that I believe that, in general, it is not appropriate to withhold any type of clinical data, and, in fact, any type of data.

As I have mentioned before, pre-registration of clinical trials and of analyses has changed the culture both for scientists and for pharmaceutical companies. Analyses of both efficacy (whether a drug work or not) and safety (what are the side effects)  should now be routinely pre-registered as part of the process, and the data presented when the study has been completed.

Again, as I have said before, for releasing individual-patients data there are additional issues such as confidentiality of patients, but there are procedures in place to do this, when ethically possible, and there are different types of processes based on whether the data are released to a public database or to an independent group of scientists for re-analyses.

I repeat again that clinical trial data – and in fact, any data – should never be withdrawn just because the researchers do not like the results!

Regarding ghostwriting, again as a scientist, to me being an author of a scientific paper requires full knowledge of the data. For a clinical trial, these include efficacy, safety, and other clinical, biological or psychological measures that are relevant to the paper.  In addition to the knowledge of the data, an author would need to be fully aware of the analyses and their implications. If you define as ‘ghostwriting’ the practice of appearing as an author on a scientific paper without such full knowledge, then let me say again that I am always against it.

Having re-read your note to me, I'm surprised at your hurt tone. I and lots of others have been damaged by treatment. This is not something to handle lightly by saying something along the lines of, "Now, don't be angry." I am angry with the system. I'm also now concerned. I had no idea whether you do clinical research or not. The issue is your practice as a clinician and that of your colleagues. I fail to see how any of you can safely treat me or those I love if you have no access to the data and if the entire literature on meds is ghostwritten.

The extreme example of this at present is the ever-increasing use of antidepressants for teens where up to 100,000 children are on them. Yet there is not one positive trial of these drugs for children who are depressed, not one. Even the Prozac trials, that got Prozac licensed, are negative. Ditto for the paroxetine trials for children when the FDA issued an approvable letter for it.

Some doctors won't be too concerned by the sufferings of their patients (out of sight, out of mind). But even for you, the worry must be that patients in general, or the managements who employ doctors, are eventually going to wonder if you're worth having. Unless someone like you gets to grips with these issues, which you're better placed to do than I, you are at risk if/when things go horribly wrong. If there is no place in the system for recognising that treatment can kill or maim, you, the prescriber, are likely to end up in the firing line. Despite what you may think about my stance on antidepressants, I don't want this to happen to you or your colleagues.

How can any prescriber at the moment relay informed consent to any of their patients? From my point of view, I'd love some sense that you were bothered by this issue, Carmine, because then I'd think we might make some progress.

As I stated, I'm surprised at your hurt tone. Yet I do find it refreshing to see a doctor who feels and shares emotion. I say this given that many doctors cannot recognize, or refuse to acknowledge, the "hurt" they cause others when blindly prescribing. Blind prescribing is common given that doctors give people antidepressants without knowing the risks because doctors, yourself included, haven't seen the data.

Why do you say I am not bothered by the data not being available - I keep saying that I am! I am also saying that the situation is improving with new rules and regulation

I have not said “don’t be angry” at the situation or the system - I said don’t be angry at me, Carmine, who is talking to you

Doctors in all specialities prescribe based on guideline; guidelines are written based on independent review of the evidence by experts, and the evidence includes safety and efficacy data. It is simply not true that all the l literature on meds is ghostwritten - and in any case, I condemn ghostwriting and I am confident that data transparency is much more advanced now.

So I am really not sure I understand where you and I disagree.

This is a very important subject we are talking about please try and stop taking things personally. I am just asking questions that I feel many may like to see your answers.

Close to all the literature on on-patent drugs is ghostwritten. Nice Guidelines, where they refer to drugs, are based on ghostwritten literature and they have no access to the data. Being independent is meaningless if the conclusions are predetermined by the ghostwriting.

Where is the evidence to show anything is better?

I disagree that the situation is, today, as grim as you depict it, although I agree that this has been an important problem in the past.

First of all, all the drugs that you and the community of harmed patients are concerned about (such as SSRIs) have been off patent for many years, often decades. The data have been released in the last few years and in fact, this is the reason why we do know so much more now about their adverse effects, as the many scientific papers on antidepressant-induced suicidal ideation or severe withdrawal symptoms testify.

Second, for the (very few) newer drugs still on patent or in development, there are clear rules and regulations for all trials to be registered before the results are known, and for all data (efficacy, safety, factors influencing response) to be published when the study has been completed.

Ghostwriting is unequivocally criticized or banned, and rightly so, by scientific journals and medical organisations.

The NICE or other experts panels have access to published scientific data which today is presented with excellent ethical and professional standard – because of the new rules and regulations, and also because of a change in culture about data transparency across scientists, pharmaceutical companies and regulatory bodies.

Has this been a problem in past? Yes, of course. But I think that the present is better and the future will be even better.

You casually claim, “the present is better and the future will be even better.” yet provide no evidence to support your claim. You don't know whether the drugs you prescribe are safe because you've never seen the clinical trial data. NICE doesn't know either as they have never seen the drug company data. It is deeply disturbing that none of these facts appears to bother you and fellow prescribers.

Patient safety cannot be a chief concern and the Hippocratic Oath cannot be honoured when ghostwriting and cherry-picked data is an accepted, routine practice. Despite your claims, things have actually gotten worse, not better. Consider:

The recent approval of esketamine, a new mind-altering drug marketed to treat depression, is based on some of the shoddiest trials ever conducted.
Current antidepressant trials in children are now being conducted in Colombia, the Russian Federation, Ukraine, American foster homes and correctional facilities (Lundbeck's vortioxetine trials). Everyone knows the reasons why and none are for the benefit of product consumers.

You should be more concerned about the data you don't see, rather than what you do see. I asked a critical question about clinical trial data and ghostwriting because this is the foundation upon which fraudulent and harmful psychiatric prescribing is built. Whether it be delusion or deceit, most psychiatrists cannot or will not acknowledge that they are unsure about drug safety. To do so would expose psychiatry's cracked foundation and bring the walls tumbling down.

I have been a drug safety advocate for more than a decade. My readers are intelligent and I respect their time. Your limp-wristed response is offensive. I must conclude that continuing our Q&A is unfortunately of little or no benefit to readers.

Thank you for your time. I will post our brief Q&A on my blog as previously promised. You are free to do the same.


Please contact me if you would like a guest post considered for publication on my blog.