Are Regulatory Bodies Prioritising Drug Company Interests Over Public Safety?

John Read
31
1835

The Disturbing Case of the Street Drug Ketamine

The UK’s Medicines & Healthcare Products Regulatory Agency [MHRA] is refusing to respond to the concerns of psychiatrists, parliamentarians, patients and other experts about the impending licensing of the street drug ketamine as a treatment for depression.

In March this year, the USA’s Food and Drug Administration approved Spravato (esketamine), on the basis of just one efficacy study.

On 17.10.19 the European Medicines Agency [EMA] issued a ‘positive opinion’ recommending the granting of marketing authorisation for esketamine for depression in adults and sent it to the European Commission, which has 67 days to make a final decision (December 23).

The MHRA (UK) has deferred a decision, pending the EMA/EC ruling. However, during the 67 days, member states can submit new information not addressed by the EMA opinion.

On 31.10.19 twelve experts, including eight psychiatrists, wrote to the MHRA and EMA.

***

Dr June Raine
Chief Executive Officer
Medicines & Healthcare Products Regulatory Agency
London E14 4PU

October 31, 2019

Dear Dr Raine

We are writing to express grave concern about the possibility that the dissociative anaesthetic agent, and known street drug of abuse, ketamine, might be approved for use in this country in the marketed form of ‘esketamine’.

There have been no trials of the efficacy of esketamine in the medium or long term. The majority of the studies of this drug (almost entirely conducted by the drug company attempting to license the drug, Janssen) are only four weeks in duration. Most of these studies find no benefit for esketamine versus placebo, and multiple adverse effects. The one positive efficacy study finds a difference between esketamine and placebo that is small and not clinically meaningful.  Esketamine is the only antidepressant that has been approved by the FDA with only one successful efficacy trial.

The longest study to date is a 16 week trial using a discontinuation design, which is almost certain to confound withdrawal effects with relapse of depression. This trial design also increases the likelihood of patients breaking blind in the drug condition.  As noted in the FDA statistical review, “perception of their treatment assignment may have been influenced by acute side effects (dissociation, sedation, etc.). FDA’s exploratory analysis suggested that changes in these side effects were associated with time relapse.”

Notably, there were six deaths in the esketamine studies, including three suicides, all in the esketamine group, with none in those assigned to placebo. Although these deaths were dismissed as unrelated by Janssen we do not believe that this worrying signal of danger should be ignored. It may well be consistent with a severe withdrawal reaction from the medication, known to occur in other medications such as antidepressants and opiates.

Short term apparent benefits of using esketamine are unsurprising, given its similarities to drugs of abuse, and no basis for approving a drug. One could achieve similar results, short term euphoria or dissociation, with various other street drugs. Indeed, we are as shocked by this recent development as we would have been had es-cocaine been submitted for approval.

If esketamine is approved for public use in the UK next month, there is no impediment to doctors prescribing this drug for weeks, months and beyond, which is precisely what we now see occurring in the US since FDA approval.

We trust that an evidence-based approach will be taken to your decision and, therefore, that no approval will be granted until multiple independent trials (i.e. not industry-sponsored) of at least a year, and preferably longer, have been conducted.

Yours

Dr John Read, Professor of Clinical Psychology, University of East London.
Dr Pat Bracken, Consultant Psychiatrist, Ireland
Dr James Davies, Medical Anthropology, University of Roehampton
Dr Peter J Gordon, Consultant Psychiatrist for Older Adults, NHS West Lothian.
Dr Rex Haigh, Consultant Psychiatrist in Medical Psychotherapy, Berkshire NHS
Dr Peter Kinderman, Professor of Clinical Psychology, University of Liverpool
Dr Irving Kirsch, Associate Director, Program in Placebo Studies, Harvard Medical School;
Professor Emeritus, Psychology: University of Connecticut (USA) & University of Hull (UK)
Dr Hugh Middleton, Psychiatrist, University of Nottingham
Dr Clive Sherlock, Psychiatrist, Oxford
Dr Derek Summerfield, Consultant Psychiatrist; Hon. Senior Clinical Lecturer – Institute of Psychiatry, Psychology & Neuroscience, King’s College, London
Dr Philip Thomas, Formerly Professor of Philosophy, Diversity & Mental Health, University of Central Lancashire; Formerly Consultant Psychiatrist
Dr Sami Timimi, Consultant Child and Adolescent Psychiatrist

***

Despite many subsequent emails, no meaningful response to the concerns raised, and research evidence provided, has been received from the MHRA. Efforts, with both the MHRA and the EMA, to obtain minutes of meetings, committee memberships and conflict of interest statements of individuals involved in esketamine decisions, have failed.

On 29.11.2019, the twelve wrote to the MHRA again, saying:

‘It is incumbent upon the MHRA to exercise their obligation, within the permitted 67 day period, to raise the various safety and efficacy issues clearly not dealt with in the EMA ‘opinion’ and insist that the procedure be referred back for further examination. We believe that failure to do this would represent a blatant failure to fulfil its remit to act in the public health interest of the citizens of the UK.’

No meaningful response has been received.

The MHRA has also failed to respond to multiple letters from the All-Party Parliamentary Group (APPG) for Prescribed Drug Dependence asking when MHRA would be discussing the drug. In October, the APPG’s chair, Sir Oliver Letwin MP, wrote to the UK regulator outlining his objections to esketamine as a drug likely to cause ‘dependence, addiction and withdrawal’. He asked MHRA not to approve esketamine, ‘at least until long-term trials have taken place and the long-term risks are fully understood’.

Members of the UK online support group, Let’s Talk Withdrawal, which represents people negatively affected by antidepressants, antipsychotics and benzodiazepines, also wrote to the MHRA requesting longer-term studies before esketamine is licensed. Their letter was not even acknowledged.

In October, the evidence for esketamine was scathingly critiqued in the Lancet, by prominent U.S. psychiatrist Dr Erick Turner (a member of the USA’s Food and Drug Administration’s Psychopharmacologic Drugs Advisory Committee).

The role of drug companies

In the U.S. it costs more than £25,000 ($33,000) to treat one patient for a year with esketamine.

The lack of transparency of these agencies is a serious matter. If they approve esketamine, on the basis of such inadequate research, it will suggest they are more interested in keeping the drug company happy than keeping the public safe.

89% of the EMA’s funding, and 100% of the MHRA’s funding, comes from drug company fees.

Both the members sent by MHRA to represent the UK on the EMA, Dr Nithyanandan Nagercoil and Dr Marie-Christine Bielsky, are ex-employees of drug companies.

The two most prominent promoters of esketamine in the UK, psychiatrists Professor Allan Young and Dr Rupert McShane, both have significant financial links with Janssen-Cilag, the maker of esketamine.

Consultant Psychiatrist, Dr Rex Haigh, a co-signatory to the 31.10 letter, commented:

‘The evidence is that ketamine is the most dangerous of the psychedelics and dissociants. We remain hopeful that unlike the USA’s FDA, our MHRA will take an evidence-based approach, ignore the drug company hype, and decline the application’

Professor Peter Kinderman (Liverpool University), another co-signatory, added:

‘This drug has been widely criminalised to protect people from the harms associated with it. While we certainly need new ways of helping people in distress, prescribing party drugs is unlikely to be the answer.’

Another co-signatory, Dr James Davies, a spokesman for the Council for Evidence-Based Psychiatry has stated:

‘We are deeply concerned about the proposed approval of esketamine. It works via an opioid mechanism and is likely to cause serious problems of addiction and withdrawal.

‘No one should forget the troubled history of psychiatric medication, where supposedly safe and effective medicines turn out to be addictive and damaging when used long term. We urge the MHRA to deny this drug a licence at least until long-term trials on safety and efficacy have been completed.’

31 COMMENTS

  1. “It introduces one key first message from me to you: Most people who take drugs are not particularly harmed by them”

    https://www.youtube.com/watch?v=FzUvtDkSO2M

    We don’t need any experts on any side to tell us stuff we already know, and stuff that would be laughable if it were not coming from people who have Govt influence.

    If only we could have him parachuted into the middle of Mexican drug gangs and let him speak there and then to the relatives of the victims of Oxycodone and Fentanyl.

    But I think that lot have it and are going to get their way. UK psych is about to get even more deluded, disturbing and abusive.

  2. Mallet therapy would do the same thing as ketamine at a fraction of the price, there being no drug cost involved in having your head smacked at regular intervals. Though I doubt anyone would look forward to mallet sessions any more than they’d seek to have ECT sessions regularly.

    • First they’d have to invent a special mallet, and give it a different and technical sounding name, then they’d need a name for the “therapy” that would sound “sciency,” get a patent on both the mallet and the process, and then “mallet therapy” could become a reality.

  3. The comparison with cocaine is wise.

    The pharmaco-medical complex intends to expand the extremely lucrative market for recreational drugs, and to seize the market shares currently held by the Mafia.

    The “scientific” method by which esketamine has been approved is applicable to any recreational drugs.

    It is therefore not only the approval of esketamine that is at stake, but the groundswell aimed at widening the market for recreational drugs: opiates, benzodiazepines, veterinary sedatives, psycho-stimulants, ecstasy, LSD, cannabis, etc.

    • Unfortunately, recreational drugs and psychiatric drugs are very similar in action, and attempts to convert street drugs into psych drugs are a natural progression from the “bad brain” viewpoint. After all, taking cocaine makes you feel better, doesn’t it? So it’s an antidepressant! Maybe a tad addictive, but hey, you have to deal with the side effect, right? They’ve already converted amphetamine sulfate into a “medical drug,” and tried to do so with meth, with a lot less success, luckily. Why not esketamine, or heroin? The difference between taking Xanax and drinking a prescribed amount of alcohol three times a day is essentially zero. The line between drug dealers and the average psychiatrist is a thin one, indeed.

      • I was thinking the same thing.
        Booze can actually be a positive drug, problem is addiction which no one knows how the heck it happens. They talk about “reward center”, “receptors”, but still no one knows anything. No one knows if “trauma” is involved, Whether “trauma” is connected to the “receptors” and the words added to psych and research talk is all gobblygook.
        Some people feel we need words, language. Psychiatry and research are areas we need a lot less language.
        It is purely self entertainment for them.
        Actually the law is really good at preventing “certain drugs” from hitting the “underground”. So the fact that I can get psychedelics so readily, is a testament to how it is all about taking autonomy away.
        Psychiatry and laws are all about “accidental injuries”
        In fact the so called illegal drug flourishes exactly how it was meant to. Economic.

        • If you haven’t read about the “Rat Park” experiment, you should. It kind of says all that needs to be said about addiction. Classic experiments have been done where rats in a cage are given a choice between pushing a button for water/food and one for cocaine, and the rats eventually choose the cocaine so often that they die, which is held up as proof that cocaine is “physically addictive” and that the rats have no choice once they’re addicted.

          But the Rat Park people put the rats in a healthy rat environment, with dirt to dig in and tubes and wheels and stuff to play with and other rats for company and so on, everything a rat would need to live a happy rat life. And they were given the same choices, and guess what? These rats picked the food and water and left the cocaine alone.

          To me, it is total proof that the “physically addicting” theory of drugs is hogwash. People, just like rats, take drugs because they’re in pain and they’re trying to alleviate it. Some of these drugs are legal, some are not, but it doesn’t matter, because if they can’t fix up their environment to meet their needs, they will instead continue to use the substance to numb out their feelings of anxiety and depression. The answer is not more drugs, but an approach to modifying the environment so it is easier for folks to meet their basic needs. We need to set up “human parks” and see how many humans choose drugs over life!

      • That is the main reason I chose to come off my drugs. Despite the suffering my withdrawal caused.

        I was brought up a teetotaler, non-smoker, “just say no” kid. if these drugs were the same as street drugs how could I continue to take them?

        BTW, a lot of little old ladies on SSRI’s would be irate if they could be convinced they’d been tricked into taking addictive, mind altering drugs by that nice-seeming doctor they trusted.

          • Remember The Lorax by Dr. Seuss?

            My guess is those pushing MI System don’t want to wreck society since an end to Western Civilization would mean no more yacht parties.

            But–like the Onceler in the picture book–their greed has made them very short sighted. And instead of trees they’re chopping down young human lives just as fast as they please.

      • You know, if they were honest about neuroleptics being major tranquilizers and didn’t wrongly and euphemistically call them “antipsychotics”, which they aren’t, I’d bet a lot of people would still choose to try them. I’d bet that if the public knew the truth about these drugs and the damage they can do long-term (and sometimes also short-term), a great deal of deeply distressed individuals would still beg to try something, even just short term and perhaps lower doses.

        What I find really appalling though is the number of people like me who were originally prescribed a psychiatric medicine off label and whose lives fell apart. I didn’t see a psychiatrist for six months after the male OB/Gyn at my primary care doctors office had drugged me with pain killers, muscle relaxers, gabapentin and psych meds. All this for “fibromyalgia” which was Lyme Disease. And at home, my drunk husband was beating me and neglecting our child while I worked. And so when the SSRI was added in and I became hypomanic and attempted suicide, it was decided I had bipolar.

        My story is not unique. Even with all the trauma in my early life, I was trying very hard to care for my second daughter, I had a fulll time job and a small apartment, and I was sick with chronic Lyme. And I was made disabled by my primary care doctor who decided all of my problems were psychological.

        I wasn’t crazy or seeing/hearings things, or suffering delusions. I was working hard and making wiser choices but with no family support and being physically ill and being beaten at home and being drugged with psych drugs, I was victimized by an industry that has spent decades lying to doctors and the general public in pursuit of runaway profits. And I’m done pretending that I was or am somehow mad. This is something that is common and has happened to hundreds of thousands if not millions of people.

        Additionally, as early as 1991, a graph was made showing the geographic prevalence of Lyme disease overlapped pretty closely with area of high numbers of scitzophreania and psychotic disorders diagnoses, which the insurance industry has collided with the IDSA and the CDC to prevent proper treatment of Lyme disease and therefore funneling a large percentage of people into psychiatric care as pyme is a neuropsychiatric illness for so many.

        So while I do think that people would still choose to use these drugs in perhaps more limited ways if the truth was widely known about them, wouldn’t it be really smarter to addrsss the issues causing widespread and growing mental distress in the population? There are well known causes of extreme states and even just unrelenting depression that drives people into psychiatric care and it behooves folks to stick to finding cures for causes and not just sedate people even if that were preferable in some extreme cases.

        The Lyme disease community has made major inroads in 2019, we have reason to celebrate.

        Unfortunately, nearly twenty years after I needed assistance of that kind, there are still VERY LIMITED resources for women (especially impoverished, young, traumatized, ill educated, minority). And the school system seems to be the perfect reservoir for inducting large numbers of children into psychiatric care. A recent NPR article speaks of the alarming rate of restraint and seclusion (and lack of oversight) in public schools with almost no palpable alarm in its tone.

        We’re almost all fat and sick and malnourished and polluted and surveilled and quantified and stratified and bought and sold on the open market and we wonder what’s wrong and what can be done and we drive ourselves to therapy and take our prescriptions and vitamins and argue about politics and religion and read our bubble news and associate with the like minded.

        Somewhere the ghost of George Carlin is whispering for the sheeple to wake the fuck up.

        So, how do we truly measure, once and for all, whether the drugs actually work? Well, with one simple question. Are the profits still rolling in? If yes, the drugs are working great for our owners. The sheeple are exactly where They want them. Sick, stupid, and entertained.

        • Kindredspirit, unfortunately the main problem with ”antipsychotics” is that many people are literally forced to take them. I did not beg to try something – like many others, I was forced to take neuroleptics when I was involuntarily committed to a mental hospital. This is one of the most barbaric aspects of psychiatry!

  4. Thank you, doctors, for speaking out against flippant approvals of dangerous, mind altering drugs. Truly it’s a shame more doctors are not speaking out against the staggering in scope psychiatric harm being done to innocent people.

    I couldn’t agree more, ‘No one should forget the troubled history of psychiatric medication, where supposedly safe and effective medicines turn out to be addictive and damaging when used long term. We urge the MHRA to deny this drug a licence at least until long-term trials on safety and efficacy have been completed.’

  5. “Despite many subsequent emails, no meaningful response to the concerns raised, and research evidence provided, has been received from the MHRA”

    Yeah, but read the letter you wrote, what would you expect. Now had you written something like “Please pay the bearer the sum of 100.000 clams” you would be getting responses to your emails and letters immediately. Just ask the executives at Janssen. It’s all about the way you put it to them, all that data and evidence is no good. Money talks, and enough money talks real dirty.

    Our regulatory body AHPRA tells me they have no problem with Community Nurses authorising the’spiking’ of citizens with benzodiazepines before they are subjected to interrogations even though they have no prescribing rights and ….. long story but these guys are so incompetent i’m surprised they even know where their offices are. So the idea of receiving a rational response from them seems a bit of a stretch. Their “Board’ has demonstrated a level of incompetence one wouldn’t expect from a third world country ruled by a dictator such as Ghadaffi (and we know how he was using psychiatric services to conceal his ‘indiscretions’)

  6. Well John,
    Good attempt.
    Have you raised similar concerns with all other drugs? Effexor, Zoloft, Wellbutrin, benzos, resiperadal….I’m sure there are more.
    I know I tried Prozac years ago and not sure why that hit the market, or any other brain stuff out there.
    I simply don’t see any difference between a drug I concoct in my kitchen and one that pharma introduced.

    Show me efficiency with no harm, but it seems no one wants to address it. To pick on one drug seems like diversion.

  7. From the linked study, full free access, worth the read: “Although the important limitations of the evidence base, esketamine was labelled as a breakthrough therapy for TRD. The strategy to approve it as REMS could help addressing some safety issues, but this will require a long time and exposure of many persons with depression to this new agent. Considering the explanatory nature of existing studies, large pragmatic trials are urgently needed to better define the place in therapy of esketamine, aiming to clarify if there is more than just smoke and mirrors.

    Finally, we argue that the EMA should take into due account all these critical issues when assessing the marketing authorisation of esketamine for Europe, and, more broadly, we call for a radical change of current regulatory rules for psychotropic drug approval.”

    https://www.cambridge.org/core/journals/epidemiology-and-psychiatric-sciences/article/esketamine-for-treatment-resistant-depression-a-trick-of-smoke-and-mirrors/F8BB2D5C3F290FE671639CBB0F31C7E9/core-reader

  8. I am really confused. There are tons of studies on pubmed that show that IV Ketamine is highly effective for various impairments such as PTSD, people attempting suicide, depression and mood instability (bipolar) and in the USA there are tons of clinics owned by private psychiatrists that charge between $250 to $600 a session. The claims are that it is close to 90% effective for these maladies. IV ketamine is non patented and cheap at around $90 a vial that will last for 20 sessions. So am I wrong about Ketamine’s effectiveness and all the discussion of its ability to “reconnect” the brain wiring etc. as well as provide miracle relief for thousands for people?

    • Psychiatry and big pharma have ALWAYS claimed miracle cures. Remember when Benzedrine was all the rage, safe, effective and non-habit forming? When that disaster was finally admitted, we had Valium, which was, wait for it, safe, effective and non-habit forming. Except that it’s one of the most addictive drugs known to man. Later on, we have claims that Prozac and the SSRIs are effective and have virtually no side effects. Well, except for increasing the rate of suicide and the occasional outburst of homicidal rage. Oops! So forgive me if I’m a tad skeptical when a party drug/tranquilizer is suddenly claimed as the miracle cure for everything. As for “rewiring the brain,” that’s a pretty tired analogy that doesn’t really correspond to any reality at all. There are no wires in the brain, and nerve channels are not in any way remotely similar to wires other than the ability to conduct and electrical signal.

      It’s important to sift through the rhetoric. EVERY drug is “safe and effective with no side effects” until the patent runs out.

      • So now I am even more confused. So what about all these patients who have been “treatment resistant” and are paying as much as $500 a session for a drug that is not patentable and costs the practitioner just $20 in drug costs per session? These patients are claiming that they got their lives back and are no longer depressed and are working. Are they delusional? What about all those hundreds and hundreds of studies worldwide that claim a 70% + response rate for varies afflictions? None of the studies using IV ketamine are drug company funded, so what is their incentive to exaggerate and lie? The scans do show greater connectivity after Ketamine sessions. The patients and the studies are lying for what purpose?

        • Never underestimate the placebo effect.
          Of course there is more than that at work. A lot of drugs bring people out of depression by producing a mild euphoria.

          I experienced this with my first time on Zoloft. But my depression came from being labeled “schizo-affective” after a bad trip on Anafranil. I got kicked out of college thanks to my label. 10 mg Haldol destroyed my ability to socialize/enjoy anything/smile.

          Mental services blamed my suicidal misery on my brain. Not being labeled hopelessly defective or drugged out on seizure causing neuroleptics.

          In the hospital someone told me I wasn’t a monster and listened while I sobbed out the year of pain I had been through. The Zoloft gave me a speedy lift. I got released for Thanksgiving.

          I went back to another college too. Full time.

          The relief lasted a month or so.

        • Shhh Gilbert, we would not want a drug that shuts down psychiatry or pharma.

          There might be the reason of selling a product? If you charge $500 per session, in order to help people who are out of jobs, due to no fault of their own, I suspect hype. How about “side effects”? How about sustaining? Long term effects?
          How about the drain on your cheque since now you can work? Why try Ketamine if other drugs worked so well? They lied about the other drugs, why not this drug?

          Who is benefitting from these trials? Is it about the client or the dealer?

      • Seems to me that Pharma saw the success of just plain old Ketamine IV and altered it to get it patented and make lots of money. They did the same for GHB and now they sell it under the brand name XYREM for $10,500 a month! An important drug that helped a lot of people sleep better and get deep slow wave sleep that cost just $10 a dose in 1999.

  9. Thank you Dr. Read and your colleagues for speaking out as too many professionals stay quiet and go along with all the corruption out of self serving “interests”. A psychiatrist I was sent to when I developed insomnia from chemo (and who had been practicing < 1 year) thoroughly mocked me in electronic records for having "side effects" to her psych drugs (including Seroquel, mirtazapine, clonazepam duloxetine, temazepam, etc) Now that it is known just how harmful these psych drugs are her Bio states she now "has an interest in use of ketamine for treatment resistant depression (TRD)" and "has supervised resident research on use of intravenous and intranasal ketamine for TRD." And she now "sits on the University of Alberta Psychiatry Residency Program Committee and is actively involved in clinical teaching to residents and medical students."

    How scary is that!?

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