Who's Hiding the Clinical Trial Benefits of Antidepressants?

First off, ponder this.

If an opponent in a pool game told you that if you use the 8 ball as the cue ball you will not foul, would you believe them? What about if they kept on insisting this claim to be true? Or would you ask questions to someone else to ascertain if the claims of your opponent were true?

Read on.

Over the past month or so I've been blocked on Twitter by three well-known psychiatrists.

Wendy Burn, a consultant psychiatrist at Leeds and York Partnership NHS Foundation Trust and president-elect of the Royal College of Psychiatrists.

Allen Frances, who was the chair of the DSM-IV Task Force and of the department of psychiatry at Duke University School of Medicine, Durham, NC. He is currently a professor emeritus at Duke.

Peter Kramer, Clinical Professor Emeritus of Psychiatry and Human Behavior. Kramer is also the author of numerous books, many of which he likes to promote on Twitter.

So, why have these three well-known, and some would say, intelligent orators, blocked me?

Well, it would appear that rather than answer a simple question I put to them, they decided to put their fingers in their ears and bury their heads in the sand. It's a question that should be answered and one that, to date, has not been adequately answered by anyone from the medical profession, the pharmaceutical industry or any global regulatory agency. It's a question the media never seem to ask either. It's a question I've put to the Royal College of Psychiatrists on many occasions too, they have just chosen to ignore me.

Wendy Burn, who regularly accepts adoration on Twitter yet fails to answer bereaved parents, was first.

My current view of her online profile looks like this.

Next up was Allen Frances, a man who changes his opinion like the wind, depending on whom he wishes to appease.

My current view of his online profile looks like this.

Finally, after attempting to answer my question with some quite unbelievable and unprofessional answers, was Peter Kramer.

My current view of his online profile looks like this.

So, three psychiatrists, all with one thing in common: An inability to answer a question that forms the crux of their beliefs. I urge anyone reading this to ask their healthcare professionals the same question and to contact me if given an answer. If three eminent psychiatrists or pharmaceutical companies, or even medicine regulators cannot answer, then I doubt very much if your average prescriber will either.

The question should be answered because it forms the basic safety and efficacy point of why antidepressants are on the market.

So, what was the question?

"Please list the benefits of antidepressants."

I asked this question because it was once put to me by an old advocate/friend of mine, Matthew Holford. It's a great question and turns the focus off the risks and onto the benefits. Remember, after the clinical trials of these drugs, which lasted between 8 & 12 weeks, a licence was granted because the "benefits outweighed the risks." We all know what the risks are because today most of them are clearly on the antidepressant labels.

Out of the three psychiatrists, Peter Kramer, who has authored such books as 'Listening to Prozac', came up with, or thought he did, an answer. The benefits are "having a good time with your kids", he told me, adding, "progress in your career."

Interesting. My response, which resulted in Kramer throwing his toys out of the pram (blocking me) was, "So, in the 8-week clinical trials for antidepressants the benefits of "having a good time with your kids" was seen. Benefits also seen in the 8-week trial was "progress in your career", is that your position, Peter?"

Ladies & gentlemen, boys & girls, we have all been duped for years and the claim that antidepressants outweigh the risks is, I believe, a fraudulent claim just as the 'depression is caused by a chemical imbalance' claim was.

It's incumbent of us all to seek an answer to this question because without an answer, without the actual truth, pharmaceutical companies and medicine regulators will continue to tell doctors that the benefits outweigh the risks - they, in turn, will continue to tell patients, who, in turn, tell friends and family members. The piss-sodden snowball will grow until we all stop it gathering more momentum.

So, next time you hear the term, "The benefits of antidepressants outweigh the risks", ask the person who is making this claim for a list of the benefits reported during the trials. Don't accept the anecdotal comments, such as, "they saved my life" or "they helped me." These are irrelevant anecdotes. What you are seeking is the list of benefits that persuaded the medicine regulators to grant these drugs a license. Ergo before all the hype came about them apparently saving lives.

Remember, suicidal ideation, self-harm and a whole host of other risks have been reported in clinical trials and we have all been told, 'Hey, there's no need to worry because there were more benefits.' Thing is, ladies & gentlemen, boys & girls, they have failed to show us a list of these benefits. They, if there are any at all, have been hidden from us in much the same way the number of suicidal subjects in clinical trials was hidden. Through various litigation we have unearthed a lot of the hidden risks but, to my knowledge, no drug company has ever been sued because antidepressants work too well.

We need a list of the benefits and we need them now!

We have all just taken their word on trust.

And we should all, rightly, be very angry!

Bob Fiddaman

The Mechanics of the MHRA

So, another response from the British medicines regulator, the MHRA, regarding the benefit vs risk ratio of the antidepressant, Prozac.

It's been painstaking trying to get to the logic behind some of their responses, in fact, it's been suggested that some of their responses to me regarding this issue have been 'obtuse'. It is, however, important that I try to keep this line of communication open with them, if only, to have their responses made public via this blog.

Regular readers will recall that I have been scratching my head regarding the MHRA's stance that one apparent benefit of taking Prozac outweighs the number of adverse events reported by Prozac users or their treating physicians - a list of which can be seen, ironically via the MHRA's own web page, here.

As suspected, the MHRA are now telling me that the list of adverse events reported for Prozac should not be "interpreted as a list of possible side effects to a medicine," furthermore, they add, "It is important to note that causality has not been proven in these reports."

Here is their full response to me - it may help if you read the previous correspondence between myself and the MHRA regarding Prozac's benefit vs risk in order - 1, 2, 3.

So, here's their latest - my response to this follows...

Dear Mr Fiddaman

Many thanks for your email of 25 November 2016.

Most medicinal products that contain one active substance exert their effect through one mechanism of action, in this case through raising the level of serotonin in the brain (which can improve symptoms of depression). In addition, most medicinal products have a range of possible side effects. It should be noted that the frequency of such side effects are considered when evaluating the benefit/risk profile of a product to determine whether it should be granted a marketing authorisation. The frequency of these side effects are also monitored after a marketing authorisation is granted to ensure that the benefit/risk profile of a product is still positive.

The Drug Analysis Print (DAP) for fluoxetine represents a listing of all suspected adverse drug reactions or side effects that have been reported to the MHRA via the Yellow Card Scheme. This includes all reports received from healthcare professionals, members of the public, and pharmaceutical companies. It is important to note that causality has not been proven in these reports; reporters are asked to submit a Yellow Card report even if they only have a suspicion that the medicine may have caused the adverse drug reaction. For this reason it is very important that the information within a DAP is not interpreted as a list of possible side effects to a medicine. The data shown in our DAPs can be very useful in helping to identify possible medicine safety issues. However, this information does not present a complete overview of the potential side effects associated with specific medicines. Conclusions on the safety and risks of medicines cannot be made on the data shown in the DAP alone. Patients should instead refer to the Patient Information Leaflet for the most complete and up to date information on possible side effects.

Best regards


The FOI Licensing Team

--

My response...

Please find my following up questions in bold font below.

(MHRA's statements are in italics.)



Most medicinal products that contain one active substance exert their effect through one mechanism of action, in this case through raising the level of serotonin in the brain (which can improve symptoms of depression). 

1. Is this a definitive answer, ie; Are you saying that you (the MHRA) have clinical and scientific evidence that, in this instance, Prozac improves depression by raising the level of serotonin in the brain? If so, could you please forward me the scientific literature that clearly shows this to be true. If this is just a 'common belief' could you please state, for the record, that the evidence of Prozac improving depression by raising the level of serotonin in the brain is inconclusive.

In addition, most medicinal products have a range of possible side effects. It should be noted that the frequency of such side effects are considered when evaluating the benefit/risk profile of a product to determine whether it should be granted a marketing authorisation. 

2. Is this based on the clinical trials that last between 8 and 12 weeks?

The frequency of these side effects are also monitored after a marketing authorisation is granted to ensure that the benefit/risk profile of a product is still positive.

3. Monitored by whom? Can you please explain the system of monitoring - ie; does monitoring include reading 'anecdotal reports of adverse events ' on Prozac forums?

The Drug Analysis Print (DAP) for fluoxetine represents a listing of all suspected adverse drug reactions or side effects that have been reported to the MHRA via the Yellow Card Scheme. This includes all reports received from healthcare professionals, members of the public, and pharmaceutical companies. It is important to note that causality has not been proven in these reports.

4. Out of all the adverse events reported for Prozac via the Yellow Card System, how many have been found to show that Prozac was the causality and how many have been shown that Prozac was not the causality?

...reporters are asked to submit a Yellow Card report even if they only have a suspicion that the medicine may have caused the adverse drug reaction. For this reason it is very important that the information within a DAP is not interpreted as a list of possible side effects to a medicine. 

5. How do you, the MHRA determine whether or not the adverse events reported via the Yellow Card System are caused by Prozac? 

The data shown in our DAPs can be very useful in helping to identify possible medicine safety issues. However, this information does not present a complete overview of the potential side effects associated with specific medicines. 

6. Thus far, you, the MHRA have given me just one benefit of Prozac, namely that it "can" improve symptoms of depression by raising the level of the neurotransmitter, serotonin, in the brain. When you suggest that it "can" are you saying that sometimes it can't? Please clarify what you, the MHRA, mean when you claim that it "can" improve symptoms of depression.

Conclusions on the safety and risks of medicines cannot be made on the data shown in the DAP alone. Patients should instead refer to the Patient Information Leaflet for the most complete and up to date information on possible side effects.

7. If a doctor, or patient, for that matter, files an adverse event via the Yellow Card System do you, the MHRA write back to them if you determine that Prozac was the causation? Do you, the MHRA, at any point, visit the reporter to try and gain more information - if so, in the past 12 months, how many times has the MHRA visited a reporter of an adverse event regarding Prozac?


Sincerely,

Bob Fiddaman

Prozac - Benefits Vs Risks - MHRA Correspondence

For a while now I've been at loggerheads with the British drug regulator, the MHRA.  (Back stories below)

I've been asking them to send me a detailed list of the benefits of taking Prozac - Yesterday they sent me the following. My response to them follows...

Dear Mr Fiddaman

Apologies for the delay in responding.

Regarding your below enquiry, benefits are considered to be the therapeutic effects of the product to improve the medical conditions for which a product licence has been granted.  These are set out as the Therapeutic Indications in the Summary of Product Characteristics (SmPC) and in the uses of the product in the Patient Information Leaflet (PIL).  To further understand these benefits, you have asked what positive thing is going to happen to alleviate your depression.  The way in which the therapeutic effects are achieved is also explained in these documents.  In the case of fluoxetine, it raises the level of the neurotransmitter, serotonin, in the brain which can improve symptoms of depression (and the other indications listed).  The MHRA does not promote medicines, but agrees in the SmPC  a factual summary of the effects of taking a particular medicine based on the results of clinical and non-clinical studies. 

I hope this answers your question.

Best regards

The FOI Licensing Team

--

My response...

Thank you for this.

So, in essence you are telling me that,  "In the case of fluoxetine, it raises the level of the neurotransmitter, serotonin, in the brain which can improve symptoms of depression." is the one benefit and that this one benefit has been measured against the risks and the MHRA have granted Prozac a licence because they see that this one benefit outweighs the following reported risks with Prozac use...

Please try and help me (and others) understand how one benefit of a product outweighs the following risks associated with Prozac use.

All risks taken from the MHRA fluoxetine Drug Analysis Print  (DAP)
(http://www.mhra.gov.uk/home/groups/public/documents/sentineldocuments/dap_19529665880175380.pdf)

Benefits v Risk Prozac Use.	Benefits It raises the level of the neurotransmitter, serotonin, in the brain which can improve symptoms of depression	Risks Blood disorders Cardiac disorders Congenital disorders Ear disorders Endocrine disorders Eye disorders Gastrointestinal disorders Asthenic conditions Death and sudden death Febrile disorders Feeling abnormal Feeling jittery Fibrosis Gait disturbance Peripheral swelling Face oedema Chest pain Drug withdrawal syndrome Hepatic disorders Immune system disorders Infections Exposure during breast feeding Foetal exposure during pregnancy Fractures and dislocations Electrocardiogram QT prolonged Heart rate increased Abnormal liver function Blood sodium decreased Weight decrease Weight increase Blood prolactin increase Platelet count decrease Haemoglobin decrease Blood creatine phosphokinase increase Blood pressure increase Blood pressure decrease Metabolic disorders Muscle & tissue disorders Neoplasms Nervous system disorders Seizures and seizure disorders Tremors Foetal growth complications Ectopic pregnancy Foetal death Abnormal behaviour Agitation Anxiety Nervousness Aggression Disinhibition Homicidal ideation Hostility Paranoia Personality change Violence-related symptoms Confusion and disorientation Delusion Depression Depersonalisation/derealisation disorders Insomnia Eating disorders Emotional and mood disturbances Fluctuating mood symptoms Impulsive behaviour Restlessness Mental disorders Tearfulness Apathy Orgasmic disorders and disturbances Panic attacks Nightmares and abnormal dreams Hallucinations Personality disorders Acute psychosis Psychotic behaviour Psychotic disorders Schizophrenia Libido decrease Libido increase Loss of libido Sleep disorders Dysphemia Bruxism Alcohol abuse Akathisia Completed suicide Intentional self-injury Suicidal ideation Thinking abnormal Tics Renal & urinary disorders Reproductive & breast disorders Respiratory disorders Skin disorders Homicide completion Vascular disorders

Bob Fiddaman.


Back stories

Classic Avoidance by the British Medicines Regulator, the MHRA

British Drug Regulator (MHRA) Dodging the Curve Ball

British Drug Regulator (MHRA) Dodging the Curve Ball

throw (sb) a curve (ball)

to surprise someone with something that is difficult or unpleasant to deal with.

Many of you will know by now that the MHRA and I have this love/hate relationship.

The MHRA, for those of you who don't know, are the equivalent of the FDA in the US, Health Canada in, um, Canada, and the TGA in Australia. Their duty is protect the public from unsafe prescription drugs, both licenced ones and ones that are illegally sold, they seem to focus heavily on fake pharmaceutical drugs more than regulate the drugs they have already granted a license to.

So, I've been at loggerheads with the MHRA regarding the whole 'benefit vs risk' ratio that they lay claim to when granting a drug a licence here in the UK.

Many people focus on the risks of these drugs, in fact my own focus used to be on the risks but after stepping out of the bubble and looking in from the outside I saw something that has been staring many of us in the face, yet we've been blind-sided and focused on the risks. We all know what the risks are because these days we are told via the patient information leaflets, albeit in watered down versions.

An old advocate friend of mine, Matthew Holford, was, to my knowledge, the first person to raise the issue regarding the "benefits" of these drugs, namely; SSRI's.

I miss Matt's rantings - he was colorful in the language he used and yet had intelligence that he could use tactically. We still correspond - the guy is a legend.

Anyway, back to the MHRA.

I have asked them a simple question that they have, on numerous occasion, failed to answer. Their latest 'answer' is no different. In fact, it would appear that they are now questioning the English Oxford Dictionary. (I've highlighted in yellow). It would also appear that whoever is answering my emails (they never leave a name) has some form of Avoidant Personality Disorder.

First off, here's the question that they seem to be struggling with...

Please provide me with a "detailed list" that shows the benefits of taking Prozac.

Their previous response to this can be seen here. I questioned that response and they have now replied. Once again, no detailed list of any benefits of Prozac has been sent to me. Once again, they have put "Final response" in the subject line.

Dear Mr Fiddaman

Many thanks for your email concerning our response to your FOI request.

Concerning Question 2, a detailed list of the benefits of taking fluoxetine are presented in the Patient Information Leaflet and the Summary of Product Characteristics for products that contain this active. As we stated in our response, the beneficial effects of the product you specifically mentioned in Question 2 (Fluoxetine 20mg Capsules – PL 17907/0374) have been shown through the clinical data submitted for the grant of the marketing authorisation for Prozac 20mg Capsules (PL 00006/0195). The current list of indications or “benefits” of taking Fluoxetine 20mg Capsules are listed in Section 4.1 of the SmPC, a link to which has been provided below:

http://www.mhra.gov.uk/home/groups/spcpil/documents/spcpil/con1474003257568.pdf

Best regards

The FOI Licensing Team.

---

So, once again, I have had to reply to them. Here's my response.

--

Dear MHRA,

I'm somewhat confused?

Are you now suggesting that 'indications' and 'benefits' have the same meaning?  I don't really want to enter into a game of semantics, but when I use the word "benefit," in this context, I want to understand how Prozac is going to help me, as the patient, overcome my depression. In other words, what positive thing is going to happen to me, which causes my depression to be alleviated, or else go away altogether?  It is not a clinical benefit to me to know that Prozac may be prescribed for depression - in fact, that information is not a benefit to anybody apart from doctors and drug companies, as far as I can establish.  Do you understand the distinction, between my definition of "benefit," and yours?

I'll cut to the chase, if I may?

I have asked you, the British drug regulator, to provide me a list of benefits, not indications.

Thus far you have sent me links that have not answered my question. In any event, I am asking specifically for a list of benefits from the MHRA and not anyone else.

You licenced a drug and cited that the benefits outweighed the risks. The risks are, as you say, clearly marked in the patient information leaflet that the drug companies provide. I have no interest in what the drug companies say, nor of the risks associated with Prozac. My question was, and still is, to you, the MHRA.

You made the decision to grant Prozac a licence after weighing up the 'benefits and risks', ergo you should be able to provide me with a detailed list of the benefits based upon which you granted Prozac a licence.

Is this going to be a series of emails between us whereby you continue to avoid the question at hand, is this how you treat all stakeholders?

PS - Once again, the subject line from you indicates that this is your 'final response'. Once again, I will decide when my question has been answered adequately, not the other way around.

Bob Fiddaman
Author/Blogger/Researcher

--


I'll let you know when they next send me a reply avoiding the question.


Bob Fiddaman.

Classic Avoidance by the British Medicines Regulator, the MHRA

I've just received this via email from the MHRA.

My question to them was one of simplicity. Their answer totally avoids the question. My response to their response has just been sent to them.

Firstly, here's the question I posed them...

A document on the MHRA website, namely; Con126183, claims that "...the benefits of taking Fluoxetine 20mg capsules outweigh the risks, hence a Marketing Authorisation has been granted."

The general public are aware of the risks but could you, the MHRA, please provide me with a detailed list of the benefits that persuaded you to grant a Marketing Authorisation?


Their reply, considering is was treated as a Freedom of Information request, defies belief. Firstly, they put 'Final Response' in the subject line of the email (More on this after you read their reply to the above question)

Fluoxetine has been shown to have beneficial effects in the listed indications for the product referenced above (Fluoxetine 20mg Capsules – PL 17907/0374), through the original data that was submitted from clinical trials conducted by Eli Lilly for the grant of a marketing authorisation for Prozac 20mg Capsules (PL 00006/0195). 

So... here's my reply to their, it has to be said, avoidance in answering my question...

Thanks for this but you have not answered question 2?

I asked you to provide me with a "detailed list" that shows the benefits of taking Prozac and nowhere in your response to me has this list been provided.

Why?

PS - I will tell you when any correspondence is "final".

Sincerely,

 

It's a simple question to answer, right? Either they have a list of detailed benefits or they don't.



Bob Fiddaman.