THE FAILURE TO FULLY INFORM PATIENTS OF THE DANGERS OF NEUROLEPTICS
Over the course of the past few months I have written to the various divisions of companies that are based in Ireland, north and south, and who manufacture what are known as ‘anti-psychotic’ drugs. What I have found in the course of this research and the responses I received is that there is a serious lack of information concerning the health risks provided in the patient information leaflet (PIL) or package leaflet that a patient receives with these drugs. The response of the Irish Medicines Board and the UK Medicines and Healthcare products Regulatory Agency, as I will show, in all of this has been very disappointing given that they claim to exist in order to monitor and ensure that medicines are safe for patients. In Ireland we have two jurisdictions of course given that N. Ireland remains part of the UK. I have for the most part concentrated on the situation in the Republic of Ireland.
The starting point for my enquiries was an extensive review (2003) of these drugs carried out by the Food and Drug Administration (FDA), the regulatory authority in the USA. Despite the many failings of this body this review was a considerably extensive and in-depth study of ‘anti-psychotics’. I am not aware of any other study that has matched it in any other country but it concluded that in relation to these drugs (atypical anti-psychotics) that the risk of hyperglycemia (high blood sugar) and diabetes has been played down or minimised by all the manufacturers to a greater or lesser degree. One particular company, Janssen Pharmaceutica received particular attention at that time because of the clear risks attached to their ‘anti-psychotic’. The FDA sent a warning letter on September 2003 to the American pharmaceutical company who manufacture Risperdal saying that Janssen’s ‘Dear Healthcare Provider’ letter was ‘false or misleading’ because:
it fails to disclose the addition of information relating to hyperglycemia and diabetes mellitus.. minimises the risk of hyperglycemia –related adverse events, which in extreme cases is associated with serious adverse events including ketoacidosis, hyperosolar coma, and death, fails to recommend regular glucose control monitoring to identify diabetes mellitus as soon as possible.. and misleading claims that risperdal is safer than other atypical antipsychotic.
Lawsuits have been filed against Janssen by patients in the USA who subsequently developed diabetes as a result of this drug, the direct result of a deliberate failure to provide information concerning this health risk by the company.
Around this time also the FDA wrote to the following manufacturers about the need to update information concerning these health risks attached to their anti-psychotic drugs.
The companies were:
AstraZeneca - who make the anti-psychotic Seroquel (quietiapine)
Bristol Myers Squibb - who make the ‘anti-psychotic’ Abilify (aripiprazole)
Eli Lilly and Company - who make the ‘anti-psychotic’ Zyprexa (olanzapine)
Novartis - who make the ‘anti-psychotic’ Clozaril (clozapine)
Pfizer - who make the anti-psychotic’ Geodon (ziprasidone)
The drug Zyprexa has also proved disastrous for many patients who have developed massive weight gain on this drug. In the FDA’s report on this drug it seems that about 29% of the patients were gaining 7% or MORE of their baseline weight. Similarly Eli Lilly have had lawsuits filed against them by patients in the USA who have developed diabetes and heart disease as a result.
Confirmation that the risk of hyperglycemia (high blood sugar) continues to be minimised by Janssen was clear to me when I contacted a representative of Janssen in Ireland. He pointed out that the PIL for the drug in Ireland states that ‘in VERY RARE CASES HIGH BLOOD SUGAR HAS BEEN REPORTED ’. This is presently as I write the statement (January 2005) on the PIL. This totally contradicts the statement above by the FDA in relation to the drug and means that patients are being lied to about the dangers of this drug. It is important to note that the level of information provided in the PIL in various countries may differ. This is where the role of the drug regulatory body in each country comes in. They should ensure that the patients are getting the most up to date information concerning health risks or ‘side –effects’. Companies will avoid full disclosure of health risks concerning these drugs if they can get away with it.
Patients in Ireland could take legal action especially if they have developed diabetes. If they have not been monitored for signs of diabetes their case is further strengthened. http://www.janssen-cilag.ie/product/pdf/pil00058.pdf
In relation to Eli Lilly they state on their PIL that: ‘SOME PATIENTS HAVE EXPERIENCED HIGH BLOOD SUGAR’. http://www.emea.eu.int/humandocs/Humans/EPAR/Zyprexa/Zyprexa.htm
As I said, according to the FDA report ‘29 % of the patients were gaining 7% or MORE of their baseline weight’ - ‘potentially clinically significant’ according to Eli Lilly itself. This clearly represents a case for legal action by patients in Ireland or anywhere else for that matter if such serious adverse effects have resulted. How many does Eli Lilly mean by ‘some patients’? It should be noted that this weight gain in most cases took less than six months! In fact the PIL states that if a patient suffers from heart disease they should tell their doctor when it fact it is clear that this drug carries a HIGH RISK OF HEART DISEASE. An American psychiatrist I have been in touch with and who spent some time on a legal case about 2 years ago, which involved a thorough review of the FDA’s Drug Approval Package on Zyprexa, can confirm the figure of 29%. I can I am sure provide any patient in Ireland who has developed diabetes or heart disease as a result of this drug and who wants to take legal action with the documented required information.
Let’s look at another of the drugs mentioned above, Abilify. If one checks the PIL one finds that the risk of hyperglycemia and diabetes if not even mentioned in the PIL in this country! The same is also true of the drug Geodon. I had a bit of trouble getting a straight answer from Pfizer in relation to that. Also in relation to Clozaril, the PIL states, "ON RARE OCCASIONS, CLOZARIL MAY CAUSE RAISED BLOOD SUGAR LEVELS AND SUGAR DIABETES ". The active substance in Clozaril is manufactured in Novartis Ringaskiddy Limited, Ringaskiddy, Cork, Ireland. In relation to Seroquel (quietiapine) the PIL states that ‘ IN RARE CASES HIGH BLOOD SUGAR HAS BEEN REPORTED’.
It is very important to note that the FDA concludes in their report that ‘olanzapine, clozapine, quietiapine and risperidone (risperdal) were all associated with ‘A STATISTICALLY SIGNIFICANT INCREASE IN RISK FOR DIABETES’. http://126.96.36.199/search?q=cache:iVonRqgG4J8J:www.fda.gov/cder/warn/2004/12195Risperdal.pdf+the+FDA+and+anti-psychotics&hl=en
This simply confirms the fact that in relation to all these drugs a clear and honest warning concerning health risks is not being outlined in the PIL for patients in this country.
WHAT IS THE RESPONSE OF THE IRISH MEDICINES BOARD (IMB)?
Well, I wrote to them expressing all my concerns in relation to the above. They wrote back (December 8, 2004) to tell me that ‘the IMB is very much aware of the need to monitor the safety aspects of the medicinal products’ and that it has taken a ‘very proactive stance’ in relation to this. They mentioned their participation in the WHO (World Health Organisation) drug monitoring programme and their membership of the EMEA (European Agency for the Evaluation of Medicinal Products).
In my reply to them I pointed out (December 21) that in that case they would or should have been aware of the research undertaken by the FDA in relation to these drugs. I asked them whether they would do more to convey the dangers of these drugs to the EMEA and others - in particular the need for a clear warning to be given on the PIL. They simply e-mailed me to say that my concerns had ‘been duly noted’ and gave me no further information as to what they would do or as to how they would heighten awareness of the dangers of these drugs. It is obvious that there is no determination to address the serious health risks that psychiatric patients are facing.
One reason why perhaps the IMB is unwilling to speak out may rest in the fact that according to the Irish Pharmaceutical Healthcare Association, which ‘represents the interests of the international research based pharmaceutical industry’ in Ireland, the pharmaceutical industry contributes approximately €3 billion a year to the Exchequer in tax payments.
Interestingly in relation to Risperdal the IMB (December 8) said it had:
recently agreed with the manufacturers and received the variation for risperdal for the patient information leaflet in relation to hyperglycemia - and this will be implemented as swiftly as procedures allow.
I found this interesting since just a few weeks prior to this I had been in touch with Janssen about the inadequacy of the information provided in the PIL which they believed wasn’t inadequate. I subsequently contacted Janssen again who refused to tell me what new information would be provided in the new updated information. No new information to date has been added though and it is possible that the new PIL will state that the risk is not ‘VERY RARE’ after all. This though is too late for the patients who have developed diabetes and heart disease. It should not be too late though for them to sue.
Psychiatrists if they were aware as they should be concerning these serious health risks and if they failed to monitor the patient for diabetes can be sued for negligence or this can be done through the local Health board for that matter. The fact of the matter is that it is up to the drug regulatory authority in each country, and in this case the Irish Medicines Board, to speak out. It is simply failing psychiatric patients, as is the vast bulk of the psychiatric profession. There is no disputing the fact that drug companies often lie about the efficacy of their drugs.
In relation to the health risks concerning diabetes I have not even mentioned the risks of neurological diseases associated with these drugs. It is now common knowledge in the medical profession and among the manufacturers of these so-called anti-psychotics that they can and do cause neurological diseases such as tardive dyskinesia, akathisia, and the potentially fatal neuroleptic malignant syndrome. In relation to all the drugs mentioned above there is not one mention of any of these diseases in the PIL provided. Instead, a reference is made to ‘involuntary movements’ or ‘shaking’ which a person may experience as ‘side effects’. It is important to understand that these are not side effects. THESE ARE DISEASES CAUSED BY THE DRUGS! Patients are not informed that these movement disorders caused by the poisoning of their nervous systems are largely irreversible. Psychiatry has clearly brought about a global epidemic of neurological diseases as a result of these drugs.
THE RESPONSE OF THE UK MEDICINES AND HEALTHCARE PRODUCTS REGULATORY AGENCY (MHRA)
I also contacted the UK Medicines and Healthcare products Regulatory Agency (MHRA) in relation to all the psychiatric drugs mentioned. Similarly inadequate warnings concerning health risks are given in the (PIL) for patients in the UK. The MHRA said that I was correct in relation to Abilify and that they would contact the EMEA (European Agency for the Evaluation of Medicinal Products) and ask for changes to be made to the PIL in relation to the failure to mention hyperglycemia and diabetes mellitus and would also raise concerns expressed (see above) in relation to zyprexa. They still maintain though that the risk of hyperglycemia is not in their view minimised in relation to most of the drugs. In N.Ireland there is a body called the Mental Health commission for N.Ireland which claims to exist for the welfare of psychiatric patients. After I wrote to the Commission about my concerns they told me that it ‘does not adopt any stance on the use or prescribing of any particular medication’. Given the health risks presented by these drugs I would have thought that this commission would have taken a more proactive stance and even have taken the step of writing to the MHRA and the drug manufacturers about this. Instead these issues have to be taken up by individuals genuinely concerned about the serious health risks.
I believe that the following warning should be given on the PIL. This warning should be seen on the same level as the warning given on a packet of cigarettes.
PATIENTS SHOULD BE TOLD THE FOLLOWING IN RELATION TO HIGH BLOOD SUGAR AND DIABETES
They should be told that hyperglycemia (high blood sugar) is in some cases associated with ketoacidosis, a complex medical condition, or hyperosmolar coma and death.
Hyperglycemia or high blood sugar happens when the body has too little, or not enough, insulin or when the body can't use insulin properly. Symptoms of hyperglycemia include polydipsia (excessive thirst), polyuria (excessive urine), polyphagia (excessive hunger) blurred vision and weakness.
Ketoacidosis develops when your body doesn't have enough insulin. Without insulin, your body can't use glucose for fuel. So, your body breaks down fats to use for energy.
When your body breaks down fats, waste products called ketones are produced. Your body cannot tolerate large amounts of ketones and will try to get rid of them through the urine. Unfortunately, the body cannot release all the ketones and they build up in your blood. This can lead to ketoacidosis.
Ketoacidosis is life threatening and needs immediate treatment. Symptoms include: shortness of breath, breath that smells fruity, nausea and vomiting, a very dry mouth.
Hyperglycemia is usually the first sign of diabetes mellitus. It should be made clear that patients need to undergo regular glucose control monitoring to identify diabetes mellitus in them as soon as possible.
DIABETES MELLITUS, commonly referred to as diabetes, means ‘sweet urine’. Elevated levels of blood sugar or glucose leads to spillage into the urine, hence the term.
There needs to be a clear warning given to patients that diabetes mellitus is a CHRONIC MEDICAL CONDITION which can last a lifetime and can be brought about by ‘anti-psychotic’ drugs.
There must be a warning that diabetes mellitus can lead to blindness, kidney failure, that it can accelerate the hardening and narrowing of the arteries (ARTERIOSCLEROSIS), leading to strokes, heart disease and blood vessel diseases.
Blood / urine testing for diabetes must be done on patients taking these drugs any longer than a few months.
IN RELATION TO THE NEUROLOGICAL DISESASES CAUSED BY THESE DRUGS the (PIL) MUST EXPLICITLY WARN ABOUT THE FOLLOWING:
TARDIVE DYSKINESIA: Patients are at risk of developing a largely irreversible, untreatable neurological disorder called tardive dyskinesia. The disease is often disfiguring with involuntary movements of the face, mouth or tongue. It can though affect any part of the body including that of the neck, shoulders, back, arms and legs, and hands and feet.
TARDIVE AKATHISIA: This involves painful feelings of inner tension and anxiety and a compulsive desire to move the body. In the extreme the patient undergoes internal torture and is unable to sit still.
NEUROLEPTIC MALIGANT SYNDROME: This is indistinguishable from an acute inflammation of the brain comparable to lethargic encephalitis and is potentially fatal. Clinical manifestations of NMS are HYPERPYREXIA (fever, high temperature), muscle rigidity, altered mental states, evidence of autonomic instability (irregular pulse or blood pressure) TACHYCARDIA (sudden, rapid racing of the heart), DIAPHORESIS (heavy perspiration), cardiac dysrhythmia (disturbance in the regular rhythm of the heartbeat). Patients should undergo regular electrocardiogram (ECG) testing. Additional signs may be increased elevated Creatine Phosphokinase. Creatine Phosphokinase (CPK) is an enzyme found predominantly in the heart, brain and skeletal muscle. When the total CPK level is substantially elevated it usually indicates injury or stress to one or more of these areas (when a muscle is damaged CPK leaks into the bloodstream). Psychiatric drugs can bring this about. By determining which isoenzyme –specific form of CPK-is elevated it can help to then determine which tissue has been damaged. Tests must be done if the patient experiences chest pain or other muscular pains.
RHABDOMYOLYSIS: rhabdomyolysis is the breakdown of muscle fibers or skeletal muscle resulting in the release of muscle fiber contents into the blood circulation. Some of these are toxic to the kidneys and frequenty result in kidney damage and even kidney failure.Various tests can be done to detect this including the CPK test. Symptoms may include abnormal urine colour ( dark , red , or cola coloured ), muscle tenderness, generalized weakness, muscle stiffness or aching, seizures and joint pain. Dead tissue skeletal muscle may cause massive fluid shifts from the bloodstream into the muscle reducing the relative fluid volume of the body and leading to shock and reduced blood flow to the kidneys.
REGULAR BLOOD AND URINE TESTS MUST BE CONDUCTED IN RELATION TO ALL THE ABOVE IF A PATIENT IS ON THESE DRUGS ANY LONGER THAN A FEW MONTHS.
Communicating this information in the PIL is essential. It will give a clear warning to the patient regarding the serious health risks. On this basis no one could in my view really argue that these drugs should be prescribed except in cases of extreme mental distress and for as short a period of time as possible –really no longer than a period of a few months .One of the real effects of these drugs is that they have a mental and emotional disabling effect on the patient and therefore in extreme situations could only be justified. We must also consider though the physical fitness of the patient given that all these drugs carry a risk of heart arttack and stroke.The fact that drug companies don’t give all this information to the patient and the fact that many psychiatrists believe patients should remain on these drugs for many years if not a lifetime is criminal in my view. The drug companies and by extension many though not all in the psychiatric profession -not to mention the so-called drug regulatory authorities- have the blood of psychiatric patients on their hands. According to the psychiatric industry 15-20% of patients long term on anti-psychotics will develp tardive dyskinesia. The figure is probably higher but if this were the case in relation to any other ‘medicine’ being prescribed there would be an absoloute outcry and the drugs withdrawn from the market. But because the drugs concern psychiatric patients few people care.
Each of the drugs mentioned above is worth around 2-4 billion a year globally to the companies mentioned.For these companies profits come before patients and especially psychiatric patients. This therefore clearly comes at the expense of the truth. These companies show nothing but contempt for the psychiatric patient and the psychiatric profession by and large has sold out its soul to them. Thankfully, to date there have been successes in the USA against these companies. We need to see the same happening in Ireland, Britain and many other countries and this pseudo and deeply harmful practice ended once and for all