Executive Summary

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Who is submitting evidence

1.  This written evidence is submitted by me, Millie Kieve, in a personal capacity and on behalf of the charity APRIL (Regd in England no 1072305).

 

 

 

I also submit on behalf of researchers and academics with whom I have had considerable correspondence, some of whom have attended and spoken at my conferences.

3.  Millie Kieve founded the charity APRIL in 1998, following the death of her daughter Karen.

 

4.  The charity exists to create awareness of psychiatric adverse reactions to medicines, withdrawal effects from medicines and drugs and anaesthetics used pre, post and during surgery, which can lead to self-harm and suicide.

 

5.  An adverse drug reaction (ADR) is defined under the EU Directive 2010/84/EU1 that came into force in July 2012 as “a response to a medicinal product that is noxious and unintended effects resulting not only from the authorised use of a medicinal product at normal doses, but also from medication errors and uses outside the terms of the marketing authorisation, including the misuse, off-label use and abuse of the medicinal product”. Link to MHRA patient Safety Alert:

https://www.england.nhs.uk/wp-content/uploads/2014/03/psa-sup-info-med-error.pdf

 

6.  Over time, a web site www.april.org.uk was established, and three conferences were organised and held in London, one with accreditation from the Royal College of Physicians.

 

7.  Speakers included professors, doctors, academics, coroners. Association of British Pharmaceutical Industries Director of Datapharm, Steve Mott spoke about how little the ABPI manual of drug data sheets were used by health professionals. This is still a problem we find as many prescribers are unfamiliar with the Summary of Product Characteristics data which with important warnings about drug interactions and ADRs. www.medicines.org.uk

 

8. Among the topics at our conferences were dependence to prescribed medicines, the types and prevalence of ADRs, and the relationship between doctors and the pharmaceutical industry and how drug trials are manipulated in favour of drug benefits. Videos of the talks may be accessed : https://vimeo.com/user1816628/videos/sort:alphabetical/format:thumbnail

 

8.  Delegates and speakers had excellent opportunities to interact and learn from each other. This is not always the case in conferences funded by the pharmaceutical industry.

 

9.  Individually, I won a Millennium Award in 2000, which paid for a research tour, during which I spoke to many parents of young people who died by suicide.

 

10.  Dr June Raine, director of the Medicines Healthcare Regulatory Agency (MHRA) invited me to many meetings over the years, and I presented a paper to promote reasons why patients should be enabled to report suspected adverse drug reactions themselves using the Yellow Card system.

 

11.  It was estimated that less than 10% of serious ADRs were reported to the MHRA by health professionals. The system was amended  to include acceptance of reports from patients but sadly the fact they can report ADRs direct to the MHRA is poorly publicised.

 

12.  I was also a keynote speaker at conferences organised by the British Computer Society, North West England Non-Medical Prescribers Conference and Therapeutics Journal Prescrire in Paris, France I have also had articles published in journals and online.

 

13.  I have written many articles over the years, notably a co-written editorial with Professor of Pharmacy Practice, Janet Krska was published in Prescriber journal https://www.kent.ac.uk/health/files/news-items/prescriber-2015.pdf

 

14.  In the above article we cited the Department of Health-led Suicide Prevention Consensus Statement (a key document for the Health Committee to consider):

https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/271792/Consensus_statement_on_information_sharing.pdf

15.  Our article highlights the Consensus Statement in support of sharing information with family or caregivers when antidepressants are prescribed. Manufacturers of most SSRI and similar antidepressants recommend the family or caregivers should be informed when the drugs are prescribed. www.medicines.org.uk contains Summary of Product Characteristics in which Manufacturers now advise informing patients’ relatives/caregivers when antidepressants are prescribed because of the known risk of suicide. Since 2008, the Summaries of Product Characteristics (SmPCs) for most antidepressants have added the following under “special warnings and precautions”: “Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.”

16.  I lost my daughter Karen in 1995 and following my research at the British Library Medical Department was shocked to find early warning signs Karen could not tolerate drugs were ignored by doctors who should have been caring for her.

 

17.  The ache in your heart when you have lost a child is indescribable.

When the death is considered to be a result of intolerance to pharmaceutical drugs, including sudden onset of psychosis or other psychological changes, there is a desire to try to prevent this tragic loss of life from affecting other families.

 

18.  I am not just a bereaved mother, I am now also an advocate for many people who have contacted APRIL with tragic stories of suicidal loss due, in their opinion, to pharmaceutical drugs causing adverse reactions or withdrawal effects.

 

19. In this capacity, one of the biggest lessons I have learned, is that so called “normal” people with no history of mental ill health, may kill themselves as a result of taking prescribed medication.

 

20.  As a bereaved mother I am in a position to understand the plight of people who, with no previous history of mental ill-health, suddenly find themselves in the mental health system. Unable to find understanding of their true condition, they suffer intolerance not only to the original drug that caused the psychiatric ADR, but also to the drugs prescribed for the ADRs. Many people descend into a downward spiral of worsening mental and physical ill-health.

 

21.  My observations are based on an enormous body of letters, phone conversations, email, and personal contact, where relatives and friends tell the personal stories of people harmed or bereaved by ADRs. This empowers me to speak for those too traumatised to speak for themselves.

 

22.  I have gained knowledge over many years following research, reading and communication with health professionals and the public. I have attended numerous inquests and done research for those in need of information about adverse drug reactions causing psychiatric changes.

 

23.  I helped the patients’ experience sections of a conference to promote the use of Yellow Card Patient Reporting. Is the Patient Voice Loud Enough?, was organised by Prescribing and Research in Medicines Management (PRIMM) and the DSRU, delegates heard tragic stories, directly from those who suffered, of how families have been torn apart by the serious side effects of prescribed medication.

http://www.alumni.nottingham.ac.uk/netcommunity/page.aspx?pid=2687

 

24.  Prior to founding APRIL, I worked for various charities, including MIND on the InfoLine and for PAPYRUS as a trustee. I found little or no attention was paid to psychiatric adverse drug reactions linked to everyday medicines, to anaesthetics and drugs used pre and post-surgery, or to withdrawal support as many drugs cause dependence.

 

25.  I helped the BBC with research for documentaries and helped listeners via the BBC Action Line.

 

26.  It has become clear there is a major problem of misdiagnosis in many cases where adverse drug reactions were not considered as the cause of a person’s distress. Drugs implicated include those for indigestion (acid

reflux), antibiotics, pain killers, tranquillisers, sleeping pills, anti-malarials, acne drugs and cardiac drugs. I have hundreds of anonymised details of the suffering, including suicidal ideation, many people encountered.

 

27.  For one drug in particular, I received over 100 reports of depression, self-harming and suicidal ideation – followed by complete recovery when the drug was stopped. I took up the issue with June Raine, and eventually  the the MHRA agreed to review the drug, known as co-cyprindiol or Dianette, a hormonal drug with steroidal effects licensed only for acne and related problems.

 

28.  While it was not licensed as a contraceptive, Dianette ( often advertised as “The Pill that gives you beautiful skin”) was often prescribed as a contraceptive. It was withdrawn by the European Medicines Agency for a while to examine the number of deaths due to thrombosis linked to the drug. The psychological effects were not an issue for the EMA, despite evidence that some women were self-harming and had made suicide attempts.

 

29.  Thankfully the MHRA took seriously the finding from the anecdotal reports and manufacturers were told to increase warnings on the patient information leaflets. The SPC now: “Post-marketing reports of severe depression (including very rare reports of suicidal ideation or behaviour) in patients using Dianette have been received. However, a causal relationship between clinical depression and Dianette has not been established.” http://www.medicines.org.uk/emc/medicine/1814

 

30.  Pharmaceutical drugs can cause severe psychiatric changes in the brain. There is an urgent need to research and educate health professionals and the public that increased dosage, polypharmacy or sudden withdrawal is not the answer to the current iatrogenic harm people are suffering.

31.  Reporting suspected ADRs and debilitating withdrawal effects from prescribed medicines should be a priority for all health professionals and families who have clear evidence of changes in personality following use of the treatment that led to psychiatric changes or suicide. The Yellow Card Sysem should be reviewed for fitness for purpose of pharmacovigilance and the findings of the 2005 Health Committee Inquiry in the Influences of the Pharmaceutical Industry should be reviewed.

32.  In an attempt to change things, Professor Anthony Avery, now Dean at the University of Nottingham, appointed me to Chair and convene the Advisory Group to the Evaluation of Patient Yellow Card Reporting, a Health Technology Assessment by six universities in 2011.

http://www.ncbi.nlm.nih.gov/pubmed/21545758

 

33.  The Evaluation found that ”the addition of patient reports to HCP reports identified 47 new 'serious' reactions not previously included in 'Summaries of Product Characteristics' ”.

 

34.  A professor involved in this study wrote to support my submission to the last Suicide Prevention Strategy for England (name of professor can be supplied to the Health Committee).

 

35.  See No 36 for the Professor’s summary to support my submission to the last Suicide Prevention Strategy.

 

36.  “I have recently been involved in a substantial evaluation of direct patient reporting of adverse drug reactions to the MHRA, with Professor Avery. Our study examined reports submitted by patients and health professionals and found that suicidal ideation was the 11th most frequently reported reaction among patient reports, constituting 0.8% of all the patient reactions we studied. It is thus not an uncommon reaction, being similar in frequency among patient reports to rash (0.9% of all reactions) and loss of appetite (0.8%). I believe that it is essential that drug therapy or withdrawal from drug therapy are included as potential contributory factors to suicide. Any strategy aimed at reducing suicide should in my view take account of these factors.”

 

37.  While the 0.8 % above may appear to be low, in terms of at least a billion prescriptions issued in the UK that translates to a potential of around 8 million people in the UK alone developing suicidal ideation caused by adverse reaction or withdrawal reactions to pharmaceutical drugs. In the light of this finding alone, more emphasis should be on education for prescribers to check the side effects are not the cause of changes in mental well being.

 

38.  Director of Suicide Prevention & Mental Health, Professor Louis Appleby, while assuring me personally that he would address the situation, has not included in his Suicide Prevention Strategy any warnings about akathisia or other drug- induced psychiatric adverse effects.

 

39.  The Health Committee needs to find out why this is and hopefully to rectify this situation.

 

40.  There is an urgent need for comprehensive and well-funded research to establish the true position – which may well be far worse than my own attempts to find out have elicited. Whatever the result, it would at least represent a true picture of the amount of iatrogenic harm in the UK – and   by extrapolation, elsewhere.

 

41. This research could draw on a careful analysis of the current MHRA database of Yellow Card reports of suspected ADRs, which includes: suicidal and self-injurious behaviour; suicide; suicide attempt; suicidal ideation; intentional overdose; self-injurious ideation; and self-injurious behaviour.

 

42. There are also ADR categories for psychotic behaviour, hallucinations, confusion, homicide, morbid thoughts, intentional overdose, suicidal depression, and insomnia, all of which can lead to suicide or sudden accidental death.

 

43.  The MHRA believes under 10% of serious ADRs are reported. Taking an example of 5 antidepressant drugs, duloxetene, fluoxetien, mirtazapine, paroxetine, venlafaxine  and two anti-smoking drugs, buproprion and varenicline. In the MHRA Drug Analysis Prints data, are reports of 26,884 psychiatric ADRs including 286 completed suicides and over 5000 reports of attempted suicide, aggressive behaviour, homicidal ideation and overdoses. The actual number of psychiatric ADRs, some leading to suicide, needs to be evaluated.

 

44. These statistics are underused and seldom publicised in an effort to reduce the number of suicides and self harming in the community.

 

45.  As a keynote speaker at British Computer Society in 2005, I was informed by a director of Emis a major computer company that warnings about drug interactions that are meant to pop up on a GPs computer are often disabled by doctors who find the pop ups annoying.

 

46.  At a recent meeting at the Kings’ Fund in August 2016, I asked Dr James Woollard (Sen Clinical Fellow MH Technology & Innovation NHS England) If there is an app for ADRs, he said ‘no ‘ but it could be done…this could be followed up by the Health Committee as doctors sometimes fail to recognize such ADRs are akathisia (extreme agitation) as an ADR and go on to increase the dose of the drug causing the problem.

 

47.  At the same meeting Deputy Director MH Strategy and Transformation Team NHS NW London collaboration of CCGs , namely Jane Wheeler, spoke of listening to the needs of the patients. I asked Jane if the development she is involved in of a mental health strategy there are plans to support people withdrawing or reducing drugs of dependence such as benzodiazepines, SSRI antidepressants and addictive pain killers. Her answer was they have no plans for such support. I believe the Health Committee could look at this strategy that will not lead to a reduction in suicides.

 

48.  Coroner’s problems in discerning if a drug was involved in a death

I was asked by a Coroner for advice on how to find if a drug he suspected has actually led to three deaths he had to hold inquests for – It was suggested by a retired Clinical Psychopharmacologist that he could contact the Poisons Unit. When he asked the Unit for assistant their response was “ We don’t help Coroners”. The committee might liaise with the Chief Coroner to find a way to produce a data base of medication used or stopped before death as well as finding support for Coroners to further their inquiries into health care issues prior to a death. True figures for suicides are difficult to assess with an increase in Narrative verdicts, where often a verdict of iatrogenic suicide would fit the case. A suicide linked to medication ADR or following surgery will not show up as such in statistics and may only be recorded if the coroner or family submit a Yellow Card report to the MHRA. If they do, the statistics held by the MHRA are not always carefully analysed as the Herxheimer/Medawar paper mentioned above found. By 2014, 18% of all inquest verdicts were unclassified or narrative. Of the 27% of those considered as death by accident or misadventure, some may have been due to medicines ADRs or withdrawal effecs. As in my daughter’s case when a tragic accident led to her death when she slipped and fell from a height. Karen was suffering confusion and dizziness following sudden withdrawal from a benzodiazepine and an error in repeat prescribing resulting in overdosing by 3 times the required dose of a harmful anti-Parkinson drug.

https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/427720/coroners-statistics-2014.pdf

 

49.  It may be useful for the Health Committee to speak to a representative of the London Transport Public Protection Unit, as they have stark information of train deaths and how many people survive being hit by a train. The PCs in the Unit have a unique opportunity to talk to people who are behaving in a strange manner as they informed me they have targeted certain stations and reduced suicides at those stations.

 

50.  I met and spoke to many senior police officers who work in the London Transport Police Public Protection Unit. My talk made them aware of the possibility that people on platforms behaving in a worrying manner could be suffering ADRs or withdrawal effects and agreed it would be possible to include any information they found on pharmaceutical drug use in reports on deaths they dealt with. The officer who was my contact left the unit, so this initiative needs to be followed up.

 

51.  In relation to the paucity of information medical students receive about ADRs, the committee may be interested to know Clinical Pharmacology and Therapeutics was removed from the guidelines on medical education in 1992 by the GMC – as recorded in their publication ‘Tomorrow’s Doctors’ it has taken years for Clinical Pharmacologists to regain a stake in medical education. It is only this year an exam to assess competence to prescribe has been established. For more information about this failure the committee could speak to Professor Simon Maxwell Clinical Pharmacologist at Edinburgh University.

 

52.  At a meeting I had with doctors at the BMA the lack of independent education, and pharmaceutical seminars was spoken about with concern.

53.    Some of my comments in the previous section could lead to action by the Health Committee and the Government.

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I believe the findings of eminent health professionals and bereaved family members are true and should be taken seriously. The Health Committee should take advantage of the opportunity to reduce suicides.

 

Millie Kieve