Acne drug Dianette (Diane-35) obtains new depression and suicide risk warning

Foreword to readers:

Thanks to women who contacted APRIL and those who have heeded our request to report side-effects for Dianette (Diane-35).

It is due to the efforts of APRIL for many years requesting the Medicines & Healthcare Products Regulatory Agency to review the emails we received from women, with detailed explanations of the way Dianette affected them, that eventually the MHRA reviewed the drug for safety issues. This review, started in 2006, led to the manufacturers adding an additional warning about depression which previously had been listed under MILD side effects.

The MHRA requested APRIL to urge these women to report using the Yellow Card system. Compliance with this request has led to reports of psychiatric adverse drug reactions (ADRs) soaring in a few years from 3% of all reports to 33% of all reports by 2011. Due to the increased number of reports recorded on Drug Analysis Prints by the MHRA the manufacturer has added the warning as mentioned below in this post.

Dianette, the hormonal acne treatment manufactured by the German pharmaceutical company Bayer, has had a label change in the UK, following a number of reports of depression and suicidal thoughts.

Patient Information Leaflets should now include this warning in each box of Dianette:

“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.”

The drug is prescribed to 62,000 British women and millions of women worldwide each year for acne and excessive body hair (hirsutism). Hundreds of adverse drug reactions and some fatalities have been reporting for people taking Dianette, also known as Diane-35 and other generic names.

In the USA the medication has not been approved by the Food and Drug Administration (FDA), and France banned the drug altogether in 2013** after its links to at least four French deaths from blood clots and 125 patients suffering serious side effects. The European medicines agency released a statement reported on BBC News (27 February 2013) about the decision of the French medicines agency ANSM to stop distribution:

“ANSM considered that Diane-35 and its generics carry a risk of thromboembolism which has been well known for many years, while their effectiveness in treating acne was only moderate and alternative treatments for acne are available.”

Dianette can be taken off-label as a contraceptive pill, but is unlicensed for this purpose due to its significantly higher risk of blood clots compared to other pills. Professor Dominique Maraninchi, director-general of the ANSM, believes doctors are giving women the drug as a contraceptive off-label too often, saying:

"Diane-35 is an acne treatment that also blocks ovulation. We have several inquiries going on that show that this non-authorised use is significant."

Between 2010 and 2013, the MHRA revealed that seven women in the United Kingdom have died whilst taking the drug, with 83 reports of side effects such as thrombosis and depression.

Last year, a Dutch report revealed up to 27 women, most of whom under 30, died from blood clots believed to be caused by Dianette.

Despite being listed as a Black Triangle Drug under further review by the medicine’s regulator, Dianette and its generic counterparts remain on license in the UK.

Earlier this year Jessica Eales, a young sailing champion, took her life after her 17th birthday, following 4 months of using Dianette as an acne treatment. The coroner Graham Short could not conclude any links between her suicide and the drug as she had not presented any noticeable signs of depression before this. The coroner quoted the European Medicines Agency review of Dianette in his report, which had concluded the benefits of the drug outweigh its risks. However, the EU report only took into account the risks in respect of thrombosis; the risk of depression and suicidal thoughts and actions was not considered in this review.

Following the death of Charlotte Porter, who died of a blood clot in 2010 whilst on Dianette, an MHRA spokesman announced: ‘Dianette is an effective medicine for treating the distressing conditions of severe acne and excessive hair […] Despite recent developments in France, we have no new concerns.’ German manufacturer Bayer said: ‘Bayer believes that Dianette has a favourable benefit-risk profile when used in accordance with the label.’

Prior to the publicity instigated by APRIL, we were told of many instances where antidepressants were prescribed to women who complained of depression, and left uninformed of the link or told to stop taking Dianette. APRIL’s research on patient safety collated 102 adverse drug reaction reports sent in by 2011 by women on their use of Dianette. Several personal accounts document that once removing themselves from the drug, their mood clears, following severe depression in some instances.  One patient described how “The cloud lifted when I stopped taking Dianette”. Woman’s hour described similar stories in their programme about contraceptive pills and mood.

This change in patient information is one step forward to informing the patient of the risks to their mental health when taking Dianette. Once a change in a patient leaflet is made, however, the GP may not be aware of the new information. However, we are hopeful that following this change in labelling, there may be further consideration of Dianette’s psychiatric side effects taken by prescribers as well as by coroners.

Crucially we urge those affected to report adverse side-effects using the Yellow Card reporting system in the UK. From this, we can build a stronger and more accurate profile of this drug for both prescribers and the prescribed to be aware of its risks.

Jacqueline Bond 

** Edit: The ANSM's decision to suspend Dianette was overruled as the European Commission's decision to maintain marketing authorisation was implemented in all EU Member states.

BLACK TRIANGLE DRUGS under High Scrutiny

Black Triangle classification on drugs your doctor may prescribe should be carefully monitored and ANY suspected adverse reactions reported to www.yellowcard.gov.uk a pharmacovigilance system we have to support as it is the only 'official' one. Please also report to the web site monitored by doctors https://www.rxisk.org   as they may take more active efforts to create awareness of newly discovered adverse drug reactions (ADRs) also please report all psychiatric ADRs to any medicine or following anaesthetics to APRIL www.april.org.uk 

Black Triangle Drugs now include Dianette (cyproterone acetate & ethinylestradiol)and Champix (Verenicline) the drug prescribed to help smokers also known as Chantix.

“The Black Triangle”

Although the Black Triangle has been used since the 1980s in the UK to indicate that a drug is under intensive surveillance, new pharmacovigilance legislation in Europe now extends the Black Triangle symbol across the EU.

The Black Triangle will have to be present in the manufacturer’s Summary of Product Characteristics (SPC) and associated packaging patient leaflet (PIL) of any product subject to additional monitoring, along with the phrase “This medicinal product is subject to additional monitoring”.

Further information about all drugs available in the UK are on the web site www.medicines.org.uk  this is the Association of British Pharmaceutical Industries (APBI) electronic medicines compendium and has masses of good information. The SPC contains more information as it contains data the manufacture must submit when the drug is first licensed and should be updated as adverse reactions not originally listed are discovered.

Additional monitoring under the Black Triangle scheme applies to:

§           all medicinal products with a new active substance

§           biological medicinal products, including biosimilars

§           Any other medicine a regulator can demonstrate a specific requirement for additional monitoring

Black Triangle status will normally last for 5 years, but can be extended if ongoing safety issues require it.

Please report ALL suspected adverse drug reactions to any drug which has a black triangle symbol next to it to www.yellowcard.gov.uk  and APRIL will appreciate information about psychiatric adverse reactions to add to our data, used to promote action and improve education for health professionals.

Black Triangle drugs in the EU full list: go to the complicated MHRA web site www.mhra.gov.uk and be patient ! click on

1.     Safety Information,

2.     MEDICINES (in left menu)

3.     How we monitor the safety of products

4.     Overview

5.     Medicines

6.     Black Triangle Medicines then right at the bottom of the page you will find a link to the latest list of drugs designated with the Black Triangle

If MHRA web site changes cause problems just put Black Triangle in search box at  www.mhra.gov.uk Unfortunately my attempts to provide a direct link to the information are unsuccessful. I have written to the MHRA to suggest the Black Triangle information should be on the home page or found with just one click.

Contraceptive Pill links to Depression on BBC radio 4 Woman's Hour Today

Contraceptive Pill links to Depression

Today on BBC Radio 4 in the excellent programme Woman's Hour, I heard a discussion about the contraceptive pill and links to depression.

I would like to congratulate the presenter, Emma Barnett for her enlightened attention to what is a serious problem for many women. Sadly so many women do not link their mood swings, depression and failure to cope, with prescribed medication including the Pill. Many women are prescribed antidepressants to help them deal with depression that may not be a problem once they stop taking a particular contraceptive or other medication.

Please refer to my campaign about Dianette ( click Dianette to link to Guardian article) as the doctor on the programme seemed to promote the fact that skin and other problems can improve with certain contraceptives.

He failed to mention that Dianette, the drug promoted for acne is the one that is not actually licensed for contraception (though it has a contraceptive action) due to higher risk of dvt, blood clots. Banned for a while by the EU this comes with warnings. It may be valuable for women considering this drug, to have their blood clotting factor checked before embarking on using Dianette (also known as Diane 35 and many other generic names.). The doctor did mention that loss of libido as a possible adverse drug reaction (ADR).

We will never know how many suicides are linked to prescribed drugs that cause depression - in other words, are not tolerated, with the addition drugs prescribed for the depression, that are also not tolerated.

You can hear the radio 4 programme on BBC iplayer Contraceptive Pill links to Depression

http://www.bbc.co.uk/programmes/b04cbv9g

Project about depression - please contribute to survey

Questions about depression?

We at APRIL have been trying for years to persuade doctors and official bodies to ensure people who are suffering adverse reaction to everyday medicines or anaesthetics or having problems related to withdrawal from prescribed drugs,  are heard and helped.

 Adverse drug reactions (ADRs)  and withdrawal effects can be depression, anxiety, insomnia, psychosis, self harming, or suicidal thoughts and actions.

Please contribute to the survey at www.depressionarq.org 

This is part of a major project about depression research. The aim is to inform research and provide a strong connection between researchers and the needs of patients.

Unfortunately if patient groups involved in this research have received substantial funding from the pharmaceutical industry, there will be attempts to cover up the extent of depression and suicides linked to medication adverse effects or withdrawal problems. It is therefore very important for those with experience of iatrogenic (treatment induced) depression or related conditions to express their views.

As difficult as it may be for those bereaved by iatrogenic related death of a loved one, we do appeal for you to please make your views known.

The survey gives patients, carers and clinicians a chance to let the organisers know what questions need to be answered. Questions can be about any aspect of depression; prevention, causes, diagnosis,
treatments or care.

Visit www.depressionarq.org to take part

Millie's comment following Margaret's story on Dr David Healy's Blog

Margaret's story on Dr David Healy's blog about the tragic death of her son following prescription of SSRI antidepressant, resulted in many comments - mine is below.

http://davidhealy.org/platonic-lies

All the statistics you quote, do not alter our own personal experiences. The facts also speak for themselves. We should take into account the concerns of eminent clinical pharmacologist Dr Andrew Herxheimer that emphasis in research is on benefits and not harms of treatment.

10 years of UK hospital admission statistics, show that the largest increase is due to adverse drug reactions (ADRs) which has risen by 76.8% – analysis done by Imperial College.

Iatrogenic (treatment induced) illness is a public health crisis. Professor Munir Pirmohamed’s well known study of hospital admissions, that excluded psychiatric, paediatric admissions, showed 1 in 16 were due to ADRs.
A study in Liverpool of children who die or suffer ADRs has already found serious problems, not least of which is how unaware the parents are of the possibility of ADRs.

Awareness a drug is linked to suicide will not stop someone who needs it from taking it. However forearmed is forewarned and knowledge may reduce the number of avoidable deaths.

All kinds of medication can cause mental changes. The manufacturers are aware of this. Sadly in the UK, since the General Medical Council guidelines for medical education were changed in 1993 – to exclude Pharmacology and Therapeutics, doctors have qualified without having to prove competence to prescribe. The do not have to know about psychiatric adverse side-effects. Most have never read the data sheets produced by the manufacturers. Everyone should see these, they clearly state the psychological risks that are well known. Professor Simon Maxwell asked medical students if they felt competent to prescribe and most said ‘no’.

The British Industry web site has data sheets which are called SPCs http://www.medicines.org.uk

Today would have been my daughter Karen’s birthday. Her death in an avoidable accident was preceded by.

Psychosis and Stevens Johnson’s skin adverse reactions to a sulphonamide drug (all known adverse side effects but not always clearly indicated on patient information).

Depression following taking a drug for hormonal problem, well known to cause depression.

Akathisia – extreme agitation preceded by a headache following taking just one tablet of fluanxol an antidepressant.

She went to see the doctor but was turned away as she had no appointment. Came home and took some sleeping pills to ‘calm herself down’ …a typical reaction to akathisia is to self harm to let out the painful agitation ‘ like wanting to jump out of my skin’ one person explained.

For the rest of this list of adverse drug reactions Karen suffered, see the web site for APRIL, the charity I founded http://www.april.org.uk

Once I put up the web site – the personal stories started to come in. Shocking details of how people were adversely affected mentally by drugs.

A man wrote to me ‘ I dreamed I was hitting my wife and when I awoke, I was’. another said ‘ I tried to push my wife out of the car – I don’t know why’ . Both men had just started taking the antidepressant Seroxat.

A headmaster fell on to a motorway, he could not remember what happened, he ended up in a wheelchair.

He had been prescribed an antidepressant, Mirtazapine, not for depression but for re occurring sore throat!

The Drug Safety Research Unit did a PEM study – post marketing study – on Mirtazapine, they found serious ‘unlabeled’ adverse reactions reported by patients who were taking the drug. I asked the Director Professor Saad Shakir, why he did not insist the regulator (MHRA) took action to add the agitation, aggression etc to the patient information and he said ” I am an academic scientist and I published the paper, that is all I have to do”.

I found a similar attitude when I spoke to Professor Louis Appleby and asked why in the Suicide Prevention Strategy for England, there is no mention of medicication causing akathisia and suicidal feelings and actions. He told me he woud ” address this”. If there were warnings about the possibility that sudden changes in a person, either becoming high, manic, or very down, could be due to the treatment, lives could be saved.

I have been communicating with Professor Appleby for 10 years, to try to have the well recorded risk of suicidal feelings due to prescribed drugs or withdrawal effects, recorded in the Suicide Prevention Strategy. So far to no avail.

He admits in the letter to Margaret on this blog, that more education is needed, well he is head of mental health, so how about it Professor Appleby? Awareness among health professionals could save lives.

Apart from my daughter, I know of several instances where people feeling suicidal or agitated have been turned away by GPs or from the A & E departments instead of action being taken to care for them in this vulnerable state. One young man, a medical student, Jon Medland, had been to his GP, another, James, son of Clare Milford-Haven who told her tragic story at our last conference, had been to a walk-in clinic and then to A&E where he was graded 4 and told to wait. Tragic consequences could have been avoided.

A & E personel, GPs and medical receptionists should be trained to recognise those at risk of suicide, as being people recently prescribed SSRIs, corticosteroids or following surgery. Addiction to codeine benzoidiazepines and sleeping pills are other areas where improved medical education and availability of withdrawal protocols could prevent suffering and tragic consequences of too sudden withdrawal.

Angela Lee suicide

Angela Lee 'staggered' and fell in front of a train according to the shocked female train driver of a train travelling at 90 miles per hour. Angela had left a note and felt that the acne drug ro-accutane (isotretionoin) had caused lasting problems. I can confirm that many people who contact me say depression, which they believe was caused by roaccutane lasts for months and years after they stop taking the drug. Angela was prescribed fluoxetine (Prozac) and Zopiclone which she was taking at the time of her death.

I sat in the Walthamstow Coroner's court and heard the evidence given to the jury and was also shocked to hear that Angela was given Dianette at the same time as she was prescribed Roaccutane. None of the journalists commented on this cocktail of drugs - all linked to causing suicidal feelings.

Another problem was the failure of health professionals who cared for Angela, to communicate by picking up a telephone to speak to each other and discuss how best to protect her from harm.

* Deaths linked to prescribed medicines

• Michael Jackson’s and other deaths linked to prescribed medicines

Sudden death is difficult to cope with, and difficult to come to terms with.

The loss of a beloved family member, leaves us in a state of disbelief, asking ourselves if there is a mistake or is it a nightmare we will wake up from.

When the death was preceded by concerns for the health or lifestyle of the person we loved, we then feel guilt and wonder if there was something we could have done to prevent the tragic loss.

The death of Michael Jackson on Thursday, should not come as a surprise to those who had knowledge of the cocktail of prescribed medicines he had become dependent on. Michael’s friends expressed concern and gave warnings it seems.

Alternatives to drugs that may help some people

The human body has remarkable powers of recovery from damage and pain and the drugs no doubt help in the immediate relief following injury or surgery. Pain can be relieved, in my experience, by experts in manipulation, using a Tens machine, or I am told, acupuncture.

People under stress who cannot sleep should try first tranquillity teas and avoid caffeine drinks. Taking up Yoga and breathing exercises can help relaxation too. However in too many cases the first resort is drugs

UK Government Inquiry into prescribed drug addiction

A recent House of Commons Inquiry organised by MP Brian Iddon, highlighted that addiction to pain killers, tranquilisers and antidepressants leads to people taking them for years longer than required for the original problem. Involunatry addiction following careless prescribing leads to devastation of lives. Careers are ruined and family life destroyed in many cases.

Other celebrity deaths linked to prescribed drugs

Prescribed drugs were implicated in several celebrity deaths. 27 year old actor Heath Ledger died from combined effects of tranquillisers, sleeping pills and antihystemine.

New York City medical examiner's office stated Heath Ledger died as the result of acute intoxication by oxycodone, hydrocodone, (pain killers) diazepam (Valium), temazepam (Restoril/Euhypnos), alprazolam, (Zanax) and doxylamine (an over the counter anti-hystemine),

When Elvis Presley died he had no previous cardiac problems and the death was due to the cocktail of addictive prescription drugs, including: Valium, Codeine, other painkillers, tranquillisers and sleeping pills.

Other celebrities deaths due to the same or similar drugs include Marilyn Monroe, Jimmie Hendrix, Dorothy Dandridge, Bruce Lee and Howard Hughes

Medicines led to deaths of ordinary folk too, my daughter, my friends brother and Helen in Manchester due to Dianette the drug I campaigned about, to name a few.

For every celebrity who’s death is linked to prescription drugs, there are thousands of ordinary folk who die and get no publicity. In many cases the drug implication is not even recorded as the cause and seldom reported to the regulator. It is estimated that over 100,000 people die in the USA due to adverse drug reactions (ADRs). A study in the UK By Liverpool professor Pirmohamed found that one in 16 emergency admission into hospital is due to ADRs. That figure excludes psychiatric, maternity, paediatric and ent admissons. So the true total may be much higher. Many prescribed drug related deaths are not even picked up by naïve coroners.

My daughter Karen’s death and a missed opportunity at the inquest

My daughter Karen died, at the age of 30, unwell and suffering dizzy spells, she slipped against a window with a faulty catch and died in an accidental fall from her bedroom window. The emphasis of the inquest was on the broken safety catch and danger of swivel windows in apartment buildings. Little attention was paid to the fact that Karen had suddenly stopped taking the highly addictive drug Temazepam and was, in error, over prescribed, for months, three times the recommended dose of a drug to deal with side effects, the anti-parkinson drug Kemadrin (procyclidine).

A verdict of ‘misadventure’ this week in Manchester at the inquest of 33 year old

A verdict of ‘misadventure’ this week in Manchester at the inquest of 33 year old Helen Schofield.

This verdict not adequately record the true cause of death or explain the inappropriate prescribing of Dianette (cyproterone acetate & ethynlestradiol) for a girl with known family cardiac risk. The drug has 4 times the risk of other drugs used for contraception, for deep vein thrombosis (dvt). Helen had lost her father at a young age due to heart attack. She had also gone with her mother to the doctor with concerns about the safey of Dianette, having read the information leaflet. She was suffering aches and pains and a sudden hacking cough. These early warning signs were dismissed by doctors in the practice. Helen was told she should stay on the drug. Her sudden death due to dvt has devastated her mother Kay who persistently asked the doctors if the drug was safe for Helen. Kay wants others to be aware of the increased risk of dvt with Dianette and is concerned that the doctors had little knowledge of the risk to her daughter.

Kay had not connected the fact that Helen had been prescribed Seroxat (paroxetine) for anxiety, another possible side effect of Dianette, as she was so perturbed about the risk of thrombosis which the health professionals ignored.

Dianette is not licensed as a contraceptive and only recommended for short courses to treat acne that failed to respond to antibiotics, or hirsuit problems. The reason for the refusal to license Dianette as a contraceptive is the 4 times greater risk of dvt, about which Helen and Kay Schofield were never warned.

APRIL’s Dianette campaign

I was distressed to hear of Helen’s death as I had campaigned for the regulatory, the Medicines Healthcare Products Regulatory Agency (MHRA) to issue a further warning to doctors about the risks of psychiatric as well as blood clots for Dianette. For years I had been writing to the MHRA and had meetings with and told Dr June Raine that Dianette is being over prescribed and for too long without warning the patients about the side effects. They reviewed the drug in 2006 but did not issue a specific warning to GP’s as they had in 2002 in their publication ‘Current Problems in Pharmacovigilance’.

The death at 27 of Daniel Galvin

Another concerned mother was Gillian, the mother of Daniel Galvin. Gillian was introduced to me by psychiatrist Dr Phil Thomas, a member of the Critical Psychiatry Group. Gillian had concerns about Daniel's deteriorating health due to the adverse effects of psychotropic drugs. Daniel had seizures linked to Olanzapine/Zyprexa and had developed Neuroleptic Malignant Syndrome (NMS), a well know side effect of psychotropic drugs that can be fatal. Gillian knew how important it was to get Daniel off the drugs and single handed, she did this. Withdrawal has to be slow and there are many problems with withdrawal effects. In the care of doctors these effects may lead to further prescribing of more and more drugs.

I think the stress and pressure led to Gillian's sudden death.

Without his mother, Daniel had to go into psychiatric care and was prescribed drugs again. I had been to visit him with his sister Ana due to her concerns that Daniel was having fits. Ana did her best to persuade the doctors to keep medication they perceived as necessary, at the lowest possible level. She told them her mother had been concerned about raised CPK levels so they agreed to do a blood test.

However Daniel was found dead in his bedroom. The drug Olanzapine / Zyprexa has been suspected of causing fits when Daniel was first treated for anxiety some years before and he was prescribed this with Sodium Valproate at the time of his death.

Bed Push Demo in memory of Daniel Galvin

I took part, with Daniel’s sister Ana, in a street demonstration in memory of Daniel. The ‘Bed Push’ demo was organised by psychologist Rufus May against the over dependence of our mental health system on the use of drugs for mental distress.

The use of psychotropic drugs may be considered by some people as helpful for an immediate crisis but suddenly stopping or increasing the doses beyond the level of human tolerance can lead to sudden death, aggressive behaviour and suicides. Cocktails of drugs are often prescribed with no reference to how the particular person can metabolise or disperse these from the body.

Pharmacogenetic tests to evaluate whether we have the enzymes and potential to successfully utilise any benefits or cope with any risk from toxicity could be used. Toxic levels of drugs not successfully dispersed by the liver enzymes can lead to the aforementioned disasters.