MHRA Dianette correspondence

History of APRIL's efforts to change the information available to patients about Dianette and the risk of it triggering depression and associated psychiatric problems.

We wrote to the Medicines and Healthcare Products Regulatory Agency (MHRA) many times to share the information we received from women about the adverse psychiatric effects they suffered when taking Dianette or Diane 35. At first no one agreed to read the reports from women who wrote to APRIL. We offered over 100 accounts of depression and related problems and evidence from the women who had stopped the drug, to show they felt a 'cloud lifted' when they did stop taking Dianette. Many had been offered antidepressants with no suggestion from their GP that stopping Dianette may be a solution to their new problems.

After many letters and a personal meeting with senior employees of the MHRA at the British Museum, when I (Millie Kieve) met with Dr Sarah Wark - it was agreed I could forward the 100 annonimised accounts from women and girls. It was agreed they would be shown to the review committee who would evaluate the evidence about Dianette.

Eventually after their review of Dianette the MHRA persuaded the manufacturers to add the following warning to the Patient Information Leaflet (PIL)

4.1 Serious side effects – see a doctor straight away -  found in the PIL July 2017

Severe depression:

Although, it is not considered a direct side effect of Dianette, some women have reported feeling depressed whilst taking Dianette. In very rare cases this has been associated with thoughts of ending their lives. If you develop severe depression, you should stop Dianette as a precaution, and see your doctor straight away.

The manufacturers added to the more detailed Summary of Product Characteristics (SPC) - a data sheet that all prescribers should be familiar with, the following statement. Link to SPC July 2017

"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."

One may wonder at the comment about a causal relationship as the data sheet for the Dianette clearly states under

  4.8 Undesirable Effects - Adverse events reported in clinical trials - found in the SPC July 2017

Common (≥ 1/100)

The MHRA responded to our many letters emails and personal visits. These are a few of the comments from longer letters:

October 2005 - from Dr Jane Woolley Pharmacovigilance Risk Assessment Group

Thank you for your email to Dr June Raine about the prescribing of Dianette and its associated risks. This has been passed to me for reply.

The MHRA shares your concerns over the prescribing of Dianette solely for contraception and has taken several steps in recent years to try and minimise this.  ......

The Patient Information Leaflet currently warns women with a present or past history of severe depressive state that their condition will need to be carefully monitored on Dianette and that depressive moods can sometimes occur in the first few months after starting Dianette. However we will be reviewing all the available data with respect to the development of psychiatric reactions in association with Dianette use. Any action that we take will therefore depend on the outcome of this review. In the meantime I would urge you to encourage the women/girls who contact you to either ask their doctors to report their symptoms to the MHRA or to report them directly throuth the Yellow Card website: www.yellowcard.gov.uk  Patient Yellow Card report forms have been made available in 4000 GP surgeries in the UK.

A phone number was supplied (now not in use) and the mention of paper forms in GP surgeries is a sore point as no one has ever seen one in a GP surgery or a pharmacy!

January 2006 - from Dr Sarah Bourne Pharmacovigilance Risk Assessment Group - Post Licensing Division

Thank you for your letter dated 8th December regarding Dianette and the issue of psychiatric reactions, in particular depression with this product. This letter has been passed to me for a response. The company have now provided a review of the relevant data which includes spontrneous reports of supected psychiatric adverse drug reactions (ADRs) and also a review of the lterature regarding this issue. The submitted data is now being assessed and a report will be presented to the next meeting of the appropriate Expert Advisory Group (EAG) of the Commission on Human Medicines (CHM).....[some info on the formation of the EAGs followed]

You raise the issue that in the Patient Information Leaflet for Dianette, depression and loss of interest in sex are included in the list of mild reactions. I agree that this does not appropriately reflect the seriousness of the reaction that may occur in some women and this is something I will ask the EAG to consider.

I (Millie Kieve) have to report that sadly the data still contains depression and loss of interest in sex as MILD reactions. I requested information about the people on the Expert Advisory Group and did not receive that information from the MHRA. I investigated and could not find anyone who may have a remote idea of the problems such MILD reactions could lead to. However the resulting extra, if guarded, warnings were a small achievement.

Links to articles relating to the above information:

Related Informations/Articles 

The Guardian published the following article about our Dianette campaign, this was then picked up by newspapers across the world. Pill under review over link to depression

Millie Kieve's story published in The Guardian about Karen Kieve ‘She told me she had lost her personality’ article

Contraceptive pill linked to depression article

Prescribing advisory blog article and our comments re Dianette article

The Pill and depression campaign by Vicky Spratt January 2027

My nightmare on the pill 

http://www.bbc.co.uk/news/magazine-38575745 article

http://www.thedebrief.co.uk/news/real-life/side-effects-of-the-pill-20170166182 article

You can follow Vicky on Twitter - Vicky Spratt (@Victoria_Spratt) | Twitter

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Band Names for Co-cyprindiol from Wikipedia

Brand names

CPA is marketed under brand names including Androcur, Androcur Depot, Androcur-100, Androstat, Asoteron, Cyprone, Cyproplex, Cyprostat, Cysaxal, Imvel, and Siterone. When CPA is formulated in combination with EE, it is also known as co-cyprindiol, and brand names for this formulation include Andro-Diane, Bella HEXAL 35, Chloe, Cypretil, Cypretyl, Cyproderm, Diane, Diane Mite, Diane-35, Dianette, Dixi 35, Drina, Elleacnelle, Estelle, Estelle-35, Ginette, Linface, Minerva, Vreya, and Zyrona. CPA is also marketed in combination with estradiol valerate as Climen, Climene, Elamax, and Femilar