Women still not being told about pregnancy risks of valproate
BMJ 2017; 358 doi: https://doi.org/10.1136/bmj.j4426 (Published 22 September 2017) Cite this as: BMJ 2017;358:j4426
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The European Medicines Agency is to be congratulated for drawing attention to the need to provide advice to women with epilepsy on the risks of taking anti-epilepsy drugs (AEDs), sodium valproate in particular. The EMA disseminated information to several European organizations in advance and had speakers from the public, industry and from those with specialist interest in epilepsy.
Almost all UK prescribing and repeat prescribing is the responsibility of General Practitioners (GPs). This includes AEDs. Almost everyone is registered with a GP, so with some caveats, evidence from a large number of practices can be taken as representative of the population. Anonymized GP data has been used to describe the commonness of epilepsy, treated with AEDs in the UK (1%), changing trends in prescribing of AEDs, and an association between sodium valproate and major congenital malformations.1-3
Each European country is different in its system of delivery of medical care and medicine. This makes it difficult to plan and implement a ‘one-size-fits-all’ change. In some Scandinavian countries, specialists monitor and prescribe for people with epilepsy. They also record data electronically allowing them to monitor risks of AEDs, and other risks. Depression is a risk for pregnant women with a potential for consequences in their offspring. Not only does depression reduce quality of life directly, but it is in turn associated with reduced medication-adherence,4 which is another important risk in pregnancy. Depression and poor medication adherence is also associated with premature death in both men and women. 1,5 Here is the rub. Focusing on one condition, one medication, and one risk is does not deliver on the combination of risks individuals experience over time, and if it does, not efficiently.
In the UK this created the raison d’être for General Practice. Over the past thirty years, GPs have gradually acquired the confidence and competence to take on advising patients to reduce the impact and risk of death from many conditions, including cervical cancer in women and vascular disease in everyone. This required GPs and the primary care team to do additional training, and develop new services, and required additional resources, year on year. The NHS estimated it spends £175m (€235m; $268m) a year on identifying people at risk from cervical cancer, referral for closer monitoring, and, if necessary, for surgical intervention.6 Managing individual’s comorbidities and their risks through life is the new normal. And there has been a decline in the negative consequences including death, for example, from papilloma virus in women and vascular disease in everyone.
UK General Practice has become a victim of its own success. GP numbers have not expanded in tandem with their expanding role. GPs are now overwhelmed with the work of managing long-term conditions, for which they originally volunteered. In this context it is understandable if the RCGP did not respond to a specific request to speak on valproate in pregnancy. This is a shame, as the absent GP can easily become a whipping-boy, castigated by experts and activists, either for not knowing enough or for not doing enough, or both. The EMA naturally wants a quick win, with no additional funding required. Providing specific advice on valproate will require more consultation. Providing self-management advice for all people with epilepsy would require time. It would require for training and service development. And like cervical cancer prevention it would require resources.
If the EMA continues with this and other public hearings, I hope they will do more to include less specialist, but nevertheless important service providers, and that General Practice steps up. All doctors, apart from neurologists report neurophobia. Fear of not knowing enough neurology probably does act as a barrier to providing good community care. Twenty years ago, we found 55% people with epilepsy reported that their epilepsy care was provided by their GP, 11% by a hospital doctor, 19% by both and 15% by neither.7 Since then the number of neurologists has nearly tripled. One might hope that this increase is associated with specialist- monitoring for more UK people with epilepsy and with education provided for more GPs and practice nurses. A useful outcome of this exercise would be that that whoever prescribes valproates agrees to identify and provide regular advice to women and girls at risk. Better still, that policy-makers and providers start exploring how ongoing structured self-management advice might be offered to everyone with epilepsy.
References
1. Ridsdale L, Charlton J, Ashworth M, Richardson MP, Gulliford MC. Epilepsy mortality and risk factors for death in epilepsy: a population-based study. Br J Gen Pract. 2011;61(586):e271-e8. DOI: 10.3399/bjgp11X572463
2. Nicholas JM, Ridsdale L, Richardson MP, Ashworth M, Gulliford MC. Trends in antiepileptic drug utilisation in UK primary care 1993–2008: Cohort study using the General Practice Research Database. Seizure. 2012;21(6):466-70. DOI: https://doi.org/10.1016/j.seizure.2012.04.014
3. Petersen I, Collings S-L, McCrea RL, Nazareth I, Osborn DP, Cowen PJ, et al. Antiepileptic drugs prescribed in pregnancy and prevalence of major congenital malformations: comparative prevalence studies. Clin Epidemiol. 2017;9:95-103. PubMed PMID: PMC5317245.
4. Ettinger AB, Good MB, Manjunath R, Edward Faught R, Bancroft T. The relationship of depression to antiepileptic drug adherence and quality of life in epilepsy. Epilepsy & Behav. 2014;36(Supplement C):138-43. DOI: https://doi.org/10.1016/j.yebeh.2014.05.011
5. Fazel S, Wolf A, Långström N, Newton CR, Lichtenstein P. Premature mortality in epilepsy and the role of psychiatric comorbidity: a total population study. Lancet. 2013;382(9905):1646-54. DOI: https://doi.org/10.1016/S0140-6736(13)60899-5
6. Public Health England. NHS cervical screening programme. 2015 [cited 2017 Sep 26]. Available from: https://www.gov.uk/guidance/cervical-screening-programme-overview.
7. Ridsdale L, Jeffery S, Robins D, McGee L, Fitzgerald A. Epilepsy monitoring and advice recorded: General practitioners' views, current practice and patients' preferences. Br J Gen Pract. 1996;46(402):11-4. PubMed PMID: 8745845.
Competing interests: No competing interests
It is very alarming that two thirds of women claim they don't know about the pregnancy risks with use of valproate.
Part of this may even be due to patients forgetting the risks involved after they have been taking the drug for many years. The author mentions that "epilepsy charities are calling on the government to make annual reviews mandatory for women taking the drug.". This already exists in many GP surgeries for patients on long term medications and I think a reminder once a year may not change the numbers greatly.
However an adjuvant brief reminder by their pharmacist who dispenses the drug every 2/3 months, warning the patient of the risk with pregnancy might be more useful?
Every time I've taken Ibuprofen from my local store I always get asked if I've suffered with an ulcer before and I tend to remember this more than the words of my doctor I might see once a year.
Competing interests: No competing interests
Women still not being told about pregnancy risks of valproate - a general practice perspective
During my F2 rotation through general practice, a MHRA bulletin (1) was circulated at the monthly clinical governance meeting. This was discussed amongst the GPs and practice nurses and the conclusions were that although most thought they were informing their patients who were taking Sodium Valproate of the risks to a child developing in utero, there was no practice specific data to back this up.
I performed an audit to assess how the practice informs patients of the risks, and whether patients were offered effective contraception. I used the MHRA toolkit (1) to draw up audit standards. The audit was undertaken at a large urban GP practice in South Devon with 17,300 registered patients. An electronic notes search identified 93 female patients taking Sodium Valproate, of which 16 met inclusion criteria for the audit (43 excluded as outside MHRA defined 'childbearing age' and 34 patients excluded who did not have Sodium Valproate dispensed in the preceding 12 months).
Of the 16 patients meeting inclusion criteria, 4 had been documented as having passed through menopause, 6 were using effective contraception, and 2 patients were recorded in the notes as not sexually active. There were 4 remaining patients who were not documented as using any contraception. These patients were contacted and 3 had passed through menopause. The 1 remaining patient was booked in for a medications review and the teratogenic risks of Sodium Valproate discussed.
There is an interesting debate to be discussed as to where responsibility for ensuring communication of teratogenic risk to these patients lies. The doctor starting Sodium Valproate in patients for long-term conditions may be in secondary care and unlikely to be providing life-long follow-up to the patient, and as such can only be expected to explain the risk at the time of starting treatment. When performing medication reviews in general practice, the GP should routinely identify patients at risk and discuss this with them. With the increasing role of community of GP-based pharmacists in general practice (2), responsibility in this area may shift to other healthcare professionals.
As this audit of a single GP practice shows, we are often already communicating this to our patients, however we must remain vigilant and ensure our patients are well informed. For many patients, Sodium Valproate is an effective medication and one which will be looked to continue, albeit with a greater understanding of the potential side-effects to an unborn child.
1) Medicines and Healthcare Products Regulatory Agency. Toolkit on the risks of valproate medicines in female patients. Feb 2016. www.gov.uk/government/publications/toolkit-on-the-risks-of-valproate-med....
2) New primary care model expands to 200 sites across England. Gareth Iacobucci. BMJ 2017;359:j4880
Competing interests: No competing interests