1. An Update on Managing Migraine in Women Kay kennis Nov 2012

2. Outline Topiramate in women of child bearing age Menstrual migraine Migraine and the use of combined hormonal contraceptives Migraine in pregnancy and lactation Migraine, the menopause and HRT

3. Topiramate in Women of Child Bearing Age Advice from CEU (FSRH) Jan 2012 (NICE more conservative) Weak enzyme inducer. If dose > 200mg / day and long term (>2 months use) then CHC and POC contra- indicated Ideally change to depot or coil (IUD and IUS ok) Could use 2 COC pills (eg 20 and 30mcg) plus extended or tricycling regimen with pill-free interval 4 days Emergency contraception – Cu-IUD best if within 120 hours UPSI or within 5 days expected ovulation. Otherwise use 2 x 1.5mg LNG if within 120 hours (outside product license). Ella One can’t be used with enzyme-inducing drugs

4. Menstrual Migraine 20-60% of women report some association Menstruation is risk factor for migraine without aura (even if woman also has attacks with aura at other times) Oestrogen withdrawal in late luteal phase No extra migraines at ovulation in trials Attacks more severe, longer lasting and less responsive to treatment

5. Management Standard diet and lifestyle modifications and avoid triggers Standard acute treatment (? Mefenamic acid – supported by trials) Prophylaxis:Use diary to confirm diagnosis –if frequent non-menstrual attacks in addition to menstrual migraine standard prophylactics best –Perimenstrual prophylaxis needs regular periods and predictable migraine

6. Perimenstrual Prophylaxis None licensed as evidence limited Try for 3 cycles before abandoning 1 st line (??) NSAIDs (esp if dysmenorrhoea/ menorrhagia). Remember contraindications and consider PPI cover. Perimenstrual triptans (most robust evidence) Perimenstrual oestrogen supplements Contraceptive strategies

7. NSAIDs for menstrual migraine Some migraine thought secondary to prostaglandins released from endometrium during menstruation NSAIDs are prostaglandin inhibitors Particularly useful if menorrhagia / dysmenorrhoea Evidence for naproxen 500mg od (or 550mg bd used prophylactically)

8. Perimenstrual Triptans Disadvantages –Increased cost –No trial showing better efficacy than standard regimens –Safety –Limited choice of abortive therapy for break through BUT did have more robust evidence Frovatriptan (2.5mg bd) or zolmitriptan (2.5mg bd – tds) –Take from day -2 for 6 days –May cause rebound headache

9. Perimenstrual Oestrogen Supplements Prevent oestrogen dip Contraindicated if H/O oestrogen dependent tumour or thromboembolism Only useful if menstruation regular and predictable (though could use fertility monitor to start Rx 10 days after ovulation) Oestradiol gel 1.5mg daily from day -2/3 for 7 days Alternative 100mcg 7 day patch Problem is delayed migraine after withdrawal (could extend to day 7 and taper dose last 2/7- no trial evidence) RARELY used even by specialist in tertiary clinic

10. Contraceptive Strategies Useful if woman also needs contraception Additional non-contraceptive benefits on premenstrual syndrome, menorrhagia and dysmenorrhoea Ok even if cycles irregular Can’t use if aura Options –Tri-cycle COC (not if aura) –Extended regimens (see next slide) –?Depot- should provide stable low levels of oestrogens but no studies (other PO methods too low dose to suppress oestrogen fluctuations)

11. Extended Combined Hormonal Contraceptive Regimens Cochrane review found extended regimens are a reasonable approach to CHC use though still off licence Women can eliminate frequency of withdrawal bleed and any associated symptoms eg migraine Strategies include –3 weeks CHC use with 4 day break (better than 7 day break as lower pregnancy risk) –Continuous use until break through bleed then 4 or 7 day break (4 thought safest)

12. Choice of Contraception in Migraine CHC contraindicated if aura Aura and CHC are independent risk factors for stroke- synergistic. Stroke risk in pt with Migraine aura increased from 4.4 to 8.5/100,000 by CHC. To 34.4 if smoker! If migraine without aura same cautions as rest of population

13. Migraine in Pregnancy Migraine without aura most likely to improve in pregnancy Management in pregnancy is essentially similar to management during non- pregnant state Women benefit from early advice on drugs Try and minimise- ok to reassure meds taken are unlikely to have caused harm, but don’t recommend unnecessarily

14. Medication in Pregnancy Acute –Paracetamol 1 st choice –Aspirin and ibuprofen (up to 600mg /day) ok to 30 weeks (AVOID aspirin in lactation) –Cyclizine and promethazine first line anti- emetics (metoclopramide reverses gastric stasis so can have dal benefit) –Sumatriptan indicated if above fail- data reassuring

15. Medication in Pregnancy Continued Prophylaxis –1 st line – Propranolol (lowest effective dose). Possible increased congenital heart defects, intrauterine growth retardation, low birth wt – but may due to underlying maternal condition. Some evidence of neonatal bradycardia, hypoglycaemia, hypotension, respiratory distress. Data on stopping 24-48H before delivery conflicting. –2 nd line – Amitriptyline (10-25mg). Aim to stop 3-4 weeks before delivery- antidepressant doses can cause tachycardia, irritability, muscle spasm and convulsion

16. Emergency Treatment in Pregnancy 2 cases of prolonged migraine aura successfully treated with IV prochlorperazine (10mg over 8 hours) plus 1mg magnesium sulfate over 15mins 6 day reducing course of steroids (60mg, 40mg, 20mg 2 days each) could be considered for long duration attacks, but not suitable for repeated use in pregnancy

17. Red Flags in Pregnancy Hypertensive disorders of pregnancy and stroke are more likely to occur in women with migraine Beware of new neurological symptoms or signs, rising BP, known risk factors for pathology or new aura Secondary headache more common in pregnancy include eclampsia, stroke, post dural puncture, cerebral angiopathy, pituitary apoplexy and cerebral venous sinus thrombosis

18. If woman develops aura for first time in pregnancy consider Imminent eclampsia Cerebral venous sinus thrombosis Thrombocytopenia May be migraine but needs admission for further investigation

19. Management of Migraine in Lactation Similar precautions to pregnancy (but don’t use aspirin) Breast feeding generally sustains the benefit of pregnancy on migraine If anti-emetics required metoclopramide and domperidone increase breast milk production so could have dual benefit Contrary to prescribing information data support use of sumatriptan in breast feeding without disruption (if necessary)

20. Management of Perimenopausal Migraine Optimise vascular risk factors in all women with migraine. Women’s Health Study (5125 women) shows active migraine with aura is a risk factor for CVA and CVD. The risk for CVA is modified by age, with greatest risk age <50 Maintaining a stable oestrogen environment can benefit oestrogen withdrawal migraine and is the most effective treatment for vasomotor symptoms (see next slide) Good prognosis after menopause for pts with perimenopausal exacerbation

21. Using HRT in Perimenopausal Migraine continued Migraine with aura is not a contraindication to HRT If aura appears for first time after starting HRT exclude TIA / other migraine mimic and reduce or stop oestrogen Patches and gels better in migraine (more stable hormone levels than tabs) Be cautious if perimenopausal and intact uterus- but continuous oestrogen with Mirena protection is better tolerated in migraineurs than cyclical combined Rx (also good if contraception required) Use lowest effective dose of oestrogen Tibolone best if oral needed

22. Alternatives to HRT in Perimenopausal Migraine Fluoxetine and venlafaxine – may increase migraine in first few weeks Gabapentin Neither are as effective as HRT for the vasomotor symptoms but may help

23. References MacGregor Headache in Pregnancy Neurol Clin 2012.pdfMacGregorMacGregor Headache in Pregnancy Neurol Clin 2012.pdfMacGregor Perimenopausal migraine in women with vasomotor symptoms Maturitas 2012.pdf Perimenopausal migraine in women with vasomotor symptoms Maturitas 2012.pdf MacGregor Progress-in-the- Pharmacotherapy-of-Menstrual- Migraine.Clinical Medicine Insights- Therapeutics 2011.pdfMacGregor Progress-in-the- Pharmacotherapy-of-Menstrual- Migraine.Clinical Medicine Insights- Therapeutics 2011.pdf

24. Summary Topiramate and contraception Menstrual Migraine Migraine and contraception Migraine in pregnancy and lactation Migraine in the perimenopause Any Questions?