11/26/2013. Acute Migraine Treatment in Pregnancy. Disclosures. Presentation outline. Matthew S Robbins, MD

Transcription

1 Acute Migraine Treatment in Pregnancy Matthew S Robbins, MD Director of Neurology Service, Einstein Division of Montefiore Director of Inpatient Services, Montefiore Headache Center Assistant Professor of Neurology, Albert Einstein College of Medicine Disclosures Honoraria Medlink neurology American College of Physicians American Headache Society Legal consulting Royalties Headache (Neurology in Practice series) - Wiley All treatments discussed herein are off-label in pregnancy 1

2 Case 1 23 year old woman G1 P0 16 weeks GA presents with severe headache acutely worse for 3 days Established episodic migraine without aura 2 months of escalation in frequency and severity Fixed bifrontal location Case 1, continued 2 weeks of white spots and streaks in the periphery of her vision OU Galactorrhea since age 19 BP 87/54 mm Hg Neurological and ophthalmological examinations unremarkable Felt unchanged after IV metoclopramide Red Flags in Headache: SNOOP S Systemic symptoms, signs, disease pregnancy? Examples Fever, weight loss, malignancy, HIV, meningismus N Neurologic symptoms, signs Papilledema, sensory, motor, diplopia, bulbar O Onset Abrupt / thunderclap O Older New headache at age 50 P Pattern change Progression, precipitation, postural Dodick DW. Semin Neurol

3 Secondary Headache Disorders Ocular / orbital Vascular Traumatic Angle-closure glaucoma Aneurysmal subarachnoid hemorrhage Acute or chronic subdural hematoma Cavernous-carotid fistula Arteriovenous malformations Epidural hematoma Acute posterior circulation ischemic stroke Subarachnoid hemorrhage Hemorrhagic stroke Intraparenchymal hemorrhage Congenital Vasculitis (including giant cell arteritis) Acute or chronic post-traumatic headache Chiari malformations Cortical vein and venous sinus 3 rd ventricle colloid cyst thrombosis Cervical artery dissection Reversible cerebral vasoconstrictive syndrome Bone and structural Skull metastases Paget s disease Extramedullary hematopoiesis Mass Lesions Primary and metastatic brain tumors Carcinomatous or lymphomatous meningitis Pituitary and sella turcica lesions Infections Herpetic or post-herpetic neuralgia Lyme disease Meningitis Encephalitis Brain abscess Acute rhinosinusitis Systemic infections Disorders of Homeostasis Acute severe hypertension Obstructive sleep apnea Hemodialysis Hypothyroidism, thyrotoxicosis Preeclampsia/eclampsia Posterior reversible encephalopathy syndrome Intracranial pressure and volume derangements Post-dural puncture headache Spontaneous intracranial hypotension Idiopathic intracranial hypertension Substance-related Medications Caffeine withdrawal Alcohol Cocaine Adapted from: Robbins MS, Lipton RB. Drugs Aging. 2010;27: Acute headache in pregnancy Series N Secondary Headache Modality Top secondary diagnoses Ramchandren (2007) Semere (2013) % Imaging 1. Sinusitis 2. Venous thrombosis 3. RPLS/ eclampsia % Imaging 1. Intracranial hemorrhage Robbins (2012) % Clinical + Imaging 1. Preeclampsia/eclampsia 2. Intercurrent infection 3. Pituitary disease Ramchandren S, Cross BJ, Liebeskind DS. AJNR 2007 Semere LG, McElrath TF, Klein AM. J Matern Fetal Neonatal Med 2013 Robbins MS et al. Presented at AHS 2012 Results: diagnoses RCVS Lobar ICH Other 9% Sickle cell crisis SLE, CKD and hyperkalemia Moyamoya with infarctions Secondary HA 57.4% Primary HA 42.6% Preeclampsia/eclampsia 25% Migraine 43% 26.5% migraine without aura 16.2% migraine with aura 14.7% status migrainosus 5.9% chronic migraine Intercurrent infection 7% Pituitary adenoma/apoplexy 6% PRES 4% Post-dural puncture 3% Venous thrombosis 3% Robbins MS et al. Presented at AHS

4 Case 1, continued Automated perimetry: bitemporal hemianopsia Prolactin 395 ng/ml ( ng/ml) MRI brain: 1.7 x 1.8 x 2.5 cm suprasellar mass, fluid-fluid level Migraine Epidemiology 1-year period prevalence Modeled migraine incidence in women Lipton RB et al. Neurology 2007 Stewart WF et al. Cephalalgia 2008 child-bearing years Migraine course in pregnancy Nappi RE, et al. Curr Pain Headache Rep 2011 >26% of migraineurs: moderate or severe headacherelated disability during early pregnancy Frederick IO, et al. Headache

5 Migraine with aura in pregnancy Migraine with aura is less likely to improve during pregnancy than migraine without aura Increased endothelial reactivity in patients with migraine and aura increased attack frequency New onset migraine with aura and aura without headache may occur in later stages of pregnancy Wright G, Patel M. BMJ 1986 Chancellor AM et al. Headache 1990 Cupini L et al. Cephalalgia 1995 Case 2 33 year old woman history of episodic migraine without aura Mean 2 attacks/month Rizatriptan, naproxen Plans for conception soon and wants to know a safe treatment plan 5

6 The Migraine Armamentarium ACUTE TREATMENTS specific treatments nonspecific treatments ADDRESS RISK FACTORS FOR PROGRESSION, COMORBIDITIES PROPHYLAXIS NONPHARMACOLOGICAL TREATMENTS FDA Category A B C D X Definition Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters). Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits. 6

7 Acute oral treatments Nonspecific therapies Acetaminophen NSAIDs Opiates Barbiturate-containing compounds Specific therapies Triptans Ergotamine compounds Dopamine antagonists / antiemetics Acetaminophen Analgesic of choice FDA category B Association with preterm birth and preeclampsia in one study Reverse causation Scialli AR et al. Reprod Toxicol 2010 NSAIDs FDA category C* 1 st trimester May inhibit implantation Cardiac abnormalities, gastroschisis (older studies) 3 rd trimester Premature ductus arteriosus closure Oligohydramnios Periventricular hemorrhage (late) Cassina M et al. Expert Opin Drug Saf

8 Opiates All cross placenta Neonatal respiratory suppression Dependence maternal and fetal Medication overuse Agent Oxycodone Codeine Hydrocodone Hydromorphone Morphine sulfate FDA Category B C C C C Little BB. Drugs and Pregnancy: A Handbook, 2006 Butalbital compounds National Birth Defects Prevention Study Association with congenital heart defects Butalbital / caffeine / APAP FDA category C Browne ML et al. Headache 2013 Triptans All FDA category C Sumatriptan exposure Any time: preterm birth Late: atonic uterus Registry: birth defect rate 4.2% (95% CI: 2.7%-6.6%) All triptans: Norwegian population registry study no associations with congenital malformations 2 nd trimester: postpartum hemorrhage aor 1.57; 95 % CI decreased platelet agreeability in severe migraine? Nezvalova-Henriksen K et al. Eur J Epidemiol

9 Ergotamine compounds Decreased uterine blood flow Increased uterine contractility FDA Category X Quebec Pregnancy Registry: DHE Complication OR (95% CI) Prematurity 4.18 ( ) Malformations 0.97 ( ) Low birth weight 1.41 ( ) Spontaneous abortions 1.97 ( ) Berard A, Kori S. Headache 2012 Dopamine antagonists / antiemetics Agent Route FDA Comments Promethazine PO, PR, IM, IV C Black box warning for IV Prochlorperazine PO, PR, IM, IV Metoclopramide PO, IM, IV B PO not generally effective Droperidol IM, IV C Black box warning for torsades Chlorpromazine PO, IM, IV C C Odansetron PO, ODT, IV C No intrinsic anti-migraine benefit Cost Adapted from Niebyl JR. NEJM 2010 Corticosteroids Orofacial clefts Association in animals, some human studies 1 st trimester exposure Dexamethasone, betamethasone Crosses placenta Corticosteroid FDA Prednisone D Dexamethasone C Methylprednisolone C Fraser FC, et al. Teratology 1995 Carmichael SL, et al. Am J Med Genet 1999 Hviid A, et al. CMAJ

10 Case 2, continued Preconception counseling: natural history of migraine in pregnancy risks and benefits of medications 1 st line APAP 1000mg 2 nd line, or if prominent nausea/vomiting prochlorperazine 25mg PR 3 rd line APAP/oxycodone 325/5mg PO Intravenous treatments Dopamine antagonists / antiemetics Metoclopramide Prochlorperazine Droperidol Chlorpromazine Dihydroergotamine (DHE-45) Corticosteroids Methylprednisolone Dexamethasone Nonsteroidal anti-inflammatory drugs Ketorolac Magnesium sulfate Anticonvulsants Valproate Levetiracetam Lidocaine 10

11 Peripheral nerve blocks Established and safe treatment for acute migraine and status migrainosus Added potential benefit of subacute benefits Blumenfeld A, et al. Headache 2013 Peripheral nerve blocks: pregnancy Small case series presented (n=4) Agent to use FDA category Lidocaine B Bupivacaine C Methylprednisolone C Triamcinolone D Robbins MS et al. Migraine Trust 2010 Blumenfeld A et al. Headache

12 Peripheral nerve blocks: pregnancy 161 AHS members surveyed in 2010 Over half perform in pregnancy Many wait until 2 nd trimester Expert consensus: use lidocaine > bupivacaine Blumenfeld A et al. Headache 2010 Blumenfeld A et al. Headache 2013 Future treatment options: devices Transcranial magnetic stimulation Safety data in depression Peripheral neurostimulation Lipton RB et al. Lancet Neurol 2010 Dodick DW et al. Headache 2010 Schoenen J et al. Neurology 2013 Case 2, continued Becomes pregnant 1 st trimester: headache frequency 1-2 days per week Treats successfully with APAP, prochlorperazine 2 nd trimester develops status migrainosus for 4 days Neurological exam normal and no red flags 12

13 Case 2, continued 3 day steroid course: prednisone 60, 40, 20mg Breaks cycle but headache returns 3 days later Peripheral nerve blocks with lidocaine performed in office definitive relief Headaches became infrequent as pregnancy advanced Had uncomplicated NSVD Acute migraine in pregnancy: Hospital Demographics 29 women, mean age 29.2 years mean gestational age 27.5 weeks (55.2% 3 rd trimester) mean of 4.3 pregnancies, 1.5 viable births Diagnoses 62.1% migraine without aura 37.9% migraine with aura 13.8% chronic migraine 31.0% status migrainosus Grossman TB, Dayal AK, Robbins MS. International Headache Congress

14 Acute migraine in pregnancy: Hospital Treatment types 86.2% oral 65.5% IV 62.1% oral and IV 10.3% peripheral nerve blocks Agents 79.3% oral APAP 58.6% IV metoclopramide 55.2% oral APAP and IV metoclopramide 34.5% oral or IV opiate 24.1% oral acetaminophen/butalbital/caffeine 6.9% IV magnesium sulfate Grossman TB, Dayal AK, Robbins MS. International Headache Congress 2013 Acute migraine in pregnancy: Population Norwegian Mother and Child Cohort Study 10.9% migraine prevalence 72.6% used anti-migraine agent in pregnancy 39.7% paracetamol 25.4% triptans (10.5% sumatriptan) 6.9% opioids (6.7% paracetamol/codeine) 4.1% ibuprofen 2.2% ergotamine Nezvalova-Henriksen K, et al. Cephalalgia

15 Acute treatment paradigm HOME OFFICE HOSPITAL APAP Peripheral nerve block (lidocaine) Metoclopramide IV Prochlorperazine IV Prochlorperazine PO, PR Promethazine PO Metoclopramide PO Lidocaine NS Ketorolac IV/IM (2 nd trimester) Peripheral nerve block (lidocaine) Magnesium sulfate IV NSAID (2 nd trimester) Corticosteroid PO (non-dexamethasone) (2 nd or 3 rd trimester) Corticosteroid IV (non-dexamethasone) (2 nd or 3 rd trimester) Ketorolac IV/IM (2 nd trimester) Lactation: acute migraine treatment Drug Hale Drugs in Pregnancy Lactation and Lactation Rating BriggsCategory Drug Hale Drugs in Pregnancy Lactation and Lactation Rating Briggs Category Simple analgesics and NSAIDs Acetaminophen L1 Compatible Aspirin L3 Potential toxicity Diclofenac L2 Probably compatible Ibuprofen L1 Compatible Indomethacin L3 Probably compatible Ketorolac L2 Probably compatible Naproxen L3 Probably compatible or L4 Migraine-specific medications Almotriptan L3 Probably compatible Eletriptan L2 Compatible Frovatriptan L3 Probably compatible Naratriptan L3 Probably compatible Rizatriptan L3 Probably compatible Sumatriptan L3 Probably compatible Zolmitriptan L3 Probably compatible Dihydroergotamine L4 Contraindicated Ergotamine L4 Contraindicated Antiemeticsand neuroleptics Metoclopramide L2 Potential toxicity Ondansetron L2 Probably compatible Prochlorperazine L3 Potential toxicity Promethazine L2 Probably compatible Chlorpromazine L3 Potential toxicity Haloperidol L2 Potential toxicity Olanzapine L2 Potential toxicity Others Butalbital L3 Potential toxicity Caffeine L2 Compatible Isometheptene L3 Probably compatible Lidocaine L2 Probably compatible Dexamethasone L3 Probably compatible Prednisone L2 Compatible Diphenhydramine L2 Probably compatible Adapted from Hutchinson S, et al. Headache

16 Tips and pearls, 1 1. Reaffirm the diagnosis in the acute headache attack that requires treatment in pregnancy. 2. Though the prognosis is favorable, women with migraine will need an acute attack treatment plan in pregnancy. 3. Acetaminophen and antiemetics are the preferred 1 st line acute agents. 4. NSAIDs, triptans, opiates could be used in selected circumstances. Tips and pearls, 2 5. Seemingly safe rescue therapies are available in pregnancy, including PO or IV corticosteroids, antiemetics, and peripheral nerve blocks. 6. Devices are likely to play a greater role in the coming years. 7. Eletriptan, APAP, and ibuprofen may be safe and effective acute agents in lactation. 16