Correspondence: Migraine in breast feeding; Gluten-free diets

Response in brief: Neither oxycodone nor ondansetron are recommended for the treatment of migraine symptoms in anyone. Oxycodone is present in breast milk and associated with CNS depression in breast fed infants, therefore use should be avoided. Ondansetron should also be avoided during breast feeding as limited evidence suggests it is present in breast milk. Migraine prophylaxis such as a beta-blocker, tricyclic antidepressant or sodium valproate may be appropriate for this patient. If migraine relief is required, options for a woman who is breast feeding include cautious use of a NSAID, prochlorperazine or triptan (breast milk discarded 12-24 hours after dose) as required.

Migraine treatment can be complicated and requires a systematic approach to the management of predisposing factors, trigger identification and avoidance, acute symptom relief and prophylaxis.

A number of factors may increase migraine frequency in women who are breast feeding, including dehydration (increased fluid intake is essential during breast feeding), change in routine (e.g. altered sleep pattern), reduced sleep, missed meals, increased stress and postnatal depression. Although there may not always be a clear association between migraines and lifestyle factors and triggers, changes can be made where practical. A plan may need to be put in place for care of the infant (e.g. by partner, family member) if the migraines (or the sedative effects of the medicine used in treatment) are severe enough to make the mother unable to continue her daily activities. The woman may wish to consider expressing and freezing milk (e.g. at the conclusion of a normal breast feed) so that a supply is available if she cannot feed during an acute attack or if there are concerns about medicines being present in the breast milk. Taking a dose of medicine at the completion of a breast feed may allow time for metabolism and excretion of at least some of the medicine prior to the next breast feed. Expressing and discarding milk post-dose may be another option for some women. A woman with recurrent severe migraine may benefit from prophylaxis rather than frequent use of acute treatments.

Acute symptom relief usually follows a four-tiered approach, with failure of treatment at one tier on three occasions being grounds to move onto the next tier:¹

• Tier one - simple analgesic (e.g. aspirin, NSAIDs) +/- antiemetic (e.g. metoclopramide, prochlorperazine)
• Tier two - rectal analgesic (e.g. diclofenac) +/- antiemetic (e.g. metoclopramide, prochlorperazine)
• Tier three - specific anti-migraine medicines (e.g. sumitriptan, rizatriptan)
• Tier four - combination treatment (e.g. sumatriptan with a NSAID)

However, not all of these medicines are appropriate for women who are breast feeding:

• Aspirin should be avoided in women who are breast feeding due to the possible risk of Reye’s syndrome in the infant. In addition, regular use of aspirin may impair platelet function in the infant if neonatal vitamin K stores are low.²
• NSAIDs should be used with caution, but the amount of diclofenac, ibuprofen and naproxen in breast milk is too small to be considered harmful.²
• There is limited information available on the effects of antiemetics on a breast fed infant. Phenothiazine derivatives (e.g. prochlorperazine) are sometimes used for short-term treatment.² A small amount of metoclopramide is present in breast milk, so it is usually avoided, however, this medicine has been used safely in women who are breast feeding to increase milk production.^2,3
• Triptans such as sumatriptan and rizatriptan may be used in a woman who is breast feeding, however, animal studies have shown that small amounts are excreted in the breast milk. Although the amount is probably too small to be harmful, it is suggested that breast milk is expressed and discarded for 12-24 hours after the dose of triptan.^2,4

Consider migraine prophylaxis

Regular use of acute migraine treatments for more than two days per week carries significant risk of initiating or escalating medication overuse headache and should be avoided. Regular requirement of acute migraine treatment for more than one day per week is an indication to evaluate how the medicine is being used, to review the diagnosis and consider migraine prophylaxis medicine.

This patient may be a good candidate for migraine prophylaxis. In general, prophylactic treatments are started at low doses and gradually increased to avoid adverse effects. Once a full dose is achieved, the medicine should be trialled for six to eight weeks. Medicines that are safe to use for migraine prophylaxis in a woman who is breast feeding include beta blockers, sodium valproate and, with caution, tricyclic antidepressants (excluding doxepin).^1,2 If sodium valproate is prescribed, ensure the woman is using effective contraception due the increased risk of congenital malformations and developmental delay with this medicine.

Opiates and ondansetron are not recommended for migraine or while breast feeding

All opiates (including codeine) are best avoided during acute migraine as they have limited benefit, can be associated with medication overuse headache and have potential for addiction.^1,5

The use of opioid medicines, particularly codeine and oxycodone, has been discouraged in women who are breast feeding due to reports of infant fatalities.^6,7 Oxycodone is present, and can accumulate, in breast milk.² A recent retrospective cohort study has reported that symptoms of central nervous system (CNS) depression were present in 20% of infants who were breast fed by mothers who took oxycodone.⁸ Symptoms of CNS depression in an infant include increased sleepiness (more than usual), not waking for feeds, difficulty breast feeding, breathing difficulties and floppiness.³

Much of the evidence regarding the safety of opioids and lactation looks at the use of these medicines for post-partum analgesia, rather than ongoing use for other indications. Although intermittent use of an opioid may be relatively safe, repeated doses should be used with caution.⁹ If oxycodone is used, the infant should be monitored for drowsiness, adequate weight gain, and achievement of developmental milestones, particularly if the medicine is taken on an ongoing basis.

Ondansetron is not indicated for the treatment of nausea and vomiting in acute migraine. In addition ondansetron should be avoided during breast feeding as evidence from animal studies suggests it is present in milk.² Although safety data is limited and some references suggest that one or two doses post-partum may be appropriate, there is no clear guidance regarding repeated use.⁹

References:

1. British Association for the Study of Headache (BASH). Guidelines for all healthcare professionals in the diagnosis and management of migraine, tension-type headache, cluster headache, medication-overuse headache. BASH, 2010. Available from: www.bash.org.uk (Accessed Jan, 2012).
2. British National Formulary (BNF). BNF 62. London: BMJ Publishing Group and Royal Pharmaceutical Society of Great Britain, 2011.
3. United States National library of Medicine. Drugs and lactation database (LactMed). Available from: http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT (Accessed Jan, 2012).
4. Clinical Knowledge Summaries (CKS). Migraine - Management. CKS, 2010. Available from: www.cks.nhs.uk (Accessed Jan, 2012).
5. Marcus D. Managing headache during pregnancy and lactation. Expert Rev Neurotherapeutics 2008;8(3):385-95.
6. Koren G, Cairns J, Chitayat D, et al. Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother. Lancet 2006;368:704.
7. Levine B, Moore K, Aronica-Pollak P, et al. Oxycodone intoxication in an infant: accidental or intentional exposure? J Forensic Sci 2004;49:1358-60.
8. Lam J, Kelly L, Ciszkowski C, et al. Central nervous system depression of neonates breastfed by mothers receiving oxycodone for postpartum analgesia. J Pediatr 2011;(In press).
9. Australian Medicines Handbook (AMH). Adelaide; AMH Pty Ltd, 2011.

A gluten-free diet should not be commenced without confirmation of a diagnosis of coeliac disease because serological testing (immunoglobulin A anti-tissue transglutaminase - IgA-tTG) for coeliac disease requires the patient to have been eating gluten every day for a minimum of six weeks before testing.¹ In addition, if serology is positive, gluten should remain in the diet until after a small intestinal biopsy has been performed, as despite debate in the current literature, biopsy remains the gold standard for diagnosis.^2,3

No test is 100% sensitive or specific, but IgA-tTG has high sensitivity (80-90%) and specificity (>95%) for coeliac disease, and is the preferred initial test.^2,4 New Zealand laboratories routinely test total serum IgA whenever an IgA-tTG test is requested and use an IgA-tTG test if an IgA deficiency is detected. Intestinal biopsy is important to determine the degree of inflammation and villous atrophy in the gut as well as to exclude other small bowel disease. Referral for biopsy is also recommended if there is a strong clinical suspicion of coeliac disease but the patient has a negative IgA-tTG result.^1,5 This is often the case in young children (aged less than five or six years), where IgA-tTG antibody testing may be less reliable.⁴

A delayed diagnosis or undiagnosed coeliac disease (even in patients with latent disease) can result in:^1,4

• Ongoing symptoms, e.g. diarrhoea, abdominal pain, bloating
• Adverse long-term complications, including osteoporosis, increased fracture risk, unfavourable pregnancy outcomes and an increased risk of malignancy, e.g. small bowel cancer, lymphoma
• Growth failure, delayed puberty and dental enamel defects in children

Strict adherence to a gluten-free diet is the only treatment for coeliac disease and is required for relief of symptoms, reversal of the small intestinal abnormalities and to reduce the risk of long-term complications.^3,5 If the decision is made to eat a gluten-free diet without testing and biopsy, the patient will lack an accurate diagnosis and will not know if they need to strictly adhere to a gluten-free diet for life.

Maintaining a gluten-free diet can have a significant effect on quality of life for the patient and their family.^4,6 Gluten is estimated to be in 70% of manufactured food products, e.g. as a component of thickeners, preservatives and colourings.⁷ If one person in a household is eating a gluten-free diet it often means that the whole family has to alter their diet. Strict adherence to a gluten-free diet requires separate handling, preparation and storage of foods. Although gluten-free food choices are generally much easier to access now, there is still considerable variation in availability throughout New Zealand. In some situations, e.g. eating out and travelling, food choices may still be extremely limited. Gluten-free foods also tend to be more expensive. A person who does not actually have coeliac disease therefore faces unnecessary hassles and extra financial costs when this is not clinically necessary. There is no evidence that a gluten-free diet is beneficial for people who do not have coeliac disease.⁴

In addition, the exclusion of many staple foods made from wheat, rye and barley which are important dietary sources of carbohydrate, energy, protein, iron, calcium and B vitamins means that a gluten-free diet may not be as nutritious as a gluten-containing diet, if nutritionally adequate alternatives are not included.⁸ Advice from a dietitian is usually required at the time of diagnosis.

Previous articles relating to coeliac disease and gluten free foods include:

• “Dietary advice for people with coeliac disease”, BPJ 15 (Aug, 2008); update BPJ Special Edition (May, 2011)
• “The investigation of coeliac disease: a follow up”, BPJ 12 (Apr, 2008)
• “Coeliac disease”, Best Tests (Mar, 2010)
• “Coeliac disease”, BPJ 9 (Oct, 2007)

References

1. National Institute for Health and Clinical Excellence (NICE). Coeliac Disease: Recognition and assessment of coeliac disease. NICE Clinical Guidelines, No. 86. NICE, 2009. Available from: www.nice.org.uk (Accessed Jan, 2012).
2. Evans K, Sanders D. What is the use of biopsy and antibodies in coeliac disease diagnosis? J Intern Med 2011;269:572-81.
3. Ludvigsson J, Green P. Clinical management of coeliac disease. J Intern Med 2011;269:560-71.
4. Steele R. Diagnosis and management of coeliac disease in children. Postgrad Med J 2011;87:19-25.
5. Walker M, Murray J. An update in the diagnosis of coeliac disease. Histopathology 2011;59:166-79.
6. Tanpowpong P, Ingham T, Lampshire P, et al. Coeliac disease and gluten avoidance in New Zealand children. Arch Dis Child 2011;[epub ahead of print]
7. Garcia-Manzanares A, Lucendo A. Nutritional and dietary aspects of celiac disease. Nutr Clin Pract 2011;26:163-73.
8. Kinsey L, Burden S, Bannerman E. A dietary survey to determine if patients with coeliac disease are meeting current healthy eating guidelines and how their diet compares to that of the British general population. Eur J Clin Nutr 2008;62:1333-42.