Use of domperidone to enhance lactation: what is the evidence?
Abstract: A perception of low milk supply is often cited as a reason to stop breastfeeding, though most mothers can produce more than enough with the right support and information. Domperidone may be used to promote lactation, and there is evidence to support its use. However, the many non-pharmacological ways in which a mother may be supported should be tried before considering domperidone.

Key words Lactation, breastfeeding support, domperidone
Subject: Lactation (Physiological aspects)
Breast feeding (Physiological aspects)
Authors: Jones, Wendy
Breward, Sharon
Pub Date: 06/01/2011
Publication: Name: Community Practitioner Publisher: Ten Alps Publishing Audience: Academic Format: Magazine/Journal Subject: Health; Health care industry Copyright: COPYRIGHT 2011 Ten Alps Publishing ISSN: 1462-2815
Issue: Date: June, 2011 Source Volume: 84 Source Issue: 6
Geographic: Geographic Scope: United Kingdom Geographic Code: 4EUUK United Kingdom
Accession Number: 257513103
Full Text: Introduction

'I stopped breastfeeding because I didn't have enough milk'.

How many times do we hear this? We all know that breastfeeding is the optimal way to nurture babies in the first six months of life (DH, 2003; Kramer and Kakuma, 2002) and that breastfeeding has many advantages for both mother and baby (Hoddinott et al, 2008). At least 98% of mothers can make more than enough milk for their baby given the correct support and information (Akre, 1989). However, insufficient breastmilk supply has been cited as a reason for stopping breastfeeding by 24% of mothers within the first two weeks of their baby's life and 53% who gave up between four and six weeks after delivery (Bolling et al, 2005).

Perceptions of low milk supply are often influenced by a lack of confidence in the mother, lack of support by family and friends and a general lack of understanding of the physiology of lactation, the importance of good attachment and frequent feeding. Symptoms ranging from colic, crying, frequent feeding and breasts that feel less full as the supply and demand mechanism of production settles (at around three to four weeks) may all be interpreted as lack of breastmilk quality or quantity (Amir, 2006).

How milk production begins

The production of a copious milk supply--lactogenesis II--begins in response to the fall in progesterone levels after the birth together with other regulatory hormones. Prolactin is the hormone that controls milk synthesis in the early weeks, when there is endocrine control of lactation. Prolactin release is inhibited by dopamine, and drugs such as bromocriptine and cabergoline (which increase dopamine levels) have been used to inhibit lactation. Drugs that reduce dopamine levels (dopamine antagonists) such as metoclopramide and domperidone (UKMi, 2010) are assumed to increase prolactin synthesis (Cox et al, 1996) without affecting milk composition (Campbell-Yeo et al, 2010).

In recent years, it has anecdotally become more common to recommend that a mother with a poor milk supply (whether perceived or actual) should take domperidone to increase her milk production by enhancing her prolactin levels.

Evidence for use of domperidone

Apart from anecdotal evidence from breastfeeding specialists (Newman and Kernerman, 2008), the evidence for the effectiveness of domperidone for promoting lactation relies on five small studies, all of which could be criticised (Anderson and Valdes, 2007). That is not to say that this drug is not effective, but that there is an absence of published evidence. This lack of evidence may mean that some GPs may be reluctant to prescribe the treatment. Although not licensed for this purpose, domperidone has been used to promote milk supply for many years (Gabay, 2002). No studies have looked at the effectiveness of domperidone being given more than two weeks after delivery to enhance lactation. However, some evidence supports its use in mothers who have delivered pre-term and who maintain their lactation over a prolonged period by expression only (ABM Protocol Committee, 2011).

What is absolutely clear is that domperidone should never be used as a substitute for, or as an 'easy' alternative to, good, effective breastfeeding support and encouragement.

Evidence for increased milk supply

Da Silva et al (2001) studied 20 women in a double-blind, placebo-controlled study. They showed a steady increase in milk production over placebo in mothers treated with domperidone 10mg three times a day. In the trial, mothers received counselling support and were double pumping. The increase in production that was achieved fell once the drug was stopped after seven days. The babies in the study were all in neonatal intensive care and the mothers were only expressing for feeds to be given via naso-gastric tube. The increase in milk volume began 48 hours after the drug was initiated and continued to the end of the trial. The study was stopped after seven days when most mothers began some level of direct breastfeeding, at which point it became impractical to measure breastmilk volume.

Only one study looked at mothers who had not delivered prematurely (Petraglia et al, 1985). One month after the study began all treated women had adequate milk production, but none of those who had not been treated with domperidone had achieved an increase in milk supply above that at the beginning of the trial. However, the mothers were only breastfeeding six or seven times a day--not generally be considered optimal in stimulating an adequate milk supply.

Is increased milk volume dose dependant?

Wan et al (2008) studied seven mothers who had delivered pre-term in a double-blind, randomised cross-over study. They used two dose regimes--10mg or 20mg three times a day. One mother taking the 20mg dose withdrew early because of severe abdominal cramps. Two others failed to respond to either dose. In four mothers, there was a significant increase in prolactin level and milk volume, with a greater response at the higher dose in three of these women. Side effects noted included abdominal cramping, constipation, dry mouth, depressed mood and headache, which were more apparent with the higher dose.

Wan et al (2008) concluded that if there is no response at a 10mg dose, there is no point in further increasing the dose. This is at variance to the anecdotal advice of Newman and Kernerman (2008), but which has not been subjected to published clinical trials.

Availability over the counter

It is possible to purchase domperidone over the counter in pharmacies under the brand name of Motilium[R]10, but because of the license application (to encourage gastric emptying) pharmacists are within their rights to refuse to sell the drug. Healthcare practitioners who recommend that mothers purchase the drug need to be aware that they are taking professional responsibility and legal liability for that action.

High doses linked with cardiac deaths

In 2004, the US Food and Drug Authority issued a warning against the use of domperidone (FDA, 2009). This followed the death of patients receiving high-dose, intravenous domperidone along with chemotherapy. All patients developed sudden-onset cardiac arrhythmias and those whose levels were measured had low potassium level (da Silva and Knoppert, 2004). There appears to be no relevance to the use of 30mg to 60mg daily oral domperidone, though use in patients with prolonged QT intervals is not recommended and when used as a galactogogue this need for caution extends to the baby.

Passage into breastmilk

Domperidone is preferred to metoclopramide because it poorly penetrates the blood-brain barrier and does not produce parkinsonian-like adverse effects or increase the risk of depression (Hale, 2011). The amount passing through breastmilk is significantly less than the dose prescribed directly to babies to control symptoms of reflux.

Weaning from domperidone

There are no studies that provide an evidence base on how long to continue domperidone in the case of inadequate lactation (ABM Protocol Committee, 2011). Anecdotally, some women feel that their supply cannot be maintained without the drug, while some can reduce the dose but not stop altogether. It is possible that domperidone is acting as a placebo to boost their confidence--we do not know and should admit the limitations of the research. Similarly, although gradual weaning from the drug has become standard, there is little evidence apart from the reports and experience of breastfeeding specialists.

Supporting mothers in practice

Two case studies have been provided to consider situations in which domperidone may or may not be appropriate (see Box 1).

Practical points in supporting a mother whose milk supply is perceived to be poor have been included (see Box 2), as has an example letter to a GP requesting a prescription for domperidone (see Box 3).

Conclusion

Domperidone is not a 'magic wand' to increase the milk supply of a mother struggling to breastfeed, and it should not be used unless accompanied by regular and effective drainage of milk from the breast. It may be a valuable tool to support mothers who have delivered pre-term and who maintain their lactation over a prolonged period by expression, or mothers who have had a poor start to breastfeeding who need to re-lactate to some extent. It is also useful for women with identified hormonal difficulties that could affect milk supply, eg hypothyroid and polycystic ovaries.

Domperidone is a relatively safe drug, but it would be unprofessional to expose a mother and baby to a drug they do not need, and all measures to improve breastfeeding management should be made and documented prior to a decision to advocate its use.

KEY POINTS

* Perceived poor milk supply can be an important factor in a mother's decision to stop breastfeeding, though it may actually be based on a lack of support or misconceptions

* The effectiveness of domperidone in promoting lactation is not backed by strong evidence, but some evidence supports its safe use when monitored and in low doses

* Domperidone can be useful in enhancing lactation, but it should be only be considered after non-pharmacological support has been found to be unsuccessful

References

Academy of Breastfeeding Medicine (ABM) Protocol Committee. (2011) Use of galactogogues in initiating or augmenting the rate of maternal milk secretion (First Revision January 2011). Breastfeed Med 6(1): 41-9.

Akre J. (1989) Infant feeding. The physiological basis. Bull World Health Organ 67 Suppl: 1-108.

Amir LH. (2006) Breastfeeding--managing 'supply' difficulties. Aust Fam Physician 35(9): 686-9.

Anderson PO, Valdes V. (2007) A critical review of pharmaceutical galactogogues. Breastfeed Mid 2(4): 229-42.

Bolling K, Grant C, Hamlyn B et al. (2007) Infant feeding survey 2005. London: NHS Information Centre.

Campbell-Yeo ML, Allen AC, Joseph KS et al. (2010) Effect of domperidone on the composition of preterm human breast milk. Pediatrics 125(1): e107-114.

Cox DB, Owens RA, Hartmann PE. (1996) Blood and milk prolactin and the rate of milk synthesis in women. Exp Physiol 81(6): 1007-20.

da Silva OP, Knoppert DC. (2004) Domperidone for lactating women. CMAJ 171(7): 725.

da Silva OP, Knoppert DC, Angelini MM et al. (2001) Effect of domperidone on milk production in mothers of premature newborns: a randomized, double-blind, placebo-controlled trial. CMAJ 164(1): 17-21.

Department of Health (DH). (2003) Infant feeding recommendation. London: DH.

Food and Drug Administration (FDA). (2009) Domperidone. See: www.fda.gov/Safety/ MedWatch/Safetylnformation/SafetyAlertsfor HumanMedicalProducts/ucm154914.htm (accessed 4 May 2011).

Gabay MP. (2002) Galactogogues: medications that induce lactation. J Hum Lact 18(3): 274-9.

Hale T. (2010) Medications and mothers' milk (13th edition). Amarillo, Texas: Hale.

Hoddinott P, Tappin D, Wright C. (2008) Breast feeding. BMJ 336(7649): 881.

Kramer MS, Kakuma R. (2002) Optimal duration of exclusive breastfeeding. Cochrane Database Syst Rev (1): CD003517.

Newman J, Kernerman E. (2008) Domperidone, getting started. See: www.drjacknewman.com/ help/Domperidone%20Getting%20Started.asp (accessed 4 May 2011).

Petraglia F, De Leo V, Sardelli S et al. (1985) Domperidone in defective and insufficient lactation. Eur J Obstet Gynecol Reprod Biol 19(5): 281-7.

UK Medicines Information (UKMi). (2010) Drug treatment of inadequate lactation. See: www.nelm.nhs.uk/en/NeLM-Area/Evidence/ Medicines-Q-A/Drug-treatment-ofinadequate-lactation (accessed 4 May 2011).

Wan EW, Davey K, Page-Sharp M et al. (2008) Dose-effect study of domperidone as a galactagogue in preterm mothers with insufficient milk supply, and its transfer into milk. Br J Clin Pharmacol 66(2): 283-9.

Wendy Jones PhD, MRPharmS Drugs in Breastmilk Helpline pharmacist and registered supporter, Breastfeeding Network

Sharon Breward MBE, QN, BFC(ABM), IBCLC, RHV, RM, RGN Infant feeding co-ordinator/specialist (West), Betsi Cadwaladr University Health Board

Correspondence: wendyjones28@aol.com

No potential competing interests declared.
Box 1. Two case studies

Breastfeeding clinic: low prolactin levels

Angela was a primigravida who attended breastfeeding clinic at six
weeks with a baby with very slow weight gain. Health visitor had
checked and adjusted attachment, but the history taken by the
infant feeding specialist revealed that Angela had already started
her menstrual period, had a history of low thyroid hormone levels
and a cyst on her ovary--all possibly indicative or contributory
factors to low prolactin levels.

A feeding plan was initiated that included 'switch feeding' with
breast compression to increase stimulation to nipple and promote
breast drainage. Angela was also asked to express with an electric
pump after as many feeds as she could manage and to use the
'hands-on' expressing technique to promote milk drainage from the
breast, ie expressing with breast compression. The GP was
approached for a prescription of domperidone of 10mg three times a
day. Over a period of a month, Angela's milk supply increased and
the baby gained weight normally. As the supply stabilised the
domperidone was reduced and eventually stopped at 12 weeks, with
some expressing maintained to promote supply.

Helpline: over-the-counter domperidone

In a call to the Drugs in Breastmilk Helpline, a mother said she
had an 18-month old baby and had recently returned to work where
she was expressing. She had noticed a drop in her milk supply and
had commenced taking 30mg domperidone three times a day, which she
was buying over the counter. All GPs in her practice had refused to
prescribe domperidone for her. Her request was that the helpline
pharmacist should contact the GPs to support her request, as she
felt it had doubled the volume of milk that she was able to
express. The request was refused and the mother counselled on
possible options for other ways to maintain her supply. The dose
that she had been taking was also discussed, since it is in excess
of normal levels and may have resulted from confusion with a
suggestion of 30mg a day.

Box 2. Supporting a mother with perceived poor milk supply

* Encourage and support her breastfeeding. Listen empathetically to
any concerns she may have or that have been raised by others who
are less supportive of breastfeeding


* Ascertain why she feels she has a low milk supply and address any
misconceptions, eg reinforce the normality of babies feeding eight
to 12 times in 24 hours. You may need to discourage the routine use
of dummies if the baby is not feeding frequently enough. Reinforce
normality of baby feeding patterns, eg 'cluster feeding' in the
evenings

* If she feels the baby is unsettled and that this indicates she
has a low milk supply, encourage periods of calming skin-to-skin
contact or encourage use of a sling to settle the baby. She may
also need guidance on feeding the baby lying down at night in order
to cope with night feeds

* Take a full breastfeeding history. A poor start to breastfeeding
can affect future milk supply if the baby has not been
breastfeeding often enough or if the mother was not expressing
often enough

* Observe a complete breastfeed. Check for effective attachment and
ensure that both breasts are offered at each feed, with the baby
coming off the first breast spontaneously having emptied it

* Check that the baby's urine and stool output are normal for their
age

* Check the baby's weight gain progress

* Check that there are no hormonal reasons why milk supply might be
low, eg polycystic ovaries, thyroid problems or retained placental
fragments

* Question if any medications--prescribed or purchased--are being
taken

* If the mother smokes encourage her to stop, since nicotine is
thought to reduce prolactin levels

* Consider whether there is a need to refer to an infant feeding
specialist or skilled breastfeeding supporter

* Consider referring to a GP for prescription of domperidone,
having provided and checked that all non-pharmacological support
has not been successful


Box 3. Suggested letter: domperidone prescription to improve
lactation

Dear Dr

Re: [details of mother and baby]

has been struggling to maintain her breastmilk supply. I have
supported her with additional breastfeeding management techniques,
including increased frequency of feeding with optimal attachment
and additional expressing.

Although we know that at least 98% of women can establish and
maintain a normal milk supply, there is evidence that this is more
difficult when mothers and babies are separated after delivery, eg
premature delivery, suffering from hormonal problems or when good
breastfeeding is not achieved initially.

Domperidone is a dopamine antagonist and has been shown to
significantly increase prolactin levels in most (although possibly
not all) lactating mothers. It is not licensed as a galactogogue,
but is considered to be a safe and effective drug to enhance
breastmilk supply in specific circumstances.

Studies have shown that the levels passing through breastmilk are
very small because of extensive first-pass metabolism and poor
bio-availability.

Mothers and babies who have evidence of cardiac problems or who are
receiving any medication that may prolong the QT interval should
not receive the drug. I would be grateful if you could check
whether there are any pre-existing contra-indications to the use of
domperidone in this case.

It would be most helpful if you could assist this mother to improve
her milk supply by providing the recommended treatment. The
suggested prescription is domperidone 10mg three times a day for 14
days, after which use will be re-assessed but may need to be
continued.

I will continue to support the mother and monitor the situation
until the problem has been resolved. If you wish to discuss this
further I can be contacted on

Yours sincerely,

A Health Visitor
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