A novel study on transdermal clonidine treatment of hyperemesisgravidarum

O Stephanssona,b

aClinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, SwedenbDepartment of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden

Linked article: This article is a mini commentary on Maina A et al., pp. 1556–62 in this issue. To view this article visit

http://dx.doi.org/10.1111/1471-0528.12757.

Nausea and vomiting are common

during pregnancy, affecting more than

50% of pregnant women. Among

these, 10–15% receive drug treatment

(Pasternak et al., N Engl J Med

2013;368:814–23). Hyperemesis grav-

idarum (HG) is defined as severe

nausea and persistent vomiting, weight

loss, ketonuria, electrolyte abnor-

malities and dehydration, and affect

approximately 1% of pregnancies.

Women with HG should be referred

to a hospital and require intravenous

hydration with multivitamins including

thiamine. Pharmacologic treatment

for HG includes: Vitamin B6, antihis-

tamines, phenothiazines, dopamine

agonists, 5-hydroxytryptamine3-receptor

antagonists, glucocorticoids or a

combination of these agents. The clinical

challenge is that these drugs may have

a limited effect on HG, and there is a

need for new treatment strategies.

In this issue of BJOG, Maina et al.

report the findings on a pilot trial

using transdermal clonidine in the

treatment for HG. Twelve patients with

HG were randomly treated with and

without clonidine for two consecutive

periods of 5 days in a randomised, dou-

ble-blind, placebo-controlled cross-

over design (RCT) study (Maina et al.,

BJOG 2014; DOI: 10.1111/1471-0528.

12757). The study found that transder-

mal clonidine treatment leads to

improvement in symptoms, with less

nausea and vomiting and reduced

morning ketonuria as well as a reduc-

tion of other antiemetic drug doses

and a smaller requirement of intrave-

nous rehydration. The study reports a

novel treatment opportunity for

women with severe nausea and vomit-

ing during pregnancy. The transder-

mal route of drug administration is an

advantage especially in patients treated

in antenatal outpatient clinics without

the need for intravenous administra-

tion. The main concern about the

study is regarding the safety in off-la-

bel use of clonidine for treatment of

HG. It is obvious that a study on only

12 patients cannot rule out risk of con-

genital malformation or other adverse

pregnancy outcomes. Clonidine has

been used for treatment of hyperten-

sive disease during pregnancy and is

categorized as category C by the FDA

(should be used during pregnancy

only if clearly needed). It crosses the

placenta but no established teratogenic

effect has so far been reported. How-

ever, safety data on use of clonidine

are limited for the first trimester of

pregnancy, which is a concern as we

therefore lack data on the most

important period for fetal organogen-

esis. Furthermore, because the low-

ered blood pressure with clonidine it

is not known how this will affect nor-

motensive pregnant women and their

fetuses.

A much larger RCT will have to

be carried out to address the safety

concerns with a novel treatment

for HG. Still, it can be difficult to

extrapolate safety data from trials

designed to study efficacy because of

power limitations. Furthermore, some

adverse outcomes such as preterm

delivery and growth retardation may

be related to HG itself and not drug

use, whereas this would not apply

for congenital malformation (Boelig

et al., Cochrane Database Syst Rev

2013;6:CD010607). In conclusion,

treatment with transdermal clonidine

may be an opportunity for women

with HG but more data on safety are

required.

Disclosure of interestsNone declared.&

1563ª 2014 Royal College of Obstetricians and Gynaecologists

Transdermal clonidine in severe hyperemesis gravidarum