Dopaminergic Therapy for the Treatment of Restless Legs Syndrome During Pregnancy
Abstract & Commentary
By Claire Henchcliffe, MD, PhD
Associate Professor of Neurology and Neuroscience, Weill Cornell Medical College
Dr. Henchcliffe reports she is on the speakers bureau and advisory board for Allergan and Teva; speakers bureau for Boehringer-Ingelheim, GlaxoSmithKline, and Novartis; advisory board for Merz; and is a consultant for Gerson Lehman Group and Guidepoint Global.
Synopsis:This small, prospective case series evaluated pregnancy outcomes of women who took levodopa, pramipexole, ropinirole, and rotigotine for treatment of restless legs syndrome during pregnancy. No major birth defects were identified with any of the treatments.
Source: Dostal M, et al. Pregnancy outcome following use of levodopa, pramipexole, ropinerole, and rotigotine for restless legs syndrome during pregnancy: A case series. Eur J Neurol 2013;20:1241-1246.
The primary purpose of this study was to assess the safety of dopamine agonist exposure during pregnancy, in particular as it relates to treatment of restless legs syndrome (RLS). Data were collected by the Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy between 1998 and 2011 via surveys of women identified through direct or physician contact. In cases of use of levodopa, pramipexole, ropinirole, and rotigotine during pregnancy, questionnaire or phone interview at time of contact and follow-up data at 8 weeks after the expected delivery date were obtained. The primary outcomes were rates of pregnancy loss and major birth defects (structural abnormalities of medical, surgical, or cosmetic relevance). Sixty-seven relevant exposures were evaluated, with 59 women completing follow-up, of whom 42 were exposed to levodopa (four in combination with dopamine agonist), 15 to pramipexole, four to ropinirole, and two to rotigotine. Medication was mostly for RLS (n = 32), but also Parkinson’s disease (n = 3), dopa-responsive dystonia (n = 4), dystonia (n = 2), and one case of a suicide attempt with extremely high levodopa exposure. All except three patients were exposed during at least the first trimester. The median daily dose of levodopa ranged from 100-1500 mg, and pramipexole from 0.8-1.0 mg daily (ranges were not provided for ropinirole and rotigotine). The major finding was that no major birth defects were reported in any group. Three of 42 levodopa-exposed pregnancies demonstrated minor abnormalities, comprising patent foramen ovale/patent ductus arteriosus, nose deformity, and clubfoot.
This paper addresses an important and difficult area of neurology — the risk of medical treatment during pregnancy. Insufficient data currently exist on the use of dopamine agonists during pregnancy to support well-informed treatment decisions for RLS. However, the prevalence of RLS during pregnancy is estimated at 12-26%, and symptoms may worsen as the pregnancy progresses, with significant impact on well being. There have been some data collected on the use of levodopa and the dopamine agonists pramipexole, rotigotine, and ropinirole during pregnancy in Parkinson’s disease and dopa-responsive dystonia, but not in the more common condition of RLS. Therefore, most physicians recommend that these drugs be stopped during pregnancy in women with RLS. It is important to note that this case series did not demonstrate an increased risk of major or minor birth defects, premature birth, or fetal growth restriction in patients receiving levodopa or pramipexole. Unfortunately, although these data do add to our experience, the number of cases is too small to establish the safety of these drugs during pregnancy. Only 67 cases were identified during the 13 years of enrollment into the database. Other limitations include the reliance of data acquisition on voluntary reporting and the acquisition of follow-up data from physicians and patients. There is more published experience of cabergoline exposure in pregnancy, mostly during the first trimester, due to its use in treatment of hyperprolactinemia. However, in the United States, cabergoline is not approved for RLS, and of the three agonists that are approved (pramipexole, ropinirole, and rotigotine) only 21 such cases are included in this study. Gabapentin is also FDA-approved for moderate-to-severe RLS in the United States, but this database does not include relevant data. Finally, any discussion of iron deficiency is lacking, and in individuals with RLS this possibility needs to be tested and treated. For neurologists, this study provides modest data regarding the use of levodopa in RLS, but the authors do not recommend use of pramipexole, ropinirole, and rotigotine during pregnancy due to scarce information. This study should prompt further systematic data collection, but it does provide a modest platform for reassuring those inadvertently exposed to these medications during pregnancy.
