For women with mild to moderate attention-deficit/hyperactivity disorder (ADHD) symptoms, we typically recommend discontinuing medication and switching to a nonpharmacologic intervention.  Although these women might experience some decrease in their level of functioning, they are generally able to forgo pharmacologic treatment and do quite well. However, there are other women with more severe symptoms which interfere significantly with their daily functioning and may potentially affect their pregnancy.  In these women, we may consider maintaining pharmacologic treatment.

Methylphenidate, the active ingredient in Ritalin and Concerta, is commonly used to treat ADHD. We now have several reports assessing its reproductive safety.  

The most recent study is a prospective, multicenter observational study in which pregnant women who contacted one of four participating Teratology Information Services (in Jerusalem, Berlin, Newcastle upon Tyne, and Toronto) were recruited between 1996 and 2013.  This cohort included women taking methylphenidate during pregnancy (n=382) and a comparison group of age-matched women who contacted the service for information regarding nonteratogenic exposures.  25.4% of the women in the methylphenidate group were also taking other psychotropic medications.

The overall rate of major congenital anomalies was similar between the two groups: 10/309 or 3.2% in the methylphenidate group vs. 13/358 or 3.6% in the non-exposed group. The rates of major congenital anomalies and cardiovascular anomalies were similar in the two groups after exclusing of genetic or cytogenetic anomalies and restricting methylphenidate exposure to the period of organogenesis (weeks 4–13 after the last menstrual period).

The exposed and non-exposed groups did differ with regard to rates of miscarriage and elective termination of pregnancy, both of which were more common in the methylphenidate group. Significant predictors for miscarriage were methylphenidate exposure (adjusted hazard ratio [HR] = 1.98; 95% CI, 1.23–3.20; P = .005) and history of miscarriage (adjusted HR = 1.35; 95% CI, 1.18–1.55; P < .001).  The authors note that the higher rate of miscarriages observed in the methylphenidate group was associated with a history of miscarriages and might also be related to the mother’s underlying disorder or indication.  

These findings are consistent with previous reports which demonstrated no increase in risk of major malformations in children with first trimester exposed to methylphenidate (reviewed here).  While these reports are reassuring with regard to the risk of malformations, these studies did not include information on other outcomes, such as gestational age or birth weight.  In a small study, methylphenidate use during pregnancy was associated with increased risk of premature birth, growth retardation and neonatal withdrawal symptoms (Debooy 1993). Unfortunately, this study included only 38 participants and was further confounded by the fact that these women were abusing methylphenidate and may have also used nicotine, alcohol and other drugs during their pregnancy.

The available data for methylphenidate suggest no increase in the risk of malformation when used at therapeutic doses; however, further study is required to determine the risk of other adverse outcomes, including preterm birth and low birthweight, in women taking therapeutic doses of stimulants.

Ruta Nonacs, MD PhD

Methylphenidate in pregnancy: a multicenter, prospective, comparative, observational study.

Diav-Citrin O, Shechtman S, Arnon J, Wajnberg R, Borisch C, Beck E, Richardson JL, Bozzo P, Nulman I, Ornoy A.

J Clin Psychiatry. 2016 May 24. [Epub ahead of print]

 

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