Abstract
Dexamphetamine, a central nervous system stimulant, is increasingly prescribed to women of childbearing age, yet data on its safety in pregnancy, particularly for narcolepsy, remains limited. This case series examined pregnancy outcomes in 10 women with narcolepsy or idiopathic hypersomnolence at the Royal Brisbane and Women's Hospital who were prescribed dexamphetamine during pregnancy. Six women continued therapy throughout pregnancy. Apart from one case complicated by congenital CMV infection, all pregnancies progressed to the late third trimester with favourable neonatal outcomes. No cases of pre-eclampsia were observed; one woman developed gestational hypertension. All neonates had normal Apgar scores, with the exception of two where the Apgars were not recorded. However, no neonates required additional ventilatory support. Our findings suggest that therapeutic dexamphetamine use for narcolepsy may not be associated with adverse obstetric or neonatal outcomes. Individualised counselling is essential to balance maternal functional needs against potential pregnancy risks.
Introduction
Dexamphetamine is a central nervous system stimulant prescribed for the management of Attention Deficit Hyperactivity Disorder (ADHD) and narcolepsy. Adult ADHD diagnoses have increased substantially in recent years, with psychostimulant prescriptions rising 1.2% annually since 2015. 1 Currently 0.5 −1.3% of pregnancies are exposed to psychostimulants, compared with <0.1% in 1998.2,3
Women are typically advised to discontinue dexamphetamine during pregnancy, which can severely impact those with narcolepsy by limiting their functional capacity in pregnancy, often preventing them from working, driving, or caring for children. Dexamphetamine use during pregnancy has been associated with miscarriage, intrauterine growth restriction, pre-eclampsia, and preterm delivery.2–6 However, existing studies focus on patients prescribed psychostimulants for treatment of ADHD, as well as recreational amphetamine users and often include patients with comorbid mental health disorders and polysubstance abuse. Research specifically examining therapeutic dexamphetamine use in pregnant women with narcolepsy is notably lacking and many retrospective studies also fail to report dosage or treatment adherence data.
This case series addresses these gaps in the literature by focusing on women prescribed dexamphetamine for medical indications other than ADHD who maintained treatment adherence. By analysing women who consistently used dexamphetamine for narcolepsy management during pregnancy, we aim to examine the relationship between therapeutic dexamphetamine use and adverse pregnancy/neonatal outcomes while minimising confounding variables.
Methods
This study was conducted at the Royal Brisbane and Women's Hospital (RBWH), utilising the hospital's obstetric medicine and pharmacy databases. Patients included in this study were required to have a confirmed diagnosis of narcolepsy type 1, type 2 or idiopathic hypersomnolence in medical records. In addition, they had to be prescribed Dexamphetamine and continue it during pregnancy. This search was conducted on records available within the past 5 years.
We performed descriptive statistical analysis to summarise patient demographics, medication use, and pregnancy outcomes. Pregnancy outcomes were analysed to identify any potential associations with the continuation of dexamphetamine during pregnancy. Patients were contacted directly to provide consent and confirm their dosing and administration of dexamphetamine during pregnancy. Outcomes were compared with existing literature on pregnancy outcomes in patients using stimulant medications during pregnancy.
Our database search identified 10 patients with narcolepsy prescribed dexamphetamine during pregnancy. Of these, four discontinued dexamphetamine use, while six continued. All cases identified where the patient continued dexamphetamine during pregnancy occurred within the preceding 3 years. Patients were treated via various Respiratory/Sleep physicians via both the public and private hospital system.
Results
All women delivered in late 3rd trimester except for one, which was complicated by CMV infection and fetal growth restriction on serial growth scans, although was on the 11th centile for Estimated fetal weight at birth (Figure 1). This baby required admission to the Neonatal Intensive Care post-partum. The remainder of the neonates were born with good APGARS, although two were not recorded. There was no evidence of fetal growth restriction and they did not require any additional support at birth (Figure 1).
No pregnancies were complicated by pre-eclampsia, although one woman was diagnosed with gestational hypertension. Most women were on a moderate dose of Dexamphetamine and continued throughout pregnancy while doses ranged from 5 to 35 mg daily, the mean dose was 20 mg daily (Figure 1). Three women chose to reduce their dose in late third trimester to 5 mg PRN due to their reduced functional demands while on maternity leave. Except for the patients who reduced their dose in third trimester, dispensing records appeared to align with both prescribed and reported dosing. There were no delivery complications related to dexamphetamine use; three women required emergency caesarean section for obstetric indications. Four women continued dexamphetamine while breast feeding (Figure 1).
Discussion
Rising psychostimulant prescription to women of childbearing age requires obstetric physicians to provide advice on the safety of these medications during pregnancy and breastfeeding. However, available data is inconsistent and often derived from studies that report retrospective dispensing records of ADHD patients, which makes interpretation challenging2,6,7
Current evidence indicates that narcolepsy itself is not linked to poorer pregnancy outcomes. Although high-quality data is limited, a 2013 European study involving 249 pregnant individuals found complication rates comparable to those seen in the broader population. 8 That said, narcolepsy may still influence pregnancy indirectly. For instance, individuals who experience cataplexy may have an increased risk of falls or injury, which could pose additional concerns during pregnancy.
Limited narcolepsy-specific pregnancy data exists due to variable treatment cessation advice. However, there are significant functional impacts for women who cease narcolepsy treatment during pregnancy. In a 2019 study of pregnant individuals with narcolepsy, 78.7% discontinued their medication (58% citing physician advice). To cope with the resulting symptoms, many adopted lifestyle adjustments, including increased sleep (72.1%), stopping work (32.6%), and avoiding driving (27.9%). 9
Data from two population cohort studies encompassing over 6200 exposed pregnancies indicate that amphetamine use in early pregnancy is not associated with an increased risk of overall congenital malformations, cardiac defects, or specific structural anomalies.10,11
Nonetheless, women are often advised to discontinue psychostimulants during pregnancy, as data on pregnancy outcomes associated with use in the second and third trimesters remain limited and inconclusive. Both ADHD and recreational drug use are associated with factors that adversely affect maternal and fetal outcomes: such as low socioeconomic status, mental health disorders, smoking, alcohol use, inadequate perinatal care, malnutrition, lifestyle stress, unsafe living conditions, and concurrent psychotropic medications. 4 These confounders are frequently underreported in retrospective studies, making it difficult to establish causality.
Historically both Cohen et al. (2017) and Poulton et al. (2018) reported a small increased pre-eclampsia and preterm birth risks with psychostimulant use in pregnancy.4,5 Cohen et al. reported that psychostimulant use during pregnancy was linked to a higher likelihood of pre-eclampsia, with an estimated risk increase of 1.29 (95% CI 1.11–1.49). 4 Similarly, Poulton et al. observed a relationship between psychostimulant exposure both prior to and during pregnancy and the development of pre-eclampsia among women in New South Wales, with an adjusted odds ratio of 1.5 (95% CI 0.8–2.6). 5 However, these associations persisted in patients who ceased treatment prior to pregnancy, even with a treatment-free period of a number of years. Therefore, the observed associations could not be clearly attributed to the stimulant medication, as ADHD or related factors could be responsible. 5
Cachamo et al. (2022) observed higher rates of adverse outcomes (pre-eclampsia, placental abruption, preterm birth, low birthweight, small for gestational age, NICU admission) with psychostimulant exposure, but found significant attenuation of these risks after confounder adjustment. 10 In addition, the study classified exposure based on dispensing records rather than actual consumption. Conversely, Rose et al. (2020) reported no significant birthweight differences between dexamphetamine-exposed mothers and controls. However, this study was limited by its small sample size and by significant differences in rates of comorbid psychiatric and substance use disorders between the two groups. 6
In 2014, a Danish-based register study suggested an association between psychostimulant exposure in early pregnancy and miscarriage. 1 However, the study also found that the rate of miscarriage was increased in women with ADHD who did not use psychostimulants during their pregnancy. Indicating ADHD may be a significant confounding factor.
A large 2024 retrospective cohort study from Western Australia reported that women who stopped dexamphetamine before 20 weeks’ gestation had higher odds of threatened termination of pregnancy (OR 2.28; 95% CI 1.00–5.15; p = 0.049). The study was unable to directly evaluate spontaneous miscarriage because only pregnancies progressing beyond 20 weeks were captured in the dataset. In contrast, continuing dexamphetamine throughout pregnancy was not associated with an increased risk of adverse maternal or neonatal outcomes compared with discontinuation. Women who were completely unexposed, having ceased treatment prior to conception, demonstrated lower risks of pre-eclampsia, hypertension, post-partum haemorrhage, and fetal distress. 12
In our six dexamphetamine-treated narcolepsy/idiopathic hypersomnia pregnancies (excluding Case 5 with congenital CMV), ADHD associations described in the literature (pre-eclampsia, growth restriction, miscarriage, NICU admissions) were not observed. NICU admissions and growth restriction are outcomes significantly affected by confounders, and in previous studies, the strength of these associations were attenuated by post hoc analysis. 3 Given they were not seen in our narcolepsy group, it is possible that these associations are linked to ADHD or lifestyle factors in previous studies, rather than narcolepsy itself, although the sample size in this study was too limited to draw definitive conclusions.
Case 3 delivered at 36 weeks with gestational hypertension. While recreational amphetamine use increases hypertensive disorders sixfold, prescribed psychostimulant associations remain inconclusive.12,13 Case 1 required treatment for hypertension in a previous pregnancy while on modafinil; however, her blood pressures were normal in her second pregnancy when she was managed with dexamphetamine.
Australian preterm birth rate is ∼10%. 14 Psychostimulant use has been associated with preterm birth, however, not specifically dexamphetamine. Our cohort was too small for population comparison. Long-term dexamphetamine use (>10 years) is associated with a slightly increased risk of hypertension and cardiovascular disease in the general population, 15 which must be weighed against mental health benefits. A similar approach to counselling could be taken in pregnancy, balancing benefits of dexamphetamine and risk of hypertensive disorders through an individualised approach.
Study limitations include small participant numbers and retrospective compliance reporting. Early miscarriages (<20 weeks) weren't captured as participants were booked after 20 weeks. While dexamphetamine use wasn't associated with poor pregnancy or neonatal outcomes, future research should examine long-term neurodevelopmental effects in exposed children.
Conclusion
Despite increasing psychostimulant use, there are no standardised guidelines for prescribing these medications during pregnancy. Pharmacological properties differ substantially between agents and confounders associated with ADHD diagnosis can also impact pregnancy outcomes. Untreated narcolepsy can cause significant functional impairment, and this study describes outcomes during pregnancy when medicated that can inform clinical decision making.
Counselling should be individualised to incorporate patient-specific factors such as the severity of their underlying condition and relevant past medical history, prescribed medication safety profile and psychosocial circumstances. This narcolepsy case series supports the safety profile of continued dexamphetamine use during pregnancy.
Pregnancy outcomes in six women diagnosed with narcolepsy who continued dexamphetamine through pregnancy. PET = Pre-eclampsia, SGA = Small for gestational age, IUGR = Intrauterine growth restriction, SCU = Special Care Unit, EFW = Estimated Fetal Weight, NICU = Neonatal intensive Care unit, Em = Emergency, CS = Cesarean Section, FTP = failure to progress,
GHTN = gestational hypertension, CMV = cytomegalovirus, APH = antepartum haemorrhage, PPH = post-partum haemorrhage.
Footnotes
Acknowledgements
We thank the staff of the Royal Brisbane and Women's Hospital for their support in patient care.
Ethical approval
This study was approved by the Metro North Hospital and Health Service Human Research Ethics Committee (HREC reference: HREC/2024/MNHA/105145). Informed consent was obtained from all individual participants included in the study.
Author contribution
KL collected data, conducted the literature review and drafted the manuscript. CS collected data and contributed to manuscript editing. EC assisted with literature review and contributed to manuscript editing. KL and AMC conceived the study, contributed to manuscript editing and provided clinical oversight. All authors reviewed and approved the final manuscript.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data availability statement
Data supporting the findings of this study are available from the corresponding author upon reasonable request.
Guarantor
Katie Lane is the guarantor for this article and accepts full responsibility for the integrity of the work.
Patient consent
Written informed consent for publication was obtained from all patients included in this case series.
Trial registration
Not applicable; this study was not a clinical trial.