By Nicole Cirino, MD, CST, IF

Reproductive Psychiatrist, Associate Professor of Psychiatry and OB/GYN, Oregon Health & Science University, Portland

SYNOPSIS: Twenty-five women with perinatal attention-deficit hyperactivity disorder were followed prospectively during pregnancy for changes in anxiety, depression, perceived stress, and functional impairment. Statistically significant differences in mood and functional impairment in the family domain were found in those who discontinued their psychostimulant.

SOURCE: Baker AS, Wales R, Noe O, et al. The course of ADHD during pregnancy. J Atten Disord 2020; Dec 11. doi: 10.1177/1087054720975864. [Online ahead of print].

The aim of this study was to characterize the maternal course of attention-deficit hyperactivity disorder (ADHD) during pregnancy for women 18 years of age and older. This observational cohort design followed 25 women with ADHD throughout pregnancy, with the initial evaluation occurring at less than 20 weeks and the two follow-up assessments at 24 weeks and 36 weeks of gestation. They used validated scales assessing ADHD illness severity, depression, anxiety, and functional outcomes. Clinician-rated scales included the Montgomery-Asberg Depression Rating Scale (MADRS), the Adult ADHD Investigator Symptoms Rating Scale (AISRS), and the Clinical Global Impression (CGI). Self-rated scales used included the Edinburgh Postnatal Depression Scale (EPDS), the Generalized Anxiety Disorder 7-item (GAD-7) scale, the Perceived Stress Scale (PSS), and the Weiss Functional Impairment Rating Scale Self-Report (WFIRS-S). Of note, the AISRS has both hyperactive-impulsive and inattentive subscales. The WFIRS-S identifies impairment from ADHD in distinct areas using the subscales Family, School, Life Skills, Self-Concept, Social Activities, and Risky Activities.

Of the 25 women, three prospective groups emerged: five women who discontinued ADHD medications (Group A); eight women who changed their ADHD medication regimen to maintain therapeutic benefits “as needed,” or PRN (Group B); and 12 women who continued their ADHD medication with no changes through pregnancy (Group C). Fifty percent of participants had a comorbid diagnosis of generalized anxiety disorder and 32% had major depressive disorder. All women were being treated initially with the psychostimulants amphetamine (64%) or methylphenidate (33%).

The results of three measures — one scale (EPDS) and two subscales (AISRS-Hyperactive and WFIRS-Family) — indicated statistically significant differences among the groups over time. The results for the AISRS-Hyperactive sub-score found adjusted mean changes of discontinuers (-0.39), the PRN group (-1.92), and maintainers (-2.78) showing a significant difference between those who discontinued medication vs. those who changed their medication of 2.39 (P = 0.0128). The total EPDS score showed adjusted mean changes of discontinuers (4.32), medication as needed (-1.01), and maintainers (-0.65), with significant differences between those who discontinued medication and those changing medication as needed (5.3, P < 0.0001) and between discontinuers and maintainers (4.98, P = 0.0009). The mean for all points of measure in all three groups did not reach clinical levels suggestive of depression (EPDS > 13). For the sum of the WFIRS-Family domain, the adjusted mean changes of discontinuers (1.55), medication as needed (-1.70), and maintainers (-1.54), showed significant differences between those who discontinued medication and those who changed medication as needed (3.3, P = 0.0309) and between discontinuers and maintainers (3.09, P = 0.0197). Of note, the WFIRS-Family subscale is scored on a 0 to 33 scale, with 33 showing the highest level of impairment.

The authors concluded there was not a clinically meaningful significant difference found between groups in terms of overall ADHD symptoms, but women who discontinued psychostimulant treatment during pregnancy had “significant impairment in family functioning” and that the “combined increase in depressed mood symptoms and functional disability in the family domain suggest that symptoms alone may not be a reliable proxy for overall functioning.”

COMMENTARY

As compared to perinatal mood and anxiety disorders (PMADs), perinatal ADHD and its primary treatment modality, psychostimulants, have a lack of systematic data in the perinatal period to guide decision making. ADHD affects approximately one in 30 women and is associated with depression, anxiety, substance use disorders, and impairment in psychosocial functioning. Psychostimulants are among the most commonly prescribed medication during pregnancy, with an estimated 1% prevalence.¹

This is in stark contrast to untreated depressive illness during pregnancy, which has a large body of literature showing adverse effects on obstetrical, perinatal, and neurobehavioral outcomes.² Untreated ADHD has not been shown, prior to this study, to cause such negative outcomes. Although this current study attempts to address this, it falls short in proving that any clinically significant impairment exists in untreated ADHD.

The small sample size of 25 women, only 13 of whom discontinued or decreased their medication, is in itself a limitation of this study. The five women who discontinued their psychostimulants in this sample showed only statistically significant impairment in three of all the areas that were assessed. Although these were statistically significant, it can be argued that these small changes are not clinically significant. The assessments measured did not show any negative effect in categories of mood (GAD-7, MADRS, CGI), perceived stress (PSS), or even total symptom burden of ADHD. The WFIRS-S did not show impairment in the other domains, including Life Skills, Self-Concept, Social Activities, or Risky Activities. Furthermore, the statistically significant measures that showed change still did not reach clinical significance, i.e., average EPDS did not reach a positive value (> 13) during any point of the observation. The WFIRS showed a mean change of 3.09. A total score change of 13 is considered clinically significant improvement.³ This contrasts with the safety profile of psychostimulants, which, although limited, have been associated with a small but significant increased rate of malformations, shorter gestational age, preterm delivery, adverse placental outcomes, and possibly increased risk of central nervous system disorder in neonates.^4,5 Although the first of its kind to address maternal adverse effects of discontinuing stimulants, the data in this study will not change my practice at this time. Psychostimulant use in pregnancy may be a higher overall risk when continued vs. discontinued.

In my practice, I encourage continuing psychostimulants only in severe ADHD, when illness severity, if untreated, can lead to more severe outcomes, such as hazardous driving, risk of job loss and income, severe difficulty parenting, or uncontrolled comorbid mood and
anxiety disorders or developmental disorders. Thoughtful behavioral and psychosocial interventions remain the preferred treatment for mild to moderate perinatal ADHD.

REFERENCES

1. Louik C, Kerr S, Kelley KE, Mitchell AA. Increasing use of ADHD medications in pregnancy. Pharmacoepidemiol Drug Saf 2015;24:218-220.
2. Yonkers KA, Wisner KL, Stewart DE, et al. The management of depression during pregnancy: A report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Gen Hosp Psychiatry 2009;31:403-413.
3. Canadian ADHD Resource Alliance. Weiss Functional Impairment Rating Scale. https://www.caddra.ca/wp-content/uploads/WFIRS-S.pdf
4. Koren G, Barer Y, Ornoy A. Fetal safety of methylphenidate–A scoping review and meta analysis. Reprod Toxicol 2020;93:230-234.
5. Baker AS, Freeman MP. Management of attention deficit hyperactivity disorder during pregnancy. Obstet Gynecol Clin North Am 2018;45:495-509.