Antenatal exposure to Wellbutrin (bupropion) does not appear to be associated with an increased risk of malformations in the exposed infant; however,  it is not known if exposure to Wellbutrin during pregnancy has any effect on the child’s neurobehavioral development. In a study from Figueroa and colleagues published in 2010, insurance claims data from 38,704 children and their families were analyzed, using information obtained from the beginning of pregnancy until age 5.  Outcomes were assessed in mothers taking selective serotonin reuptake inhibitors (SSRIs) or Wellbutrin before, during or after the pregnancy.  This study sought to determine the risk of ADHD in exposed infants.  Children up to the age of 5 were identified as having ADHD if they had an outpatient or inpatient claim with a primary or secondary diagnosis of ADHD or a prescription claim for stimulants.

As anticipated, a diagnosis of ADHD in the mother or father was associated with higher rates of ADHD diagnosis in the children.  A diagnosis of bipolar disorder (OR = 5.08), psychotic disorders (OR = 4.05), and depressive disorders (OR = 2.58) in the mother, but not in the father, increased the risk of ADHD in the child.

Higher rates of ADHD were observed in infants exposed to bupropion during pregnancy (OR = 3.63), especially during the second trimester (OR = 14.66); in contrast, there was no increase in ADHD risk in those exposed to SSRIs (OR = 0.91).

Although this study indicates a strong association between Wellbutrin exposure and increased risk of ADHD in the child, this association does not necessarily imply causation.  We cannot assume that mothers who choose to take Wellbutrin are identical to those who choose to take an SSRI.  Thus there may be confounding factors – ones not fully measured in this study — that contribute to increased risk of ADHD.

We do know that other environmental factors have been shown to increase the risk of ADHD in the child.  Exposure during pregnancy to alcohol, tobacco, cocaine and heroin (Knopik et al, 2006; Milberger et al, 1996; Linares et al, 2006; Ornoy et al, 2001), perinatal complications such as prematurity or low birth weight (Ben Amor et al, 2005; Lou et al, 1996), or maternal obesity (Rodriguez et al, 2008) have all been identified as ADHD risk factors. In addition, exposure to stress during pregnancy (Huizink et al, 2007; Van Der Bergh, 2004) or mental illness after birth (including postpartum depression) have also been associated with worse pregnancy outcomes and increased risk of ADHD in the child (Grizenko et al, 2008; Carter et al, 2001).  Given the limitations of the claims database, the researchers were not able to control for m any of these potential confounders.  Further studies are needed to better delineate the effects of Wellbutrin on the neurobehavioral development of the child.

Snezana Milanovic, MD

 

References

Ben Amor L, Grizenko N, Schwartz G, et al. Perinatal complications in children with attention-deficit hyperactivity disorder and their unaffected siblings. J Psychiatry Neurosci. 2005;30:120–126.

Carter AS, Garrity-Rokous FE, Chazan-Cohen R, Little C, Briggs- Gowan MJ. Maternal depression and comorbidity: predicting early parenting, attachment security, and toddler socialemotional problems and competencies. J Am Acad Child Adolesc Psychiatry. 2001;40:18 –26.

Coghill D, Banaschewski T. The genetics of attention-deficit/ hyperactivity disorder. Expert Rev Neurother. 2009;9:1547–1565.

Grizenko N, Shayan YR, Polotskaia A, Ter-Stepanian M, Joober R. Relation of maternal stress during pregnancy to symptom severity and response to treatment in children with ADHD. J Psychiatry Neurosci. 2008;33:10 –16.

Figueroa R. Use of antidepressants during pregnancy and risk of attention-deficit/hyperactivity disorder in the offspring. J Dev Behav Pediatr. 2010;31(8):641-648.

Huizink AC, Dick DM, Sihvola E, Pulkkinen L, Rose RJ, Kaprio J. Chernobyl exposure as stressor during pregnancy and behaviour in adolescent offspring. Acta Psychiatr Scand. 2007;116:438–446.

Linares TJ, Singer LT, Kirchner HL, et al. Mental health outcomes of cocaine-exposed children at 6 years of age. J Pediatr Psychol. 2006;31:85–97.

Lou HC. Etiology and pathogenesis of attention-deficit hyperactivity disorder (ADHD): significance of prematurity and perinatal hypoxic-haemodynamic encephalopathy. Acta

Paediatr. 1996;85:1266–1271.

Knopik VS, Heath AC, Jacob T, et al. Maternal alcohol use disorder and offspring ADHD: disentangling genetic and environmental effects using a children-of-twins design. Psychol Med. 2006;36:1461–1471.

Milberger S, Biederman J, Faraone SV, Chen L, Jones J. Is maternal smoking during pregnancy a risk factor for attention deficit hyperactivity disorder in children? Am J Psychiatry. 1996;153:1138–1142.

Nulman I, Rovet J, Stewart DE, Wolpin J, Pace-Asciak P, Shuhaiber S, Koren G. Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study. Am J Psychiatry. 2002 Nov;159(11):1889-95.

Ornoy A, Segal J, Bar-Hamburger R, Greenbaum C. Developmental outcome of school-age children born to mothers with heroin dependency: importance of environmental factors. Dev Med Child Neurol. 2001;43:668–675.

Rodriguez A, Miettunen J, Henriksen TB, et al. Maternal adiposity prior to pregnancy is associated with ADHD symptoms in offspring: evidence from three prospective pregnancy cohorts. Int J Obes (Lond). 2008;32:550–557.

Rowland AS, Lesesne CA, Abramowitz AJ. The epidemiology of attention-deficit/hyperactivity disorder (ADHD): a public health view. Ment Retard Dev Disabil Res Rev. 2002;8:162–170.

Van den Bergh BR, Marcoen A. High antenatal maternal anxiety is related to ADHD symptoms, externalizing problems, and anxiety in 8- and 9-year-olds. Child Dev. 2004;75:1085–1097.

 

Related Posts