Children exposed to the antidepressant drug bupropion (Wellbutrin) in utero have a 3-fold increased risk of Attention Deficit Hyperactivity Disorder compared with kids whose mothers did not take the drug during pregnancy.
The findings, from a multiple logistic regression analysis of claims-based data from nearly 40,000 families, were published in the July edition of the Journal of Developmental & Behavioral Pediatrics.
The author, Dr. Roberto Figueroa of the Department of Psychiatry, Mount Sinai School of Medicine, New York, said the study objective was to identify parental factors, including psychiatric diagnoses and use of psychoactive medication, which might increase the risk of ADHD in young children.
Dr. Figueroa found that children exposed to bupropion in utero had a 3.5-fold increased risk of being diagnosed with ADHD by the time they were five years old. If bupropion exposure occurred during the second trimester, the odds ratio for ADHD increased to 14.6 (Figueroa R. J Dev Behav Pediatr. 2010 Jul 6. Epub ahead of print).
There was no increased risk of ADHD in children exposed to selective serotonin reuptake inhibitors, all of which, like bupropion, can cross the placenta. In an interview with Holistic Primary Care, Dr. Figueroa said this makes sense if you consider the mechanisms of action of the various antidepressants.
“Bupropion is the only antidepressant that affects the dopaminergic system in the brain, and ADHD is associated with abnormalities in the dopaminergic system. SSRI’s may have other long-term impacts on development, but they do not affect dopamine, and in this analysis they don’t correlate with ADHD. With bupropion, the drug’s mechanism of action certainly fits with one of the main aspects of ADHD, so you might expect to see a correlation.”
Dr. Figueroa stressed that correlation does not mean causation, and he hesitated to draw any strong clinical conclusions from his findings. “Going from claims data to brain biochemistry to clinical recommendations is very tricky. We cannot say that bupropion causes ADHD, and I would not say that you should always avoid using bupropion during pregnancy. (Learn more about when and how to taper off an antidepressant drug in Helping Patients Step Off Antidepressants from HPC's Fall 2010 edition.)
How Little We Know
However, it is essential to be aware that, “when you’re giving a psychoactive drug to a pregnant woman, you are not only increasing the levels of that drug in her brain, you are also increasing the levels in the fetus’ brain. In effect, you’re giving the drug to both. Who would advocate giving an antidepressant to an infant? But in reality, that’s what’s happening when you give antidepressants during pregnancy. It’s just that the infant hasn’t been born yet.”
The reality is, there’s very little scientific information about the long-term developmental effects of fetal exposure to psychoactive meds. Dr. Figueroa said that if his study has any real clinical message, it is that physicians need to recognize the extent to which they are flying blind.
“We prescribe these drugs as if we know they are safe. In truth, we really don’t know what the long term developmental effects on children will be. We have plenty of short-term data on birth defects and premature delivery in women taking antidepressants in pregnancy. Generally these drugs are considered safe during pregnancy. But ‘safety in pregnancy’ does not account for developmental issues in the kids when they’re 5 or 10 or 15 years old.”
Dr. Figueroa said that when he started looking at these questions, he was surprised by how little was actually known about the effects of in utero exposure. “It’s scary because a lot of people have been taking these drugs for a long time. Are they affecting babies’ brains? We really don’t know.”
He said he has no information on whether maternal use of herbs or nutraceuticals advocated for treatment of depression (ie, St. John’s Wort, SAMe, L-tryptophan) would have any potential adverse consequences on children. Likewise, the fetal impact of Ritalin itself—the most widely prescribed ADHD drug—is a big unknown. Presumably, anything that affects dopamine could potentially increase ADHD risk.
These are open questions requiring a lot more research. While there may well be times when it is appropriate to prescribe bupropion for a pregnant woman, physicians should not automatically assume long term safety, and should take that route only after other options have been explored. “There are psychotherapeutic approaches that have been shown as effective or more effective than taking antidepressants. Obviously, psychotherapy is very safe for the baby,” Dr. Figueroa told Holistic Primary Care.