Antidepressant use in pregnancy linked to ADHD

“Pregnant women who take anti-depressants 'could raise their child's risk of ADHD',” reports the Mail Online, saying that this could explain “the rise in children with short attention spans”.

The study in question compared children with attention deficit hyperactivity disorder (ADHD) or autistic spectrum disorders (ASD) with children without these conditions. It found that children with ADHD, but not those with ASD, were more likely to have had mothers who took antidepressants during pregnancy.

The main limitation to this study is that there is no certainty the antidepressants were having an effect, or whether other factors were at play. The researchers did try to take factors such as the mother’s depression itself into account, but acknowledge that other factors may have affected the findings. The fact that the link was no longer significant once the severity of women’s psychiatric illness was taking into account adds weight to the suggestion that other factors were involved.

While medications, including antidepressants, are generally avoided in pregnancy, the benefits of taking them may outweigh potential risks in some circumstances. Depression is a serious condition, which can have serious consequences if left untreated during pregnancy.

If you are taking antidepressants and are pregnant or planning to get pregnant, talk to your doctor. However, you should not stop taking your medicines unless advised to do so by your doctor.

Where did the story come from?

The study was carried out by researchers from Massachusetts General Hospital and other healthcare and research institutes in the US. It was funded by the US National Institute for Mental Health Research. Some of the authors declared receiving consulting fees or research support, having equity holdings or being on scientific advisory boards for various pharmaceutical companies. The study was published in the peer-reviewed medical journal Molecular Psychiatry.

The study was covered reasonably by the Mail, which highlighted early on in its story that any risk of taking antidepressants needed to be balanced against the risk of not treating a woman’s depression. It also very sensibly reported on current guidance from the National Institute for Health and Care Excellence (NICE) on when antidepressants should be used in pregnancy.

What kind of research was this?

This was a case-control study looking at whether exposure of a foetus to antidepressants in the womb might increase the risk of the child having ASD or ADHD in childhood. The researchers report that some previous studies have found a link, while others have not.

It would be unethical for researchers to randomly assign pregnant women with depression to receive or not receive antidepressants just to assess potential harms to the baby. Therefore, this type of study (called an observational study) is the most feasible way of investigating these links. The limitation to this type of study, however, is that factors other than antidepressants could be causing the link seen. For example, the depression itself might have an effect, or genetic factors contributing to the woman’s depression might also increase the child’s risk of ASD or ADHD. The researchers took measures to try and take some factors into account, particularly that ADHD and ASD might be associated with maternal depression itself. However, their effect may not be removed completely.

What did the research involve?

The researchers used data routinely collected from one healthcare group in the US. They identified children diagnosed with ADHD or ASD (cases), and compared them with similar children who did not have these conditions (controls). They looked at whether the mothers of children with these conditions were more likely to have taken antidepressants during their pregnancies. If this was the case, this would suggest that the antidepressant use might be linked to an increased risk of these conditions.

The researchers identified cases diagnosed between 1997 and 2010, among children aged from two to 19, who had been delivered at the three hospitals that were part of the healthcare group. For each case child, they identified three “control” children, who were:

not diagnosed with ADHD, ASD or an intellectual disability
born in the same year, ideally, or within three years if not enough controls could be found
born at the same hospital
born at the same term – either full-term or preterm (premature)
of the same sex
of the same race/ethnicity
of the same health insurance type (this acted as an indicator of socioeconomic status)

Children for whom no matching controls could be identified were excluded, but those with only one or two matched controls were included. The researchers ended up with 1,377 children with ASD, 2,243 children with ADHD and 9,653 healthy control children for analysis.

The children’s mothers were also identified from the healthcare database and birth certificate data. They identified whether the mothers had been prescribed antidepressants:

at any time before pregnancy
in the three months before conceiving the child
at any time during pregnancy (also broken down into first, second or third trimester prescriptions)

They also identified how long the prescription lasted (how many days’ worth of antidepressants the woman was prescribed).

The researchers then analysed whether prenatal antidepressant use was more or less common in mothers of cases or controls. These analyses took into account the factors that the children were matched for (such as gender and race) as well as maternal age and household income.

They also took into account whether the mother had been diagnosed with depression, looked at the effects of different types of antidepressant, an indicator of how severe the woman’s illness was (assessed by how much treatment she received and presence of other psychiatric diagnoses) – and exposure to two types of non-antidepressant medication (one drug to prevent vomiting that affected serotonin levels – something that some antidepressants also do – and any antipsychotics).

What were the basic results?

Maternal depression was associated with increased risk of ASD and ADHD in adjusted analyses.

Between 3% and 6.6% (approximately) of children with ADHD or ASD had mothers who had taken antidepressants either before pregnancy or during pregnancy, compared to 1% to 3.5% (approximately) of control children.

Before taking into account other factors, taking antidepressants before pregnancy or during pregnancy was associated with an increased risk of ASD and ADHD. After taking into account factors including maternal depression, taking antidepressants before pregnancy was associated with an increase in the odds of ASD (odds ratio (OR) 1.62, 95% confidence interval (CI) 1.17 to 2.23), but not of ADHD (OR 1.18, 95% CI 0.86 to 1.61). Taking antidepressants during pregnancy was associated with an increase in the odds of ADHD (OR 1.81, 95% CI 1.22 to 2.70) but not of ASD (OR 1.10, 95% CI 0.70 to 1.70).

The researchers found that if they took into account measures of how severe the woman’s illness was (how much treatment she was receiving, and whether she had other psychiatric conditions), the link between antidepressant exposure during pregnancy and ADHD was no longer statistically significant.

The researchers found no link between the anti-vomiting drug and ASD or ADHD risk, while there was a suggestion of a link between maternal antipsychotic use during pregnancy and ASD, but not ADHD.

How did the researchers interpret the results?

The researchers concluded that the association between maternal prenatal antidepressant use and ASDs in the children was probably due to the depression itself, rather than antidepressant use.

Maternal prenatal antidepressant use did appear to be associated with a modest increase in ADHD in the child, although this may still be due to other factors rather than the antidepressants themselves, they said. The researchers note that this potential risk needs to be weighed up against the considerable consequences of not treating the mother’s depression.

Conclusion

This study suggests a potential link between women taking antidepressants during pregnancy and an increased risk of ADHD, but not ASDs, in their children. The limitation to this type of study is that factors other than the antidepressants, such as the depression itself, or genetic factors increasing both depression and ADHD risk, might be causing the effect seen.

The researchers used various methods to take this into account, but acknowledge that other factors could still be having an effect. While the link with ADHD remained significant after taking maternal depression into account, it did not remain significant after taking into account measures of how severe the woman’s illness was.

Other limitations to the study include the following:

It could only assess what prescriptions the mothers received, and not whether they took them.
It could not directly assess how severe a woman’s illness was; they had to rely on data that was routinely collected on the types of treatment she was receiving and her previous diagnoses. This is unlikely to capture severity as well as a more direct assessment could.
If children or mothers were diagnosed or treated outside of the healthcare grouping being assessed, this information would not be available to the researchers, and this could affect results.

It is important to know that no one factor is likely to cause ADHD or ASD. These conditions are complex, and we are not yet entirely sure what causes the majority of cases. Both genetic and non-genetic (known as “environmental”) factors are thought to potentially play a part.

Medications are used sparingly in pregnancy to reduce any risk of harm to the developing foetus. However, if a woman’s condition could have serious consequences if untreated, then the woman and their doctor may decide that the benefits outweigh the harms.

NICE has guidance on how to treat depression if planning a pregnancy and during pregnancy and breastfeeding. In general, it recommends considering alternatives to antidepressant treatment, and considering doctor-supervised withdrawal of antidepressants for women already taking them. However, under certain circumstances it advises considering antidepressant treatment, such as if the women has not responded to non-drug therapies.