No Firm Answers on Prenatal Antidepressant Use and Autism Risk

Fran Lowry

June 15, 2018

MIAMI — A new meta-analysis of studies that examined prenatal antidepressant (AD) exposure as a risk factor for autism spectrum disorder (ASD) shows there is wide variation in the definition and selection of comparison groups and that this leads to discordant conclusions with respect to risk.

Dr Monica Vega

"Studies that compared populations suggest antidepressant exposure increases autism risk, but psychiatric and family-based comparisons do not support this conclusion," Monica L. Vega, MD, from Jackson Hospital, Miami University School of Medicine, Florida, told Medscape Medical News.

The results were presented here at the American Society of Clinical Psychopharmacology (ASCP) 2018 annual meeting.

Wide Variation

In 2014, the Agency for Healthcare Research and Quality of the US Department of Health and Human Services issued a position statement that said studies of prenatal antidepressant safety were inadequate to allow well-informed decisions because comparison groups did not consist exclusively of women with depression.

"Existing meta-analyses, concluding that prenatal AD exposure is associated with autism, did not evaluate the impact of comparison group designation. We wanted to address this gap in the literature in the current meta-analysis," Vega said.

Vega and her group searched seven databases and found 14 studies, including observational studies, that reported odds ratios (ORs) or hazard ratios (HRs) for ASD following antidepressant exposure.

Several of the studies used more than one approach. Thirteen studies reported results using a population-based comparison group; five studies used both population-based comparison groups and psychiatric comparison groups; and four used population-based comparison groups and discordant sibling comparison groups.

The studies that used a population-based approach showed significant estimates of autism for exposure to any antidepressant, with an HR of 1.42 (95% confidence interval [CI], 1.22-1.65) and an OR of 1.43 (95% CI, 1.21-1.68).

These population-based comparison group studies also yielded significant estimates of ASD for exposure to selective serotonin reuptake inhibitors (SSRIs), with an HR of 1.53 (95% CI, 1.37 - 1.72) and an OR of 1.55 (95% CI, 1.36 - 1.75).

On the other hand, the studies that also used psychiatric comparison groups showed no significant associations of antidepressants and autism (HR = 1.16; 95% CI, 0.79 - 1.72; OR = 1.12; 95% CI, 0.84 - 1.48) or for SSRIs and autism (HR = 1.25, 95% CI, 0.79 - 1.79; OR = 0.99, 95% CI, 0.65-1.52).

In addition, studies that used discordant sibling comparison groups actually showed a protective effect of SSRIs against autism (OR = 0.79; 95% CI, 0.69 - 0.97).

Other estimates using the sibling comparison group for antidepressants or SSRIs were insignificant. The HR for antidepressants was 0.95 (95% CI, 0.69 - 1.31), and the OR was 0.87 (95% CI, 0.58 - 1.30). For SSRIs, the HR was 0.82 (95% CI, 0.60 - 1.12).

Better-Designed Studies Needed

Taken altogether, a final composite analysis showed no significant effect of exposure to antidepressants (HR = 0.97; OR = 1.16) or to SSRIs (HR = 0.99; OR = 1.18).

"It's kind of crazy, with some studies, the population-based studies, showing a risk and the others showing no risk or even a protective effect," Vega said.

Dr Marlene Freeman

"Future studies need to have a better design to address this concern. When we are finding such discording results, it tells us that we need to do a better job in the way we conduct future studies," she said.

"These findings underscore that the potential risks of fetal exposure to a medication must be considered in the context of other variables that affect obstetrical, neonatal, and neurodevelopment outcomes," Marlene P. Freeman, MD, Harvard Medical School, Boston, Massachusetts, told Medscape Medical News.

"Variables such as maternal illness during pregnancy, parental psychiatric illness during the early childhood years, and genetic factors can also drive adverse outcomes," Freeman, who was not part of the study, said.

"These must be disentangled to ascertain risk of medication exposure," she said.

Dr Vega and Dr Freeman report no relevant financial relationships.

American Society of Clinical Psychopharmacology (ASCP) 2018. Abstract W2, presented May 30, 2018.

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