This population based nested case-control study incorporated data from a Swedish registry in which 4429 cases of autism spectrum disorder (1828 with and 2601 without intellectual disability) and 43,277 age and sex matched controls in the full sample (1679 cases of autism spectrum disorder and 16,845 controls with data on maternal antidepressant use nested within a cohort (n=589,114) of young people aged 0-17 years were evaluated.
Researchers reported that in the subsample with available data on drugs, this association was confined to women reporting antidepressant use during pregnancy (3.34, 1.50 to 7.47, P=0.003), irrespective of whether selective serotonin reuptake inhibitors (SSRIs) or non-selective monoamine reuptake inhibitors were reported. Assuming an unconfounded, causal association, antidepressant use during pregnancy explained 0.6% of the cases of autism spectrum disorder.
The researchers concluded that in utero exposure to both SSRIs and non-selective monoamine reuptake inhibitors (tricyclic antidepressants) was associated with an increased risk of autism spectrum disorders, particularly without intellectual disability. However, whether this association is causal or reflects the risk of autism with severe depression during pregnancy requires further research.
NICE have produced a clinical guideline on the management of antenatal and postnatal depression, and state that when choosing an antidepressant for pregnant or breastfeeding women, prescribers should, while bearing in mind that the safety of these drugs is not well understood, take into account that:
• tricyclic antidepressants, such as amitriptyline, imipramine and nortriptyline, have lower known risks during pregnancy than other antidepressants
• most tricyclic antidepressants have a higher fatal toxicity index than selective serotonin reuptake inhibitors (SSRIs)
• fluoxetine is the SSRI with the lowest known risk during pregnancy