Disentangling antidepressants from maternal psychiatric disease
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Antidepressant use before and during pregnancy may be associated with an increased risk of psychiatric disorders in offspring, according to the results of a population-based cohort study published Sept. 7 in the BMJ.

There have been contradictory findings in the literature about whether in utero exposure to SSRIs is associated with autism spectrum disorder and ADHD. “However, these studies did not investigate the overall risk of psychiatric disorders, which is important because differentiating between overlapping symptoms and diagnosing specific disorders are challenging in children and adolescents,” Xiaoqin Liu, MD, PhD, of Aarhus University in Denmark, and her coauthors wrote (BMJ 2017;358:j3668. doi: 10.1136/bmj.j3668).

Antonio_Diaz/Thinkstock
To address this, they used data from Danish national registries to follow 905,383 liveborn singletons from birth for a maximum of 16.5 years.

Participants were categorized into four groups based on maternal use of antidepressants; unexposed, antidepressant discontinuation (if the mother had used in the 2 years before but not during pregnancy), antidepressant continuation (if the use happened in the 2 years before pregnancy and during it), and new users (if antidepressant use happened only during pregnancy).

The study found that children whose mothers used antidepressants both in the 2 years before pregnancy and during pregnancy had a 27% higher incidence of any psychiatric disorder, compared with children whose mothers had used antidepressants but discontinued them before becoming pregnant (95% confidence interval, 1.17-1.38).

This figure was adjusted for factors such as maternal age and psychiatric history at delivery, psychiatric treatment in the 2 years before pregnancy, other psychotropic medications used during pregnancy, and paternal psychiatric history at the time of delivery.

Any maternal antidepressant use was associated with an increased risk of psychiatric disorders in the offspring, compared with the unexposed group. The 15-year cumulative incidence of psychiatric disorders in offspring was 8% in the unexposed group, 11.5% in the discontinuation group, 13.6% in the continuation group, and 14.5% in the new user group.

There were no differences in risk between children exposed to SSRI monotherapy and those exposed to non-SSRI monotherapy, although the statistical precision for the latter was low, the researchers noted. However, they did see a lower risk of psychiatric disorder in children who were exposed only during the first trimester, compared with those exposed in the second or third trimesters.

The researchers suggested that the association between in utero exposure and the risk of psychiatric disorders in offspring may be the result of a combination of underlying maternal disorders and in utero antidepressant exposure. “We speculated that this increased risk could be due to the severity of underlying maternal psychiatric disorders because mothers with severe symptoms are more likely to continue treatment during pregnancy,” they wrote.

The researchers cautioned that discontinuation of treatment could lead to psychiatric episodes that could have long-lasting effects on both mother and child.

The investigators reported support from several research foundations, as well as institutional grants from Sage Therapeutics and Janssen. No conflicts of interest were declared.

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Only the most severely sick women have drugs prescribed during pregnancy. Consequently, confounding by indication is a major challenge in pharmacoepidemiological studies. Including a disease comparison group with women discontinuing antidepressants before pregnancy, as in Liu and her colleagues’ study, offers an important advantage over studies that use only healthy comparison groups because it allows researchers to disentangle the effect of antidepressants from the underlying maternal psychiatric disease.

It is important that researchers report absolute risks to facilitate communication between clinicians and pregnant women. For example, if prenatal exposure to antidepressants is associated with a 23% increased risk of autism in children, and if we assume a baseline prevalence of autism of 1%, then for every 10,000 women who continue treatment during pregnancy, 23 additional cases of autism would occur. This number may be alarming to some patients and reassuring to others.
 

Hedvig Nordeng, PhD, Angela Lupattelli, PhD, and Mollie Wood, PhD, are from the University of Oslo. These comments are adapted from an accompanying editorial (BMJ 2017;358:j3950 doi: 10.1136/bmj.j3950). No conflicts of interest were declared.

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Only the most severely sick women have drugs prescribed during pregnancy. Consequently, confounding by indication is a major challenge in pharmacoepidemiological studies. Including a disease comparison group with women discontinuing antidepressants before pregnancy, as in Liu and her colleagues’ study, offers an important advantage over studies that use only healthy comparison groups because it allows researchers to disentangle the effect of antidepressants from the underlying maternal psychiatric disease.

It is important that researchers report absolute risks to facilitate communication between clinicians and pregnant women. For example, if prenatal exposure to antidepressants is associated with a 23% increased risk of autism in children, and if we assume a baseline prevalence of autism of 1%, then for every 10,000 women who continue treatment during pregnancy, 23 additional cases of autism would occur. This number may be alarming to some patients and reassuring to others.
 

Hedvig Nordeng, PhD, Angela Lupattelli, PhD, and Mollie Wood, PhD, are from the University of Oslo. These comments are adapted from an accompanying editorial (BMJ 2017;358:j3950 doi: 10.1136/bmj.j3950). No conflicts of interest were declared.

Body

 

Only the most severely sick women have drugs prescribed during pregnancy. Consequently, confounding by indication is a major challenge in pharmacoepidemiological studies. Including a disease comparison group with women discontinuing antidepressants before pregnancy, as in Liu and her colleagues’ study, offers an important advantage over studies that use only healthy comparison groups because it allows researchers to disentangle the effect of antidepressants from the underlying maternal psychiatric disease.

It is important that researchers report absolute risks to facilitate communication between clinicians and pregnant women. For example, if prenatal exposure to antidepressants is associated with a 23% increased risk of autism in children, and if we assume a baseline prevalence of autism of 1%, then for every 10,000 women who continue treatment during pregnancy, 23 additional cases of autism would occur. This number may be alarming to some patients and reassuring to others.
 

Hedvig Nordeng, PhD, Angela Lupattelli, PhD, and Mollie Wood, PhD, are from the University of Oslo. These comments are adapted from an accompanying editorial (BMJ 2017;358:j3950 doi: 10.1136/bmj.j3950). No conflicts of interest were declared.

Title
Disentangling antidepressants from maternal psychiatric disease
Disentangling antidepressants from maternal psychiatric disease

 

Antidepressant use before and during pregnancy may be associated with an increased risk of psychiatric disorders in offspring, according to the results of a population-based cohort study published Sept. 7 in the BMJ.

There have been contradictory findings in the literature about whether in utero exposure to SSRIs is associated with autism spectrum disorder and ADHD. “However, these studies did not investigate the overall risk of psychiatric disorders, which is important because differentiating between overlapping symptoms and diagnosing specific disorders are challenging in children and adolescents,” Xiaoqin Liu, MD, PhD, of Aarhus University in Denmark, and her coauthors wrote (BMJ 2017;358:j3668. doi: 10.1136/bmj.j3668).

Antonio_Diaz/Thinkstock
To address this, they used data from Danish national registries to follow 905,383 liveborn singletons from birth for a maximum of 16.5 years.

Participants were categorized into four groups based on maternal use of antidepressants; unexposed, antidepressant discontinuation (if the mother had used in the 2 years before but not during pregnancy), antidepressant continuation (if the use happened in the 2 years before pregnancy and during it), and new users (if antidepressant use happened only during pregnancy).

The study found that children whose mothers used antidepressants both in the 2 years before pregnancy and during pregnancy had a 27% higher incidence of any psychiatric disorder, compared with children whose mothers had used antidepressants but discontinued them before becoming pregnant (95% confidence interval, 1.17-1.38).

This figure was adjusted for factors such as maternal age and psychiatric history at delivery, psychiatric treatment in the 2 years before pregnancy, other psychotropic medications used during pregnancy, and paternal psychiatric history at the time of delivery.

Any maternal antidepressant use was associated with an increased risk of psychiatric disorders in the offspring, compared with the unexposed group. The 15-year cumulative incidence of psychiatric disorders in offspring was 8% in the unexposed group, 11.5% in the discontinuation group, 13.6% in the continuation group, and 14.5% in the new user group.

There were no differences in risk between children exposed to SSRI monotherapy and those exposed to non-SSRI monotherapy, although the statistical precision for the latter was low, the researchers noted. However, they did see a lower risk of psychiatric disorder in children who were exposed only during the first trimester, compared with those exposed in the second or third trimesters.

The researchers suggested that the association between in utero exposure and the risk of psychiatric disorders in offspring may be the result of a combination of underlying maternal disorders and in utero antidepressant exposure. “We speculated that this increased risk could be due to the severity of underlying maternal psychiatric disorders because mothers with severe symptoms are more likely to continue treatment during pregnancy,” they wrote.

The researchers cautioned that discontinuation of treatment could lead to psychiatric episodes that could have long-lasting effects on both mother and child.

The investigators reported support from several research foundations, as well as institutional grants from Sage Therapeutics and Janssen. No conflicts of interest were declared.

 

Antidepressant use before and during pregnancy may be associated with an increased risk of psychiatric disorders in offspring, according to the results of a population-based cohort study published Sept. 7 in the BMJ.

There have been contradictory findings in the literature about whether in utero exposure to SSRIs is associated with autism spectrum disorder and ADHD. “However, these studies did not investigate the overall risk of psychiatric disorders, which is important because differentiating between overlapping symptoms and diagnosing specific disorders are challenging in children and adolescents,” Xiaoqin Liu, MD, PhD, of Aarhus University in Denmark, and her coauthors wrote (BMJ 2017;358:j3668. doi: 10.1136/bmj.j3668).

Antonio_Diaz/Thinkstock
To address this, they used data from Danish national registries to follow 905,383 liveborn singletons from birth for a maximum of 16.5 years.

Participants were categorized into four groups based on maternal use of antidepressants; unexposed, antidepressant discontinuation (if the mother had used in the 2 years before but not during pregnancy), antidepressant continuation (if the use happened in the 2 years before pregnancy and during it), and new users (if antidepressant use happened only during pregnancy).

The study found that children whose mothers used antidepressants both in the 2 years before pregnancy and during pregnancy had a 27% higher incidence of any psychiatric disorder, compared with children whose mothers had used antidepressants but discontinued them before becoming pregnant (95% confidence interval, 1.17-1.38).

This figure was adjusted for factors such as maternal age and psychiatric history at delivery, psychiatric treatment in the 2 years before pregnancy, other psychotropic medications used during pregnancy, and paternal psychiatric history at the time of delivery.

Any maternal antidepressant use was associated with an increased risk of psychiatric disorders in the offspring, compared with the unexposed group. The 15-year cumulative incidence of psychiatric disorders in offspring was 8% in the unexposed group, 11.5% in the discontinuation group, 13.6% in the continuation group, and 14.5% in the new user group.

There were no differences in risk between children exposed to SSRI monotherapy and those exposed to non-SSRI monotherapy, although the statistical precision for the latter was low, the researchers noted. However, they did see a lower risk of psychiatric disorder in children who were exposed only during the first trimester, compared with those exposed in the second or third trimesters.

The researchers suggested that the association between in utero exposure and the risk of psychiatric disorders in offspring may be the result of a combination of underlying maternal disorders and in utero antidepressant exposure. “We speculated that this increased risk could be due to the severity of underlying maternal psychiatric disorders because mothers with severe symptoms are more likely to continue treatment during pregnancy,” they wrote.

The researchers cautioned that discontinuation of treatment could lead to psychiatric episodes that could have long-lasting effects on both mother and child.

The investigators reported support from several research foundations, as well as institutional grants from Sage Therapeutics and Janssen. No conflicts of interest were declared.

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Key clinical point: Children exposed to antidepressants in utero have a significantly increased risk of psychiatric illness.

Major finding: Children whose mothers took antidepressants both before and during pregnancy are 27% more likely to develop psychiatric illness than are those whose mothers stopped taking antidepressants before pregnancy.

Data source: A population-based cohort study in 905,383 liveborn singletons.

Disclosures: The investigators reported support from several research foundations, as well as institutional grants from Sage Therapeutics and Janssen. No conflicts of interest were declared.

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