The average age of diagnosis for speech/language disorders among the children was 4.4 years; for scholastic disorders, 3.5 years; and for motor disorders, 7.7 years.
In addition to having a large sample size and 14-year follow-up, the new study is believed to be the first to evaluate the three key measures of mental function.
“To our knowledge, no previous study examined associations between maternal SSRI use and clinical speech/language, scholastic, or motor disorders in offspring,” the authors write.
Dr Brown said it was not surprising that a greater risk was found only for speech and language disorders, not other disorders.
“Antidepressant effects are not expected to affect development of all neural circuits,” he explained. “It is also possible that there might be findings if larger numbers of cases are included.”
Neurobiological studies are needed to better understand the mechanisms of the speech and language effects, he added.
“To date, these have not been conducted to examine speech and language function,” Dr Brown noted. “Serotonin does play a significant role in the development of neural circuits, however, and thus the finding is plausible.”
No Causal Link
In an accompanying commentary, Lee S. Cohen MD, and Ruta Nonacs, MD, PhD, of the Ammon-Pinizzotto Center for Women’s Mental Health, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, write that the study addresses the common concern regarding the effects of the use of SSRIs, or any drug, on the fetus during pregnancy, but it does not address the issue of the risks of treatment vs nontreatment.
“Data suggest a prevalence of SSRI use of 5% to 10% during pregnancy, and regardless of the current reproductive safety data for SSRIs, even women with highly recurrent or long-term depression invariably prefer to avoid fetal exposure to these medications if at all possible,” they write.
“But the current report does not answer whether exposure to SSRIs or untreated depression during pregnancy are in equipoise with respect to neurodevelopmental toxicity or if, over the long-term, one confers greater risk.”
In further commenting on the study to Medscape Medical News, Shari I. Lusskin, MD, clinical professor of psychiatry, obstetrics, gynecology, and reproductive sciences at the Icahn School of Medicine at Mount Sinai in New York City, agrees, noting several important limitations.
“I think the study does not lend support for a causal relationship between SSRI exposure and developmental delays, despite the positive findings,” she says.
“This is another example of studies which attempt to answer important questions about the long-term effect of medication exposure during pregnancy but are not able to answer those questions fully due to limitations.”
The authors note that key limitations include the fact that severity of maternal depression may have confounded the results, and data on maternal alcohol use was not available. Dr Lusskin noted that further limitations include a lack of information on such key factors as the specific types of drugs used, the trimester of use, and parental IQ.
“If the parents have developmental delays or limited intellectual function, then the children may have delays as well, so any neurodevelopmental study really needs to control for parental IQ.”
Dr Lusskin also questioned the duration of the speech and language delays. “If the child was diagnosed at age 2.8, for instance, the question is whether they still have the diagnosis at age 6.”
She added that overall, heavy emphasis should still be placed on treatment of depression in pregnant women.
“This study does not change my clinical recommendation that depression be treated to remission during pregnancy and postpartum to minimize negative effects on the child.”
Regarding information on the type of drug and trimester, Dr Brown told Medscape the researchers “didn’t have a sufficient number of cases to examine those questions in this study but hope to do so in a future study.”
He also underscored the editorialists’ concerns regarding untreated depression.
“Of course, depression in pregnancy is harmful to the mother with regard to subjective distress and impairment in functioning. Depression in pregnancy also has adverse outcomes, as we observed in this study,” Dr Brown said.
He noted that although nonpharmacologic alternatives, such as psychotherapy and transcranial magnetic stimulation, are available for treatment during pregnancy, the decision should be carefully considered with respect to the patients’ needs.
“For severe depression such as depression that included suicidality or psychosis, it may be more advisable in many cases to maintain the SSRI treatment, because the risks of recurrence could outweigh the potential risk of speech and language disorders,” Dr Brown said.
“This decision should be made by the patient in consultation with her physician.”
The study received funding from the National Institutes of Health, the Sackler Foundation of Columbia University, and Turku University. The authors have disclosed various relationships with industry, which are listed in the original article. Dr Lusskin is consultant and director of psychopharmacologic agents at the Reproductive Toxicology Foundation, a nonprofit foundation. She is also a peer reviewer for UpToDate and is a consultant to Pfizer, Inc, regarding Zoloft and Effexor litigation.
JAMA Psychiatry. Published online October 12, 2016