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SSRI Exposure Linked to Abnormal Fetal Neurobehavioral Development

In this study, scientists in the Netherlands added new information to the evidence base linking the use of SSRI antidepressants by pregnant women with damaging effects on the neurobehavioral development of the fetus and newborn.

Several studies have found associations between maternal use of SSRIs and neurodevelopmental defects in babies, including autism, low Apgar scores, and delays in achieving developmental milestones at 6 and 19 months. The authors of this study explain that infants exposed to SSRIs during pregnancy are often seen to exhibit restlessness, jitteriness, and sleep disturbances at birth. However, it is unknown if these symptoms are withdrawal symptoms – a consequence of separation from the mother at birth - or the result of drug effects on fetal development that were ongoing before birth. This research was designed to help answer that question by examining the effects of SSRIs on the developing fetus.

Several studies have found associations between maternal use of SSRIs and neurodevelopmental defects in babies, including autism, low Apgar scores, and delays in achieving developmental milestones at 6 and 19 months.Women being treated for a psychiatric disorder (primarily depression) who took SSRIs throughout their pregnancies were compared to a group of healthy women with no history of psychiatric or other illnesses who did not take antidepressants and whose babies were born healthy at full term with no complications. To separate the effects of SSRIs from the possible effects of the psychiatric disorder itself, the study design included a third group of women who were also being treated for a psychiatric disorder but discontinued medication use early in their pregnancies or before conception. The medicated and unmedicated groups (those under psychiatric care) had similar scores on tests measuring anxiety and depression.

Ultrasonographic observations of fetal behavior were made at the beginning and end of the second trimester and near term. The effects of SSRIs were studied for low, standard, and high drug dosages. The researchers found that fetuses exposed to standard or high SSRI dosages showed increased bodily activity at the beginning and end of the second trimester. The non-rapid eye movement (non-REM) sleep of the SSRI exposed fetuses was particularly disrupted by increased bodily activity near term. These effects were not seen in the non-medicated groups. The SSRI effects on the fetus were dose related.

These results indicate that exposure to SSRIs, not the mother's mental or emotional condition, are causing the fetal neurobehavioral effects seen in this study. At near term, say the authors, a fetus would normally show "episodes of rest and activity … linked to absence and presence of eye movements, respectively." The disruption of non-REM sleep and the presence of activity during a period that should be marked by rest is, say the authors, "abnormal," and could be a precursor to long-term neurobehavioral effects.

Though not mentioned in this study, the negative effects of SSRI antidepressants on sleep in adults are well established, and include the agitated bodily movement seen in this study. Dr. John Winkelman, an assistant professor of psychiatry at Harvard Medical School, summarized the sleep effects of SSRIs on normal volunteers in Psychiatry Weekly. According to Dr. Winkelman, SSRIs have profound effects on REM sleep, which contributes to subjective and behavioral toxicity for sleep." One result is vivid dreams in which "patients can end up acting out their dreams by thrashing, kicking, or propelling themselves out of bed." (SSRI users frequently report having nightmares.) The condition is known as REM sleep disorder and as far back as 2003,the New York Times reported that "sleep clinics are also seeing a number of patients who develop some symptoms associated with REM sleep disorder while taking Prozac, Zoloft or others of the newer generation of antidepressant drugs called selective serotonin reuptake inhibitors or S.S.R.I.'s." The story noted that "some people taking the drugs experience muscle jerks or other movements during sleep or waking."

If SSRIs can have these effects on normal adults, it should come as no surprise that the drugs could have similar and perhaps even more profound effects on a developing baby.

Summary Information

SSRI exposure linked to abnormal fetal neurobehavioral development

Eduard JH Mulder 1, Frederique FT Ververs 2, Roel de Heus 1, and Gerard HA Visser 1

  1. Department of Perinatology and Gynecology, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The Netherlands
  2. Department of Clinical Pharmacy, University Medical Centre, Utrecht, The Netherlands

Neuropsychopharmacology 2011 Sept 1;36(10):1961-71. Published online 27 Apr 2011.

A financial contribution in laboratory costs came from The Netherlands Brain Foundation.

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