Neonatal Drug Withdrawal Risk Increased With Opioid Plus Psychotropic Drugs

infant in intensive care unit
infant in intensive care unit
Risk for neonatal drug withdrawal was substantially higher in newborns exposed to both opioids and psychotropic drugs than in those exposed to opioids alone.

Newborns of women using prescription opioids and psychotropic medications during pregnancy are at a higher risk for neonatal drug withdrawal than those exposed to opioids alone, according an observational cohort study published in the BMJ.

Krista F. Huybrechts, PhD, from the Department of Medicine at the Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, and colleagues gathered data from the nationwide Medicaid Analytic Extract for 2000-2010 for 201,275 publicly insured pregnant women who had filled at least 1 opioid analgesic prescription within 45 days of delivery.

Among this group, 14,183 (7.0%) had also filled a prescription for an antidepressant, 993 (0.5%) for an atypical antipsychotic (referred to as an antipsychotic hereafter), 5361 (2.7%) for benzodiazepine, 501 (0.3%) for gabapentin, and 10,105 (5.0%) for a nonbenzodiazepine hypnotic (referred to as Z drug hereafter).

The overall risk for neonatal drug withdrawal was substantially higher among women who were using both opioid and psychotropic medications vs women using opioids alone. In an adjusted analysis, the risk increased for antidepressants (1.34; 95% CI, 1.22-1.47), antipsychotics (1.20; 95% CI, 0.95-1.51), benzodiazepines (1.49; 95% CI, 1.35-1.63), gabapentin (1.61; 95% CI, 1.26-2.06), and Z drugs (1.01; 95% CI, 0.88-1.15).

The risk for neonatal drug withdrawal nearly doubled with exposure to 2 or more psychotropic medications vs exposure to 1 additional psychotropic medication (2.05 [95% CI, 1.77-2.37] vs 1.37 [95% CI, 1.26-1.49], respectively).

“[C]linicians should be cautious in prescribing these medications together in late pregnancy and in prescribing psychotropic medications to women with known or suspect illicit opioid use,” noted Dr Huybrechts and colleagues. “Our findings also imply that it will be important for neonatologists and pediatricians to rethink treatment protocols for infants born to women who were prescribed multiple drugs during their pregnancy.”

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Study Limitations

  • Researchers did not have meconium or cord toxicology to document fetal exposure.
  • Although the results showed a doubling of risk in infants exposed to 2 or more medications, pediatricians may be more likely to diagnose infants with drug withdrawal when aware of the exposure to polypharmacy.
  • The study did not evaluate the infants of women who were taking buprenorphine or methadone as a maintenance treatment.
  • The study evaluated severity of drug withdrawal using secondary proxies, as Finnegan scores were not available.
  • The study did not have data on breast-feeding, which may reduce the severity of drug withdrawal.
  • The data used reflected women who filled an opioid and psychotropic medication, but there is no direct evidence the women took the medications or took them as intended, which could mean the risk was understated.


  1. Huybrechts KF, Bateman BT, Desai RJ, et al. Risk of neonatal drug withdrawal after intrauterine co-exposure to opioids and psychotropic medications: cohort study. BMJ. 2017;358:j3326.