Mixing Opioid and Psychotropic Drugs Boosts Neonatal Withdrawal Risk

Bridget M. Kuehn

August 02, 2017

Infants exposed to opioids and psychotropic drugs during pregnancy have a 30% to 60% higher risk of experiencing neonatal withdrawal, a study has found. That risk doubles when multiple psychotropic drugs are prescribed alongside opioids.

Krista Huybrechts, PhD, assistant professor of medicine at Harvard Medical School, Boston, Massachusetts, and colleagues published their findings August 2 in the BMJ.

"[O]ur findings suggest that among women using prescription opioids during pregnancy, co-exposure to antidepressants, benzodiazepines, and gabapentin might be associated with an increased risk of drug withdrawal in the neonate," the authors write.

The researchers analyzed data on more than 200,000 women insured by Medicaid who filled a prescription for an opioid analgesic within 45 days of delivery. The absolute risk for neonatal withdrawal after opioid exposure during pregnancy was just 1.0%, but the risks increased with concomitant exposure to psychotropic drugs. The highest absolute risk was seen in babies exposed to opioids and gabapentin (11.4%).

The relative risk for withdrawal was 34% higher for babies exposed to opioids and antidepressants, 49% higher with concomitant use of opioids and benzodiazepines, and 61% with concomitant use of opioids and gabapentin compared with opioid use alone. No similar increase in withdrawal risk was seen in babies exposed to opioids and antipsychotics or opioids and nonbenzodiazepine hypnotics. The risk for withdrawal doubled when neonates were born having been exposed to multiple psychotropic drugs and opioids.

Infants exposed to both psychotropic drugs and opioids also had more severe withdrawal symptoms.

The findings suggest "clinicians should be cautious in prescribing these medications together in late pregnancy and in prescribing psychotropic medications to women with known or suspected illicit opioid use," the authors write. "Because pain and mental health conditions often occur together, co-exposure will be unavoidable in many instances."

A US infant is born experiencing drug withdrawal approximately once every 25 minutes, the authors explain. Babies born with this complication may not feed or sleep well and may be irritable, and in severe cases, they may have seizures, poor thermoregulation, difficulty breathing, or failure to thrive.

Although some cases are associated with maternal use of illicit opioids, growing use of prescription opioids among pregnant women also contributes. Between 14% and 22% of US pregnancies are complicated by prescription opioid use, the researchers add.

These complications are among many linked to rising use of prescription opioids in the United States during the last 2 decades, which has contributed to an epidemic of overdoses that now claims more lives annually than car crashes, Stephen Patrick, MD, MPH, assistant professor of pediatrics and public policy at Vanderbilt School of Medicine, Nashville, Tennessee, and colleagues note in an accompanying editorial.

"Given the rise and scope of the US opioid epidemic, it should not be a surprise that nearly every segment of society has been affected," they write.

In addition to having implications for prenatal treatment, the results may help better target newborn withdrawal screening and influence treatment protocols for polydrug-exposed babies, the editorialists write. They say comprehensive, evidence-based strategies for opioid prescribing during pregnancy are needed. Specifically, they highlight the importance of interventions in both public health and clinical settings that promote the health of women and their babies, starting before pregnancy through after birth.

"As the US opioid epidemic accelerates in complexity, there is an urgent need to focus resources on this issue, including expansion of research funding for drug safety in pregnancy and improvement of outcomes for mothers and infants affected by opioid use disorder, more funding for prevention of the disorder, and an expansion of treatment options for affected mothers and their infants," the editorialists wrote.

The authors disclose consulting for AstraZeneca and UCB, as well as study funding from Eli Lilly, Pfizer, Baxalta, Boehringer Ingelheim, and GlaxoSmithKline. These consulting and study funds were unrelated to the study topic, the authors report. The editorial authors have disclosed no relevant financial relationships.

BMJ. 2017;358:j3326, j3616. Article, Editorial

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