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In utero coexposure to opioids, psychotropic medications ups risk of neonatal drug withdrawal

Stephen Padilla
09 Aug 2017

The use of psychotropic medications during pregnancy, in addition to antidepressants, benzodiazepines and gabapentin, appears to be associated with an increased risk and severity of neonatal drug withdrawal, suggests a recent study.

“In this cohort of 201,275 pregnancies in women who used prescription opioids close to delivery, we observed a 30 to 60-percent increase in the risk of neonatal drug withdrawal associated with coexposure to antidepressants, benzodiazepines and gabapentin,” researchers said.

Infants exposed in utero to prescription opioids had a 1.0-percent absolute risk for neonatal drug withdrawal, which went as high as 11.4 percent for those exposed to opioids coprescribed with gabapentin. [BMJ 2017;358:j3326]

The relative risk adjusted for propensity score among neonates exposed in utero to prescription opioids was 1.34 (95 percent CI, 1.22 to 1.47) with concomitant exposure to antidepressants, 1.49 (1.35 to 1. 63) with benzodiazepines, 1.61 (1.26 to 2.06) with gabapentin, 1.20 (0.95 to 1.51) with antipsychotics, and 1.01 (0.88 to 1.15) with nonbenzodiazepine hypnotics (Z drugs).

The results for gabapentin are in line with previous observations of withdrawal symptoms in the adult population after abrupt terminations of high-dose gabapentin, as well as observations in a recently published case series of 19 infants exposed prenatally to both opioids and gabapentin. [Clin Neuropharmacol 2001;358:245-6; Ann Pharmacother 2016;358:229-33; J Pediatr 2017;358:286-8]

“This is especially concerning as gabapentin is being prescribed more often for control of pain,” researchers said. “It has also been suggested that gabapentin is sometimes used illicitly to enhance the ‘high’ associated with methadone treatment.”

Furthermore, neonates born to women who used two or more psychotropic medications along with opioids during pregnancy had a twofold increased risk of withdrawal (2.05; 1.77 to 2.37). Moreover, it appeared that withdrawal severity was increased in neonates exposed to both opioids and psychotropic medications compared with opioids alone.

The findings of elevated risks of drug withdrawal among neonates born to women using opioids with concomitant exposure to antidepressants, benzodiazepines or gabapentin suggest that clinicians should be prudent in prescribing such medications together in late pregnancy and in prescribing psychotropic drugs to women with known or suspected illicit opioid use.

“Because pain and mental health conditions often occur together, coexposure will be unavoidable in many instances. In those cases, our findings might be helpful in risk stratification for exposed infants,” researchers said.

“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,” they added.

In this observational cohort study, researchers observed pregnant women with public insurance who were exposed to opioids around the time of delivery and their liveborn infants. Interventions included in utero exposure to psychotropic drugs, particularly atypical antipsychotics, benzodiazepines, gabapentin and Z drugs, with prescriptions filled within the same time window as prescriptions for opioids.

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