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Significant increase in neonatal drug withdrawal with combination drug use
There was a 30% to 60% increase in the risk for of neonatal drug withdrawal associated with co-exposure to psychotropic medications and opioids compared with opioids alone, according to a cohort study just published in BMJ.
“Whereas intrauterine exposure to psychotropic medications has been used as a risk stratification factor the risks of neonatal drug withdrawal in those exposed to opioids during the pregnancy with or without co-exposure to individual and combinations of psychotropic medications have not previously been examined,” Krista F. Huybrechts, MS, PhD, of the department of medicine, Brigham and Women’s Hospital and Harvard Medical School, and colleagues wrote. “Little is therefore known about how this risk varies by the type of psychotropic medication or about the risks associated with psychotropic polypharmacy.”
To gather more information, researchers looked at the impact of in utero co-exposure to antidepressants, atypical antipsychotics, benzodiazepines, gabapentin, and nonbenzodiazepine hypnotics (Z drugs), among newborns of 201,275 pregnant women with prescriptions for these drugs filled within the same time window as opioid prescriptions. The women were part of the Medicaid Analytic eXtract from 2000 to 2010.
Researchers found that the absolute risk for neonatal drug withdrawal ranged from 1% in infants exposed in utero to prescription opioids alone to 11.4% for those exposed to opioids co-prescribed with gabapentin.
In addition, among infants exposed to prescription opioids and when adjusted for propensity score, the RRs for neonatal drug withdrawal were 1.01 (95% CI, 0.88-1.15) for those also exposed to Z drugs; 1.2 (95% CI, 0.95-1.51) for those exposed to antipsychotics; 1.34 (95% CI, 1.22-1.47) for those exposed to antidepressants; 1.49 (95% CI, 1.35-1.63) for those exposed to benzodiazepines; and 1.61 (95% CI, 1.26-2.06) for those exposed to gabapentin.
Researchers found that exposure to two or more psychotropic medications along with opioids was associated with a twofold increased risk of withdrawal (RR = 2.05; 95% CI, 1.77-2.37), and the withdrawal’s graveness speared increased in neonates exposed to both opioids and psychotropic medications compared with opioids alone.
“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. Because pain and mental health conditions often occur together, co-exposure will be unavoidable in many instances. In those cases, our findings might be helpful in risk stratification for exposed infants,” Huybrechts and colleagues wrote. “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.
In a related editorial, Stephen W. Patrick, MD, MPH, MS, of Vanderbilt University, and colleagues wrote that the study underscores the need for additional research that considers both mother and unborn child.
“There remains a paucity of clinical guidance for obstetricians and pediatricians caring for the mother-child unit; development of a strategy will help to prioritize the development of specific evidence,” they wrote. “To be effective, the strategy would specify opportunities for intervention in clinical and public health settings in all time periods related to prepregnancy, antepartum/prenatal, peripartum/perinatal, and postpartum/infancy.”
– by Janel Miller
Disclosure: Huybrechts reports receiving funding from Eli Lilly and Pfizer. Patrick reports no relevant financial disclosures. Please see the study for a full list of the other author’s relevant financial disclosures