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Opioids such as neonatal morphine solution and methadone are commonly used to treat clinical symptoms of opiate withdrawal, but may prolong drug exposure and duration of hospitalization. A study published in the Journal of Pediatric Pharmacology and Therapeutics demonstrated a significantly shorter wean duration in infants treated with methadone compared to diluted tincture of opium. Methadone possesses a longer half-life in children than morphine, which may allow less frequent daily dosing and provide steady serum concentrations to prevent neonatal withdrawal symptoms.

Non-pharmacological approaches to treat neonatal symptoms include swaddling the infant in a blanket, minimizing environmental stimuli, and monitoring sleeping and feeding patterns. Breastfeeding is also associated with a decreased need for pharmacological treatment while promoting infant attachment and bonding. These approaches may lessen the severity of NAS and also lead to shorter hospital stays.