Current management of the neonatal abstinence syndrome: a critical analysis of the evidence.
OBJECTIVE
To systematically and critically analyse and summarise the published evidence for the rational choice of pharmacologic treatment of the neonatal abstinence syndrome (NAS), a frequently observed condition in neonates born to mothers who are dependent on physically addicting drugs.


METHODS
Studies comparing different pharmacological agents for the treatment of NAS were identified utilising MEDLINE and additionally the references cited in pertinent articles. The identified studies were critically analysed regarding their study designs and outcome measures. The reported data for the comparative efficacy of the drugs were summarised and evaluated.


RESULTS
Fourteen studies were identified, most of them comparing treatment of NAS with phenobarbital, paregoric or diazepam. However, none of these studies was conducted in a double-blind fashion. Frequently, treatment allocations were not properly randomised. Prenatal drug exposure varied and was often not sufficiently verified. Outcome measures and their evaluations differed widely. Due to the different study objectives and flaws in study design, a combined analysis of the published data in the form of a meta-analysis was not deemed possible. When attempting to compare efficacy, diazepam appears to be less efficacious in treating NAS than phenobarbital or paregoric. The relative efficacy of paregoric and phenobarbital appears to depend upon the antenatal exposure of the neonate and on the outcome measure of the study. Only two studies evaluate the efficacy of pure opioids, none of them in direct comparison to paregoric. It remains questionable whether paregoric, which contains the central stimulant camphor and a large amount of alcohol, should be the opioid of choice for the treatment of NAS.


CONCLUSIONS
Most published studies were conducted prior to the development of clinical epidemiology and modern study design and thus yielded only very limited comparative data on the benefits of different treatment protocols. There is very little evidence regarding the efficacy of different pharmacological therapy regimens to treat NAS. More studies are required to produce the evidence needed to allow a rational choice between treatment modalities of NAS and thus to ensure optimal care of the neonates suffering from this condition.
Theis
J G
JG
Department of Pediatrics, Hospital for Sick Children, University of Toronto, Ont., Canada.
Selby
P
P
Ikizler
Y
Y
Koren
G
G
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002746:Chlorpromazine / Q000008:administration & dosage / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards*; D003000:Clonidine / Q000008:administration & dosage / Q000627:therapeutic use; D003975:Diazepam / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000627:therapeutic use; D007231:Infant, Newborn; D016239:MEDLINE; D008691:Methadone / Q000008:administration & dosage / Q000627:therapeutic use; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use; D009357:Neonatal Abstinence Syndrome / Q000188:drug therapy*; D009892:Opium / Q000008:administration & dosage / Q000627:therapeutic use; D010276:Parasympatholytics / Q000008:administration & dosage / Q000627:therapeutic use; D010634:Phenobarbital / Q000008:administration & dosage / Q000627:therapeutic use; D013565:Sympatholytics / Q000008:administration & dosage / Q000627:therapeutic use
D000701:Analgesics, Opioid; D000927:Anticonvulsants; D014150:Antipsychotic Agents; D006993:Hypnotics and Sedatives; D010276:Parasympatholytics; D013565:Sympatholytics; D009020:Morphine; D009892:Opium; C017652:paregoric; D003000:Clonidine; D003975:Diazepam; D002746:Chlorpromazine; D008691:Methadone; D010634:Phenobarbital