Clonidine as an Adjunct Therapy to Opioids for Neonatal Abstinence Syndrome: A Randomized, Controlled Trial

Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
PEDIATRICS (Impact Factor: 5.47). 05/2009; 123(5):e849-56. DOI: 10.1542/peds.2008-0978
Source: PubMed


To determine if oral clonidine would reduce the duration of opioid detoxification for neonatal abstinence syndrome.
Infants with intrauterine exposure to methadone or heroin and neonatal abstinence syndrome (2 consecutive modified Finnegan scores of > or =9) were enrolled at 2 hospitals during 2002-2005 and followed until final hospital discharge. All enrolled infants (80) received oral diluted tincture of opium according to a standardized algorithm and were randomly assigned to receive oral clonidine (1 microg/kg every 4 hours) (40 infants) or placebo (40 infants). Primary outcome was duration of opioid therapy. Secondary outcomes included the amount of opium required to control symptoms, number of treatment failures, and differences in blood pressure, heart rate, and oxygen saturation.
The median length of therapy was 27% shorter in the clonidine group (11 [95% confidence interval: 8-15 days]) than in the placebo group (15 days [95% confidence interval: 12-17 days]). In the clonidine group, 7 infants required restarting opium after initial discontinuation versus none in the placebo group, with the total length of treatment/observation remaining significantly less in the clonidine group. Higher dosages of opium were required by 40% of the infants in the placebo group versus 20% in the clonidine group. Treatment failures occurred in 12.5% of the infants in the placebo group versus none in the clonidine group. Hypertension, hypotension, bradycardia, or desaturations did not occur in either group. Three infants in the clonidine group died as a result of myocarditis, sudden infant death syndrome, and homicide, all after hospital discharge and before 6 months of age.
In this randomized, double-blind trial, adding clonidine to standard opioid therapy for detoxification from in utero exposure to methadone or heroin reduced the duration of pharmacotherapy for neonatal abstinence without causing short-term adverse cardiovascular outcomes. A larger trial is indicated to determine long-term safety.

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Available from: Lauren M Jansson, Oct 08, 2015
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    • "Another pharmacological agent, which demonstrates some promise and may have the potential to be an alternative to opiates, is clonidine, an α2-adrenergic receptor agonist. Preliminary trials have suggested that clonidine compared to, or in addition to, opiates markedly reduces treatment failure, withdrawal symptoms, duration of therapy, and/or duration of opiate use and maximum dosage required [72–74]. Given the possible safety issues associated with clonidine, however, the guidelines recommend that further clinical trials are required to establish its efficacy and safety in the long term [6, 28]. "
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    ABSTRACT: Illicit drug use with opiates in pregnancy is a major global health issue with neonatal withdrawal being a common complication. Morphine is the main pharmacological agent administered for the treatment of neonatal withdrawal. In the past, morphine has been considered by and large inert in terms of its long-term effects on the central nervous system. However, recent animal and clinical studies have demonstrated that opiates exhibit significant effects on the growing brain. This includes direct dose-dependent effects on reduction in brain size and weight, protein, DNA, RNA, and neurotransmitters-possibly as a direct consequence of a number of opiate-mediated systems that influence neural cell differentiation, proliferation, and apoptosis. At this stage, we are stuck between the devil and the deep blue sea. There are no real alternatives to pharmacological treatment with opiates and other drugs for neonatal opiate withdrawal and opiate addiction in pregnant women. However, pending further rigorous studies examining the potential harmful effects of opiate exposure in utero and the perinatal period, prolonged use of these agents in the neonatal period should be used judiciously, with caution, and avoided where possible.
    International Journal of Pediatrics 05/2011; 2011(6):935631. DOI:10.1155/2011/935631
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    ABSTRACT: To review the literature regarding the use of alpha(2)-agonists in the treatment and prevention of iatrogenic opioid abstinence syndrome (IOAS) in critically ill patients. Primary literature was identified through a search of MEDLINE (1950-June 2009), EMBASE (1988-June 2009), International Pharmaceutical Abstracts (1970-June 2009), and the Cochrane Library (1996-June 2009), using the names of individual alpha(2)-agonists and the following key words: children, opioid withdrawal, opioid, and adult. Relevant abstracts from the Society of Critical Care Medicine, reference citations from selected articles, and manufacturers' product information were also reviewed. All English-language articles identified from the data sources were evaluated. Three retrospective studies and 6 case reports/series representing 44 patients were included for analysis. Central alpha(2)-agonists are thought to minimize symptoms of IOAS by decreasing presynaptic outflow of catecholamines. Successful use of clonidine and dexmedetomidine for management of IOAS has been reported. Lofexidine, an alpha(2)-agonist not yet approved in the US, may offer similar withdrawal symptom relief but has yet to be studied in the intensive care setting. Although the quality of studies identified was limited, preliminary evidence does provide some support for the use of transdermal clonidine and injectable dexmedetomidine in the treatment and prevention of IOAS. These agents were shown to facilitate discontinuation of opioids and to minimize withdrawal symptoms with few reported adverse events. Central alpha(2)-agonists appear to be effective and safe second-line agents for treatment and prevention of IOAS. Further studies should be conducted to determine their role in the therapy of patients with IOAS.
    Annals of Pharmacotherapy 09/2009; 43(9):1506-11. DOI:10.1345/aph.1M161 · 2.06 Impact Factor
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    ABSTRACT: The objective of this retrospective study is to compare the medical treatment of neonatal narcotic abstinence syndrome with clonidine and chloral hydrate with the commonly used combination therapy of morphine and phenobarbital. From 1998 to 2008, a total of 133 newborns suffering from neonatal narcotic abstinence syndrome were treated at our clinic. All of these patients were born to mothers who had received methadone substitution for drug addiction during the course of pregnancy. Twenty-nine patients received clonidine and chloral hydrate, and 64 patients were treated with morphine and phenobarbital for abstinence syndrome. The duration of treatment was significantly shorter in the clonidine/chloral hydrate group (median: 14 days vs. 35 days). Correspondingly, the period of hospitalization was also considerably shorter in the clonidine/chloral hydrate group (median: 32 days vs. 44 days). In addition, patients in the clonidine/chloral hydrate group exhibited markedly reduced withdrawal symptoms. This study suggests that a treatment of neonatal abstinence syndrome with clonidine in omission of opiates is possible without causing short-term adverse cardiovascular effects. Considering the retrospective design of the study, controlled and prospective trials are needed.
    Acta Paediatrica 10/2009; 99(2):209-14. DOI:10.1111/j.1651-2227.2009.01547.x · 1.67 Impact Factor
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