Buprenorphine compared with methadone in opioid-dependent pregnant women: How does it affect neonatal abstinence syndrome?

BACKGROUND: The growing opioid epidemic in the United States has led to increasingly high rates of neonatal abstinence syndrome (NAS). Preliminary studies have shown that buprenorphine maintenance treatment (BMT) may lead to better outcomes for infants than methadone maintenance treatment (MMT). OBJECTIVES: The authors gathered recent evidence to answer the following PICO (population, intervention, comparison, and outcome) question: In opioid-dependent pregnant women, how does buprenorphine compared with methadone administration affect NAS? DATA SOURCES: A literature search was completed in PubMed, Scopus, Embase, and Web of Science databases and limited to the past 5 years. The following parameters were analyzed in the articles: NAS occurrence, length of hospital stay in days, NAS treatment length, and amount of pharmacotherapy administered to treat NAS. CONCLUSIONS: In comparison to methadone, buprenorphine exposure in utero is associated with significantly shorter hospital stays for the infant after delivery, shorter length of NAS treatment, and decreased frequency/duration of pharmacotherapy for NAS symptoms in the infant. IMPLICATIONS FOR PRACTICE: Based on the findings, a weak recommendation can be made for the use of BMT over MMT in opioid-dependent pregnant women. However, further research is necessary to definitively recommend buprenorphine over methadone use in this population, especially regarding the effect of maternal severity of addiction on adherence to BMT, and long-term effects of in utero buprenorphine exposure.

Pharmacometric Modeling of Naloxegol Efficacy and Safety: Impact on Dose and Label.

Naloxegol is a peripherally acting µ-opioid receptor antagonist that was developed for the treatment of opioid-induced constipation. Modeling and simulation of naloxegol efficacy and tolerability informed selection of doses for phase III studies and provided comprehensive dosage recommendations for the naloxegol US package insert.

'Naloxone works': The politics of knowledge in 'evidence-based' drug policy.

For over 20 years, drug policy experts have been calling for the wider availability of naloxone, to enable lay overdose witnesses to respond to opioid overdose events. However, the 'evidence base' for peer-administered naloxone has become a key point of contention. This contention opens up critical questions about how knowledge ('evidence') is constituted and validated in drug policy processes, which voices may be heard, and how knowledge producers secure privileged positions of influence. Taking the debate surrounding peer-administered naloxone as a case study, and drawing on qualitative interviews with individuals (n = 19) involved in the development of naloxone policy in Australia, we examine how particular kinds of knowledge are rendered 'useful' in drug policy debates. Applying Bacchi's poststructuralist approach to policy analysis, we argue that taken-for-granted 'truths' implicit within evidence-based policy discourse privilege particular kinds of 'objective' and 'rational' knowledge and, in so doing, legitimate the voices of researchers and clinicians to the exclusion of others. What appears to be a simple requirement for methodological rigour in the evidence-based policy paradigm actually rests on deeper assumptions which place limits around not only what can be said (in terms of what kind of knowledge is relevant for policy debate) but also who may legitimately speak. However, the accounts offered by participants reveal the ways in which a larger number of ways of knowing are already co-habiting within drug policy. Despite these opportunities for re-problematisation and resistance, the continued mobilisation of 'evidence-based' discourse obscures these contesting positions and continues to privilege particular speakers.

Naltrexone treatment restores menstrual cycles in patients with weight loss-related amenorrhea.

OBJECTIVE: To evaluate whether the efficacy of naltrexone administration in patients with hypothalamic amenorrhea correlates to the response to an acute naloxone test. DESIGN: Thirty patients with hypothalamic amenorrhea associated with weight loss were studied. After naloxone test (4 mg in bolus IV) patients were divided into two groups: group A, nonresponsive (n = 15) and group B, responsive (n = 15). Group A underwent two cycles of hormonal replacement therapy with E2 patches and medroxyprogesterone acetate. Then all patients were administered naltrexone at the dosage 50 mg/d orally for 6 months. A third group of 10 amenorrheic patients were treated with oral placebo with the same schedule. RESULTS: Plasma gonadal steroid levels increased in all patients and in 24 of 30 patients the menstrual bleeding occurred within 90 days from the beginning of treatment. After 6 months from naltrexone discontinuation, 18 of 24 patients still showed the occurrence of menstrual cycles. Luteinizing hormone plasma levels and LH pulse amplitude increased after 3 months of treatment and remained unchanged 6 months after naltrexone suspension. Plasma FSH levels did not show any change in any patient. The body mass index increased after 3 months in all patients who menstruated. Patients treated with placebo did not show any significant change in gonadotropins and gonadal steroid plasma levels. CONCLUSIONS: The present study supports the efficacy of naltrexone therapy for patients with hypothalamic amenorrhea either responsive or nonresponsive to naloxone test.

Development of drug delivery systems for use in treatment of narcotic addiction.

The long term goal of the NIDA narcotic antagonist program of developing an implantable, biodegradable, naltrexone/PLGA matrix system which will sustain the delivery of naltrexone to biological systems for one month has been achieved. The dosage forms which provide the desired delivery characteristics are 1.5 mm diameter beads composed of 70% by weight naltrexone base in 40,000 molecular weight, 90L/10G poly (L(+)-lactic-co-glycolic acid). Other dosage forms, including 1.5 mm diameter rods which provide 6 months' naltrexone release, finely divided injectable powders which provide up to 30 days' naltrexone release, and 1.5 mm diameter rods which provide 2 weeks' sustained delivery of morphine, have also been investigated. In vitro and in vivo release rates have been determined by measuring chemical concentrations in pH 7 buffer solution and urine, respectively. In vivo efficacy of naltrexone sustained delivery devices has been measured by direct challenge with morphine (Dewey-Harris mouse tail-flick test) and inhibition of morphine self-administration in monkeys. Good Manufacturing Practices documentation has been developed and used to produce a large batch of the 1.5 mm diameter naltrexone bead dosage forms at an FDA-registered pharmaceutical manufacturer. These beads, produced at the University of North Carolina School of Pharmacy, are awaiting use in human clinical trials.

A behavioral paradigm for the evaluation of narcotic antagonists.

We have developed an experimental paradigm for the behavioral evaluation of narcotic antagonists. The study specifically examined the heroin-seeking behavior of hard-core narcotic addicts on a research ward under blocked and unblocked conditions. Each patient served as his own control. A long-term follow-up program in the community, with aftercare services, was utilized to determine the relationship between behavior observed on the research ward and behavior that occurred in the community. While preliminary one-month follow-up data offered some cause for an optimistic view of narcotic antagonist treatment, behavioral data observed on the research ward raised serious doubts about the possibility of extinguishing heroin self-administration with antagonists. The behavioral data were not consistent with laboratory descriptions of extinction. Rather, the data suggested that narcotic antagonist programs should emphasize the development of contingencies for the reinforcement of narcotic antagonist self-administration to ensure an opiate-free state, instead of focusing on an extinction approach.