Changes in hospital and out-patient events and costs following implant naltrexone treatment for problematic alcohol use.

The harmful use of alcohol places a considerable burden on the community, both socially and financially. The aim of this study was to determine if the use of implant naltrexone is associated with a reduction in health care events and costs in patients treated for problematic alcohol use. Ninety four patients (60.6% male) treated between 2002 and 2007 were matched against state hospital, emergency department (ED), mental health out-patients and mortality data sets for 6 months prior to and 6 months post treatment. The number of patients, events, and costs associated with each health event were compared before and after treatment. Overall health care events and costs were reduced from $509033 prior to treatment to $270001 following treatment. Costs associated with hospital admission showed the most significant reduction, falling from $424605 (82 admissions/36 patients) before treatment to $203462 (43 admission/24 patients) after. While costs associated with ED attendances also fell ($74885 to $54712), costs associated with mental health out-patient attendances increased ($9543 to $11827). The use of implant naltrexone was associated with a reduction health events and costs in patients with problematic alcohol use in the first 6 months following treatment.

Use of subcutaneous flumazenil preparations for the treatment of idiopathic hypersomnia: A case report.

Idiopathic hypersomnia (IH) is a rare sleep disorder, recently hypothesized to be related to the production of a molecule that facilitates the binding of gamma-aminobutyric acid (GABA) to the GABA receptor. This paper reports on the treatment of a patient with IH who was treated with a 96-hour continuous low dose (4 mg/day) infusion of a benzodiazepine antagonist, flumazenil, followed by a slow-release flumazenil implant. The use of flumazenil mitigated the patient's IH symptoms including excessive daytime sleepiness, sleep drunkenness and self-reported cognitive problems. The case both provides a possible treatment and system for short (subcutaneous (SC) administration) and longer term (implant) flumazenil delivery. Current data supports the need for further research into the use of flumazenil for the treatment of IH and to develop long term flumazenil delivery systems.

Withdrawal and psychological sequelae, and patient satisfaction associated with subcutaneous flumazenil infusion for the management of benzodiazepine withdrawal: a case series.

Our group and others internationally have previously reported data on the use of low-dose flumazenil administered intravenously for the management of benzodiazepine withdrawal. This paper describes the first reported use of subcutaneous flumazenil infusion in the management of acute benzodiazepine withdrawal. Self-reported withdrawal symptoms and psychological state and anxiety sequelae were collected at baseline and then at intervals to 5 days following initiation of subcutaneous flumazenil infusion. Data indicate that patient subjective benzodiazepine withdrawal symptoms were well managed, with significant reduction in psychological distress seen over the duration of treatment. Perceived difficulty in performing everyday functions was positively correlated with withdrawal severity and improved over treatment. Patients reported high treatment comfort, willingness to undertake a future subsequent treatment using this technique, and willingness to recommend this treatment to a friend. This small proof-of-concept study indicates that subcutaneous flumazenil infusion has excellent tolerability, efficacy and improvement on measures of psychological distress. Given this technique is less invasive and requires fewer staff resources compared with intravenous administration, it may prove a significant asset in the management of benzodiazepine withdrawal.

Hepatitis C virus eradication in intravenous drug users maintained with subcutaneous naltrexone implants.

UNLABELLED: The effectiveness of HCV antiviral therapy in patients who have undergone recent drug dependency treatment and continue to inject drugs sporadically is presently not clear. Patients attending a community-based drug rehabilitation and naltrexone implant clinic from October 2002 until March 2005 were screened for HCV infection and if positive offered further assessment and treatment with interferon and ribavirin therapy. The first 50 patients to commence HCV therapy and complete at least 6 months follow-up were prospectively studied. ETR response (HCV PCR negative) was 34/50 (68%) and SVR 6 months post-treatment was 31/50 (62%). Viral eradication was maintained in those 22 patients that have had 12 months or more post-treatment follow-up. Eleven (22%) patients stopped therapy early due to side effects or poor compliance. Only two patients with an ETR likely reinfected due to unsafe injection practices. One was re-treated and achieved an SVR. Of the patients achieving a 6-month SVR, 17 of 31 patients reported no further IDU and 13 of 31 patients occasional IDU during treatment and this was maintained after HCV treatment cessation. 46% of patients received antidepressant and/or antipsychotic medication during treatment. CONCLUSION: This study of HCV treatment in a community-based subcutaneous naltrexone implant clinic found antiviral therapy resulted in a 62% SVR. This result is comparable to that reported in hospital-based clinics in non-IDU patients. The side effect profile and compliance was also similar. HCV antiviral therapy should be offered to this large and currently under treated group.

Transfer of naltrexone and its metabolite 6,beta-naltrexol into human milk.

The excretion of naltrexone and its primary metabolite 6,beta-naltrexol in breast milk from a 30-year-old lactating opiate addict undergoing oral naltrexone pharmacotherapy (5 mg/d) was studied. Concentrations of naltrexone and 6,beta-naltrexol in serial milk and plasma samples taken over a 19.3-hour period of a dose interval at steady state were measured by gas chromatography. The calculated infant dose relative to the maternal weight was 0.03% for naltrexone and 0.83% (as naltrexone equivalents) for 6,beta-naltrexol. Total relative infant dose estimated for the complete 24-hour dose interval was 1.06%. Her 6-week-old breastfed infant was healthy, achieving expected milestones, and showed no adverse effects. Only 6,beta-naltrexol was detected in infant plasma and at a very low concentration of 1.1 micro g/L. Use of naltrexone during breastfeeding should be undertaken only after an individual risk benefit analysis.

Blood morphine levels in naltrexone-exposed compared to non-naltrexone-exposed fatal heroin overdoses.

The aim of this study was to investigate the association between prior exposure to naltrexone and increased risk of fatal heroin overdose using a review of toxicology reports for heroin-related fatalities between July 1997 to August 1999 for two groups: those treated with oral naltrexone and those who were not treated. Additional information for the oral naltrexone group was obtained from clinic files. Naltrexone-treated deaths were identified from the patient database at the Australian Medical Procedures Research Foundation (AMPRF), Perth, Western Australia (WA) through the Western Australian Department of Health, Data Linkage Project. Non-treated cases were identified from the database at the Forensic Science Laboratory, State Chemistry Centre (WA). We identified and investigated blood morphine concentrations following 21 fatal heroin overdoses with prior exposure to naltrexone and in 71 non-naltrexone-exposed cases over the same time period. The proportion of deaths where heroin use was a major contributing factor was little different in the non-naltrexone compared to the naltrexone-exposed group. Furthermore, in 'acute opiate toxicity' deaths, blood morphine levels were lower in non-naltrexone-exposed compared with naltrexone-exposed cases. Although there was a higher number of deaths designated as rapid (i.e. occurring within 20 minutes) in the naltrexone-exposed (89%) compared with the non-exposed group (72%) this was not statistically significant. Other drug use in relation to heroin-related fatalities is discussed. Findings do not support the hypothesis that prior exposure to naltrexone increases sensitivity to heroin toxicity.