Improving clinical outcomes for naltrexone as a management of problem alcohol use

Despite being a relatively effective and safe treatment, the clinical management of alcohol abuse/dependence by oral naltrexone can be compromised due to the patient''s non-compliance with daily use of this medication. Over the past decade an increasing body of research has suggested that the use of sustained release depot naltrexone preparations can overcome this issue and deliver improved clinical outcomes. However, at the same time, research findings from diverse areas of pharmacogenetics, neurobiology and behavioural psychology have also been converging to identify variables including genetic markers, patient psychosocial characteristics and drug use history differences, or clusters of these variables that play a major role in mediating the response of alcohol abuse/dependent persons to treatment by naltrexone. While this article does not attempt to review all available data pertaining to an individual alcohol dependent patient''s response to treatment by naltrexone, it does identify relevant research areas and highlights the importance of data arising from them. The characterization of clinical markers, to identify those patients who are most likely to benefit from naltrexone and to tailor a more individual naltrexone treatment, will ultimately provide significant benefit to both patients and clinicians by optimizing treatment outcome.     

Treatment of alcohol use disorder in patients with liver disease

Alcohol contributes to more than 5% of global mortality, and causes more than half of all liver-related deaths. The Alcohol Use Disorders Identification Test (AUDIT) can be used to detect those patients with hazardous drinking and alcohol dependence who will benefit from psychosocial and pharmacological alcohol treatment. Psychosocial treatments range from brief interventions and cognitive behavioral therapy, to experimental neuropsychological treatments. Psychosocial intervention can be combined with acamprosate or naltrexone as first line pharmacological treatments. For patients with liver disease, abstinence increases survival and is therefore an important treatment goal. Acamprosate is a good choice, as it prevents relapse to drinking with a number needed to treat of 12. There are no reports indicating high risks of liver toxicity for acamprosate or naltrexone, but evidence is scarce. We recommend vigorous screening for alcohol use disorder in liver disease patients, followed by psychosocial intervention and complemented by pharmaceutical therapy.     

What place does naltrexone have in the treatment of alcoholism?

Despite two recent negative trials, most controlled clinical studies have found that when naltrexone is added to substance abuse treatment or counselling, significantly less heavy drinking is done by the patients who are willing to take most of the prescribed naltrexone. Naltrexone also reduces urges to drink and makes any slips back into drinking less pleasant. Therefore, naltrexone can be a useful adjunct to substance abuse counselling or rehabilitation programmes, as one of many tools that clinicians and patients use. However, beneficial effects are limited in scope. Naltrexone mostly does not increase the chance of staying completely abstinent but rather reduces the intensity or frequency of any drinking that does occur. Many alcohol-dependent individuals are medically ineligible or are unwilling to take naltrexone, many who start naltrexone do not continue with it and many who comply with it do not benefit. Compliance is greater for individuals who experience fewer adverse effects and who have stronger beliefs in the benefits of naltrexone, suggesting that clinicians can increase compliance by helping patients to manage adverse effects and by bolstering patients' beliefs in the benefits of naltrexone. Alcohol-dependent individuals who are most likely to benefit from naltrexone seem to be those with close relatives who also had alcohol problems, or who have stronger urges to drink or who are more limited in cognitive abilities. Some individuals may benefit from a higher dose, particularly people with lower blood concentrations of the medication, and individuals who achieve good results may benefit from a longer course of treatment with naltrexone. In these ways, treatment can be targeted to increase the likelihood of beneficial outcomes with naltrexone.     

Relative drug safety and efficacy: any help for the practitioner?

Approaches are discussed for assuring that the most useful entity is prescribed when a drug is the treatment of choice. Several attributes of pharmaceutical preparations that are likely to influence health status are mentioned. Three models for increasing drug-of-choice prescribing are discussed: the regulatory model, the formulary model, and the drug use review model. Four options regarding formulary preparation are presented: the federal government, a consortium of professional groups, regional expert committees, or local groups. Research is needed to determine which methods hold promise for increasing the frequency of rational prescribing.     

Influences on prescribing: the perceptions of general practitioners in two primary care trusts

We describe results from a postal questionnaire sent to all GPs (general practitioners) in two East London primary care trusts investigating perceived influences of prescribing and their attitudes towards the local formulary The strongest influencing factors on prescribing are: “the drug is recommended by a specialist or peer”, “guidelines”‘ and “GP's own previous experience of the drug” The weakest influencing factors are: “visits from drug representatives”, “advertisements in journals and magazines” and “internet information” GPs need, agree and comply with local formularies but they do not use them much; still, GPs are influenced by local formularies but the influence of pharmaceutical advisers remains uncertain The more we know about what influences prescribing, the better we can design steering interventions so that drugs are being prescribed wisely and cost effectively     

Gender differences with high-dose naltrexone in patients with co-occurring cocaine and alcohol dependence

This is a randomized, double-blind, placebo-controlled clinical trial that evaluated the efficacy of a higher-than-typical daily dose of naltrexone (150 mg/day), taken for 12 weeks, in 164 patients (n = 116 men and n = 48 women) with co-occurring cocaine and alcohol dependence. Patients were stratified by gender and then randomly assigned to either naltrexone or placebo, and to either cognitive–behavioral therapy or a type of medical management. The two primary outcomes were cocaine use and alcohol use. Significant Gender × Medication interactions were found for cocaine use via urine drug screens (three way, with time) and self-reports (two way) for drug severity (two way) and alcohol use (two way). The type of psychosocial treatment did not affect outcomes. Thus, 150 mg/day naltrexone added to a psychosocial treatment resulted in reductions in cocaine and alcohol use and drug severity in men, compared to higher rates of cocaine and alcohol use and drug severity in women.     

The use of pharmacoeconomic data in formulary selection

Pharmacists are encouraged to improve their knowledge and use of pharmacoeconomic data in formulary selection. The formulary selection process has changed significantly in recent years. Among its most significant uses is its potential for cost containment strategies. An overview is presented of the origin as well as the potential impact of pharmacoeconomic data. The need to balance the economic benefit with the clinical advantages for any proposed new drug for formulary inclusion remains the most critical decision to be made by pharmacists.     

AMCP Format dossier requests: manufacturer response and formulary implications for one large health plan

BACKGROUND: The Academy of Managed Care Pharmacy (AMCP) Format for Formulary Submissions, a template for health plans to use in developing formulary submission guidelines, has been widely adopted since its initial release in 2000. Many health plans request a dossier (a standardized set of clinical and economic evidence prepared by pharmaceutical manufacturers) to provide information for consideration during the formulary decision-making process. While dossier quality has reportedly improved over time, there is no recent research examining the response rate to dossier requests and the quality of dossiers received. OBJECTIVE: To perform an evaluation of pharmaceutical manufacturers. response to a request for a product dossier prepared using the AMCP Format, and to determine if dossier receipt was associated with a favorable formulary placement. METHODS: The pharmacy and therapeutics (P&T) committee of a mid-Atlantic health plan with approximately 3 million members reviewed 43 drug products from February 2004 through December 2005. A university-based clinical evaluation subcontractor requested dossiers in the AMCP Format by telephone and e-mail from the manufacturers. drug information center about 8 weeks before the committee meeting. A retrospective evaluation of the materials received from the manufacturers was performed. A logistic regression model was developed to determine if dossier receipt increased the likelihood of second-tier copayment formulary placement for new product reviews. RESULTS: Dossiers were requested for 43 products. We received dossiers for 25 products (58%), other drug information (e.g., journal reprints, product labeling) for 10 products (23%), a formulary kit for 4 products (9%), and no response for the remaining 4 products (9%). Of the 25 dossiers, 21 (84%) generally followed the AMCP Format. Unlocked interactive budget impact models were included in 5 dossiers (20%), and modeling reports (without an unlocked interactive model) were included in 12 dossiers (48%). Dossiers were more likely to be received when the time between U.S. Food and Drug Administration (FDA) approval and dossier request was >/- 4 months (65% vs. 27% when <4 months; P <0.05) and when requested from a large manufacturer (top 25 in sales) compared with smaller manufacturers (75% vs. 43%; P <0.05). Dossier receipt did not improve a product.s likelihood for preferred formulary placement; none of the new products for which dossiers were received were assigned to the second copayment tier compared with 33% of the new products with no supporting dossier. The logistic regression model failed to find any correlation between dossier receipt and preferred formulary placement. CONCLUSIONS: Manufacturers met the request for a dossier nearly three fifths of the time. The dossiers were of high quality and generally followed the AMCP Format; the models included in dossiers varied widely in their design and utility. The product manufacturer.s size and the time between FDA approval and dossier request influenced the likelihood of dossier receipt. Receipt of a dossier did not appear to influence the likelihood of a product attaining preferred formulary status.     

Acamprosate and naltrexone treatment for alcohol dependence: an evidence-based risk-benefits assessment

This paper provides an evidence-based risk-benefit assessment of acamprosate and naltrexone in the treatment of alcohol dependence. A risk-benefit assessment is based on the premise that the choice of treatment depends on a number of factors, notably the adverse event profile and efficacy. An evidence-based approach attempts to operationalize how such risk-benefit assessments are made to inform physician choices. This approach involves a systematic assessment of all published double-blind, placebo-controlled trials. Based on this review, we conclude acamprosate and naltrexone are both useful in the treatment of alcohol dependence. However, the two drugs act in different ways in the brain, and their clinical profiles are different. Treatment effects seem to be more reliable for acamprosate, and this drug is better tolerated. The safety of the two drugs in combination has been supported by two independent double-blind studies, and combination treatment may offer an advantage for some patients.     

Use of naltrexone in the treatment of alcohol use disorders in patients with concomitant major mental illness

We report the use of naltrexone for treatment of alcohol use disorder in patients with major psychiatric illness. We reviewed the records of 72 mentally ill outpatients treated with naltrexone for alcohol use disorders at a community mental health center. The psychiatric diagnoses included major depression (n = 37), schizophrenia (n = 17), bipolar illness (n = 11), schizoaffective disorder (n = 7), and gender identity disorder (n = 4). Sixty-one patients (85%) had histories of psychiatric hospitalization. Total retention in naltrexone treatment for at least eight weeks was 81.9%: 5 (6.9%) were lost to follow-up, and 8 (11.1%) discontinued the medication because of side effects, primarily nausea. Patients showed good clinical response to naltrexone, with 82% reducing their drinking by at least 75%, and only 17% relapsing at eight weeks. We conclude that naltrexone is useful in the treatment of dually-disordered patients. The hypothesis that clinical response to naltrexone is facilitated by active alcohol drinking during treatment is discussed.     

Drinking behavior and motivation for treatment among alcohol-dependent liver transplant candidates

Alcohol misuse is the second most common indication for liver transplantation in the United States. Our post-transplant alcoholism treatment trial suggested that current interventions might not be transferable to liver transplantees. We sought to identify differences between patients awaiting liver transplantation and alcoholics entering treatment without severe liver disease. Thirty transplant patients were compared to thirty naltrexone study patients on medical status, alcohol and drug use, alcohol craving, motivation for treatment, psychiatric symptoms, and psychosocial problems. Lifetime alcohol consumption was greater for transplant patients compared to naltrexone patients. In contrast to the naltrexone group, transplant patients denied craving for alcohol and showed little motivation for alcoholism treatment. Groups did not differ on other psychosocial measures. Liver transplant patients differ from patients in alcoholism treatment trials on measures of alcohol consumption, alcohol craving and motivation for treatment. Alcoholism interventions should accommodate their medical condition and boost motivation for continued abstinence.     

Medication assisted treatment of drug abuse and dependence: global availability and utilization

Clinical trials and clinical studies, using patented drugs and drugs off patent, provide data that impact the best treatment practices for substance abuse and dependence. In the United States, medications have been approved for use in the treatment of both alcohol and opioid dependence. Medications are used in the detoxification from drug abuse and dependence in the symptomatic relief of withdrawal. For long term treatment or medical maintenance treatment, medications eliminate the physiological effects of drug use by blocking drug-receptor binding in the brain. Therefore, patented drugs showing interactions with neurotransmitters in the brain, are attractive candidates for treatment efficacy trials. An effective long term treatment paradigm for reducing drug dependence is the combinatorial use of medications that block the effects of drug use with behavior change counseling and psychotherapy. Medications used for the long term treatment of opioid dependence are methadone, buprenorphine, and naltrexone. Pharmacotherapies used in the treatment of alcohol dependence include acamprosate, antabuse and naltrexone. A reliable indicator for successful treatment of drug dependence is time in treatment. Patients remain in long term treatment when they perceive that their health care environment is supportive and non-stigmatizing and with a good patient-provider relationship where their needs are identified and met. Additional medications are needed for individual comprehensive substance abuse treatment plans, particularly for individuals who abuse stimulants. Patented drugs remain an important source of candidate pharmacotherapies comprising medication assistant treatment, part of a comprehensive treatment plan for drug dependence that addresses the medical, social, and psychological needs of the patient. Adapting this drug treatment paradigm globally requires identifying and testing new drug candidates while building and changing programs to patient centered treatment programs that promote access to care and treatment and integrate medical, psychological, and social services.     

Trends in the adoption of medications for alcohol dependence

Increasing attention is being paid to the development and dissemination of effective pharmacotherapies for the treatment of alcohol and other drug dependence. However, numerous structural and philosophical barriers impede the widespread adoption of these treatment approaches in everyday clinical practice. Research is needed to understand and overcome this gap. Drawing upon data collected from 2 large samples of substance abuse treatment providers at multiple time points, this article examines the prevalence and correlates of the adoption of the currently available pharmacotherapies for alcohol dependence: disulfiram, oral naltrexone, and acamprosate. These data suggest that the proportion of treatment programs using pharmacotherapies for alcohol dependence has been declining over time. In addition, the proportion of patients to whom these medications are prescribed is notably low. The adoption of disulfiram and naltrexone is significantly more likely in programs that are accredited, employ at least 1 physician, offer integrated care for patients with co-occurring psychiatric conditions, derive proportionately more revenue from commercial insurance payers, and have fewer linkages with the criminal justice system. Preliminary data suggest that the early adoption of acamprosate is following a similar pattern. Recommendations for addressing challenges to the diffusion of pharmacotherapies for alcohol dependence are presented.     

信息技术在我院处方集系统管理中的应用

目的:利用现代信息技术对我院处方集系统进行管理,以提高医院药事管理水平。方法:以我院的信息技术平台为基础,从药品采购、处方评价、药品信息等方面围绕处方集系统进行现代化管理。结果:信息技术的应用,使医院药品采购环节更加规范;使处方评价更加规范、准确、高效;使药品信息的获取更加方便、快捷、准确。结论:现代信息技术使药事管理变得更加快捷、高效,将在医院处方集系统管理中得到更为广泛的应用。     

What Oregon's parity law can tell us about the federal Mental Health Parity and Addiction Equity Act and spending on substance abuse treatment services

Background

The Paul Wellstone and Pete Domenici Mental Health Parity and Addiction Equity Act of 2008 (MHPAEA) requires commercial group health plans offering coverage for mental health and substance abuse services to offer those services at a level that is no more restrictive than for medical-surgical services. The MHPAEA is notable in restricting the extent to which health plans can use managed care tools on the behavioral health benefit. The only precedent for this approach is Oregon's 2007 state parity law. This study aims to provide evidence on the effect of comprehensive parity on utilization and expenditures for substance abuse treatment services.

Methods

A difference-in-difference analysis compared individuals in five Oregon commercial plans (n = 103,820) from 2005 to 2008 to comparison groups exempt from parity in Oregon (n = 19,633) and Washington (n = 39,447). The primary outcome measures were annual use and total expenditures.

Results

Spending for alcohol treatment services demonstrated statistically significant increase in comparison to the Oregon and Washington comparison groups. Spending on other drug abuse treatment services was not associated with statistically significant spending increases, and the effect of parity on overall spending (alcohol plus other drug abuse treatment services) was positive but not statistically significant from zero.

Conclusions

Oregon's experience suggests that behavioral health insurance parity that places restrictions on how plans manage the benefit may lead to increases in expenditures for alcohol treatment services but is unlikely to lead to increases in spending for other drug abuse treatment services.     

Use of Naltrexone in the Treatment of Alcohol Use Disorders in Patients with Concomitant Major Mental Illness

Abstract

We report the use of naltrexone for treatment of alcohol use disorder in patients with major psychiatric illness. We reviewed the records of 72 mentally ill outpatients treated with naltrexone for alcohol use disorders at a community mental health center. The psychiatric diagnoses included major depression (n = 37), schizophrenia (n = 17), bipolar illness (n = 11), schizoaffective disorder (n = 7), and gender identity disorder (n = 4). Sixty-one patients (85%) had histories of psychiatric hospitalization. Total retention in naltrexone treatment for at least eight weeks was 81.9%: 5 (6.9%) were lost to follow-up, and 8 (11.1%) discontinued the medication because of side effects, primarily nausea. Patients showed good clinical response to naltrexone, with 82% reducing their drinking by at least 75%, and only 17% relapsing at eight weeks. We conclude that naltrexone is useful in the treatment of dually-disordered patients. The hypothesis that clinical response to naltrexone is facilitated by active alcohol drinking during treatment is discussed.