Buprenorphine for the treatment of opioid dependence.

PURPOSE: The clinical issues surrounding the use of buprenorphine for the treatment of opioid dependence are reviewed. SUMMARY: Opioids continue to be some of the most frequently reported prescription medications in substance abuse- related cases. A semisynthetic derivative of thebaine, buprenorphine hydrochloride is a partial mu-opioid receptor agonist and kappa-receptor antagonist with a long duration of action. The pharmacokinetic and pharmacodynamic profiles of buprenorphine are not well characterized. The ethical and legal issues associated with the maintenance treatment of opioid dependence are complex. Clinical trials have compared the efficacy of methadone, buprenorphine, and buprenorphine-naloxone for the detoxification and maintenance treatment of opioid dependence. Based on the available literature, it appears that buprenorphine, buprenorphine-naloxone, and methadone are similarly efficacious for the treatment of opioid-dependent patients. Buprenorphine-naloxone has less potential for abuse and diversion. The adverse-effect profiles for buprenorphine, buprenorphine-naloxone, and methadone are similar. Once-weekly office visits for patient evaluation and dispensing of buprenorphine seem feasible and convenient for both practitioners and patients. The three phases of opioid maintenance treatment are induction, stabilization, and maintenance. It is good practice for the admitting physician to consult with the patient's addiction treatment provider, when possible, to obtain the patient's treatment history. CONCLUSION: Buprenorphine is an attractive option for the pharmacologic treatment of opioid dependence. Compliance and adherence to buprenorphine therapy for opioid-dependent patients remain clinical issues. Future research efforts should focus on improving compliance and adherence to buprenorphine therapy.

Acamprosate for the treatment of alcohol dependence.

BACKGROUND: Both inpatient and outpatient treatment centers that focus solely on psychosocial therapies for the treatment of alcohol dependence have high relapse rates. Thus, extensive research has focused on the development of pharmacologic moieties to attenuate the craving for alcohol after acute alcohol detoxification. Three drug therapies are currently approved by the US Food and Drug Administration (FDA) for this purpose: disulfiram, naltrexone, and acamprosate. The latter was approved by the FDA in 2004. OBJECTIVE: This article describes the pharmacologic properties and clinical usefulness of acamprosate for the treatment of alcohol dependence. METHODS: Relevant information was identified through searches of MEDLINE (1966 to March 2005), International Pharmaceutical Abstracts (1970-2005), Current Contents (1996-2005), and Cumulative Index to Nursing and Allied Health Literature (1982-Week 2, 2004) using the key words acamprosate, alcohol dependence, and alcoholism (MeSH). RESULTS: Acamprosate limited to randomized, controlled clinical trials yielded 33 hits in MEDLINE. Twenty-two articles were reviewed for efficacy end points, and 10 were reviewed for pharmacology and pharmacokinetics data. Acamprosate plus pharmacokinetics and pharmacodynamics yielded 19 hits, some of which were duplicates from the previously described search. Acamprosate plus meta-analysis (MeSH) yielded 5 hits, naltrexone plus meta-analysis (MeSH) yielded 9 hits, and disulfiram plus meta-analysis yielded 3 hits. The most recent review articles and their reference lists were assessed to ensure completeness of literature searches. Based on these searches, acamprosate is known to be an analogue of taurine and gamma-aminobutyric acid (GABA), 2 central nervous system neuromodulators. Acamprosate is thought to share some of the cellular actions of taurine affecting GABA and glutaminergic receptors in the nucleus accumbens, a brain region that may be responsible for the reinforcing effects received after alcohol consumption. Acamprosate is thought to also suppress excitation-induced calcium entry that results from chronic alcohol exposure, thereby altering the conformation of the N-methyl-d-aspartate receptors. The percentage of patients taking acamprosate who were completely abstinent throughout the different durations of the studies varied from approximately 18% to 61%, compared with 4% to 45% with placebo. Diarrhea was the most common adverse effect accompanying acamprosate therapy, and this was generally described as dose related and transient. CONCLUSIONS: Acamprosate is associated with modest treatment effects. Its efficacy is similar to naltrexone, and the combination of acamprosate and naltrexone appears to be more efficacious than acamprosate alone, when combined with psychosocial interventions.

The Medicare Part D drug benefit: lessons from the experience with drug discount cards.

The Medicare Modernization Act of 2003 provides federal assistance to eligible beneficiaries by paying for their prescription medications. While the full program will be implemented in January 2006, a transitional drug discount card program has been ongoing since mid-2004. This paper reviews some of the operational details of that program and the hurdles created by the complexity of the program. By carefully looking back on these hurdles, perhaps one can anticipate some of the problems that will likely be encountered when the full program is implemented and assist patients in realizing its maximum benefits.

Bioidentical hormone therapy: a review.

OBJECTIVE: The terms "natural" or "bioidentical" hormone therapy (NHT) are used to describe hormone treatment with individually compounded recipes of certain steroids in various dosage forms, including dehydroepiandrosterone, pregnenolone, testosterone, progesterone, estrone, estradiol, and estriol. Based on the results of a person's salivary hormone levels, the final composition of the compounded dosage form is individualized to that specific person. Proponents claim that NHT is better tolerated than manufactured products. This paper is intended to review the concept of NHT and to determine whether there is sufficient scientific evidence to support its use. DESIGN: A literature search was performed in Medline using the following MeSH terms and key words: drug combinations; progestational hormones; hormone replacement therapy; endometrium; estrogen replacement therapy; climacteric; menopause; estradiol; estrogens; progesterone; drug monitoring; and drug compounding. Current Contents, International Pharmaceutical Abstracts, Cochrane Database of Systematic Reviews, Lexis Nexis, Google, Medscape, MD Consult, and clinicaltrials.gov were searched with key words. RESULTS: There are a few observational studies and clinical trials comparing conventional hormone therapy with bioidentical hormone therapy. Studies generally lacked adequate study design, including small sample sizes and comparison of inequivalent doses, to prove safety and efficacy. Little evidence was found to support individualized hormone dosing based upon saliva hormone concentrations. CONCLUSION: Evidence suggests that, although individualized hormonal products may decrease some symptoms of menopause, it seems they have no proven advantage over conventional hormone therapies and their use is not supported by evidence regarding pharmacokinetics, safety, and efficacy.

Putting an Ecstasy test kit to the test: harm reduction or harm induction?

OBJECTIVE: To evaluate the DanceSafe Complete Adulterant Screening Kit for Ecstasy with regard to its accuracy in identifying 3,4-methylenedioxymeth-amphetamine (MDMA) and methylenedioxyamphetamine (MDA) derivatives and its ability to detect certain contaminants. METHODS: In part 1, 39 street-grade tablets purported to be MDMA were tested with the Marquis, Mecke, and Simon's reagents provided by the DanceSafe testing kit. The tablets then were submitted to gas chromatography-mass spectrometry for identification of active ingredients. In part II, seven known drugs of abuse were tested with the Marquis, Mecke, and Simon's reagents. These drugs were codeine, dextromethorphan, dihydrocodeine, ketamine, MDMA, morphine, and d-norpropoxyphene. RESULTS: The Marquis, Mecke, and Simon's reagents did not differentiate pure MDMA from adulterated forms. They lacked both sensitivity and specificity for the purpose of MDMA identification when tested by persons unfamiliar with these reagents. Also, experienced toxicologists using this unfamiliar procedure generated false-positive results. CONCLUSIONS: Neither the Marquis, Mecke, nor Simon's reagents should be used by the public for harm reduction purposes. These agents do not help identify pure MDMA tablets. Gas chromatography-mass spectrometry remains the most sensitive and specific testing method for identifying MDMA and its contaminants.

Bioidentical hormone therapy: a panacea that lacks supportive evidence.

PURPOSE OF REVIEW: In the practice of 'bioidentical hormone therapy', it is our belief that pharmacists are compounding bioidentical hormone therapy with the best intentions. These pharmacists are, however, ill informed regarding the lack of scientific underpinning associated with the efficacy and safety of the practice of bioidentical hormone therapy. It is the purpose of this review to systematically examine the scientific rigor of the arguments posed by the proponents of bioidentical hormone therapy, and to differentiate the practice of bioidentical hormone therapy from the legitimate practice of pharmacy compounding. RECENT FINDINGS: Most medical organizations have in essence refuted the bioidentical hormone therapy claims as unsubstantiated. The profession of pharmacy needs to address this issue in an authoritarian, scientific way, outside of the compounding issue. SUMMARY: Bioidentical or natural hormones are expected to have similar efficacy and safety profiles as the commercially available hormonal therapies that have been studied in clinical trials, regardless of whether the active principle hormones are compounded by individual pharmacies or manufactured by large companies. Estriol is a weak estrogen that is not Food and Drug Administration approved for use as a prescription drug in the United States; thus, clinical trials are necessary to demonstrate the efficacy and safety profile for estriol. Further, supplementary clinical trials are necessary to determine whether there are efficacy or safety differences between natural progesterone and synthetic progestin, as studies to date are inconclusive.

Vitamin C and vitamin E for Alzheimer's disease.

OBJECTIVE: To evaluate the literature on supplemental vitamin C and vitamin E therapy in the prevention and treatment of Alzheimer's disease (AD). DATA SOURCES: Literature retrieval was accessed through MEDLINE (1966-March 2005) using the key words antioxidants, vitamin C, vitamin E, Alzheimer's disease, and dementia. International Pharmaceutical Abstracts (1970-March 2005), Current Contents (1996-March 2005), Cochrane Database of Systematic Reviews (1994-March 2005), and Ebsco's Academic Search Elite (1975-March 2005) were searched with the same key words. STUDY SELECTION AND DATA EXTRACTION: Articles related to the objective that were identified through PubMed were included. DATA SYNTHESIS: Oral supplementation of vitamin C (ascorbic acid) and vitamin E (D-alfa-tocopherol acetate) alone and in combination have been shown to decrease oxidative DNA damage in animal studies in vivo, in vitro, and in situ. Recent results of a prospective observational study (n = 4740) suggest that the combined use of vitamin E 400 IU daily and vitamin C 500 mg daily for at least 3 years was associated with the reduction of AD prevalence (OR 0.22; 95% CI 0.05 to 0.60) and incidence (HR 0.36; 95% CI 0.09 to 0.99). Contradicting this is a previous prospective observational study (n = 980) evaluating the relationship between 4 years of vitamin C and E intake and the incidence of AD, which detected no difference in the incidence of AD during the 4-year follow-up. Recent meta-analysis results suggest that doses of vitamin E > or =400 IU daily for more than one year are associated with increased all-cause mortality. Mega-trial results suggest that vitamin E doses > or =400 IU daily for 6.9 years in patients with preexisting vascular disease or diabetes mellitus increase the incidence of heart failure, with no other outcome benefits noted. CONCLUSIONS: In the absence of prospective, randomized, controlled clinical trials documenting benefits that outweigh recently documented morbidity and mortality risks, vitamin E supplements should not be recommended for primary or secondary prevention of AD. Although the risks of taking high doses of vitamin C are lower than those with vitamin E, the lack of consistent efficacy data for vitamin C in preventing or treating AD should discourage its routine use for this purpose.

Evaluation of online drug references for identifying over-the-counter solid oral dosage forms.

OBJECTIVE: To evaluate six drug references for their usefulness in identifying over-the-counter (OTC) solid oral dosage forms (SODFs). DESIGN: Retrospective evaluation of a convenience sample of requests for product identification. SETTING: Drug information center that accepts information requests from health care providers and law enforcement officials throughout the state in which it is located. PARTICIPANTS: Researchers. INTERVENTIONS: Using a convenience sample of 68 nonprescription drugs and 41 dietary supplements obtained from the drug information center's question and answer database, researchers sought to identify the SODFs using six drug-identification online databases. MAIN OUTCOME MEASURE: Likelihood of identifying a SODF with a given reference, reported as the percentage identified and the corresponding 95% confidence interval. RESULTS: Overall, 88.2% of nonprescription drugs could be identified using all six references. The highest percentage of nonprescription drugs (77.9%) were identified using Identidex, followed by Ident-A-Drug (67.6%), Drug Identifier (45.6%), RxList (39.7%), Lexi-Drug ID (33.8%), and Clinical Pharmacology (17.6%). Using Ident-A-Drug and RxList together led to the identification of two fewer nonprescription drugs than did Identidex at approximately 5% of the cost. Only 15 (37.5%) of the dietary supplements had an identifying imprint on the dosage form, and 7 (46.6%) of the imprinted products were identified. But overall, only 17.1% (7 of 41) of dietary supplements could be identified, as none of the products without imprints could be positively identified. CONCLUSION: Using these six online references, nonprescription drugs could be identified more frequently than could dietary supplements. The lack of imprints on many dietary supplements is an impediment to identification of these products.

Review of pregnancy labeling of prescription drugs: is the current system adequate to inform of risks?

Evidence-based medicine that is designed to guide benefit/risk drug therapy decisions does not exist for pregnant women. The types of studies that do exist are usually conducted in animals, which may not reflect human benefits and risks. The types of studies that do exist in humans are typically limited and, at best, may show an "association" between a particular drug therapy and an undesirable effect. This review outlines the difficulties that are associated with the assessment of the benefits/risks of drug therapy during pregnancy, the history of the Food and Drug Administration regulations for labeling prescription drugs, and the strengths and weaknesses of the current Food and Drug Administration pregnancy labeling system. Proposed changes to the current system are reviewed.