Report on Treatment of Alcohol Dependence

Two relatively new medications, naltrexone (Trexan) and acamprosate, show promise in the treatment of patients with alcohol dependence, according to a study sponsored by the Agency for Health Care Policy and Research (AHCPR) under its evidence-based practice program. The document “Pharmacotherapy for Alcohol Dependence” is the third in a series of evidence reports and technology assessments sponsored by the AHCPR to provide comprehensive, science-based information on common, costly conditions and health care technologies. The study's conclusions are based on a systematic review of the best available evidence from published research.

Disulfiram (Antabuse), naltrexone, acamprosate, serotonergic agents and lithium (Eskalith) were evaluated with regard to treating the core symptoms of alcohol dependence, such as craving, relapse, abstinence and total drinking or nondrinking time. Limited evidence or mixed results were found in controlled clinical trials for the effectiveness of disulfiram, serotonergic agents and lithium in the treatment of persons with alcohol dependence. Naltrexone and acamprosate were found to help reduce the urge to drink, decrease the frequency with which a person drinks and, in some studies, improve abstinence. Naltrexone has been in use only since 1994, and acamprosate has recently been granted investigational drug status in the United States.

The report suggests that future research on the treatment of alcohol dependence should address the effectiveness of long-term maintenance for patients on those medications proven to work alone, the effectiveness of combinations of medications and the optimal combinations of drug and psychosocial therapies. The report also stresses the need for new therapies that are more effective than anything currently available. The relationship of pharmacotherapy to patient heterogeneity needs to be better understood, including effects related to gender, severity of depression, co-existing mental disorders and the interactions of these factors.

A summary of the report is available on the AHCPR Web site at http://www.ahcpr.gov. The full report may be obtained free from the AHCPR Publications Clearinghouse by calling 800-358-9295 or by writing AHCPR, P.O. Box 8547, Silver Spring, MD 20907.

Statement on New Therapies for Autism

In a statement reviewing the basis for two new therapies for autism, the American Academy of Pediatrics (AAP) emphasizes that, at this time, the use of auditory integration training and facilitated communication does not appear warranted, except within research protocols. The statement, published in the August 1998 issue of Pediatrics, explains that no good controlled studies of auditory integration training support its use, and current scientific data on facilitated communication show that it is ineffective. The AAP believes that families who spend time and resources pursuing these controversial therapies should be advised to return to proven behavioral and educational interventions. According to the AAP, physicians should help families obtain and review information and be aware of current data on both therapies as they become available. The auditory integration training method in this statement is the one introduced by Guy Berard in France in the 1960s and recently introduced in this country.

Celecoxib for Arthritis

Celecoxib (Celebrex) has been approved by the U.S. Food and Drug Administration for use in relieving the signs and symptoms of osteoarthritis and adult rheumatoid arthritis. It is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic and antipyretic activities. According to the manufacturer, celecoxib works by inhibiting cyclooxygenase-2 (COX-2), an enzyme that plays a role in pain and inflammation. However, it does not inhibit the cyclooxygenase-1 (COX-1) enzyme that helps maintain the normal stomach lining.

In clinical trials of over 13,000 patients and healthy volunteers, celecoxib was shown to be as effective as the prescription-strength NSAID naproxin in treating arthritis pain and inflammation. The recommended therapeutic dose for use in osteoarthritis is 200 mg daily, administered as a single dose, or 100 mg administered twice daily. For use in rheumatoid arthritis, the recommended therapeutic dosage is 100 mg to 200 mg, given twice daily.

In clinical trials, celecoxib was associated with a statistically significant reduction in the incidence of upper gastrointestinal ulcers, compared with results obtained with ibuprofen and naproxen. Persons with a known allergic reaction to celecoxib, sulfonamides, aspirin or NSAIDs should not use celecoxib. Although celecoxib has a low potential to cause stomach ulcers, the manufacturer states that ulcerations could occur without warning signs. Physicians and patients should be alert for signs and symptoms of gastrointestinal bleeding. For complete prescribing information, call 800-753-0352, ext. 704.

Progress Report on Alzheimer's Disease

The Alzheimer's Disease Education and Referral (ADEAR) Center of the National Institute on Aging (NIA) has published a document titled “Progress Report on Alzheimer's Disease, 1998.” The 58-page report describes Alzheimer's disease research in three broad areas: causes and risk factors, diagnosis and treatment, and caregiving.

Discussions in the document include recent research focusing on changes in the brain in patients with Alzheimer's disease, genetic factors in Alzheimer's disease, advances in understanding the disorder, and advances in diagnosing, treating and preventing Alzheimer's disease. It also includes summaries of research conducted by eight other components of the National Institutes of Health, along with the future direction that researchers of Alzheimer's disease should take.

According to ADEAR, Alzheimer's disease is the most common cause of dementia among persons 65 years of age or older. It affects nearly 4 million Americans—and slightly more than one half of these persons receive care at home. The prevalence of Alzheimer's disease doubles every five years beyond age 65 years. The report emphasizes that some studies have shown that nearly one half of all persons age 85 years or older have symptoms of Alzheimer's disease.

The report states that, last year, NIA-funded scientists made important advances in understanding Alzheimer's disease, including learning more about a new risk factor in some minorities, identifying many of the roles of presenilin proteins 1 and 2, and locating new sites on human chromosomes that sometimes may be involved in causing Alzheimer's disease. It is hoped that these findings will lead to new treatments and strategies for prevention.

The ADEAR Center now offers publications and research news on the Internet at http://www.nia.nih.gov/alzheimers. The Web site includes the full text of the progress report. A free copy of the report can also be obtained by calling ADEAR Center at 800-438-4380 or writing to ADEAR Center, P.O. Box 8250, Silver Spring, MD 20907–8250.

FDA Warning on Products Containing GBL

The U.S. Food and Drug Administration (FDA) has issued a warning about use of products containing gamma butyrolactone (GBL). The FDA has received at least 55 reports of adverse health effects, including one death, in persons consuming over-the-counter products containing GBL. In 19 of these cases, the individuals became unconscious or comatose, and several required intubation. Other reported effects include seizures, vomiting, slow breathing and slow heart rate.

GBL is also known by the chemical names 2(3H)-furanone dihydro; butyrolactone; 4-butyrolactone; dihydro-2(3H)-furanone; 4-butanolide; 2(3H)-furanone, dihydro; tetrahydro-2-furanone; and butyrolactone gamma. According to the FDA, brand names include Renewtrient, Revivarant or Revivarant G, Blue Nitro or Blue Nitro Vitality, GH Revitalizer, Gamma G and Remforce. Some of the labels on these products include claims to build muscles, improve physical performance, enhance sex, reduce stress and induce sleep.

The FDA has asked manufacturers to voluntarily recall these products. The FDA requests that physicians report any adverse events from these products to FDA's MedWatch program at 800-332-1088.

First Oral Micronized Progesterone

The U.S. Food and Drug Administration has approved the first oral micronized progesterone (Prometrium) for use with estrogen therapy in the prevention of endometrial hyperplasia in postmenopausal women who have not had a hysterectomy. Prometrium was previously approved for the treatment of secondary amenorrhea.

Prometrium is a progesterone synthesized from yams and is structurally identical to the endogenous progesterone found in a woman's body. According to the manufacturer, micronization makes the progesterone easier for the body to absorb.

Results of the Postmenopausal Estrogen/Progestin Interventions trial showed that micronized progesterone reduces a woman's risk of developing endometrial hyperplasia, when compared with estrogen taken alone. It does not appear to negate the positive effects of estrogen on high-density lipoprotein cholesterol levels.

The suggested dosage for Prometrium capsules used in hormone replacement therapy is 200 mg taken orally once a day, in the evening, for 12 sequential days per 28-day cycle.

Women who are allergic to peanuts, have severe liver disease, have known or suspected breast cancer or are pregnant should not take Prometrium. Common side effects include breast tenderness, dizziness, abdominal bloating and vaginal discharge.

Abacavir for Treatment of HIV Infection

Abacavir (Ziagen) has been approved by the U.S. Food and Drug Administration for the treatment of human immunodeficiency virus (HIV) infection in combination with other anti-retroviral drug regimens in adults and children over three months of age. Abacavir is a nucleoside analog reverse transcriptase inhibitor (NRTI). It is taken twice daily and can be incorporated into multidrug regimens, according to the manufacturer.

The accelerated approval of abacavir was based on results from three controlled studies of up to 24 weeks in duration. There currently are no results available from trials evaluating long-term suppression of HIV infection with abacavir.

In clinical trials to date, the most commonly reported adverse events were headache, nausea, vomiting, malaise and diarrhea. A potentially fatal hypersensitivity has been associated with the use of abacavir in at least 5 percent of patients. Symptoms of this reaction may include skin rash, fever, nausea, abdominal pain and severe tiredness. An abacavir hypersensitivity reaction registry has been established by the manufacturer, and physicians should register patients with symptoms of hypersensitivity by calling 800-270-0425.

All NRTIs can cause lactic acidosis, a fatal metabolic disturbance that causes an abnormal buildup of lactic acid.