Med Check

The combination of naltrexone and ondansetron decreases alcohol craving in alcohol-dependent persons, a study in the April Archives of General Psychiatry showed. Hugh Myrick, M.D., and colleagues from the Medical University of South Carolina used functional magnetic resonance imaging to study 90 alcohol-dependent and 17 control volunteers for their brain's reaction to various alcohol-related cues. The volunteers were randomized to receive naltrexone 50 mg, ondansetron 0.50 mg, both, or placebo daily in a double-blind fashion. Neither ondansetron nor naltrexone alone showed any significant effect on alcohol craving compared with placebo. Upon alcohol cues, the ventral striatum was activated differently in alcohol-dependent and control subjects. Those taking both naltrexone and ondansetron had the largest decrease in alcohol-induced ventral striatum activation. Subjects who took naltrexone alone, but not ondansetron alone, also had a statistically significant decrease in activation compared with placebo. Ondansetron is an antagonist of the serotonin 5HT₃ receptor.

This study was funded by the National Institute on Alcohol Abuse and Alcoholism.

An abstract of “Effect of Naltrexone and Ondansetron on Alcohol Cue-Induced Activation of the Ventral Striatum in Alcohol-Dependent People” is posted at<archpsyc.ama-assn.org/cgi/content/abstract/65/4/466>. 


An Australian study found that an implanted naltrexone product significantly reduced the risks of opioid-related overdose and nonoverdose hospitalization in patients with heroin dependence during three and a half years of treatment. Hanh Ngo, B.Sc., and colleagues from the University of Western Australia School of Psychiatry and Clinical Neurosciences retrospectively reviewed the long-term outcomes of 522 patients who received methadone maintenance treatment and 314 who received the subcutaneous naltrexone implant—a formulation not available in the United State but marketed in Australia—that releases therapeutic levels of naltrexone into the body for five to six months. While effective in reducing opioid-related hospital admissions from baseline, naltrexone implantation was associated with increased likelihood of nonopioid-drugrelated hospital admissions (for example, dependence and withdrawal). Patients who received methadone had a significant increase in the risk of opioid-related hospital admissions, but not for nonopioid admissions.

The study was published in the April Archives of General Psychiatry and funded by the Australian National Health and Medical Research Council and the Western Australia Department of Health's Office of Mental Health.

An abstract of “Comparing Drug-Related Hospital Morbidity Following Heroin Dependence Treatment With Methadone Maintenance or Naltrexone Implantation” is posted at<archpsyc.ama-assn.org/cgi/content/abstract/65/4/457>. 


The addition of atorvastatin (Lipitor) to a regimen of donepezil (Aricept) does not appear to have an effect on Alzheimer's disease symptoms, a large study sponsored by Pfizer has found. In the 18-month study, atorvastatin 80 mg combined with donepezil 10 mg did not significantly improve cognition and global functioning compared with donepezil and placebo in 640 patients with mild-to-moderate Alzheimer's disease.

The study results were presented at the annual meeting of the American Academy of Neurology in April.


The FDA has confirmed that the generic bupropion extended-release 300 mg tablets, manufactured by Impax Laboratories and distributed by Teva Pharmaceuticals, is equivalent to Wellbutrin XL 300 mg, the brand-name formulation of the drug. The agency had been investigating 85 reports of loss of efficacy and new or worsening side effects in some patients who switched from the brand-name to the generic formulation. After evaluations of both brand-name and generic tablets, the agency concluded that the generic product is “bioequivalent and therapeutically equivalent to (interchangeable with)” the brand-name drug.

The FDA announcement is posted at<www.fda.gov/cder/drug/infopage/bupropion/TE_review.htm>. 


The drug-regulatory agency in the United Kingdom decided not to file criminal charges against GlaxoSmithKline (GSK) for failing to disclose serious safety risks associated with its antidepressant paroxetine (Seroxat). After four years of investigation, the Medicines and Healthcare Products Regulatory Agency concluded that it would not win a criminal case against GSK, but nevertheless criticized the company for withholding adverse clinical data from regulators. Paroxetine has been linked to increased suicidal thoughts and behaviors in pediatric patients, and both U.K. and U.S. regulatory agencies issued strong warnings in 2003 and 2004 for this and other antidepressants.


An FDA alert sent to psychiatrists, health care professionals, and the public warns of a suspected link between montelukast (Singulair), a leukotriene receptor antagonist used to treat asthma and allergy, and suicidal thinking and behavior. The agency is investigating postmarketing surveillance data to assess this suspected association. Merck, which makes montelukast, added warnings for tremor, depression, suicidality, and anxiousness to the product's prescribing label and patient information in 2007 and 2008. The FDA announcement stated that the evaluation is expected to take nine months from March of this year and that it is not advising the discontinuation of the medication at this time.

The FDA announcement is posted at<www.fda.gov/cder/drug/early_comm/montelukast.htm>. 


Reps. Peter DeFazio (D-Ohio) and Pete Stark (D-Calif.) have introduced the Physician Payments Sunshine Act of 2008 (HR 5605) that, if enacted into law, mandates pharmaceutical and medical-device companies to report all gifts to physicians exceeding $25 in value and to make this information publicly available. Sens. Charles Grassley (R-Iowa) and Herb Kohl (D-Wisc.) have cosponsored a similar bill, S 2029.


GSK distributed a “Dear Healthcare Professional” letter in March that warned of the risk of neuropsychiatric events associated with zanamivir inhalation powder (Relenza), a drug used to treat acute influenza symptoms in adults and children aged 7 or older. Events including seizures, hallucinations, delirium, and abnormal behaviors have been reported in postmarketing surveillance, mostly from Japan. Some cases involved death. The neurologic and behavioral adverse events “appear to be uncommon based on usage data” and “were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution,” the letter stated.


Eli Lilly and Co. has paid $15 million to settle a lawsuit with the state of Alaska. The settlement did not admit any wrongdoing. The state government of Alaska accused the company of having concealed from health care professionals and the public important information about side effects of its antipsychotic drug olanzapine (Zyprexa), including weight gain and metabolic abnormalities.


Otsuka America Pharmaceutical Inc. recently agreed to pay $4 million to settle a lawsuit filed by the U.S. Department of Justice over allegations of illegal promotion of unapproved indications of the antipsychotic drug aripiprazole (Abilify), which is comarketed by Otsuka and Bristol-Myers Squibb (BMS). BMS had previously settled with the government in the same cases for more than $500 million in 2007 (Psychiatric News, November 16, 2007).


A clinical trial of a vaccine for treating Alzheimer's disease—a trial known as ACC-001—has been suspended by its makers, Elan Corp. and Wyeth, because of potentially serious side effects in one patient in the study. The patient developed skin lesions that were severe enough for hospitalization and suspected of being a manifestation of vasculitis. ▪