Regulatory Briefs

• Forest Laboratories Inc. announced last month that it had received approval from the FDA to market an oral solution of its new Lexapro (escitalopram). The new formulation of the SSRI spinoff of the company’s Celexa, Forest says, “will provide treatment benefits to a wider range of patients, including the elderly and others who have difficulty swallowing tablets.”

• Forest is also pushing to increase Lexapro’s market share through filing a supplemental new drug application to the FDA to market the drug for the treatment of generalized anxiety disorder. The application included data from three placebo-controlled studies in patients with the disorder.

Industry Briefs

• Data presented at the annual meeting of the American College of Neuropsychopharmacology indicate that risperidone (Janssen’s Risperdal) is effective at treating acute mania as a stand-alone medication therapy. In a multicenter trial comparing risperidone and placebo in hospitalized patients with bipolar I disorder, those taking risperidone had twice the improvement of those taking placebo. (Antianxiety medications and supportive care were allowed during the study, but no other antipsychotic, antidepressant, or mood-stabilizing medications.) Patients who received from 1 mg to 6 mg of risperidone daily (with an average of 4.1 mg) had statistically significant reductions in YMRS scores as quickly as day three of the three-week study. Patients also markedly improved, as measured by the CGI-severity scale.

In the United States risperidone is approved only for the treatment of schizophrenia; however, it is approved as an adjunctive treatment for acute mania in 13 other countries.

• Decision Resources, an independent pharmaceutical-analysis firm, expects atomoxetine (Eli Lilly and Co.’s Strattera) to gain 25 percent of the attention-deficit/hyperactivity disorder (ADHD) treatment market by the time it looses patent protection in 2006. Firm analysts say the drug’s approval in seven major pharmaceutical markets (approval is pending in France, Spain, Italy, Germany, United Kingdom, and Japan; it was recently approved in the United States) will give individuals with ADHD a nonstimulant alternative that will create significant competition.

• Galen Holdings, PLC, the Irish pharmaceutical giant, has announced that it has signed a tentative agreement to acquire all rights to market and sell Sarafem (fluoxetine) from Lilly. The agreement is contingent on regulatory approval. Lilly will continue to manufacture and supply the drug to Galen for the next three years.

Research Briefs

• Atypical antipsychotic drugs that antagonize the binding of dopamine have been shown to varying degrees to elevate prolactin levels in humans. Some forms of breast cancer in women have been shown to be prolactin dependent. Harvard researchers studied more than 110,000 women in a retrospective cohort study from January 1, 1988, to June 30, 1995. The cohort exposed to prolactin-elevating antipsychotic medications was found to have a 16 percent increase in the occurrence of breast cancer, compared with an age-matched cohort of women who had never taken the drugs. The researchers concluded that the findings should spur follow-up, but no change in treatment strategies is warranted.

(Arch Gen Psychiatry2002; 59:1147-1154)

• The December issue of European Neuropsychopharmacology features a series of articles on advances in brain imaging and what the technology can reveal about mental illness. Included is a review article looking at human PET and SPECT neuroreceptor occupancy studies and how those studies help elucidate drug action in the human brain. Antipsychotic interaction with dopamine receptors is reviewed, as well as antidepressant interaction with serotonin transporters and receptors. Benzodiazepine, methylphenidate, and cocaine neurotransmitter interactions are also reviewed.

(Eur Neuropsychopharm2002; 12: 503-511)

• A new study from the Neuroimaging in Mood and Anxiety Disorders Section at the National Institute of Mental Health confirms previous work indicating that primary major depressive disorder is associated with abnormal metabolism in limbic and paralimbic structures of the mesotemporal and prefrontal cortices. Researchers used PET imaging to look at glucose metabolism in patients with MDD before and after treatment with antidepressant therapy.

(Eur Neuropsychopharm2002; 12: 527-544)

• A team at Brookhaven National Laboratory has confirmed earlier reports that methylphenidate, at therapeutic doses, blocks more than 50 percent of the dopamine transporters in the human brain, resulting in a significantly enhanced level of extracellular dopamine. The article also discusses the drug’s inherent low potential for addiction, when administered as intended, due to the time it takes for the increase to occur after dosing. Addictive potential, the team noted, is tied to a rapid increase in dopamine levels, which could be achieved with methylphenidate only through illicit intravenous administration.

(Eur Neuropsychopharm2002; 12: 557-566)

• Atomoxetine (Lilly’s Strattera) appears to be effective in treating symptoms of ADHD in school-aged girls, a population in which few drug studies have traditionally been completed for the disorder. A company-funded study looked at 51 girls, aged 7 to 13, randomized to the new norepinephrine reuptake inhibitor or placebo. Patients treated with atomoxetine saw a nearly 2.5-fold decrease (improvement) in their scores on the ADHD rating scale. In addition, those taking the drug saw improvements in both the inattentive subscale and the hyperactive/inattentive subscale. Ratings on the Connors’ Parent Rating Scale and the CGI-ADHD scales were also statistically significant for those taking atomoxetine, but not for those taking placebo.

(Pediatrics2002; 110:e75)

• Using the FDA’s spontaneous adverse-event reporting system (MedWatch), researchers looked for postmarketing reports of adverse events for olanzapine (Lilly’s Zyprexa) and categorized them by age. The group found that reports of extrapyramidal syndrome complaints were similar across age groups, and reports of tardive dyskinesia were comparable in adolescents (aged 10 to 19) and adults. Children (birth to 9 years), however, had an overrepresentation of sedation, weight gain, liver function abnormalities, and tardive dyskinesia. Adolescents had an overrepresentation of sedation, weight gain, liver function abnormalities, and prolactin elevation. The authors cautioned, however, that reporting bias is likely to be inherent in the system, tending to cause underreporting of events. ▪