• The Food and Drug Administration granted final marketing approval to Reckitt Benckiser to distribute Subutex (buprenorphine HCl) and Suboxone (buprenorphine HCl/naloxone HCl) for the treatment of opioid dependence. Under the Drug Addiction Treatment Act of 2000, prescription of either medication is limited to physicians who have met certain qualifying and registration requirements. Buprenorphine is classified as a Schedule III narcotic under the Controlled Substances Act.
• The Office of the Inspector General of the Department of Health and Human Services filed notice on October 3 in the Federal Register of its "Draft OIG Compliance Program Guidance for Pharmaceutical Manufacturers." The notice of the draft guidance also calls for public comment before December 2. Under the new guidance, the government warned drug companies that they must not offer financial incentives or "other tangible benefits" to doctors, pharmacists, or other health care professionals to prescribe or recommend any particular drug or to switch patients from one medication to another. IG Janet Rehnquist indicated that many common practices used in marketing and sales of prescription drugs "could run afoul of federal fraud and abuse laws." The draft guidance is posted on the Web at www.seniors.gov/articles/1002/draft-pharma-guide.htm.
• Generic manufacturer Barr Laboratories was successful in its court fight against Shire over the ADHD medication Adderall. Barr had sued after Shire invoked its right to block automatic approval of Barr’s application to market a generic version of the mixed amphetamine salts preparation. The court agreed with Barr that Shire’s patent had expired, and subsequently the FDA approved Barr’s application to market the generic.
• Overseas, the Irish Medicines Board on October 16 ordered GlaxoSmithKline to recall all stocks of Seroxat (the EU brand of paroxetine) released to wholesalers because the patient leaflet for the Irish market fails to warn about possible suicidal behavior. The company had worked with the board to change the wording in the leaflets at he end of 2001 and added new wording saying, "Suicidal thoughts may increase in the first few weeks of treatment." The board said that’s not good enough. Regulators want stronger wording "to include a reference to suicidal behavior and depression," the board said in a statement.
• Citing IMS Health’s National Prescription Audit data, Wyeth Pharmaceuticals said last month that its combined serotonin/norepinephrine reuptake inhibitor, Effexor (venlafaxine), is now the fastest-growing product in the $13 billion U.S. antidepressant market. The reason for the surge in sales, the company asserted in a press release, is the result of a new analysis of pooled data that the company said concludes that Effexor was more effective than Lilly’s Prozac (fluoxetine), GlaxoSmithKline’s Paxil (paroxetine), and Solvay’s Luvox (fluvoxamine) in an eight-week study of achieving remission with antidepressant therapy.
• A company-funded study presented at the European Stanley Foundation Conference on Bipolar Disorder in Freiburg, Germany, in mid-September examined the use of AstraZeneca’s Seroquel (quetiapine) as an adjunctive medication to mood stabilizers in the treatment of acute mania. The study suggests that the atypical antipsychotic is safe and effective in reducing symptoms of acute mania and the psychotic symptoms that sometimes accompany it. Nearly twice as many patients treated with Seroquel saw full resolution of their symptoms (based on Young Mania Rating Scale scores) than patients who received placebo. Typical side effects of Seroquel, including somnolence, headache, and dry mouth, were noted in this study.
• A company-funded multicenter clinical trial of 248 children between the ages of 6 and 13 with ADHD indicates that Cephalon’s Provigil (modafinil) significantly improved symptoms on the teacher-completed school version of the ADHD Rating Scale IV. The greatest significance was seen with a dose of 300 mg once a day. The side effects were consistent with Provigil’s current labeling, with insomnia being the most frequently reported.
• Psychiatric Genomics, a Gaithersburg, Md., company specializing in the development of small-molecule drugs for treatment of mental illness, announced last month a collaborative agreement with the National Institute of Psychiatry and Neurology in Budapest, Hungary. The agreement allows company researchers to use the institute’s collection of central nervous system tissue from both normal controls and people diagnosed with mental illness.
• Forest Laboratories announced late last month that it was pulling its application for approval of memantine for the treatment of moderate-to-severe Alzheimer’s disease. The company, which had filed the application July 31, will refile incorporating new clinical trials data (reported in this column last month) indicating that memantine is a safe and effective adjunct treatment to existing treatment with Pfizer’s Aricept (donepezil). The company hopes to refile the application by the end of the year.
• In a similar move, Johnson and Johnson’s Ortho-McNeil division, according to IMS Health, has delayed its long-awaited application to market Topamax (topiramate) for acute mania. The company is said to be awaiting analysis of very recently completed clinical trials for inclusion in the application.
• Olanzapine (Lilly’s Zyprexa) was significantly superior to haloperidol in reducing negative symptoms in elderly patients with chronic schizophrenia during an acute exacerbation, according to a small Israeli study (20 patients). PANSS total score decreased (that is, showed improvement) from 84 at baseline to 65 after six weeks of treatment with olanzapine, but decreased only from 79 to 74 with haloperidol. PANSS negative scores decreased from 19 at baseline to 15 on olanzapine, but increased (worsened) from 18 to 20 on haloperidol. CGI scores decreased with both medications; however, olanzapine was associated with a significantly greater reduction (improvement). Both groups of subjects experienced roughly equal weight gain.
(Prog NeuroPsychopharmacol and Biol Psychiatry
• Low-dose risperidone (Janssen’s Risperdal) at 2 mg a day is effective in significantly reducing both positive and negative symptoms by eight weeks in acutely psychotic, neuroleptic-naïve patients with a first episode of a psychotic disorder. Although efficacy—measured with the Brief Psychiatric Rating Scale and the CGI, among other scales—was not significantly different between doses of 2 mg and 4 mg, the lower dose was associated with significantly lower levels of motor dysfunction.
(J Clin Psychiatry
• Quetiapine appears to hold promise in reducing psychotic behavior in patients with Alzheimer’s disease while not causing a deterioration in cognitive function, according to a new study from Ohio State University researchers. In the 12-week study, patients were given doses of 50 mg to 150 mg and assessed using the ADAS-Cog and NPI. Patients receiving quetiapine showed significant decreases in delusions and aggression based on NPI scores. ADAS-Cog scores showed no statistically significant change over the 12 weeks.
(Alzheimer Dis Assoc Disord
• In a separate study of 30 adolescents with mania or mixed bipolar I disorder, adding quetiapine to existing divalproex treatment was associated with a statistically significant improvement in scores on the Young Mania Rating Scale (YMRS) compared with divalproex alone. Eighty-seven percent of patients taking the combination experienced a 50 percent or greater reduction in their YMRS score, compared with 53 percent of those taking divalproex plus placebo. No significant difference was seen in baseline to endpoint in safety measures, although sedation (rated as mild to moderate) was significantly more common in patients taking the combination.
(J Am Acad Child Adolesc Psychiatry
• Treating generalized anxiety disorder (GAD) with medication lowers the risk of developing comorbid depression, according to an analysis of data from the National Comorbidity Survey. Among the nearly 8,100 individuals studied, however, there was no significant association between either having seen a mental health professional for GAD or having received a prescription for an anxiolytic and lower risk of depression. Only patients who took the medication had a lower risk of major depression.
(Am J Psychiatry
• Exposure to tricyclic antidepressants or fluoxetine during fetal development does not appear to be associated with adverse effects in a child’s global, IQ, or language development or temperament among children in preschool and in the first to third grades. In contrast, a mother’s depression is associated with less cognitive and language achievement by her children. As a result, the study’s authors concluded, adequate antidepressant therapy should be initiated and maintained during pregnancy and postpartum.
(Am J Psychiatry
2002; 159:1889-1895) ▪