Regulatory Briefs

• The U.S. Food and Drug Administration on December 19 granted final approval to Novartis Pharmaceuticals to market the original atypical antipsychotic Clozaril (clozapine) “for the treatment of recurrent suicidal behavior in patients with schizophrenia and schizoaffective disorder who are at chronic risk.” The FDA granted the brand name drug market exclusivity for the new indication for three years. The newly approved indication does not apply to generic clozapine.

The action was based on data from the International Suicide Prevention Trial (InterSePT) that tested the efficacy of Clozaril in reducing suicidal behaviors against olanzapine (Eli Lilly and Co.’s Zyprexa) (Psychiatric News, December 6, 2002). In that trial, Clozaril was found to reduce the risk of suicide attempts and hospitalization to prevent suicide by 26 percent compared with olanzapine. An FDA Talk Paper on the approval is posted on the FDA Web site at www.fda.gov/bbs/topics/ANSWERS/2002/ANS01184.html.

• The FDA last month issued a consumer alert on importation of Clozaril, as well as several other drugs that are being brought into the United States and sold illegally from Web sites. Such sales circumvent FDA controls on the distribution of the listed drugs, which are designed to ensure that the medications are prescribed safely. The agency warned consumers not to buy any of the drugs over the Internet because the drugs obtained via Web sites usually are not accompanied by these safety controls. The alert is posted on the Web at www.fda.gov/bbs/topics/NEWS/2002/NEW00856.html.

Industry Briefs

• Janssen Pharmaceutica submitted a Supplemental New Drug Application to the FDA last month, requesting marketing approval for Risperdal (risperidone) as both mono and adjunctive therapy in the treatment of patients with manic symptoms associated with bipolar disorder. The application is based on five double-blind, Phase III clinical trials involving close to 900 patients. Risperdal is already approved in 13 countries as adjunctive therapy for bipolar mania, along with a mood stabilizer. Currently, olanzapine is the only antipsychotic approved for treatment of acute mania.

• Avera Pharmaceuticals Inc., a privately held, developmental-stage pharmaceutical company, has licensed to Lilly a novel compound offering promise as a treatment for schizophrenia and depression. According to the agreement, Avera acquired worldwide rights to the drug and supportive intellectual property in exchange for up-front as well as future payments. Avera will be responsible for filing an Investigational New Drug Application with the FDA, as well as the design and execution of a clinical development program, including clinical trials.

• Wyeth Pharmaceuticals announced last month that Effexor XR (venlafaxine) is effective in significantly relieving patients’ physical and emotional symptoms related to both depression and generalized anxiety disorder. During presentations at the annual meeting of the American College of Neuropsychopharmacology (ACNP) in Puerto Rico, data covering 18,441 patients were presented showing that patients experienced equal levels of relief, regardless of the initial severity of their symptoms.

• Also at the ACNP meeting, data were presented on a pooled analysis of three positive studies indicating that escitalopram (Forest’s Lexapro) is effective in significantly reducing anxiety symptoms in patients with generalized anxiety disorder, compared with placebo. The multicenter, double-blind trials followed 800 patients for eight weeks. Patients received 10 mg a day for the first four weeks then 10 to 20 mg a day for the remaining four weeks. Significant improvements, as rated by the Hamilton Anxiety Scale, the CGI-I, and the CGI-S, were seen as early as at the end of the first week.

Research Briefs

• Galantamine (Janssen Pharmaceutica’s Reminyl) was effective in clinical trials, but it has received mixed reviews since its debut on the market. A new study reveals that the drug’s ambiguous reputation may be due to the very nature of the Clinician’s Interview Based Impression of Change, plus Caregiver’s Input (CIBIC-Plus), a common assessment tool used in clinical trials of medications for Alzheimer’s disease as well as in private practice. A Canadian team reviewed the narrative content of clinicians’ notes from randomized controlled clinical trials of galantamine and found that, in general, while most patients were rated on the CIBIC-Plus as “no change,” considerable change was actually seen. Patients who showed a combination of cognitive, functional, and/or behavioral improvement on the drug were consistently rated as improved, while patients with only cognitive improvements without any functional or behavioral improvement were rated as having either only mild improvement or no change. Patients with functional improvements not matched by cognitive improvement were rated as having not improved. The researchers concluded that the CIBIC-Plus overall rating may not be as important as the actual clinicians’ notes in determining patient outcomes.

(Dement Geriatr Cogn Disord 2003; 15:26-33)

• A significant concern in treating patients with Alzheimer’s disease has been justifying the high cost of medications indicated for the disease. A Swedish team of researchers looked at long-term costs of using donepezil (Eisai/Pfizer’s Aricept) versus placebo. Patients received donepezil, 5 mg a day for the first 28 days, followed by 10 mg a day through 52 weeks, or placebo. At week 52 patients taking donepezil had gained significant functional benefits relative to placebo, and caregivers reported that patients treated with donepezil required an average of 400 fewer hours of care over the yearlong study compared with patients treated with a placebo. Seventy-seven percent of the annual cost of $1,280 per patient for donepezil was offset by other savings; thus, the annual total costs for patients taking donepezil were $16,438 compared with $16,174 for the placebo group. When caregiver time, medication, and other health care costs were analyzed, the total annualized costs for donepezil-treated patients was $24, 969 versus $26,066 for those receiving placebo, representing a total cost savings of $1,097.

(Dement Geriatr Cogn Disord 2003; 15:44-54)

• Peripheral edema may be far more common than the 3 percent observed in postmarketing data in patients taking olanzapine (Lilly’s Zyprexa). In a review of 49 outpatients taking the drug, 28 (57 percent) exhibited some level of edema, including five (10.2 percent) with severe swelling. Overall, no significant differences were found to be associated with gender, length of time taking olanzapine, dose of the drug, or other diagnoses or medications. In those experiencing some level of edema, only increased age was associated with increasing severity of edema.

(Int Clin Psychopharmacol 2003; 18:57-59)

• Mirtazapine (Organon’s Remeron) appears to be effective in reducing the number and intensity of panic attacks, as well as anticipatory anxiety in patients with panic disorder. In an open-label study of 45 patients, 11 of whom had comorbid major depression, mirtazapine was administered at an established dose of 30 mg daily for three months. Patients were assessed at weeks 2 and 4, then monthly. Subjects showed statistically significant improvements on all psychometric measures.

(Int Clin Psychopharmacol 2003; 18:35-38)

• Patients with obsessive-compulsive disorder who require the addition of an atypical antipsychotic to the standard serotonin reuptake inhibitor therapy have been found to almost always relapse when the antipsychotic is withdrawn. A small retrospective chart review of 18 patients with OCD who had responded to the addition of either haloperidol, pimozide, risperidone, or olanzapine found that discontinuation of the antipsychotic for any reason while continuing their SRI resulted in a relapse rate of 83.3 percent (15 patients) within one year of stopping the antipsychotic. However, 13 relapsed within eight weeks of stopping the antipsychotic.

(Int Clin Psychopharmacol 2003; 18:23-28) ▪