• The Food and Drug Administration (FDA) in April approved Risperdal M-Tab (risperidone), an orally disintegrating form of the atypical antipsychotic marketed by Johnson & Johnson’s Janssen Pharmaceutica unit. The tablets, which dissolve on contact with saliva, allow for ease of administration as well as rapid absorption and are thought to benefit patients in an acutely agitated state, when giving an injection or requiring the patient to swallow a regular tablet is either not appropriate or safe. The drug will compete with Eli Lilly’s Zyprexa Zydisk (orally disintegrating olanzapine).
• Package inserts for all forms of Risperdal (risperidone) will now be required to include a warning regarding an increased risk of stroke in elderly patients, following an April agreement between Johnson & Johnson and the FDA. The company is also sending out thousands of "Dear Doctor" letters. A similar letter was issued in Canada last fall noting 37 reports of stroke or stroke-like events resulting in 16 deaths. However, the company also cited a pair of studies in which elderly patients with dementia had a statistically significant higher incidence of stroke compared with nondementia patients.
• A settlement appears close in the whistle-blower lawsuit involving Pfizer’s Neurontin (gabapentin). A former medical liaison for Warner Lambert, which was acquired by Pfizer in 2000, claims the company worked to boost sales of the drug by promoting its use in nearly a dozen unapproved indications including treatment for anxiety disorders, bipolar disorder, and migraine headache. Although the company admitted no wrongdoing, at issue is several hundred million dollars in claims paid by Medicaid and other government programs as a result of the alleged marketing of the drug for unapproved uses.
• Mirtazapine (Organon’s Remeron) may induce serotonin syndrome, according to a case report. An 85-year-old woman developed sudden confusion and dysarthria, which progressed to mutism, facial dyskinesias, generalized tremors, and rigidity with cognitive blunting within several days of a first dose of the drug. Upon withdrawing the medication, the patient had only residual hypertonia after two weeks. (Clin Neuropharmacol
• Sertraline (Pfizer’s Zoloft) and paroxetine (GlaxoSmithKline’s Paxil) have lower fetal-to-maternal blood level ratios in pregnant women taking antidepressants than either fluoxetine (Lilly’s Prozac and generics) or citalopram (Forest’s Celexa). Sertraline showed the lowest level of placental passage, while citalopram showed the highest level. (Am J Psychiatry
• While both trazodone (Apothecon’s Desyrel and generics) and nefazodone (Bristol-Myers Squibb’s Serzone) cross the placenta, both may be safe in pregnant women taking antidepressants. In a study of 147 Canadian women, there was no statistically significant difference in the rate of major malformations of children born to mothers taking either drug, compared with placebo. (Can J Psychiatry
• Early response to mirtazapine (Organon’s Remeron) and paroxetine (GlaxoSmith-Kline’s Paxil) appears to predict a later stable response and remission in patients with major depression. Improvement occurred within two weeks in 73 percent of 109 patients taking mirtazapine and 65 percent of patients taking paroxetine. After two weeks, the response rates for both drugs did not significantly increase. Of those who responded early, the majority obtained stable response or remission. (J Clin Psychiatry
• Venlafaxine (Wyeth’s Effexor) may provide patients with more depression-free days than fluoxetine (Lilly’s Prozac and generics), paroxetine (GlazoSmithKline’s Paxil), or fluvoxamine (Solvay’s Luvox). Venlafaxine patients experienced an average of 18.8 days free of depression during an eight-week trial, compared with 13.6 days for patients taking the other SSRIs and 7.4 for patients taking placebo. (J Clin Psychiatry
• Olanzapine (Lilly’s Zyprexa), a pharmacologic analogue of clozapine (Novartis’s Clozaril and generics), may also cause immune suppression, as does clozapine. Following isolated recent reports, Turkish investigators looked at immune-cell surface antibodies in 20 patients treated with olanzapine. Following three months of treatment with olanzapine, surface CD8 antibodies had significantly increased, leading to a decrease in the CD4/CD8 antibody ratio, compared with pretreatment values. That change in the antibody ratio is a marker of immune suppression. (Prog Neuropsychopharmacol Biol Psychiatry
• Treatment with antipsychotic medications associated with weight gain appears to lead to a significant reduction in quality of life for persons with schizophrenia. Among 286 patients, 19 percent gained from one to 10 pounds, and 12 percent gained from 11 to 20 pounds. Weight gain was significantly associated with self-reported poorer quality of life and reduced well-being and vitality. (Psychiatr Serv
• Nizatidine (Reliant’s Axid) may have an early transient effect in limiting weight gain associated with olanzapine (Lilly’s Zyprexa), but the effect appears to be diminished over time and largely eliminated by 16 weeks of concomitant therapy. Significantly less weight gain was seen in patients when 300 mg of nizatidine was added to olanzapine through weeks 3 and 4; however, the difference in weight gain at 16 weeks was not significantly different in the treatment group compared with the group on olanzapine plus placebo. (Eur Neuropsychopharmacol
• While olanzapine (Lilly’s Zyprexa) appears to be effective as a monotherapy to treat mania, it does not appear to protect against depressive symptoms in bipolar disorder. In a small study, 15 patients with acute mania were followed for eight weeks in an open-label, uncontrolled trial of olanzapine. The majority of patients experienced significant improvements in mania ratings but limited or no improvement in depression ratings, leading the authors to conclude that the drug is an effective "antimanic" medication but is not effective as a "mood stabilizer." (Int Clin Psychopharmacol
• Clozapine (Novartis’s Clozaril and generics) is not only effective in patients with treatment-resistant schizophrenia, but also appears to be effective in patients with treatment-resistant schizoaffective disorder and bipolar disorder with psychotic features. In a 48-month naturalistic study of 101 patients, those with bipolar and schizoaffective disorders improved more than did those with schizophrenia. In addition, patients with bipolar disorder had the shortest time to response. (J Clin Psychiatry
• Ziprasidone (Pfizer’s Geodon), which acts through a receptor-binding profile unique among atypical antipsychotics, is safe and effective and has a rapid onset of action in the acute treatment of mania in patients with bipolar I disorder, according to data from a clinical trial released last month. Over three weeks of treatment, 40 mg to 80 mg of ziprasidone twice a day produced rapid and sustained patient improvements in all primary and most secondary measures by endpoint. The drug was well tolerated with a low rate of extrapyramidal symptoms, no weight gain, and no clinically significant change in vital signs, including heart rate and electrocardiogram recordings. (Am J Psychiatry
• Sustained-release bupropion, compared with placebo, appears to triple the number of women with a history of depression who are able to quit smoking. Prior research had indicated that women tend to report more negative mood during smoking withdrawal and as a result are more prone to relapse. About 25 percent of nearly 900 smokers taking bupropion had not relapsed after one year, while only 8.5 percent of those taking placebo were still abstaining. (Nicotine Tob Res
• Desipramine (Aventis’s Norpramin and generics) appears to increase significantly the length of time people addicted to cocaine remain in treatment programs. In a double-blind, placebo-controlled, eight-week trial, subjects were recruited from urban drug-treatment programs and randomly assigned to receive desipramine, carbamazepine (Novartis’s Tegretol and others), or placebo. Both drug groups self-reported significant improvements in mood; however, no significant difference was seen in sustained abstinence or in the proportion of positive drug screens. (Am J Addict
• Fluoxetine (Lilly’s Prozac and generics) appears to be useful in the treatment of youth with anxiety disorders. More than 61 percent of patients randomly assigned to fluoxetine showed significant improvement on anxiety rating scales over 12 weeks versus 35 percent for those randomized to take placebo. The drug was well tolerated except for headache and gastrointestinal side effects. (J Am Acad Child Adolesc Psychiatry
• Of the 62 new medications introduced in the United States during 2001, Shire’s Adderall XR (sustained-release mixed amphetamine salts) and Pfizer’s Geodon (ziprasidone) made it into the top 10 money makers, based on calendar 2002 sales, according to a report by MedAdNews. Adderall XR was fifth with $295 million in U.S. sales, and Geodon was eighth with $222 million in first-year sales.
• Donepezil (Eisai/Pfizer’s Aricept) may benefit dementia patients overall, regardless of the source of the dementia, according to an industry-sponsored presentation at last month’s annual meeting of the American Academy of Neurology. Stephen Salloway, M.D., an associate professor of neurology at Brown University Medical School, reported that a greater proportion of patients showed improvements in cognition, behavior, and activities of daily living on donepezil compared with placebo, regardless of whether patients had vascular dementia or dementia due to Alzheimer’s disease.
• Rivastigmine (Novartis’s Exelon) helps patients with moderate to severe Alzheimer’s disease maintain a greater level of independent living compared with placebo, according to a new analysis of data from more than 1,500 patients also reported during an industry-sponsored presentation at last month’s annual meeting of the American Academy of Neurology. Rene Spiegel, a professor of clinical psychology at the University of Basel, Switzerland, reported that the most robust effects were seen with patients who had more advanced Alzheimer’s disease. ▪