• The U.S. Food and Drug Administration (FDA) approved
risperidone long-acting injection for maintenance treatment of
bipolar I disorder as a monotherapy or an adjunct to lithium or valproate.
Risperidone injection is manufactured by Janssen Pharmaceuticals, a subsidiary
of Johnson and Johnson, and was approved for treatment of schizophrenia in
2003. The May 18 approval was based on two randomized, double-blind,
In one of the trials, about 300 patients with bipolar I disorder who had
been stabilized on risperidone long-acting injection were randomized to either
the same dose of the active injection or placebo as monotherapy. The primary
endpoint, time to relapse to a mood episode, was delayed significantly in the
group receiving risperidone injection compared with the placebo group. In the
other trial, 240 patients who were already on lithium or valproate and still
symptomatic for bipolar symptoms were first given risperidone long-acting
injections for 16 weeks of open-label treatment, then randomized to
double-blind treatment of either active or placebo injections while remaining
on oral mood stabilizers for 52 weeks. Again, the time to relapse was later in
the active-injection group than the placebo group. The updated product label
is posted at<www.janssen.com/janssen/shared/pi/risperdalconsta.pdf>.
• The FDA has approved lamotrigene orally disintegrating
tablets (ODT) for marketing in the United States, according to a May
11 GlaxoSmithKline announcement. The ODT formulation was deemed to be
bioequivalent to lamotrigene tablets and was expected to be available in 25
mg, 50 mg, 100 mg, and 200 mg strengths starting in July.
A June 1 announcement by Glaxo said that lamotrigene
extended-release tablet has been approved by the FDA for once-daily
adjunct therapy for epilepsy in patients aged 13 or older. Patients with
partial seizures currently taking immediate-release lamotrigene tablets twice
daily can be converted directly to once-a-day extended-release tablets using
the same total daily dosage, according to the company.
• Schering-Plough announced on June 2 that it had filed a marketing
authorization application with the European Medicines Agency for
asenapine sublingual tablets for the treatment of
schizophrenia and manic episodes of bipolar I disorder. In the United States a
new drug application for asenapine is under FDA review for acute treatment of
schizophrenia and manic or mixed episodes in bipolar I disorder.
• The FDA announced on June 12 that it had requested manufacturers of
montelukast, zafirlukast, and zileuton
to add a precaution about neuropsychiatric adverse reactions in the drugs'
prescribing information. These drugs belong to the class of leuokotriene
modifiers used primarily to treat asthma and allergies. The agency received
multiple case reports of mood and behavioral changes, including agitation,
aggression, anxiety, depression, insomnia, irritability, and suicidal thinking
and behavior associated with these medications. Additional information and
FDA's safety review are posted at<www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm165489.htm>
• At the 2009 annual meeting of the American Society of Clinical
Oncology on May 30, Medco Health Solutions, a large pharmacy benefit manager,
and Indiana University School of Medicine presented the results of a joint
study that indicated a significant interaction between
tamoxifen and certain antidepressants. This interaction was
associated with a two-fold increase in the risk of breast cancer recurrence in
women who were taking tamoxifen. Because tamoxifen is a prodrug activated by
the cytochrome P450 CPY2D6 isoenzyme, potent inhibitors of this isoenzyme can
reduce the availability of the active metabolite of tamoxifen in the body.
Many selective serotonin-reuptake inhibitors (SSRIs) are known to inhibit
CYP2D6 to various degrees.
This study was a retrospective analysis of almost 1,300 women with breast
cancer in the Medco database who were treated with tamoxifen, with an average
of 2.7 years of follow-up. The women who were taking an SSRI that was a
moderate to potent CYP2D6 inhibitor (fluoxetine, paroxetine, or sertraline)
concurrently with tamoxifen had a 16 percent rate of cancer recurrence in two
years, which was significantly higher than the 7.5 percent recurrence rate in
women who took no CYP2D6 inhibitor (reference cohort). The risk ratio was 2.2.
Women who took a weak CYP2D6 inhibitor SSRI (citalopram, escitalopram, or
fluvoxamine), had a recurrence rate of 8.8 percent, which was not
statistically significantly different from the reference cohort.
• In May, Eli Lilly and Company started two phase-3 pivotal trials to
test the efficacy and safety of solanezumab (also known as
LY2062430) in treating mild to moderate Alzheimer's disease (AD). Solanezumab
is a monoclonal antibody aimed at neutralizing amyloid beta, the protein
believed to be largely responsible for the pathogenesis of AD. In earlier
investigations, this monoclonal antibody was shown to bind to amyloid beta and
prevent the protein from aggregating in the brain. The company said 2,000
patients worldwide were expected to be enrolled in the randomized,
double-blind, placebo-controlled, 18-month trials. The antibody is
administered by intravenous infusion once every four weeks. The primary
endpoints are whether the drug will slow the cognitive and functional decline
of AD compared with placebo.
• Positive results from a phase-3 clinical trial of
vilazodone were announced by Clinical Data Inc., the company
developing this drug for treatment of major depressive disorder. Vilazodone is
both an SSRI and a partial serotonin 5-HT1A receptor agonist. This
randomized, double-blind, placebo-controlled trial assigned 481 patients with
major depressive disorder to either vilazodone or placebo treatment for eight
weeks. The vilazodone group achieved a greater reduction in the
Montgomery-Asberg Depression Rating Scale score than the placebo group, and
the difference was statistically significant. The changes from baseline on
17-item Hamilton Depression Rating Scale scores in both groups also differed
significantly. The vilazodone group had a 4.3 percent discontinuation rate due
to adverse events, versus 1.7 percent in the placebo group. The most common
adverse events associated with vilazodone were diarrhea, nausea, and headache.
The company said it intended to file a new-drug application with the FDA
seeking the approval of vilazodone for treatment of major depression.
• Three phase-3 clinical trials of Lu AA21004 have
produced disappointing results for the drug as a potential treatment for major
depressive disorder, according to a June 8 announcement by H. Lundbeck A/S, a
Danish pharmaceutical company, and its U.S. partner, Takeda Pharmaceuticals.
In two of the trials, the drug at 2.5 mg and 5 mg doses did not show a
statistically significant difference from placebo in depression symptom
reduction. In the third trial, the 5 mg and 10 mg doses showed mixed results,
with significant differences in some but not other endpoints when compared
with placebo. The companies said they plan to reevaluate the therapeutic dose
for regulatory submission. The molecule is in phase-3 development for
treatment of generalized anxiety disorder.
• AstraZeneca, the defendant in a civil lawsuit involving its
antipsychotic drug quetiapine, received a judgment in its
favor in Delaware. The plaintiff was a Kansas woman who claimed that
quetiapine caused her to develop diabetes. In the June 2 ruling, the superior
court judge granted the company's request to exclude the testimony of a
plaintiff's medical expert and issued a summary judgment in favor of the
company. Thousands of other injury suits involving quetiapine are still