FDA Approves Once-Daily Formulation of Alzheimer’s Drug
Namenda XR™ (memantine hydrochloride) has been approved by the U.S. Food and Drug Administration for the treatment of moderate to severe dementia of the Alzheimer’s type. Namenda XR is a 28-mg once-daily extended-release formulation of Namenda, a twice-daily immediate release formulation that was approved in 2003.
The safety and efficacy of Namenda XR were established in a randomized, double-blind, placebo-controlled trial of 677 outpatients already taking a cholinesterase inhibitor. The results indicate that patients treated with Namenda XR experienced statistically significant benefits in cognition and clinical global status compared with placebo.
Source.“Forest and Merz Announce FDA Approval of Namenda XR for the Treatment of Moderate to Severe Dementia of the Alzheimer’s Type.” (2010, June 21). Retrieved June 24, 2010, from http://www.medicalnewstoday.com/articles/192583.php.
Staccato Inhaler System Shows Quick Agitation Reduction
Results of clinical studies in patients with schizophrenia or bipolar disorder demonstrated that Staccato® loxapine (AZ-004), currently under review by the U.S. Food and Drug Administration, reduced agitation in patients, regardless of the level of agitation at baseline. Improvement in agitation levels were observed as early as 10 minutes after dosing on the standard components of agitation as measured by the Positive and Negative Syndrome Scale-Excited Component (PEC). These and other efficacy and safety data from clinical trials involving more than 700 patients and study participants were presented at the American Psychiatric Association annual meeting.
The new efficacy results came from two randomized, double-blind, placebo-controlled Phase III clinical trials in which loxapine was administered via inhalation using the Staccato system, which delivers thermally generated drug aerosol to the deep lungs for rapid systemic absorption. Adults ages 18 to 65 who met Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for schizophrenia or bipolar I disorder, and showed a relevant degree of agitation at baseline, were included in the trials. A total of 344 patients with schizophrenia and 314 patients with bipolar I disorder were randomized to receive either 0 mg, 5 mg, or 10 mg of AZ-004 in an inpatient treatment facility. Up to three dosages of AZ-004 could be administered to each patient during the 24-hour study period.
The primary efficacy assessment in the studies was the change from baseline at 2 hours post-dose using the total PEC score. In each study, change from baseline for each of the five items comprising the total PEC score (hostility, uncooperativeness, excitement, poor impulse control, and tension, each scored 1 to 7) was determined starting at 10 minutes post-dose. In addition, patients were grouped by baseline severity of agitation (median split) using the total PEC scores for each study, and response rates for the higher and lower agitation populations were compared.
Each of the five items comprising the PEC scale improved with AZ-004 treatment, with differences from placebo starting at 10 minutes after dosing. On average, each item improved 1 to 2 units from baseline over the first 2 hours post-dose for both patient groups. The median PEC score at baseline was 17 across the two studies. For the 10-mg dosage groups and patients having a total PEC score of 17 or less at baseline, there was, on average, a total PEC score improvement of 8.3 and 8.5 units for patients with schizophrenia and bipolar disorder, respectively. For patients having a total PEC score of higher than 17 at baseline, there was, on average, a total PEC score improvement of 8.9 and 9.7 units for patients with schizophrenia and bipolar disorder, respectively.
Source.“Staccato®Loxapine (AZ-004) Reduced Signs and Symptoms of Agitation as Early as Ten Minutes After Dosing in Patients with Schizophrenia or Bipolar Disorder.” (2010, May 26). Retrieved June 25, 2010, from http://www.prnewswire.com/news-releases/staccator-loxapine-az-004-reduced-signs-and-symptoms-of-agitation-as-early-as-ten-minutes-after-dosing-in-patients-with-schizophrenia-or-bipolar-disorder-94953929.html.
Medical Food Eases Depression Symptoms
Data presented at the American Psychiatric Association’s annual meeting suggest a benefit to combining the prescription medical food L-methylfolate (Deplin®) with an antidepressant agent at the start of treatment. The retrospective analysis showed a significantly greater improvement in depression symptoms in a shorter period of time when patients with major depressive disorder (MDD) were started on combination therapy.
Researchers performed a retrospective two-arm chart review of 242 adults, ages 18 to 70, with a primary diagnosis of MDD (single or recurrent), a Clinical Global Impression-Severity (CGI-S) score of 4 (moderately ill) or 5 (markedly ill), and were experiencing some degree of functional impairment. Charts of eligible patients were divided into a combination group (selective serotonin reuptake inhibitor [SSRI] or serotonin norepinephrine reuptake inhibitor [SNRI] in combination with L-methylfolate 7.5 to 15 mg at treatment initiation; n = 95) or a control arm (SSRI or SNRI monotherapy at treatment onset; n = 147). Data were recorded on patient characteristics, including pre-treatment versus treatment scores using the CGI-S scale.
The study demonstrated that:
- 2.5 times more patients achieved major improvements in their depressive symptoms, functionality, and behavior on combination therapy than on antidepressant monotherapy.
- Patients on combination therapy experienced 23% more rapid improvement than those taking antidepressant monotherapy (p = 0.03). The more rapid time to major improvement demonstrated in the combination group was sustained throughout the study period (approximately 2 years).
- By 60 days, patients on combination therapy had already experienced a significant improvement (p = 0.011) in their CGI scores compared with those on antidepressant monotherapy.
Source.“Study Shows Combining L-Methylfolate with an Antidepressant at the Start of Treatment Significantly Improves Depression Symptoms.” (2010, May 24). Retrieved June 25, 2010, from http://www.prnewswire.com/news-releases/study-shows-combining-l-methylfolate-with-an-antidepressant-at-the-start-of-treatment-significantly-improves-depression-symptoms-94766094.html.
Class, Type of Antidepressant Does not Influence Suicide Risk
Among adults beginning antidepressant therapy, the risk of suicide or suicide attempts does not appear to vary by individual type or class of medication, according to a report in the Archives of General Psychiatry. The study sought to address whether the risk of suicide is equal across antidepressant classes and agents after adjustment for selection factors, or whether particular regimens with safety advantages should be prescribed preferentially in adult populations.
The researchers analyzed health care utilization data from 287,543 adults in British Columbia, Canada, who had initiated antidepressant therapy between 1997 and 2005. During the first year of antidepressant agent use, a total of 846 adults in this population either attempted (751) or completed (104) suicide. Most of these events occurred in the first 6 months after beginning treatment.
There was no clinically meaningful difference in risk among individuals taking different classes of medications, including selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic agents, and other newer and atypical agents. In addition, no significant differences were found among individual medications, including fluoxetine (Prozac®), citalopram (Celexa®), fluvoxamine (Luvox®), paroxetine (Paxil®), and sertraline (Zoloft®).
Source.“Risk of Suicide, Suicide Attempt Similar Across Types of Antidepressant Medication.” (2010, April 29). Retrieved June 25, 2010, from http://www.medicalnewstoday.com/articles/187823.php.
FDA Reviewing New Drug for Depression
The U.S. Food and Drug Administration has accepted for filing a New Drug Application (NDA) for vilazodone for the treatment of major depressive disorder (MDD). Vilazodone is a dual-acting potent and selective serotonin reuptake inhibitor and a 5-HT1A receptor partial agonist.
The NDA submission is based on a comprehensive development program for vilazodone, which included two randomized, double-blind, placebo-controlled Phase III clinical trials. In both of these 8-week trials, the efficacy of vilazodone was shown to be superior to placebo with statistically significant results for the primary endpoint and for multiple secondary measures of the symptoms of depression. Results from efficacy measures in an uncontrolled 52-week study were consistent with these findings. The NDA is supported by a database of nearly 2,900 participants.
Source.“Clinical Data, Inc. Announces FDA Acceptance of New Drug Application for Vilazodone for the Treatment of Major Depressive Disorder.” (2010, May 24). Retrieved June 25, 2010, from http://www.drugs.com/nda/vilazodone_100524.html.