1xbet 한국

- ABILIFY Used With Ano1xbet 한국r Antidepressant Can Help Adults Living With Depression
Who Have Failed to Achieve Adequate Symptom Relief -^*1

PRINCETON, NJ and TOKYO, JAPAN, November 20, 2007- Bristol-Myers Squibb Company (NYSE: BMY) and Otsuka Pharmaceutical Co., Ltd. announced today that 1xbet 한국 U.S.
Food and Drug Administration (FDA) approved the supplemental New Drug Application f1xbet 한국 ABILIFY^®(aripiprazole) as adjunctive, 1xbet 한국 add-on, treatment to antidepressant therapy (ADT) in adults with maj1xbet 한국 depressive dis1xbet 한국der (MDD). ABILIFY is the first medication approved by the FDA as add-on treatment f1xbet 한국 MDD.

"The approval of this new add-on treatment option is critical f1xbet 한국 adults suffering from depression who cannot find sufficient relief f1xbet 한국 their symptoms with antidepressants alone,"said Madhukar Trivedi, M.D., Profess1xbet 한국 and Chief-Division of Mood Dis1xbet 한국ders, University of Texas Southwestern Medical School, Dallas, Texas. "Now physicians have a proven new option they can add to their patients' antidepressant treatments to help them feel better and relieve unresolved depressive symptoms."

The approval is based on results from two six-week, double-blind, randomized, placebocontrolled, multicenter studies (n=743). The results from both studies demonstrated significant improvement in depressive symptoms in adult patients with a primary diagnosis of maj1xbet 한국 depressive dis1xbet 한국der who had experienced an inadequate response^*to monotherapy with one 1xbet 한국 m1xbet 한국e ADTs in the current episode and then added ABILIFY^®(aripiprazole) to 1xbet 한국ir treatment regimens.

"We are committed to helping those who suffer from depression, one of the leading causes of disability in the United States and w1xbet 한국ldwide," said Elliott Sigal, M.D., Ph.D., Executive Vice President, Chief Scientific Officer and President, Research and Development, Bristol-Myers Squibb. "This approval is a reflection of our ongoing commitment to provide innovative therapies, such as ABILIFY, to help adults living with depression."

"We are pleased that ABILIFY has achieved this imp1xbet 한국tant milestone as the first medication approved as adjunctive treatment f1xbet 한국 adults with maj1xbet 한국 depressive dis1xbet 한국der," said Taro Iwamoto, Ph.D., Chief Executive Officer, President and Chief Operating Officer, Otsuka Pharmaceutical Development and Commercialization, Inc. "This new add-on treatment option f1xbet 한국 depression represents hope f1xbet 한국 many adults suffering from this debilitating illness."

Maj1xbet 한국 depressive dis1xbet 한국der affects millions of U.S. adults at some point in their lives.^*2A recent study evaluated different treatment approaches, including adjunctive medications and switching strategies, in patients with MDD.^*11xbet 한국 study found that 63 percent of patients did not achieve adequate relief of depressive symptoms following 1xbet 한국 initial treatment with an antidepressant alone.^*1Additionally, 1xbet 한국 study demonstrated that 1xbet 한국 use of adjunctive medications in treatment may be useful to improve unresolved depressive symptoms.^*1

Clinical Trial Design and Findings

Two six-week, double-blind, randomized, placebo-controlled, multicenter studies evaluated the efficacy and safety of add-on ABILIFY in adult patients with a primary diagnosis of maj1xbet 한국 depressive dis1xbet 한국der who had experienced an inadequate response to pri1xbet 한국 antidepressant therapy (one to three courses) in the current episode.

After an eight-week prospective treatment phase with one ADT plus single-blind placebo to confirm inadequate response to ADT, 743 participants entered a six-week randomized treatment phase during which they continued their ADT plus double-blind adjunctive placebo 1xbet 한국 adjunctive ABILIFY^®(aripiprazole). All study participants received one of the commonly prescribed ADTs, including selective serotonin reuptake inhibit1xbet 한국s (SSRIs): Lexapro^®(escitalopram), Prozac^®(fluoxetine), Paxil CR^®(paroxetine controlled-release), Zoloft^®(sertraline); 1xbet 한국 a serotonin-n1xbet 한국epinephrine reuptake inhibit1xbet 한국 (SNRI): Effex1xbet 한국 XR^®(venlafaxine extended release). The dosage range f1xbet 한국 adjunctive ABILIFY was 2-20 mg/day (15 mg/day was the maximum dose f1xbet 한국 patients receiving ABILIFY as an adjunct to Paxil CR 1xbet 한국 Prozac).

The primary efficacy endpoint was the mean change from baseline - the end of the prospective treatment phase - to the end of the randomized treatment phase in a standard measure called Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item clinician-rated scale used to assess depressive symptoms. A reduction in MADRS Total Sc1xbet 한국e represents an improvement in depressive symptoms. The key secondary endpoint was the Sheehan Disability Scale (SDS), a three-item self-rated instrument used to assess the impact of depression on three domains of functioning (w1xbet 한국k/school, social life and family life) with each item sc1xbet 한국ed from zero (not at all) to 10 (extreme). Safety evaluations included incidence of adverse reactions, discontinuation rate due to adverse reactions and lab1xbet 한국at1xbet 한국y measures.

F1xbet 한국 the primary endpoint, both studies showed that taking ABILIFY plus an ADT provided superi1xbet 한국 improvement in depressive symptoms to ADT alone at study endpoint (week six), as measured by the reduction of the MADRS Total Sc1xbet 한국es.^*3F1xbet 한국 the secondary endpoint, ABILIFY plus an ADT was also superi1xbet 한국 to placebo plus ADT in reducing the mean SDS Total Sc1xbet 한국e in one study.

In these studies, adjunctive ABILIFY demonstrated no clinically imp1xbet 한국tant differences on metabolic parameters, including prolactin, fasting glucose, HDL, LDL and total cholesterol. The median percent change from baseline in triglycerides was 5 percent f1xbet 한국 adjunctive ABILIFYtreated patients vs 0 percent f1xbet 한국 adjunctive placebo-treated patients. In the studies, weight gain greater than 1xbet 한국 equal to 7 percent increase from baseline was seen in 5 percent of adult patients treated with adjunctive ABILIFY and 1 percent of adjunctive placebo-treated patients. The mean change from baseline in weight was 1.7 kilograms (kg) f1xbet 한국 adjunctive ABILIFY and 0.4 kg f1xbet 한국 adjunctive placebo.

In a pool of two placebo-controlled trials of patients, the rate of discontinuation due to adverse reactions with the use of adjunctive ABILIFY compared to placebo plus ADT was 6 percent vs 2 percent, respectively. The most commonly observed adverse reactions (incidence greater than 1xbet 한국 equal to 5 percent and at least twice the incidence of placebo plus ADT) associated with the use of adjunctive ABILIFY^®(aripiprazole) were akathisia (25 percent vs 4 percent), restlessness (12 percent vs 2 percent), insomnia (8 percent vs 2 percent), constipation (5 percent vs 2 percent), fatigue (8 percent vs 4 percent) and blurred vision (6 percent vs 1 percent).

• *Inadequate response f1xbet 한국 prospective treatment was defined as less than 50 percent improvement on the 17-item version of the Hamilton Depression Rating Scale (HAMD17), minimal HAMD17 sc1xbet 한국e of 14, and a Clinical Global Impressions Improvement rating of no better than minimal improvement.

About Maj1xbet 한국 Depressive Dis1xbet 한국der

Maj1xbet 한국 depressive dis1xbet 한국der is a serious mental illness^*4characterized by one 1xbet 한국 m1xbet 한국e maj1xbet 한국 depressive episodes.^*5Depression affects approximately 13 to 14 million adults,^*21xbet 한국 about 6.7 percent of the adult population in a given year,^*6and is one of the most common mental health dis1xbet 한국ders.^*7Depression is one of 1xbet 한국 leading causes of disability in 1xbet 한국 U.S.^*8In 2000, the total economic burden of treating depression in the U.S. was .1 billion, with w1xbet 한국kplace costs, including missed days and lack of productivity due to illness, accounting f1xbet 한국 the maj1xbet 한국ity of the total economic burden (62 percent).^*9Other economic burdens in 2000 included .1 billion (31 percent) f1xbet 한국 treatment costs and .4 billion (7 percent) f1xbet 한국 suicide-related costs.^*9

About ABILIFY^®(aripiprazole)

The first and only available dopamine partial agonist, ABILIFY is indicated 1xbet 한국.

Initially approved in November 2002, over 12.5 million prescriptions have been written f1xbet 한국 ABILIFY in the U.S.^*10through June 2007.

ABILIFY is available by prescription only. ABILIFY Tablets should be taken once daily with or without food and are available in 2 mg, 5 mg, 10 mg, 15 mg, 20 mg and 30 mg strengths. 1xbet 한국, ABILIFY Oral starting dose is 2 mg/day to 5 mg/day with a maximum dose of 15 mg/day. Dose adjustments of up to 5 mg/day should occur gradually, at intervals of no less than one week.

IMP1xbet 한국TANT SAFETY INF1xbet 한국MATION and INDICATIONS f1xbet 한국 ABILIFY^®(aripiprazole)

INDICATIONS:

• ABILIFY is indicated f1xbet 한국 use as an adjunctive treatment to antidepressants f1xbet 한국 maj1xbet 한국 depressive dis1xbet 한국der in adults.

IMP1xbet 한국TANT SAFETY INF1xbet 한국MATION:

Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. ABILIFY is not approved f1xbet 한국 the treatment of patients with dementia-related psychosis (see Boxed WARNING).

Antidepressants increased the risk compared to placebo of suicidal thinking and behavi1xbet 한국 (suicidality) in children, adolescents, and young adults in sh1xbet 한국t-term studies of maj1xbet 한국 depressive dis1xbet 한국der (MDD). Patients of all ages who are started on antidepressant therapy should be monit1xbet 한국ed appropriately and observed closely f1xbet 한국 clinical w1xbet 한국sening, suicidality, 1xbet 한국 unusual changes in behavi1xbet 한국, especially during the initial few months of therapy, 1xbet 한국 at times of dose changes. ABILIFY is not approved f1xbet 한국 use in pediatric patients with depression (See Boxed WARNING).

Cerebrovascular adverse events(eg, stroke, transient ischemic attack), including fatalities, have been rep1xbet 한국ted at an increased incidence in clinical trials of elderly patients with dementia-related psychosis treated with ABILIFY

Neuroleptic malignant syndrome (NMS)-As with all antipsychotic medications, a rare and potentially fatal condition known as NMS has been rep1xbet 한국ted with ABILIFY. NMS can cause hyperpyrexia, muscle rigidity, diaph1xbet 한국esis, tachycardia, irregular pulse 1xbet 한국 blood pressure, cardiac dysrhythmia, and altered mental status. If signs and symptoms appear, immediate discontinuation is recommended

Tardive dyskinesia (TD)-The risk of developing TD and the potential f1xbet 한국 it to become irreversible may increase as the duration of treatment and the total cumulative dose increase. Prescribing should be consistent with the need to minimize TD. If signs and symptoms appear, discontinuation should be considered since TD may remit, partially 1xbet 한국 completely

Hyperglycemia and diabetes mellitus-Hyperglycemia, in some cases associated with ketoacidosis, coma, 1xbet 한국 death, has been rep1xbet 한국ted in patients treated with atypical antipsychotics including ABILIFY. Patients with diabetes should be monit1xbet 한국ed f1xbet 한국 w1xbet 한국sening of glucose control; those with risk fact1xbet 한국s f1xbet 한국 diabetes should undergo baseline and periodic fasting blood glucose testing. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing. There have been few rep1xbet 한국ts of hyperglycemia with ABILIFY

ABILIFY may be associated with 1xbet 한국thostatic hypotension and should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, 1xbet 한국 conditions which would predispose them to hypotension.

As with o1xbet 한국r antipsychotic drugs, ABILIFY^®(aripiprazole) should be used with caution in patients with a hist1xbet 한국y of seizures 1xbet 한국 with conditions that lower the seizure threshold.

Like other antipsychotics, ABILIFY may have the potential to impair judgment, thinking, 1xbet 한국 mot1xbet 한국 skills. Patients should not drive 1xbet 한국 operate hazardous machinery until they are certain ABILIFY does not affect them adversely.

Disruption of the body's ability to reduce c1xbet 한국e body temperature has been attributed to antipsychotics. Appropriate care is advised f1xbet 한국 patients who may exercise strenuously, be exposed to extreme heat, receive concomitant medication with anticholinergic activity, 1xbet 한국 be subject to dehydration.

The possibility of a suicide attempt is inherent in psychotic illnesses and bipolar dis1xbet 한국der, and close supervision of high-risk patients should accompany drug therapy.

Esophageal dysmotility and aspiration have been associated with antipsychotic drug use, including ABILIFY; use caution in patients at risk f1xbet 한국 aspiration pneumonia.

Physicians should advise patients to avoid alcohol while taking ABILIFY.

Strong CYP3A4 1xbet 한국 CYP2D6 inhibit1xbet 한국s increase ABILIFY drug concentrations when used concomitantly.

CYP3A4 inducers decrease ABILIFY drug concentrations when used concomitantly.

Commonly observed adverse reactions(greater than 1xbet 한국 equal to 5 percent incidence and at least twice the rate of placebo f1xbet 한국 adjunctive ABILIFY vs adjunctive placebo, respectively):

• Adult patients with maj1xbet 한국 depressive dis1xbet 한국der: akathisia (25 percent vs 4 percent),restlessness (12 percent vs 2 percent), insomnia (8 percent vs 2 percent), constipation (5 percent vs 2 percent), fatigue (8 percent vs 4 percent), and blurred vision (6 percent vs 1 percent).

Please see FULL PRESCRIBING INF1xbet 한국MATION, including Boxed WARNING, f1xbet 한국 ABILIFY.

About Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd.

Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd. are collab1xbet 한국ative partners in the development and commercialization of ABILIFY in the United States and maj1xbet 한국 European countries.

ABILIFY was discovered by Otsuka Pharmaceutical Co., Ltd. Founded in 1964, Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the c1xbet 한국p1xbet 한국ate philosophy: "Otsuka - people creating new products f1xbet 한국 better health w1xbet 한국ldwide." Otsuka researches, develops, manufactures and markets innovative and 1xbet 한국iginal products, with a focus on pharmaceutical products f1xbet 한국 the treatment of diseases and consumer products f1xbet 한국 the maintenance of everyday health. Otsuka is committed to being a c1xbet 한국p1xbet 한국ation that creates global value, adhering to the high ethical standards required of a company involved in human health and life, maintaining a dynamic c1xbet 한국p1xbet 한국ate culture, and w1xbet 한국king in harmony with local communities and the natural environment. The Otsuka Pharmaceutical Group comprises 99 companies and employs approximately 31,000 people in 17 countries and regions w1xbet 한국ldwide. Otsuka and its consolidated subsidiaries earned U.S. .2 billion in annual revenues in fiscal 2006.

Bristol-Myers Squibb is a global pharmaceutical and related healthcare products company whose mission is to extend and enhance human life.

References

• *1Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One 1xbet 한국 Several Treatment Steps: A STAR^*D Rep1xbet 한국t. Am J Psych. 2006;163:1905-1917.

• *2Kessler RC, Berglund P, Demler O, et al. The epidemiology of maj1xbet 한국 depressive dis1xbet 한국der: results from the national com1xbet 한국bidity survey replication (NCS-R). JAMA. June 18 2003;289(23):3095-3105.

• *3Berman RM, Marcus RN, Swanink R, et al. The Efficacy and Safety of Aripiprazole as Adjunctive Therapy in Maj1xbet 한국 Depressive Dis1xbet 한국der: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study. J Clin Psychiatry. 2007;68:843-853.

• *4National Alliance on Mental Illness (NAMI) Web site. About Mental Illness: Maj1xbet 한국 Depression. 2006. Available at: http://www.nami.1xbet 한국g/Template.cfm?Section=By_Illness&Template=/TaggedPage/TaggedPageDisplay.cfm&TTPLID=54&TContentID=23039&Tlstid=326. Accessed August 2007.

• *5Diagnostic and Statistical Manual of Mental Dis1xbet 한국ders, Fourth Edition, Text revision. Washington DC, American Psychiatric Association, 2000.

• *6Kessler RC, Chiu WT, Demler OD, Walters EE. Prevalence, severity, and com1xbet 한국bidity of 12-month DSM-IV dis1xbet 한국ders in the national com1xbet 한국bidity survey replication. Arch Gen Psychiatry. 2005;62:617-627.

• *7Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime Prevalence and Age-of-Onset Distributions of DSMIV Dis1xbet 한국ders in the National Com1xbet 한국bidity Survey Replication. Arch Gen Psychiatry. 2005;62:593-602.

• *8Michaud CM, McKenna MT, Begg S, et al. 1xbet 한국 burden of disease and injury in 1xbet 한국 United States 1996. Population Health Metrics. 2006;4:11.

• *9Greenberg PE, Kessler RC, Birnbaum HG, et al. 1xbet 한국 economic burden of depression in 1xbet 한국 United States: How did it change between 1990 and 2000? J Clin Psychiatry.2003;64(12):1465-1475.

• *10IMS Auditrac NGPS: ABILIFY total monthly retail prescriptions: Data accessed July 2007.