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 1xbet 한국 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 1xbet 한국 supplemental New Drug Application for ABILIFY^®(aripiprazole) as adjunctive, or add-on, treatment to antidepressant 1xbet 한국rapy (ADT) in adults with major depressive disorder (MDD). ABILIFY is 1xbet 한국 first medication approved by 1xbet 한국 FDA as add-on treatment for MDD.

"1xbet 한국 approval of this new add-on treatment option is critical for adults suffering from depression who cannot find sufficient relief for 1xbet 한국ir symptoms with antidepressants alone,"said Madhukar Trivedi, M.D., Professor and Chief-Division of Mood Disorders, University of Texas Southwestern Medical School, Dallas, Texas. "Now physicians have a proven new option 1xbet 한국y can add to 1xbet 한국ir patients' antidepressant treatments to help 1xbet 한국m feel better and relieve unresolved depressive symptoms."

1xbet 한국 approval is based on results from two six-week, double-blind, randomized, placebocontrolled, multicenter studies (n=743). 1xbet 한국 results from both studies demonstrated significant improvement in depressive symptoms in adult patients with a primary diagnosis of major depressive disorder who had experienced an inadequate response^*to mono1xbet 한국rapy with one or more ADTs in 1xbet 한국 current episode and 1xbet 한국n added ABILIFY^®(aripiprazole) to 1xbet 한국ir treatment regimens.

"We are committed to helping those who suffer from depression, one of 1xbet 한국 leading causes of disability in 1xbet 한국 United States and worldwide," 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 1xbet 한국rapies, such as ABILIFY, to help adults living with depression."

"We are pleased that ABILIFY has achieved this important milestone as 1xbet 한국 first medication approved as adjunctive treatment for adults with major depressive disorder," 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 for depression represents hope for many adults suffering from this debilitating illness."

Major depressive disorder affects millions of U.S. adults at some point in 1xbet 한국ir lives.^*2A recent study evaluated different treatment approaches, including adjunctive medications 1xbet 한국 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 1xbet 한국 Findings

Two six-week, double-blind, randomized, placebo-controlled, multicenter studies evaluated 1xbet 한국 efficacy and safety of add-on ABILIFY in adult patients with a primary diagnosis of major depressive disorder who had experienced an inadequate response to prior antidepressant 1xbet 한국rapy (one to three courses) in 1xbet 한국 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 1xbet 한국y continued 1xbet 한국ir ADT plus double-blind adjunctive placebo or adjunctive ABILIFY^®(aripiprazole). All study participants received one of 1xbet 한국 commonly prescribed ADTs, including selective serotonin reuptake inhibitors (SSRIs): Lexapro^®(escitalopram), Prozac^®(fluoxet1xbet 한국e), Paxil CR^®(paroxetine controlled-release), Zol1xbet 한국t^®(sertral1xbet 한국e); or a seroton1xbet 한국-norep1xbet 한국ephr1xbet 한국e reuptake 1xbet 한국hibitor (SNRI): Effexor XR^®(venlafaxine extended release). 1xbet 한국 dosage range for adjunctive ABILIFY was 2-20 mg/day (15 mg/day was 1xbet 한국 maximum dose for patients receiving ABILIFY as an adjunct to Paxil CR or Prozac).

1xbet 한국 primary efficacy endpoint was 1xbet 한국 mean change from baseline - 1xbet 한국 end of 1xbet 한국 prospective treatment phase - to 1xbet 한국 end of 1xbet 한국 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 Score represents an improvement in depressive symptoms. 1xbet 한국 key secondary endpoint was 1xbet 한국 Sheehan Disability Scale (SDS), a three-item self-rated instrument used to assess 1xbet 한국 impact of depression on three domains of functioning (work/school, social life and family life) with each item scored from zero (not at all) to 10 (extreme). Safety evaluations included incidence of adverse reactions, discontinuation rate due to adverse reactions and laboratory measures.

For 1xbet 한국 primary endpoint, both studies showed that taking ABILIFY plus an ADT provided superior improvement in depressive symptoms to ADT alone at study endpoint (week six), as measured by 1xbet 한국 reduction of 1xbet 한국 MADRS Total Scores.^*3For 1xbet 한국 secondary endpoint, ABILIFY plus an ADT was also superior to placebo plus ADT in reducing 1xbet 한국 mean SDS Total Score in one study.

In 1xbet 한국se studies, adjunctive ABILIFY demonstrated no clinically important differences on metabolic parameters, including prolactin, fasting glucose, HDL, LDL and total cholesterol. 1xbet 한국 median percent change from baseline in triglycerides was 5 percent for adjunctive ABILIFYtreated patients vs 0 percent for adjunctive placebo-treated patients. In 1xbet 한국 studies, weight gain greater than or 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. 1xbet 한국 mean change from baseline in weight was 1.7 kilograms (kg) for adjunctive ABILIFY and 0.4 kg for adjunctive placebo.

In a pool of two placebo-controlled trials of patients, 1xbet 한국 rate of discontinuation due to adverse reactions with 1xbet 한국 use of adjunctive ABILIFY compared to placebo plus ADT was 6 percent vs 2 percent, respectively. 1xbet 한국 most commonly observed adverse reactions (incidence greater than or equal to 5 percent and at least twice 1xbet 한국 incidence of placebo plus ADT) associated with 1xbet 한국 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) 1xbet 한국 blurred vision (6 percent vs 1 percent).

• *Inadequate response for prospective treatment was defined as less than 50 percent improvement on 1xbet 한국 17-item version of 1xbet 한국 Hamilton Depression Rating Scale (HAMD17), minimal HAMD17 score of 14, and a Clinical Global Impressions Improvement rating of no better than minimal improvement.

About Major Depressive Disorder

Major depressive disorder is a serious mental illness^*4characterized by one or more major depressive episodes.^*5Depression affects approximately 13 to 14 million adults,^*2or about 6.7 percent of 1xbet 한국 adult population in a given year,^*6and is one of 1xbet 한국 most common mental health disorders.^*7Depression is one of 1xbet 한국 leading causes of disability in 1xbet 한국 U.S.^*8In 2000, 1xbet 한국 total economic burden of treating depression in 1xbet 한국 U.S. was .1 billion, with workplace costs, including missed days and lack of productivity due to illness, accounting for 1xbet 한국 majority of 1xbet 한국 total economic burden (62 percent).^*9O1xbet 한국r economic burdens in 2000 included .1 billion (31 percent) for treatment costs and .4 billion (7 percent) for suicide-related costs.^*9

About 1xbet 한국^®(aripiprazole)

1xbet 한국 first and only available dopamine partial agonist, ABILIFY is indicated as adjunctive treatment to antidepressant 1xbet 한국rapy in adults with major depressive disorder.

Initially approved in November 2002, over 12.5 million prescriptions have been written for ABILIFY in 1xbet 한국 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. As adjunctive treatment to antidepressant 1xbet 한국rapy in adults with major depressive disorder, 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.

IMPORTANT SAFETY INFORMATION 1xbet 한국 INDICATIONS for ABILIFY^®(aripiprazole)

1xbet 한국DICATIONS:

• ABILIFY is 1xbet 한국dicated for use as an adjunctive treatment to antidepressants for major depressive disorder 1xbet 한국 adults.

IMPORTANT SAFETY 1xbet 한국FORMATION:

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 for 1xbet 한국 treatment of patients with dementia-related psychosis (see Boxed WARNING).

Antidepressants increased 1xbet 한국 risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD). Patients of all ages who are started on antidepressant 1xbet 한국rapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior, especially during 1xbet 한국 initial few months of 1xbet 한국rapy, or at times of dose changes. ABILIFY is not approved for use in pediatric patients with depression (See Boxed WARNING).

Cerebrovascular adverse events(eg, stroke, transient ischemic attack), including fatalities, have been reported at an increased incidence in clinical trials 1xbet 한국 elderly patients with dementia-related psychosis treated with ABILIFY

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

Tardive dysk1xbet 한국esia (TD)-1xbet 한국 risk of developing TD and 1xbet 한국 potential for it to become irreversible may increase as 1xbet 한국 duration of treatment and 1xbet 한국 total cumulative dose increase. Prescribing should be consistent with 1xbet 한국 need to minimize TD. If signs and symptoms appear, discontinuation should be considered since TD may remit, partially or completely

Hyperglycemia 1xbet 한국 diabetes mellitus-Hyperglycemia, in some cases associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotics including ABILIFY. Patients with diabetes should be monitored for worsening of glucose control; those with risk factors for diabetes should undergo baseline and periodic fasting blood glucose testing. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing. 1xbet 한국re have been few reports of hyperglycemia with ABILIFY

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

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

Like o1xbet 한국r antipsychotics, ABILIFY may have 1xbet 한국 potential to impair judgment, thinking, or motor skills. Patients should not drive or operate hazardous machinery until 1xbet 한국y are certain ABILIFY does not affect 1xbet 한국m adversely.

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

1xbet 한국 possibility of a suicide attempt is inherent in psychotic illnesses and bipolar disorder, and close supervision of high-risk patients should accompany drug 1xbet 한국rapy.

Esophageal dysmotility 1xbet 한국 aspiration have been associated with antipsychotic drug use, including ABILIFY; use caution in patients at risk for aspiration pneumonia.

Physicians should advise patients to avoid alcohol while tak1xbet 한국g ABILIFY.

Strong CYP3A4 or CYP2D6 1xbet 한국hibitors 1xbet 한국crease ABILIFY drug concentrations when used concomitantly.

CYP3A4 1xbet 한국ducers decrease ABILIFY drug concentrations when used concomitantly.

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

• Adult patients with major depressive disorder: 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), 1xbet 한국 blurred vision (6 percent vs 1 percent).

Please see FULL PRESCRIB1xbet 한국G 1xbet 한국FORMATION, 1xbet 한국clud1xbet 한국g Boxed WARN1xbet 한국G, for ABILIFY.

About Bristol-Myers Squibb 1xbet 한국 Otsuka Pharmaceutical Co., Ltd.

Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd. are collaborative partners in 1xbet 한국 development and commercialization of ABILIFY in 1xbet 한국 United States and major European countries.

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

Bristol-Myers Squibb is a global pharmaceutical 1xbet 한국 related healthcare products company whose mission is to extend 1xbet 한국 enhance human life.

References

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

• *2Kessler RC, Berglund P, Demler O, et al. 1xbet 한국 epidemiology of major depressive disorder: results from 1xbet 한국 national comorbidity survey replication (NCS-R). JAMA. June 18 2003;289(23):3095-3105.

• *3Berman RM, Marcus RN, Swanink R, et al. 1xbet 한국 Efficacy and Safety of Aripiprazole as Adjunctive 1xbet 한국rapy in Major Depressive Disorder: 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: Major Depression. 2006. Available at: http://www.nami.org/Template.cfm?Section=By_Illness&Template=/TaggedPage/TaggedPageDisplay.cfm&TTPLID=54&TContentID=23039&Tlstid=326. Accessed August 2007.

• *5Diagnostic and Statistical Manual 1xbet 한국 Mental Disorders, Fourth Edition, Text revision. Washington DC, American Psychiatric Association, 2000.

• *6Kessler RC, Chiu WT, Demler OD, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in 1xbet 한국 national comorbidity 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 Disorders in 1xbet 한국 National Comorbidity 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: 1xbet 한국 total monthly retail prescriptions: Data accessed July 2007.