Women undertaking a ten week program of 75 minute Restorative Yoga (RY) classes gained positive differences in aspects of mental health such as depression, positive emotions, and spirituality (feeling calm/peaceful) compared to the control group. The study, published in a special issue of Psycho-Oncology focusing on physical activity, shows the women had a 50% reduction in depression and a 12% increase in feelings of peace and meaning after the yoga sessions.

RY is a gentle type of yoga which is similar to other types of yoga classes, moving the spine in all directions but in a more passive and gentle way. Props such as cushions, bolsters, and blankets provide complete physical support for total relaxation with minimal physical effort, and so people in differing levels of health can practice yoga more easily.

44 women took part in the study, with 22 undertaking the yoga classes and 22 in the waitlist control group. All of the women had breast cancer; 34% were actively undergoing cancer treatment while the majority had already completed treatment. All participants completed a questionnaire at the beginning and end of the ten week program, asking them to evaluate their quality of life through various measures. The results clearly showed that the women who had been given the RY classes experienced a wide range of benefits compared to the control group (who were later all invited to attend identical RY classes).

“Evidence from systematic reviews of randomized trials is quite strong that mind-body therapies improve mood, quality of life, and treatment-related symptoms in people with cancer. Yoga is one mind-body therapy that is widely available and involves relatively reasonable costs,” said lead researcher Suzanne Danhauer, Ph.D., based at Wake Forest University School of Medicine. “Given the high levels of stress and distress that many women with breast cancer experience, the opportunity to experience feeling more peaceful and calm in the midst of breast cancer is a significant benefit.”

The study found that women who started with higher negative emotions and lower emotional well-being derived greater benefit from the gentle yoga intervention compared to the control group. Women in the gentle yoga group also demonstrated a significant within-group improvement in fatigue, while no such change was noted for the control group.

“This was a pilot study to identify the worthiness and feasibility of conducting a larger randomized control trial on restorative yoga and women with breast cancer,” added Danhauer. “Our results are very promising and will allow us to embark on a much larger scale study.”

Cytochrome P450 (CYP450) gene testing is currently not recommended to guide treatment with selective serotonin reuptake inhibitor (SSRI) drugs for patients with depression, concludes an expert panel report in the December issue of Genetics in Medicine, published by the American College of Medical Genetics (ACMG) and by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

“In the absence of supporting evidence, and with consideration of other contextual issues, EGAPP discourages use of CYP450 testing for patients beginning SSRI treatment until further clinical trials are completed,” according to the statement by the independent Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (http://www.egappreviews.org). The underlying EGAPP initiative was developed by the National Office of Public Health Genomics at the Centers for Disease Control and Prevention, with the goal of supporting evaluation of genetic tests and other genomic applications that are in transition from research to clinical and public health practice.

The SSRI antidepressants, such as fluoxetine (Prozac) and sertraline (Zoloft), are the mainstay of treatment for depression in the United States. However, treatment is not always effective patients and doctors sometimes must try several different drugs and doses. Recent studies have found that variations in certain CYP450 genes (coding for enzymes that metabolize SSRIs) can lead to differences in enzyme function that may affect the response to SSRIs.

Potentially, testing for CYP450 gene variations could provide benefit by guiding the initial choice or dose of SSRI for patients with depression. The U.S. Food and Drug Administration recently approved a CYP450 test that may help individualize drug treatment for a wide variety of commonly prescribed drugs, including SSRIs. Specific applications of this test, however, require validation.

The EGAPP Working Group based their recommendation on a commissioned systematic review of the research evidence on CYP450 gene testing by the U.S. Agency for Healthcare Research and Quality. Other factors considered included the quality of the evidence, gaps in current knowledge, and contextual issues related to the introduction of testing into clinical practice. Technical studies showed that the test was highly accurate in detecting common CYP450 gene variations, although less data was available for uncommon variations.

Further analysis focused on how well the test performed in predicting key clinical outcomes. The available data showed no consistent association between the results of CYP450 gene testing and the clinical response to SSRIs that is, their effect on symptoms of depression. There was also no evidence that CYP450 testing predicted the risk of side effects, or that the results guided doctors’ selection of SSRI drug or dosage.

In the absence of data that testing influences treatment or outcomes, there is a risk that the CYP450 test could increase costs without helping patients. There is also a possibility of harmful effects, such as less effective treatment or inappropriate use of genetic information.

The Working Group’s findings don’t mean that CYP450 testing is not potentially useful. Rather, there is currently “insufficient evidence” either for or against the use of CYP450 testing in patients beginning SSRI treatment for depression. The report includes some suggestions for future studies that might help to fill gaps in knowledge regarding the use of CYP450 testing for antidepressant treatment.

The recommendation is the first to be issued by the EGAPP initiative. “This first release from EGAPP has helped us understand some of the challenges we face in evaluating genomic innovations, such as the quality of research designs, dealing with data that are proprietary, scant evidence on benefits and harms, and the lack of comparisons with current practice, of testing in typical populations, and of information about cost and cost-effectiveness,” said EGAPP Chair Alfred Berg, MD, MPH, of the University of Washington.

About the American College of Medical Genetics

Founded in 1991, the ACMG (http://www.acmg.net) provides education, resources and a voice for the medical genetics profession. To make genetic services available to and improve the health of the public, the ACMG promotes the development and implementation of methods to diagnose, treat and prevent genetic disease. Members include biochemical, clinical, cytogenetic, medical and molecular geneticists, genetic counselors, and other health care professionals committed to the practice of medical genetics. Genetics in Medicine, now published monthly, is the official journal of the ACMG.

About Lippincott Williams & Wilkins

Lippincott Williams & Wilkins (http://www.lww.com) is a leading international publisher for healthcare professionals and students with nearly 300 periodicals and 1,500 books in more than 100 disciplines publishing under the LWW brand, as well as content-based sites and online corporate and customer services. LWW is part of Wolters Kluwer Health, a leading provider of information and business intelligence for students, professionals and institutions in medicine, nursing, allied health, pharmacy and the pharmaceutical industry. Wolters Kluwer Health is a division of Wolters Kluwer, a leading global information services and publishing company with annual revenues (2006) of €3.4 billion and approximately 18,450 employees worldwide. Visit WoltersKluwer.com.

Lippincott Williams & Wilkins
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Researchers at Cedars-Sinai Medical Center’s Department of Psychiatry and Behavioral Neurosciences are seeking participants for a clinical trial examining whether two polyunsaturated Omega-3 fatty acids are effective treatments for depression.

The two fatty acids being studied — docosahexanoic acid (DHA) and eicosapentanoic acid (EPA) — are found naturally in fish oil, flaxseed and walnuts. Previous studies have indicated that nutritional supplements that contain Omega-3 fatty acids can be an effective treatment for depression, but this is the first to systematically test the two specific fatty acids against each other and against placebo in a large sample of people with major depression. DHA and EPA have anti-inflammatory properties and help stabilize brain cell membranes, both of which play a role in mood regulation.

The National Institutes of Health (NIH)-sponsored study, held in collaboration with Massachusetts General Hospital, will recruit a total of 300 adults ages 18-80 who are experiencing significant symptoms of major depressive disorder and are in good health. The five-year study is designed to test the safety, effectiveness and tolerability of DHA and EPA against each other and a placebo. Participants will receive one of the two drugs or a placebo for eight weeks in a randomized, double-blind manner.

Major depression affects at least 15 percent of the adult population. Unlike normal emotional experiences of sadness, loss or passing mood states, major depression is persistent and can significantly interfere with an individual’s thoughts, behavior and physical health. While it can be effectively treated, it is a leading cause of disability in the U.S. and in many other countries.

The Cedars-Sinai team, lead by principal investigator and department chair Mark Hyman Rapaport, M.D., will examine the effect of the therapies on participants’ symptoms, quality of life and psychosocial function. They will also examine how fatty acids in the blood and proteins involved in immune function are affected by Omega-3s. Participants will receive free and confidential evaluation and treatment as part of the study. No healthcare insurance is required. A comprehensive medical evaluation – including physical examination, laboratory tests and EKG – may be provided at no charge.

“The reported side effects of Omega-3 treatments have been mild and include upset stomach and a fishy taste in the mouth. There do not appear to be risks to the liver or adverse interactions with most other medications,” said Rapaport, though he added that people who have bleeding disorders or who are taking blood thinners should not use Omega-3 fatty acids. “This study is one of several investigations of alternative and complementary medicine that our department has pursued over the past decade. Expanding our psychiatry studies to include natural treatments has shown promising benefits to patients suffering from a variety of mental illnesses.”

One of only 10 hospitals in California whose nurses have been honored with the prestigious Magnet designation, Cedars-Sinai Medical Center is one of the largest nonprofit academic medical centers in the Western United States. For 19 consecutive years, it has been named Los Angeles’ most preferred hospital for all health needs in an independent survey of area residents. Cedars-Sinai is internationally renowned for its diagnostic and treatment capabilities and its broad spectrum of programs and services, as well as breakthroughs in biomedical research and superlative medical education. It ranks among the top 10 non-university hospitals in the nation for its research activities and its human research protection program is fully accredited by the Association for the Accreditation of Human Research Protection Programs, Inc. (AAHRPP).

Cedars-Sinai Medical Center

Novel treatment strategies for major depression with broader treatment success or a more rapid onset of action would have immense impact on public health, a new study published in the December 1st issue of Biological Psychiatry explains. This new study reports findings that support the evaluation of a potential new antidepressant agent.

According to the lead author on this study, Kamilla Miskowiak, MSc: “Although depression is often related to problems in the chemistry of the brain, recent evidence also suggests that there may be structural problems as well with nerve cells not being regenerated as fast as normal or suffering from toxic effects of stress and stress hormones.” This led the researchers to evaluate the effects of erythropoietin (Epo), a hormone naturally produced by the kidneys that stimulates the formation of red blood cells and is known as a treatment for anemia. The authors explain that new evidence shows that Epo also “has neuroprotective and neurotrophic effects in animal models and affects cognitive and associated neural responses in humans,” suggesting that it may be a candidate in the treatment of depression.

In this study, Miskowiak and colleagues evaluated the effects of Epo on the neural and cognitive processing of emotional information in healthy volunteers using functional magnetic resonance imaging (fMRI). They found that Epo regulated the emotional responses of those volunteers that received it, similar to the effects of current antidepressants. Ms. Miskowiak explains that “this finding provides support to the idea that Epo affects neural function and may be a candidate agent for future treatment strategies for depression.” John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, confirms its potential: “Epo appears to have neurotrophic effects in the brain in animals. The current data suggest that Epo may modulate human brain activity associated with the processing of emotion. Together, there may now be sufficient evidence to justify evaluating the antidepressant effects of Epo and related compounds in humans.”

As in most fields of medicine, psychiatry researchers are working to identify specific types of patients, through their individual genetic variations, that may better benefit from particular drugs or combinations of drugs than other patients. A new study, published in Biological Psychiatry’s December 1st issue, investigated whether depressed patients with a particular genetic variation would better respond to the addition of lithium to their treatment regimen, as opposed to an antidepressant-only treatment.

Adli and colleagues recruited acutely depressed patients who were unresponsive to an antidepressant-only treatment, and augmented their therapy with lithium, the most common medication used to treat bipolar disorder. They then genotyped these patients for variations in the GSK3B gene. This gene codes for the enzyme glycogen synthase kinase 3-beta, which is inhibited by lithium. Mazda Adli, M.D., corresponding author on the project, explains their findings: “[We] found that antidepressant non-responders with depression show a significantly better response to a subsequent lithium augmentation if they carry at least one C-allele as opposed those patients carrying two T-alleles, which is in line with the previous findings regarding this genetic polymorphism.” In other words, patients who carried a specific genetic variation, the C-allele, were more likely to get better with the addition of lithium to their treatment than patients with other variations of the GSK3B gene.

John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, comments, “Over the past several years, preclinical studies have suggested that GSK3-beta was a key molecular switch related to the clinical effectiveness of lithium. This hypothesis is supported by this report from Adli et al. They find that variation in the GSK3-beta gene is related to lithium response in patients, further implicating GSK3-beta as a potential target for antidepressant treatment.” Dr. Adli adds, “If replicable, the findings of this study could be an important step towards an individually tailored antidepressive treatment plan for patients with depression as well as for the identification of possible new drug targets.”

Forest Laboratories, Inc. (NYSE: FRX) and H. Lundbeck A/S announced preliminary top-line results from a phase III study of LEXAPRO (escitalopram oxalate) in the treatment of adolescents, aged 12-17, with Major Depressive Disorder (MDD). These results indicate that patients treated with LEXAPRO experienced statistically significant improvement in symptoms of depression, as measured by the study’s primary endpoint, the Children’s Depression Rating Scale-Revised (CDRS-R), compared to placebo. The CDRS-R is a commonly used clinician-rated instrument that covers 17 symptom areas of depression relevant to adolescents, including impaired schoolwork, difficulty having fun, social withdrawal, physical complaints, and low self-esteem. Additional data from this study are expected to be presented in 2008.

Researchers estimate that up to eight percent of adolescents are affected by depression.(1) However, FDA-approved treatment options for this population are limited. LEXAPRO is not currently approved by the FDA for use in pediatric patients.

“Depression is a significant problem among adolescents, and frequently goes under-recognized and under-treated in this age group. These data support that LEXAPRO has potential as an effective treatment option for adolescents with depression,” said Ivan Gergel, M.D., Senior Vice President of Scientific Affairs and President of the Forest Research Institute.

About the Study

A double-blind, parallel-group, placebo-controlled phase III study to evaluate the safety and efficacy of LEXAPRO in the treatment of depressed adolescents, aged 12-17, was conducted in multiple centers across the U.S. During the eight week study, 316 patients were randomized to receive either LEXAPRO 10-20 mg (n=158) or placebo (n=158). The primary endpoint was change from baseline to Week 8 on the Children’s Depression Rating Scale – Revised (CDRS-R) using last observation carried forward (LOCF) approach. The study showed statistically significant improvement in patients treated with LEXAPRO relative to placebo (p=0.022).

The trial also showed that LEXAPRO was generally well-tolerated. Overall premature discontinuation rates (all causes including adverse events) were [19%] for patients receiving LEXAPRO and [15%] for patients receiving placebo.

Future Development Plans

“Based on these positive results and results of other studies, we see potential for LEXAPRO, already established as an effective treatment for adults with depression, as a treatment for adolescents with MDD. Subject to ongoing communication with the FDA and our review of the full study results for the just completed trial, we intend to file in 2008 for an adolescent depression indication for LEXAPRO,” said Ivan Gergel, M.D.

Depression and Adolescents

Adolescent depression is characterized by persistent sadness and loss of interest in usual activities.(3) While the brain chemistry of depression is not fully understood,(4) research suggests that depression is caused by an imbalance of certain chemicals in the brain, most notably serotonin.(5)

Despite advances and progress in identifying and treating mental disorders in adolescents, epidemiologic studies indicate that only 20-35 percent of depressed patients in this age group currently receive treatment.(6) Depression is a chronic disease(3) that requires medical attention and treatment, and if left untreated, may have serious consequences.(7)

For adolescents who suffer from depression, psychotherapy, cognitive- behavior therapy, interpersonal therapy and medication play an important role in the management of their illness.(2) Patients on antidepressant treatment should also be closely monitored by healthcare providers, family members and other caregivers.

About LEXAPRO

LEXAPRO is an SSRI being studied as a treatment for adolescents with MDD. LEXAPRO is indicated for the initial and maintenance treatment of major depressive disorder and generalized anxiety disorder (GAD) in adults. LEXAPRO is thought to work by helping to restore the brain’s chemical balance. It is believed to increase the availability of serotonin, a substance in the brain believed to influence mood. In adults, LEXAPRO 10 mg/day is a well-tolerated therapy, with drop-out rates due to adverse events comparable to placebo in depression and low in the treatment of GAD. LEXAPRO has been prescribed to over 16 million people.(11)

Important LEXAPRO Information

Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Antidepressants increased the risk of suicidality (suicidal thinking and behavior) in children, adolescents, and young adults in short-term studies in Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of antidepressants in children, adolescents, or young adults must balance the risk to clinical need. Patients of all ages started on antidepressant therapy should be closely monitored and observed for clinical worsening, suicidality, or unusual changes in behavior, especially at the beginning of therapy or at the time of dose changes. This risk may persist until significant remission occurs. Families and caregivers should be advised of the need for close observation and communication with the prescriber. LEXAPRO is not approved for use in pediatric patients.

LEXAPRO is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs), pimozide, or in patients with a hypersensitivity to escitalopram oxalate. As with other SSRIs, caution is indicated in the coadministration of tricyclic antidepressants (TCAs) with LEXAPRO. As with other psychotropic drugs that interfere with serotonin reuptake, patients should be cautioned regarding the risk of bleeding associated with the concomitant use of LEXAPRO with NSAIDs, aspirin, or other drugs that affect coagulation. The most common adverse events reported with LEXAPRO vs placebo (approximately 5 percent or greater and approximately twice that of placebo) were nausea, insomnia, ejaculation disorder, somnolence, increased sweating, fatigue, decreased libido, and anorgasmia. Further information on LEXAPRO is provided in the FDA approved Package Insert.

About Forest Laboratories and Its Products

Forest Laboratories (http://www.frx.com) is a U.S.-based pharmaceutical company dedicated to identifying, developing and delivering products that make a positive difference in peoples’ lives. Forest Laboratories’ growing product line includes LEXAPRO(R) (escitalopram oxalate), an SSRI indicated for adults for the initial and maintenance treatment of major depressive disorder and generalized anxiety disorder; Namenda(R) (memantine HCl), an N-methyl D- aspartate (NMDA)-receptor antagonist indicated for the treatment of moderate to severe Alzheimer’s disease; and Campral(R) (acamprosate calcium), indicated in combination with psychosocial support for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation. In addition to our growing product line, Forest also co-promotes the Daiichi Sankyo, Inc. products Benicar(R)* (olmesartan medoxomil), an angiotensin receptor blocker, Benicar HCT(R)* (olmesartan medoxomil-hydrochlorothiazide), an angiotensin receptor blocker and diuretic combination product, and AZOR(TM)* (amlodipine and olmesartan medoxomil) a calcium channel blocker and angiotensin receptor blocker combination product, all indicated for the treatment of hypertension.

Azor is a trademark of Daiichi Sankyo, Inc.; Benicar and Benicar HCT are registered trademarks of Daiichi Sankyo, Inc.; and Campral is a registered trademark of Merck Sante s.a.s., subsidiary of Merck KGaA, Darmstadt, Germany.

Except for the historical information contained herein, this release contains forward-looking statements within the meaning of the Private Securities Litigation Reform act of 1995. These statements involve a number of risks and uncertainties, including the difficulty of predicting FDA approvals, the acceptance and demand for new pharmaceutical products, the impact of competitive products and pricing, the timely development and launch of new products, and the risk factors listed form time to time in the Forest Laboratories’ Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and any subsequent SEC filings.

References

1. Jellinek MS, Snyder JB. Depression and suicide in children and adolescents. Pediatr Rev 1998;19: 255-64. Birmaher B, Brent D, et al. Practice parameters for the assessment and treatment of children and adolescents with depressive disorders. J Am Acad Child Adolesc Psychiatry. 1998;37(suppl 10):63S-82S.Note: securing primary source

2. Bhatia, MD S.K., Bhatia, MD S.C., Childhood and Adolescent Depression. American Family Physician. 2007:Volume 75, Number 1

3. National Institute of Mental Health. Depression. Accessed November 1, 2007, at http://www.nimh.nih.gov/health/topics/depression/index.shtml

4. Mayo Clinic. Depression. Accessed November 1, 2007, at http://www.mayoclinic.com/health/depression/DS00175/DSECTION=3Paragraph2

5. Mayo Clinic. Depression. Accessed November 1, 2007, at http://www.mayoclinic.com/health/depression/DS00175/DSECTION=3Paragraph1

6. Burns BJ, Costello EJ, Angold A, et al. Children’s mental health service use across service sectors. Health Aff (Millwood).1995;14:147- 159. Leaf PJ, Alegria M, Cohen P, et al. Mental health service use in the community and schools: results from the four-community MECA Study. Methods for the Epidemiology of Child and Adolescent Mental Disorders Study. J Am Acad Child Adolesc Psychiatry. 1996;889-897. Note: securing primary source

7. Mayo Clinic. Depression. Accessed November 1, 2007, at http://www.mayoclinic.com/health/depression/DS00175/DSECTION=7 Complications section, Paragraph 1

8. Grunbaum JA, Kann L, Kinchen SA, Williams B, Ross JG, Lowry R, et al. Youth risk behavior surveillance – United States, 2001. MMWR Surveill Summ 2002; 51:1-62

9. Anderson RN. Deaths: leading causes for 2000. Natl Vital Stat Rep 2002:50:1-85

10. Gibbons RD, Brown CH, Hur K, Marcus SM, Bhaumik DK, Erkens JA, Herings RM, Mann JJ. Early Evidence on the effects of regulators’ suicidality warnings on SSRI prescriptions and suicide in children and adolescents. Am J Psychiatry. 2007 Sep; 164(9):1356-63

11. Wolters Kluwer Health. LEXAPRO projected Unique Patient Counts Since Launch. August 2007.

Researchers at the University of Pennsylvania School of Medicine and other study sites have found that transcranial magnetic stimulation (TMS) — a non-invasive technique that excites neurons in the brain via magnetic pulses passed through the scalp — is a safe and effective, non-drug treatment with minimal side effects for patients with major depression who have tried other treatment options without benefit.

This study — the largest to-date studying TMS as a standalone treatment for major depression — appears in the December 1st issue of Biological Psychiatry.

“TMS provides a well-tolerated treatment option to patients whose depression is otherwise treatment resistant,” says John P. O’Reardon, MD, Associate Professor of Psychiatry at Penn, and lead study author. “Since TMS is administered via the scalp and therefore goes directly to the brain, it allows the patient to avoid bodily side effects such as weight gain, sedation and/or sexual function.”

The study was conducted at 23 sites in the U.S., Australia, and Canada, and involved 301 medication-free patients with major depression who had not benefited from prior treatment. The patients were randomized to active or sham TMS for 4-6 weeks. Response and remission rates with active TMS were approximately twice those of sham. Additionally, there were no unexpected, serious side effects, and less than 5% of patients discontinued their TMS due to side effects. This is about three times better tolerated and safer than standard medications, which have about a 15% discontinuation rate due to side effects.

Dr. O’Reardon further comments, “As indicated by recent large scale, government-sponsored, studies of existing treatment options for major depression conducted by the National Institute of Health (the STAR-D reports), there is a great need to develop new, effective treatments for patients, especially those not benefiting from first line interventions. The results of this study indicate that TMS offers new hope to patients in this regard.”

Additional study authors are H. Brent Solvason, Philip G. Janiak, Shirlene Sampson, Keith E. Isenberg, Ziad Nahas, William M. McDonald, David Avery, Paul B. Fitzgerald, Colleen Loo, Mark A. Demitrack, Mark S. George, and Harold A. Sackeim.

Disclosure: Dr. O’Reardon has received grant support from BMS, Cyberonics, Lilly, Magstim, Neuronetics, Pfizer, and Sanofi; acted as a consultant for Lilly and Neuronetics; and is a member of speakers bureaus for BMS, Cyberonics, and Lilly.

PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System.

Penn’s School of Medicine is currently ranked #3 in the nation in U.S.News & World Report’s survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

The University of Pennsylvania Health System includes three hospitals — its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation’s “Honor Roll” hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation’s first hospital; and Penn Presbyterian Medical Center — a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.

Bristol-Myers Squibb Company (NYSE: BMY) and Otsuka Pharmaceutical Co., Ltd. announced that the U.S. Food and Drug Administration (FDA) approved the supplemental New Drug Application for ABILIFY(R) (aripiprazole) as adjunctive, or add-on, treatment to antidepressant therapy (ADT) in adults with major depressive disorder (MDD). ABILIFY is the first medication approved by the FDA as add-on treatment for MDD.

“The approval of this new add-on treatment option is critical for adults suffering from depression who cannot find sufficient relief for their 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 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, placebo-controlled, multicenter studies (n=743). The 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 monotherapy with one or more ADTs in the current episode and then added ABILIFY to their treatment regimens.

“We are committed to helping those who suffer from depression, one of the leading causes of disability in the 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 therapies, such as ABILIFY, to help adults living with depression.”

“We are pleased that ABILIFY has achieved this important milestone as the 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 their lives.(2) A recent study evaluated different treatment approaches, including adjunctive medications and switching strategies, in patients with MDD.(1) The study found that 63 percent of patients did not achieve adequate relief of depressive symptoms following the initial treatment with an antidepressant alone.(1) Additionally, the study demonstrated that the 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 major depressive disorder who had experienced an inadequate response to prior 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 or adjunctive ABILIFY. All study participants received one of the commonly prescribed ADTs, including selective serotonin reuptake inhibitors (SSRIs): Lexapro(R) (escitalopram), Prozac(R) (fluoxetine), Paxil CR(R) (paroxetine controlled-release), Zoloft(R) (sertraline); or a serotonin-norepinephrine reuptake inhibitor (SNRI): Effexor XR(R) (venlafaxine extended release). The dosage range for adjunctive ABILIFY was 2-20 mg/day (15 mg/day was the maximum dose for patients receiving ABILIFY as an adjunct to Paxil CR or 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 Score 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 (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 the 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 the reduction of the MADRS Total Scores.(3) For the secondary endpoint, ABILIFY plus an ADT was also superior to placebo plus ADT in reducing the mean SDS Total Score in one study.

In these studies, adjunctive ABILIFY demonstrated no clinically important differences on metabolic parameters, including prolactin, fasting glucose, HDL, LDL and total cholesterol. The median percent change from baseline in triglycerides was 5 percent for adjunctive ABILIFY-treated patients vs 0 percent for adjunctive placebo-treated patients. In the 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. The 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, 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 or equal to 5 percent and at least twice the incidence of placebo plus ADT) associated with the use of adjunctive ABILIFY 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).

About Major Depressive Disorder

Major depressive disorder is a serious mental illness(4)characterized by one or more major depressive episodes.(5) Depression affects approximately 13 to 14 million adults,(2) or about 6.7 percent of the adult population in a given year,(6) and is one of the most common mental health disorders.(7) Depression is one of the leading causes of disability in the U.S.(8) In 2000, the total economic burden of treating depression in the U.S. was $83.1 billion, with workplace costs, including missed days and lack of productivity due to illness, accounting for the majority of the total economic burden (62 percent).(9) Other economic burdens in 2000 included $26.1 billion (31 percent) for treatment costs and $5.4 billion (7 percent) for suicide- related costs.(9)

About ABILIFY

The first and only available dopamine partial agonist, ABILIFY is indicated as adjunctive treatment to antidepressant therapy in adults with major depressive disorder.

Initially approved in November 2002, over 12.5 million prescriptions have been written for ABILIFY in the U.S.(10) through 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 therapy 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 and INDICATIONS for ABILIFY

INDICATIONS:

– ABILIFY is indicated for use as an adjunctive treatment to antidepressants for major depressive disorder in adults.

IMPORTANT SAFETY INFORMATION:

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 the treatment of patients with dementia-related psychosis (see Boxed WARNING).

Antidepressants increased the 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 therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior, especially during the initial few months of therapy, 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 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 reported with ABILIFY. NMS can cause hyperpyrexia, muscle rigidity, diaphoresis, tachycardia, irregular pulse or 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 for 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 or completely

Hyperglycemia and 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. There 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 them to hypotension.

As with other antipsychotic drugs, ABILIFY should be used with caution in patients with a history of seizures or with conditions that lower the seizure threshold.

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

Disruption of the 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.

The possibility of a suicide attempt is inherent in psychotic illnesses and bipolar disorder, 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 for aspiration pneumonia.

Physicians should advise patients to avoid alcohol while taking ABILIFY.

Strong CYP3A4 or CYP2D6 inhibitors increase ABILIFY drug concentrations when used concomitantly.

CYP3A4 inducers decrease ABILIFY drug concentrations when used concomitantly.

Commonly observed adverse reactions (greater than or equal to 5 percent incidence and at least twice the 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), and blurred vision (6 percent vs 1 percent).

Please see FULL PRESCRIBING INFORMATION, including Boxed WARNING, for ABILIFY.

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

Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd. are collaborative partners in the development and commercialization of ABILIFY in the 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 the 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 the treatment of diseases and consumer products for the maintenance of everyday health. Otsuka is committed to being a corporation that creates global value, adhering to the 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 the natural environment. The 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. $7.2 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.

For more information and FULL PRESCRIBING INFORMATION, including Boxed WARNING, visit: http://www.abilify.com

Visit Bristol-Myers Squibb at: http://www.bms.com

Visit Otsuka Pharmaceutical Co., Ltd. at: http://www.otsuka-global.com

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

References

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

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

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

(4) National Alliance on Mental Illness (NAMI) Web site. About Mental Illness: Major Depression. 2006. Accessed August 2007.

(5) Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text revision. Washington DC, American Psychiatric Association, 2000.

(6) Kessler RC, Chiu WT, Demler OD, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the national comorbidity survey replication. Arch Gen Psychiatry. 2005;62:617-627.

(7) Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime Prevalence and Age-of-Onset Distributions of DSM-IV Disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62:593-602.

(8) Michaud CM, McKenna MT, Begg S, et al. The burden of disease and injury in the United States 1996. Population Health Metrics. 2006;4:11.

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

(10) IMS Auditrac NGPS: ABILIFY total monthly retail prescriptions: Data accessed July 2007.

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

http://www.bms.com

Antidepressants should not be ruled out as treatment for young people with depression, especially since recent studies have shown no connection between these medications and suicide in younger patients, according to an article in the latest Medical Journal of Australia.

Professor Robert Goldney, Professor of Psychiatry at The University of Adelaide, says it is important to look at all the available evidence, not just randomised clinical trials, before making assumptions about a link between antidepressants and suicidal behaviour.

“Real-life clinical monitoring may be the only way in which clinicians and drug regulators can make reasoned decisions about some treatments,” Prof Goldney says.

In his article, Prof Goldney reviewed several such studies from around the world, and found little evidence to suggest antidepressant use made young people prone to suicide.

“Furthermore, there is concern that the reduced prescribing of antidepressants to young people may be associated with an increase in youth suicide in the United States,” Prof Goldney says.

In light of this, he says, it is not unexpected that one study concluded that the benefits of antidepressants appear to be much greater than the risks from suicidal behaviour or attempts.

Prof Goldney says that his review of recent research should not be interpreted as promoting uncritically the use of antidepressants in young people.

“Antidepressants are not necessarily first-line treatment, and they should be used only as an adjunct to psychosocial and cognitive behavioural therapies, and after consultation with the patient and family.”

No antidepressant has as yet been approved for use in major depression in children and adolescents in Australia.

The Medical Journal of Australia is a publication of the Australian Medical Association.

A new report indicates that young adults who have suffered from depression within the past year are at a higher risk of initiating substance use including cigarette smoking and use of alcohol or illicit drugs. The findings, based on the largest national survey on substance use and health, were reported today by the Substance Abuse and Mental Health Services Administration (SAMHSA).

The release of this report coincides with the Great American Smokeout – a national observance in support of being free of tobacco use and addiction. The data from the report highlight the relationship between depression and the impulse to begin smoking in young adults.

Depression and the Initiation of Cigarette, Alcohol, and Other Drug Use among Young Adults indicates that 9.4 percent of people aged 18 to 25, or approximately 3 million young adults in the United States experienced one or more major depressive episodes in the past year.

The National Survey on Drug Use and Health (NSDUH), the source for this report, defines a major depressive episode as a period of two weeks or longer during which there is depressed mood or loss of interest or pleasure and the presence of at least four other symptoms that reflect a change in functioning. These include problems with sleep, eating, energy, concentration and self-image. This definition is consistent with the one used by the American Psychiatric Association.

“Today is the Great American Smokeout – a day when we pause to recognize ongoing efforts to draw attention to the health benefits of avoiding cigarettes,” said SAMHSA Administrator Terry Cline, Ph.D. “This study clearly reveals that too often people turn to cigarettes or other substances to try to deal with depression, creating a double jeopardy for their health and well-being.”

Among the report’s notable findings were that young adults experiencing major depressive episodes within the past year were:

- Approximately 60 percent more likely to have initiated cigarette use than those in their age group who had not experienced depression in the past year (12.7 versus 7.8 percent, respectively).

- Approximately 35 percent more likely to have initiated alcohol use than those in their age group who had not experienced depression in the past year (33.7 versus 24.8 percent).

- Twice as likely to have initiated use of an illicit drug as those in their age group who had not experienced depression in the past year (12.0 versus 5.8 percent).

- Twice as likely to start abusing pain relief medication than were their contemporaries who had not experienced recent depression (7.1 versus 2.8 percent).

The report is also notable because of the size of the database — nearly 135,000 interviews with persons aged 12 or older, including almost 45,000 young adults – and it was conducted during the course of the 2005 and 2006 NSDUH surveys. This database is one of the largest and most detailed of its kind.

Substance Abuse and Mental Health Services Administration