Patients with bipolar disorder and comorbid
obsessive-compulsive disorder (OCD) are more likely to have a
history of suicide attempts, rapid cycling, and alcohol dependence
compared with their peers without anxiety comorbidities, study
results show.

“The data in this report support the notion that comorbid OCD is
fairly common, is associated with disease severity, and has
important consequences regarding symptom- and patient-rated
outcomes,” comment Flávio Kapczinski (Hospital de
Clínicas de Porto Alegre, Brazil) and colleagues.

The prominence of anxiety in general and OCD in particular among
patients with bipolar disorder has long been acknowledged. Recent
studies have tried to investigate the illness burden of OCD, but
comparisons have usually been made between those with and without
OCD comorbidity.

“This is little informative because those patients with any
comorbidity tend to differ in a number of measures from those with
‘pure’ bipolar disorder,” the researchers explain in the journal
Comprehensive Psychiatry.

To address this, they performed a cross-sectional study of
lifetime comorbidities in 259 patients with bipolar disorder, using
anxiety comorbidities as a “more rigorous control group with the
aim of uncovering more specific correlates of OCD comorbidity in
bipolar disorder.”

Kapczinski et al report that lifetime prevalence of any
anxiety disorder was 55.6%, and of OCD, 12.4%. Current prevalence
of OCD was 8.5%; although no cases were detected during mania, it
was diagnosed in 8.4% of those in a euthymic phase, 13.9% of those
depressed, and 13.0% of those with mixed episodes.

The researchers note that this fits with recent studies showing
that obsessions or compulsions may remit during mania to reappear
in depression.

Compared with patients with no anxiety comorbidity, those with
lifetime OCD were more likely to be women (61.8% vs 84.4%), to have
a longer period of untreated illness (8 vs 13 years), have a
lifetime history of suicide attempts (35% vs 70%), rapid cycling
(14% vs 39%), and alcohol dependence (10% vs 31%).

Patients with OCD also had higher depression and anxiety symptom
scores than those without anxiety comorbidity, but fewer manic
symptoms.

Meanwhile, when compared with patients with other lifetime
anxiety disorders, those with OCD comorbidity had a lower quality
of life on the social domain.

Kapczinski et al comment: “Patients with OCD are troubled
by thoughts and behaviors, which seem frequently repugnant and
further restrict their social functioning.

“They also often incite friends or family members to engage in
their illness-related behaviors, which may result in conflict.”

MedWire (www.medwire-news.md) is an independent clinical news
service provided by Current Medicine Group, a trading division of
Springer Healthcare Limited. © Springer Healthcare Ltd;
2010

Free abstract

• ">
• First Time-Door Is Open For Family Discussion Of Bipolar Disorder

The postmortem brains of patients with schizophrenia and bipolar disorder show an altered phospholipid profile, namely a decrease in omega-6 long-chain polyunsaturated fatty acids (PUFA), study results show.

However, levels of the omega-3 PUFA docosahexaenoic acid (DHA) were preserved, suggesting a “unique metabolic alteration associated with schizophrenia and bipolar disorder,” say Hee-Yong Kim (National Institutes of Health, Bethesda, Maryland, USA) and colleagues in the Journal of Psychiatric Research.

A previous study of total fatty acid composition in the orbitofrontal cortex of patients with schizophrenia showed a 20% decrease in DHA relative to normal controls, and a reciprocal increase in omega-6 PUFAs.

While the prefrontal cortex has been intensively studied in the pathophysiology of schizophrenia and bipolar disorder, less attention has been given to the role of the hippocampus.

In the current study, the researchers assessed phospholipid composition in postmortem hippocampus samples from 35 individuals with schizophrenia, 34 individuals with bipolar disorder, and 35 mentally healthy controls using liquid chromatography/electrospray ionization-mass spectrometry.

They found no significant differences among the samples in levels of omega-3 PUFAs or any of the phospolipid species phosphatidylserine (PS), phosphatidylethanolamine (PE), or phosphatidylcholine (PC).

Kim and colleagues note that this contradicts previous findings in the cortex, suggesting that DHA loss “may not be a general phenomenon, but specific to certain regions of the diseased brain.”

However, there was a 10.6% decrease in the omega-6 PUFA, docosapentaenoic acid (DPA) in schizophrenia samples and a 7.5% decrease in bipolar disorder samples relative to those from controls. Meanwhile, another omega-6 PUFA arachidonic acid was decreased by 5.3% in schizophrenia and 2.9% in bipolar disorder samples relative to controls.

Furthermore, looking within the phospholipid classes there were several omega-6 PUFA subspecies that were reduced in schizophrenia and bipolar disorder samples, for example among the PC fraction 16:0,20:4, 16:0,22:5, and 18:0,22:5 were all reduced relative to controls.

“Our findings on the loss of DPA, particularly in specific phospholipid classes, suggest an involvement of this fatty acid and related metabolism in the neuropathology of schizophrenia or bipolar disorder, although the mechanism for this decreased is unclear,” Kim and colleagues conclude.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

Free abstract

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Patients with bipolar disorder are more than twice as likely to experience suicidal behavior if they also have alcohol use disorders, survey findings show.

Maria Oquendo, from Columbia University in New York, USA, and colleagues report, however, that despite this increased risk for suicidal behavior, patients with bipolar disorder and alcohol use disorders did not receive more psychiatric treatment.

“This was the case even though bipolar respondents with alcohol use disorder had considerably higher rates of drug use disorders and were more often afflicted with character pathology,” the researchers say.

They therefore suggest that “interventions to improve adherence and venues to make care more accessible for this population with high disease burden would be of utility.”

The team analyzed data on 1643 patients from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) with a lifetime diagnosis of bipolar disorder.

More than half (54%) of the patients met the criteria for alcohol use disorder on the National Institute on Alcohol Abuse and Alcoholism Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV version.

These patients were at greater risk for suicide attempt than individuals without alcohol use disorders, at an odds ratio of 2.25.

The researchers note that the bipolar patients with alcohol use disorders were more likely than those without such disorders to have comorbid nicotine dependence and drug use disorders. However, these comorbidities did not increase the risk for suicidal behavior among the bipolar patients and did not confer additional risk to that associated with alcohol use disorders.

Patients with alcohol use disorders had an earlier age at onset of bipolar disorder and a propensity to endorse alcohol use as self-medication, relative to other patients. But neither these factors nor the number of previous major depressive episodes experienced affected the link between alcohol use and suicidal behavior.

“Given the high disease burden suffered by these individuals and the increased risk for morbidity and mortality when bipolar disorder and alcohol use disorder are comorbid, targeting them for treatment is a public health imperative,” Oquendo and team conclude in the Journal of Clinical Psychiatry.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

Free abstract

Gender differences in bipolar I disorder are associated with memory function and may contribute to poor functional outcome particularly in men, UK researchers report.

They found gender by diagnosis interactions in patients with bipolar I disorder were present in immediate memory, both auditory and visual, but not in general intellectual ability, concept formation, and perseveration or response inhibition.

The researchers also note that it is unlikely that their findings “relate to potential differences in illness severity between men and women with bipolar I disorder,” because both patient groups were comparable in terms of age of onset, duration of illness, number of episodes or hospitalizations and global assessment of functioning (GAF) scores.

They evaluated the performances of 86 remitted patients with bipolar I disorder (36 men and 50 women) and 46 mentally healthy individuals (21 men and 25 women) on a series of cognitive tasks.

On the Weschler Memory Scale-III (WMS-III), patients with bipolar I disorder performed significantly worse than mentally healthy controls in immediate visual and auditory memory and auditory delayed memory, but not in visual delayed memory or auditory recognition delayed memory.

When the effects of gender were assessed, women with bipolar I disorder did not perform significantly worse than control women on any of these WMS-III variables, whereas men with bipolar I disorder performed significantly worse than men without the disorder in auditory (average score 96.5 vs 113.2) and visual immediate (92.2 vs 110.7) memory, and marginally worse in auditory delayed memory (92.3 vs 103.3).

Compared with women with bipolar I disorder, men with the condition performed worse in immediate memory (102.4 vs 93.4, respectively) and auditory delayed memory (105.8 vs 92.3), but not significantly so. Immediate memory was significantly correlated with male patients’ overall level of functioning, however, underscoring the importance of memory function in the outcome of bipolar disorder.

Further analysis of the abnormalities in immediate memory test performance, which could reflect either encoding or retrieval, showed that it was retrieval deficits that were greater in men than women with bipolar I disorder.

“This is further supported by the finding of gender differences in delayed auditory memory in bipolar disorder,” say Sophia Frangou, from King’s College London, and colleagues in the journal Psychological Medicine.

They conclude: “Our results support the notion that gender may modulate the degree of immediate memory dysfunction in bipolar disorder and its impact on overall level of function.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

Free abstract

• Lack Of Grey Matter In Brain Is Linked To Schizophrenia And Bipolar Disorder
• ">

Among bipolar disorder patients living in the community, previous manic episodes appear to impair disability at work and in family life, whereas previous depressive episodes seem to impact on social life disability, study results show.

Reporting their findings in the journal Psychiatry Research, Luis Gutierrez-Rojas (University of Granada, Spain) and colleagues say that “clinicians should make every effort to prevent relapses, to efficiently treat residual symptoms, and to enhance the social support of these patients.”

In the 2004 Global Burden of Disease study, bipolar disorder was reported to be the seventh and eighth leading cause of years lived with a disability for men and women, respectively.

To investigate mediators of this disability in work, social, and family life, the researchers interviewed 108 outpatients with bipolar disorder regarding previous course-of-illness and current psychopathology.

Work disability was defined as being on a disability pension or in the process of obtaining it; while social life or family life disability was defined by a score of 7 or less in the respective subscales of the Sheehan Disability Scale.

At least one type of disability (work, social, family) affected around half of the patients while two types affected 37%.

Work disability was significantly associated with previous repeated manic episodes, three or more hospitalizations, and current depressive symptoms, and inversely associated with education.

Social life disability significantly increased with the number of hospitalisations, previous repeated depressive episodes, and current depressive symptoms.

Current nicotine dependence and lack of social support were also significantly associated with work and social life disability, respectively.

Family life disability significantly increased with the number of hospitalizations, previous repeated manic episodes, and current depressive symptoms.

“This study shows that disability affects an important proportion of bipolar disorder patients and that previous course-of-illness variables, particularly a high number of manic episodes, and current psychopathology - as indicated by the presence of nicotine dependence or depressive symptoms - may be indicators of disability,” Gutierrez-Rojas and colleagues conclude.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

Free abstract

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• If Bipolar Disorder Is Over-Diagnosed, What Are The Actual Diagnoses?

Researchers have identified several clinical characteristics that could help predict the onset of a first episode of psychotic mania in patients who have risk factors for or are vulnerable to bipolar disorder.

“Before onset of a first episode of psychotic mania, patients go through a phase of change from previous mental state, suggesting indicated prevention strategies could be applied if this prodromal phase was better defined,” note Philippe Conus, from Universite Lausanne in Switzerland, and colleagues.

To determine what factors might characterize this prodromal phase, the team measured risk factors and markers of vulnerability in 22 participants of a large first-episode psychotic mania cohort study started in 2001, when patients aged 15 to 29 experiencing a first episode of psychosis were enrolled.

They also used the General Behavior Inventory (GBI) and the Initial Mania Prodrome Questionnaire (IMPQ) to retrospectively assess clinical characteristics of the patients in the 12 months before the emergence of mania. The average duration of the prodrome period for the patients was 20.9 weeks.

As reported in the Journal of Affective Disorders, the researchers identified phenomenological manifestations experienced by more than 50% of patients during the 12 months preceding mania onset that could be grouped into three categories: mood symptoms, sleep changes, and behavioral or other symptoms.

Specifically, with regard to mood, 50% of patients displayed progressive development of attenuated manic symptoms culminating into mania, 30% first developed depressive symptoms and then attenuated manic symptoms culminating into mania, while 18% developed attenuated manic symptoms and then went through a phase of successive depressive and hypomanic stages before developing into full-blown mania.

Sleep changes comprised primarily disrupted sleep and reduced sleep or need for sleep, occurring in 83.3% and 61.1% of patients, respectively.

General behavioral symptoms commonly seen during the prodrome phase included increased stress, impaired functioning, and concentration problems.

The researchers note, however, that these factors globally are likely to have low specificity, saying: “Early identification of patients at risk to develop a first episode of psychotic mania is unlikely to be possible in the basis of symptoms alone.”

However, they also noted some risk factors and vulnerability makers that were relatively common in the patients, and which in addition to these clinical symptoms could signal impending first-episode mania.

The risk factors included family history of affective disorder or past as well as recent exposure to a traumatic event, while the vulnerability markers were developmental delay, cyclothymic traits, previous depressive episodes, and recent increase in levels of substance use.

Conus et al point out that as their study involved a small number of patients and was retrospective, their findings need to be validated in larger prospective studies.

“Nevertheless, this study was conducted mainly in order to generate hypotheses… and as such… the uniqueness of the sample and the comprehensive multi-method and multi-formant assessment undertaken are likely to offer an important complement to the existing literature,” they conclude.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

Free abstract

• A Combination Of Common Genetic Variations Can Lead To Schizophrenia
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Researchers suggest that sustained attention deficit is an endophenotype for bipolar disorder that is maintained during asymptomatic states.

They also report that this deficit occurs independently of clinical severity, defined by psychotic history and number of episodes and hospitalizations.

The team, led by Jose Antonio Cabranes, from Clinico San Carlos Hospital in Madrid, Spain, used the Continuous Performance Test (DS-CPT) to evaluate sustained attention in 143 euthymic patients with bipolar disorder and 105 mentally healthy controls.

The test involves six blocks of 80 trials in total, taking approximately 8 minutes to complete. These six blocks are then combined into three blocks of 160 trials, which allow the study of early, middle, and late attention stages. Performance on the test was analyzed by “accuracy” measures (correct responses and false alarms), efficiency measures (reaction time), and measures derived from signal detection theory (sensibility and response criterion).

Patients with bipolar disorder had fewer hits, longer reaction times, and lower sensibilities than controls in all blocks.

In block 1, 8.5% of bipolar disorder patients scored below the fifth percentile of the control group, signifying a global clinical significant deficit in sustained attention, while in blocks 2 and 3, 8.9% and 11.7% of patients scored below the fifth percentile, respectively.

For both patients and controls, sustained attention worsened with increasing age and improved with years of education and premorbid IQ.

After controlling for these factors in regression analysis, the researchers found that sustained attention performance in bipolar disorder patients correlated significantly with age of illness onset, age of first hospitalization, and duration of illness, but not with severity of illness.

The researchers also point out in the journal Acta Psychiatrica Scandinavica that sustained attention tended to be worse in patients who were unemployed.

“It is therefore possible that cognitive alterations might worsen patients’ life quality and functioning, including employment and productivity at work,” they say.

Cabranes and team add that further research is needed to determine if sustained attention disturbances are present from the onset of illness and become more obvious as the disorder progresses, and if they are modified by medication.

“These studies would also help to clarify the stability of the deficit, the last criteria that an endophenotype should satisfy,” they conclude.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

Free abstract

• Long-Term Tolerability And Safety Data Of Abilify(R) In Combination Treatment For Patients With Bipolar I Disorder

A year ago, a study by Rhode Island Hospital and Brown University researchers reported that fewer than half the patients previously diagnosed with bipolar disorder received an actual diagnosis of bipolar disorder after using a comprehensive, psychiatric diagnostic interview tool — the Structured Clinical Interview for DSM-IV (SCID). In this follow-up study, the researchers have determined the actual diagnoses of those patients. Their study is published in the July 28 ahead of print online edition of The Journal of Clinical Psychiatry.

Under the direction of lead author Mark Zimmerman, MD, director of outpatient psychiatry at Rhode Island Hospital, the researchers’ findings indicate that patients who received a previous diagnosis of bipolar disorder that was not confirmed by a SCID, they were significantly more likely to be diagnosed with borderline personality disorder as well as impulse control disorders.

Their research involved the study of 82 psychiatric outpatients who reported that they received a previous diagnosis of bipolar disorder that was not later confirmed through the use of the SCID. The diagnoses in these patients were compared to 528 patients who were not previously diagnosed with bipolar disorder. The study was conducted between May 2001 and March 2005.

Zimmerman, who is also an associate professor of psychiatry and human behavior at The Warren Alpert Medical School of Brown University, says, “In our study, one quarter of the patients over-diagnosed with bipolar disorder met DSM-IV criteria for borderline personality disorder. Looking at these results another way, nearly 40 percent (20 of 52) of patients diagnosed with DSM-IV borderline personality disorder had been over-diagnosed with bipolar disorder.”

The results of the study also indicate that patients who had been over-diagnosed with bipolar disorder were more frequently diagnosed with major depressive disorder, antisocial personality disorder, posttraumatic stress disorder and eating and impulse disorders.

Zimmerman and colleagues note that “we hypothesize that in patients with mood instability, physicians are inclined to diagnose a potentially medication-responsive disorder such as bipolar disorder rather than a disorder such as borderline personality disorder that is less medication-responsive.”

In their previously published study that concluded bipolar disorder was over-diagnosed, they studied 700 patients. Of the 700 patients, 145 reported they had been previously diagnosed as having bipolar disorder; however, fewer than half of the 145 patients (43.4 percent) were diagnosed with bipolar disorder based on the SCID. The authors state that the over-diagnosis of bipolar disorder can have serious consequences, because while bipolar disorder is treated with mood stabilizers, no medications have been approved for the treatment of borderline personality disorder. As a result, over-diagnosing bipolar disorder can unnecessarily expose patients to serious medication side effects, including possible impact to renal, endocrine, hepatic, immunologic and metabolic functions.

Zimmerman concludes, “Because evidence continues to emerge establishing the efficacy of certain forms of psychotherapy for borderline personality disorder, over-diagnosing bipolar disorder in patients with borderline personality disorder can result in the failure to recommend the most appropriate forms of treatment.”

The report is from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) Project, for which Zimmerman is the principal investigator. Zimmerman said, “The MIDAS project is unique in its integration of research quality diagnostic methods into a community-based outpatient practice affiliated with an academic medical center.”

Along with Zimmerman, other researchers involved in the study include Camile Ruggero, PhD; Iwona Chelminski, PhD and Diane Young, PhD, all of Rhode Island Hospital and Brown University.

Founded in 1863, Rhode Island Hospital (www.rhodeislandhospital.org) in Providence, RI, is a private, not-for-profit hospital and is the largest teaching hospital of the Warren Alpert Medical School of Brown University. A major trauma center for southeastern New England, the hospital is dedicated to being on the cutting edge of medicine and research. Many of its physicians are recognized as leaders in their respective fields of cancer, cardiology, diabetes, emergency medicine and trauma, neuroscience, orthopedics, pediatrics, radiation oncology and surgery. Rhode Island Hospital receives nearly $50 million each year in external research funding. It is home to Hasbro Children’s Hospital, the state’s only facility dedicated to pediatric care, which is ranked among the top 30 children’s hospitals in the country by Parents magazine. Rhode Island Hospital is a founding member of the Lifespan health system.

Source:
Nancy Cawley Jean

Lifespan

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One of the most well-known psychological tools is the Rorschach Inkblot Test. A viewer looks at ten inkblots, one at a time, and describes what they see. The rationale behind this test is the idea that certain aspects of the subject’s personality will be exposed as they are interpreting the images, allowing for the possible diagnosis of various psychological disorders. However, does the inkblot really reveal all? Psychological Science in the Public Interest, a journal of the Association for Psychological Science, published an exhaustive review of all data on the Rorschach (and other similar “projective” tests) in 2000. Such meta-analyses are major undertakings, so although this report is a few years old, it remains the most definitive word on the Rorschach. According to authors Scott O. Lilienfeld of Emory University, James M. Wood of University of Texas at El Paso, and Howard N. Garb of the University of Pittsburgh, despite its popularity, the Rorschach may not be the best diagnostic tool and practitioners need to be cautious in how they use this technique and interpret their results.

The Rorschach Inkblot Test was developed in the 1920s, but was already mired in controversy within 30 years (critics argued that it was not always administered in a standardized way and evidence for its reliability was lacking). However, the Rorschach was revived in the 1970s with the publication of John Exner’s Comprehensive System (CS), which detailed standards and norms for analyzing results. The CS was credited with providing a concrete, scientific basis for the Rorschach tested and it became widely used in clinical and forensic settings.

Proponents of the CS claimed that it also provided a wealth of information for non-patient adults and children. However, critics of this system argue that the norms established by CS are out of date and based on small sample sizes. Furthermore, the CS norms are not representative of the population and actually classify a portion of normal subjects as having pathological tendencies. Many studies have also called into question the scoring reliability of the CS; that is, a number of experiments have shown that two practitioners will score one subject very differently using the CS method. The authors observe that “disagreements can have particularly serious implications if the test results are used to reach important clinical or legal recommendations.”

In addition, some studies suggest that there may be a cultural bias associated with the CS. Research has shown that Blacks, Hispanics, and Native Americans score differently on a number of variables in the CS compared to White Americans. The authors note that “similar discrepancies have been reported for CS scores in Central and South American countries as well as in several European countries.” These findings suggest that any CS data acquired from various racial and cultural groups should be interpreted with extreme caution.

The authors acknowledge that not all the news concerning the Rorschach Inkblot Test is bad: There is evidence that this tool may be useful in identifying patients with schizophrenia, bipolar disorder, and borderline personality disorder. They note, however, that the Rorschach has not been shown to be related to Major Depressive Disorder, Antisocial Personality Disorders, or Posttraumatic Stress Disorder.

Overall, the authors suggest that due to the inconsistent literature on the Rorschach Inkblot Test and other related psychological tools, practitioners should be very selective when they use these assessments and use them in ways which have strong empirical support. “Whenever possible,” the authors conclude, “forensic and clinical evaluations should be based on more dependable assessment techniques, such as structured psychiatric interviews and well-validated self-report indexes.”

Source:
Barbara Isanski

Association for Psychological Science

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Schering-Plough Corporation (NYSE: SGP) announced that the U.S. Food and Drug Administration (FDA) Psychopharmacologic Drugs Advisory Committee voted unanimously in favor of SAPHRIS(R) (asenapine) sublingual tablets as effective and safe for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults and in favor of use in acute treatment of schizophrenia in adults. If approved by FDA, SAPHRIS would be the first psychotropic drug to be approved initially for both of these indications.

“We are very pleased with the outcome of today’s advisory committee meeting and appreciate the panel’s careful consideration of the efficacy and safety data for SAPHRIS,” said Thomas P. Koestler, Ph.D., executive vice president and president, Schering-Plough Research Institute. “In clinical studies, SAPHRIS has demonstrated efficacy combined with an attractive metabolic safety profile. SAPHRIS has the potential to address a significant unmet need for patients with schizophrenia and bipolar I disorder, including patients starting treatment and those who need alternative treatment options when switching or re-initiating therapy. We will continue to work with FDA to bring SAPHRIS to the U.S. market as soon as possible so that patients can benefit from this new medication.”

While the FDA is not bound by the committee’s recommendations, the agency carefully considers them before making a final decision on approval. After reviewing the SAPHRIS data, the committee voted in favor of SAPHRIS as effective (by counts of 12/0/0 and 10/2/0, yes/no/abstain) and safe (12/0/0 and 10/0/2) for the bipolar I disorder and schizophrenia indications, respectively. In addition, the committee voted on the overall balance of safety and efficacy by counts of 12/0/0 and 9/1/2 for the bipolar I disorder and schizophrenia indications, respectively.

The New Drug Application (NDA) for SAPHRIS includes efficacy data from a clinical trial program involving more than 3,000 patients in schizophrenia and bipolar mania trials, and is supported by safety data in 4,500 patients, with some treated for more than two years.

In Europe, a Marketing Authorization Application (MAA) for asenapine, under the brand name SYCREST(R), is currently under review by the European Medicines Agency (EMEA) for the treatment of schizophrenia and manic episodes associated with bipolar I disorder. The application will follow the Centralized Procedure.

Schering-Plough acquired asenapine in November 2007 through its acquisition of Organon BioSciences, which developed the product.

About Schizophrenia

Schizophrenia is a chronic, disabling brain disorder that is characterized by hallucinations, delusions and disordered thinking. The condition affects about 24 million people worldwide (or seven in every 1,000 adults in the population), including more than two million people in the United States and more than four million people in Europe. Although there are a number of medications available for patients, treatment success for any antipsychotic agent can be unpredictable because patients often respond differently to various medications. Among patients with schizophrenia who are being treated with antipsychotics, nearly three in four patients discontinue therapy within 18 months due to either poor tolerability or incomplete efficacy. Metabolic safety, including weight gain, elevation of lipid levels (dyslipidemia) and glucose dysregulation, is an important consideration with any antipsychotic treatment. Patients often need to switch treatments in order for physicians to balance effective treatment with the long-term safety of their patients.

About Bipolar I Disorder

Bipolar I disorder (also known as manic depression) is a chronic, episodic illness characterized by mania (episodes of elevated moods, extreme irritability, decreased sleep and increased energy), depression (overwhelming feelings of sadness, suicidal thoughts), or a combination of both. It is the sixth leading cause of disability in the world, affecting approximately 1 to 5 percent of adults, including 10 million Americans. About half of the patients with bipolar disorder who recover in response to treatment experience recurrence two years later. Patients may experience a high rate of failure due to lack of efficacy or side effects, including metabolic side effects. Poor tolerability frequently leads to treatment discontinuation even when the treatment is providing some benefit. To help manage this challenge, patients often receive multiple medications or need to switch treatments.

About Schering-Plough

Schering-Plough is an innovation-driven, science-centered global health care company. Through its own biopharmaceutical research and collaborations with partners, Schering-Plough creates therapies that help save and improve lives around the world. The company applies its research-and-development platform to human prescription, animal health and consumer health care products. Schering-Plough’s vision is to “Earn Trust, Every Day” with the doctors, patients, customers and other stakeholders served by its colleagues around the world.

SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press release includes certain “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the clinical development of, the commercial plans for and the potential market for SAPHRIS/SYCREST. Forward-looking statements relate to expectations or forecasts of future events. Schering-Plough does not assume the obligation to update any forward-looking statement. Many factors could cause actual results to differ materially from Schering-Plough’s forward-looking statements, including uncertainties in the regulatory process, among other uncertainties. For further details about these and other factors that may impact the forward-looking statements, see Schering-Plough’s Securities and Exchange Commission filings, including Part II, Item 1A. “Risk Factors” in the Company’s second quarter 2009 10-Q, filed July 24, 2009.

Source: Schering-Plough Corporation

• DTNBP1 gene mutations linked to bipolar disorder]]>