MSD Receives European Approval Of Its Atypical Antipsychotic Medication SYCREST(R) For The Treatment Of Manic Episodes In Bipolar I Disorder

MSD (MSD is a tradename of Merck & Co., Inc., with headquarters in Whitehouse Station, N.J., U.S.A). announced today that the European Commission has approved the Marketing Authorization Application (MAA) for SYCREST® (asenapine) sublingual tablets for the treatment of moderate to severe manic episodes associated with bipolar I disorder in adults. Today's decision was based on recommendations from the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP). The Commission Decision applies to all 27 European Member States.


"Bipolar I disorder is difficult to manage, and patients frequently discontinue therapy for a variety of reasons," said Eduard Vieta, M.D., Ph.D., professor of psychiatry at the University of Barcelona, and director of the Bipolar Disorders Program of the Hospital Clinic, Barcelona, Spain. "Having multiple treatment options is vital for patients, and asenapine represents a new option for this serious disease."


The European Commission approval of SYCREST, an atypical antipsychotic, for the treatment of manic episodes in bipolar I disorder, was based on a review of efficacy data from a clinical trial program, which included nearly 1,300 patients with bipolar mania. SYCREST is marketed as SAPHRIS® (asenapine) sublingual tablets in the United States.


Clinical Trial Overview


Efficacy of SYCREST was demonstrated in two similarly-designed, three-week, randomized, double-blind, placebo- and active-controlled (olanzapine) monotherapy trials of adult patients who had bipolar I disorder with an acute manic or mixed episode with or without psychotic features. Asenapine demonstrated superior efficacy to placebo in the reduction of manic symptoms over three weeks. A statistically significant difference between asenapine and placebo was seen as early as day two.


These pivotal short-term studies were extended via a nine-week, double-blind, non-inferiority study to assess maintenance of efficacy and safety for up to 12 weeks. Maintenance of effect during the episode after 12 weeks of randomized treatment was observed. These studies were further extended for 40 weeks to assess safety for up to a total 52 weeks.


Additionally, efficacy of SYCREST as adjunctive therapy to the mood stabilizers lithium or valproate was demonstrated in a 12-week, placebo-controlled trial involving 326 patients with a manic or mixed episode of bipolar I disorder, with or without psychotic features. The addition of asenapine as adjunctive therapy in patients who were partially non-responsive to lithium or valproate monotherapy for two weeks at therapeutic serum levels resulted in superior reduction of manic symptoms versus lithium or valproate alone at weeks three and 12.


"SYCREST reflects MSD's ongoing commitment to innovative therapies in the area of neuroscience," said Armin Szegedi, M.D., head of Psychiatry, Neuroscience Clinical Research, Merck. "Today's approval provides a new treatment for patients in Europe that is intended to help address the needs of one of the most serious mental illnesses."















Approximately 4,500 subjects, including more than 3,150 patients in phase II/III studies, have contributed to asenapine's safety and tolerability data. In clinical studies, asenapine was generally well tolerated. The most common side effects seen in more than 10% of patients included somnolence and anxiety. Other common side effects seen in between one and 10 patients per 100 included weight gain, increased appetite, dystonia (slow or sustained muscle contractions), akathisia (restlessness), dyskinesia (involuntary muscle contractions), parkinsonism (slow movements, tremor), sedation, dizziness, dysgeusia (change in taste), oral hypoaesthesia (numb feeling of the tongue or in the mouth), increase in alanine aminotransferase (liver protein levels), muscle rigidity, and fatigue. SYCREST is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.


In the combined short-term and long-term SYCREST trials, the mean change in body weight for asenapine was 0.8 kg. The proportion of subjects with clinically significant weight gain (≥ 7 % weight gain from baseline at endpoint) in the short-term bipolar mania trials was 6.5% for asenapine compared to 0.6% for placebo.


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.


Important Safety Information


Elderly patients with dementia-related psychosis


Elderly patients with dementia-related psychosis treated with antipsychotic substances are at an increased risk of death. Sycrest is not approved for the treatment of patients with dementia-related psychosis and is not recommended for use in this particular group of patients.


Neuroleptic Malignant Syndrome


Neuroleptic Malignant Syndrome (NMS), characterised by hyperthermia, muscle rigidity, autonomic instability, altered consciousness and elevated serum creatine phosphokinase levels, has been reported to occur with antipsychotics, including asenapine. Additional clinical signs may include myoglobinuria (rhabdomyolysis) and acute renal failure. If a patient develops signs and symptoms indicative of NMS Sycrest must be discontinued.


Seizures


In clinical trials, cases of seizure were occasionally reported during treatment with asenapine. Therefore, Sycrest should be used with caution in patients who have a history of seizure disorder or have conditions associated with seizures.


Suicide


The possibility of a suicide attempt is inherent in psychotic illnesses and bipolar disorder and close supervision of high-risk patients should accompany treatment.


Orthostatic hypotension


Asenapine may induce orthostatic hypotension and syncope, especially early in treatment, probably reflecting its О±1-adrenergic antagonist properties. Elderly patients are particularly at risk for experiencing orthostatic hypotension. In clinical trials, cases of syncope were occasionally reported during treatment with Sycrest. Sycrest should be used with caution in elderly patients and in patients with known cardiovascular disease (e.g., heart failure, myocardial infarction or ischemia, conduction abnormalities), cerebrovascular disease, or conditions that predispose the patient to hypotension (e.g., dehydration and hypovolemia).


Tardive dyskinesia


Medicinal products with dopamine receptor antagonistic properties have been associated with the induction of tardive dyskinesia characterised by rhythmical, involuntary movements, predominantly of the tongue and/or face. In clinical trials, cases of tardive dyskinesia were occasionally reported during treatment with asenapine. The onset of extrapyramidal symptoms is a risk factor for tardive dyskinesia. If signs and symptoms of tardive dyskinesia appear in a patient on Sycrest, discontinuation of treatment should be considered.


Hyperprolactinaemia


Increases in prolactin levels were observed in some patients with Sycrest. In clinical trials, there were few adverse reactions related to abnormal prolactin levels reported.


QT interval


Clinically relevant QT prolongation does not appear to be associated with asenapine. Caution should be exercised when Sycrest is prescribed in patients with known cardiovascular disease or family history of QT prolongation, and in concomitant use with other medicinal products thought to prolong the QT interval.


Hyperglycaemia and diabetes mellitus


Hyperglycaemia or exacerbation of pre-existing diabetes has occasionally been reported during treatment with asenapine. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia or bipolar disorder and the increasing incidence of diabetes mellitus in the general population. Appropriate clinical monitoring is advisable in diabetic patients and in patients with risk factors for the development of diabetes mellitus.


Dysphagia


Esophageal dysmotility and aspiration have been associated with antipsychotic treatment. Cases of dysphagia were occasionally reported in patients treated with Sycrest.


Body temperature regulation


Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic medicines. From the clinical trials, it is concluded that clinically relevant body temperature dysregulation does not appear to be associated with asenapine. Appropriate care is advised when prescribing Sycrest for patients who will be experiencing conditions that may contribute to an elevation in core body temperature, e.g. exercising strenuously, exposure to extreme heat, receiving concomitant medicinal products with anticholinergic activity or being subject to dehydration.


Patients with severe hepatic impairment


Asenapine exposure is increased 7-fold in patients with severe hepatic impairment (Child-Pugh C). Therefore, Sycrest is not recommended in such patients.


Parkinson's disease and dementia with Lewy bodies


Physicians should weigh the risks versus the benefits when prescribing antipsychotic medicinal products, including Sycrest, to patients with Parkinson's disease or dementia with Lewy Bodies (DLB) since both groups may be at increased risk of Neuroleptic Malignant Syndrome as well as having an increased sensitivity to antipsychotics. Manifestation of this increased sensitivity can include confusion, obtundation, postural instability with frequent falls, in addition to extrapyramidal symptoms.


Drug Interactions


Caution should be used when asenapine is taken in combination with other centrally acting medicinal products. Patients should be advised to avoid alcohol while taking SYCREST. Additionally, SYCREST should be co-adminsitered cautiously with fluvoxamine (a CYP1A2 inhibitor) and with medicinal products that are both substrates and inhibitors of CYP2D6 (e.g., paroxetine).


For full prescribing information, please refer to the Summary of Product Characteristics.


Source:

MSD


View drug information on Saphris.

Treatment Of Depression: Latest NIMH Study

Michael Fitzpatrick, executive
director of the National Alliance on Mental Illness (NAMI) today issued the
following statement on the new Sequenced Treatment Alternatives to Relieve
Depression (STAR*D) study results published this week in the American
Journal of Psychiatry:



The latest stage in the landmark STAR*D study funded by the National
Institute of Mental Health (NIMH) demonstrates the importance of giving
people access to the best possible, most effective medication -- right from
the start.



Overall, almost 70% of patients with depression in the study were
helped by one or more drugs. Approximately 40% achieved remission of
symptoms on their first drug and 30% in the second. On the third and fourth
tries, 14% and 13% respectively, we now learn achieved remission. Treatment
is often a progressive, incremental process.



In the real world, one size does not fit all. Managed care plans and
state Medicaid formularies must not restrict threshold choices made by
front-line physicians. The physician-patient relationship is critical in
setting expectations and emphasizing the importance of staying on
medication.



Greater scientific research is needed to achieve better, fast-acting,
long-lasting alternatives.



Star*D results on the effectiveness of counseling also have not yet
been published, which is a critical piece of the treatment puzzle.



Depression kills. Remission saves lives. Complete elimination of
symptoms means a return to family, friends and productivity. The personal,
social and economic benefits of effective treatment are enormous.



In 2005, NAMI conducted a survey that complements Star*D findings. On
average, the majority of patients with depression who were surveyed had
tried four medications.



A majority experienced six or more episodes of depression in their
lifetimes, but only 34% ever discussed the possibility of relapse with a
physician. Less than 25% were aware of differences between full and partial
remission of symptoms. Only 25% had received talk therapy or counseling.


NAMI

nami

Alternative Treatments For Depression: Transcranial Magnetic Stimulation (TMS) May Improve Mood, But Awaits FDA Approval

While common treatments for depression such as prescription drugs, psychotherapy and electroconvulsive therapy usually provide relief from even the most severe cases for depression, there are people who do not feel they benefit from these treatments, and because of such look for alternative means to combat this serious medical condition.


One other option is Transcranial Magnetic Stimulation (TMS), which hasn't yet been approved by the Food and Drug Administration to treat depression, but may be available through a clinical trial.


This non-invasive method excites neurons in the brain by using weak electric currents, which are delivered to the brain by rapidly changing magnetic fields, also known as electromagnetic induction.


It is believed that this nerve stimulation improves mood and there's some evidence it may make nerve-cell connections more efficient. Because of this, TMS has shown promise as a non-invasive treatment of depression.


Alternative to Electroconvulsive Therapy?


For people who cannot find relief from traditional treatments for depression, TMS may seem to be a more desirable treatment than electroconvulsive therapy (ECT), which it has been compared to, simply because it is non-invasive, does not require anesthesia, and is not associated with convulsions, all of which are associated with ECT.


TMS also appears to have fewer and less serious side effects, such as memory loss and confusion, both of which are associated with ECT.


How TMS Works


Completely non-invasive and painless, TMS involves placing an electromagnetic coil against the patient's scalp. An electric current passes through this coil that creates a magnetic pulse, which causes small electrical currents in the brain.


These currents stimulate nerve cells in the region of the brain involved in mood regulation and depression.


Why It Works


Physicians and medical researchers are not yet exactly clear on why this nerve cell stimulation works; however, it is believed that stimulating the brain can change how it works and that by stimulating the regions associated with mood regulation, mood can be improved.


In some types of TMS, brain activity is suppressed. In other types, brain activity is increased. In either case, the changes may be associated with improved mood. These improvements in symptoms may last for days or weeks, according to the Mayo Clinic, a not-for-profit medical practice with locations in Minnesota, Arizona and Florida.


Keep in mind that researchers are still trying to determine the best dosage of stimulation and the best area of the brain to stimulate.


Who May Benefit


Remember, TMS remains experimental, which means it is not to be used as a first-line treatment against depression. Currently, it is only available in the United States through clinical trials.















In countries where TMS has been approved to treat depression, it's generally used to treat people who haven't experienced improvements with standard treatments.


To determine if you or someone you know is a candidate for this experimental procedure, you will need talk to your doctor to see if it may be a good option for you or for a loved one who is suffering from depression.


Who Should Not Undergo TMS


Certain people should not undergo TMS because of increased or unknown risks to their health. These include anyone with: metal implants in the head, who may be pregnant or who has a pacemaker.


Additionally, TMS is not suited for patients who suffer from recurring migraines, who has had a stroke or who has a family history of seizures. And, if you have had neurosurgery, TMS is not for you.


TMS Side Effects


Despite being non-invasive, TMS does pose a risk of adverse side effects, with the most concerning being the increased risk of seizure. Because of that risk, the International Society for Transcranial Stimulation (ISTS) advises "that the procedure be performed only when medical help is quickly available and that those who administer it be trained as first responders who can provide emergency medical help," according to the Mayo Clinic.


According to the ISTS, other common side effects and adverse health problems associated with TSI include lightheadedness, headache, pain at the site where the electromagnetic coil is placed against the scalp, tingling, spasms or contractions of facial muscles.


The Long-Term Outlook


Because TMS prompts changes in brain function, it is important to understand that there may be unknown long-term adverse side effects associated with the treatment.


While research has not yet determined any negative long-term side effects, it is important to talk to your medical doctor or mental health specialist to understand the possibilities here and to weigh these carefully with your medical professional.


Remember, TMS is currently available through clinical trials only, so your treating physician or mental health professional will have to help you find a clinical trial that will work for you and your unique situation.


About the Author
Kellie Fowler is an award-winning writer and has written for Associated Press, PR Newswire, Fortune 500 companies, newspapers, national business and healthcare magazines. She is regular contributor to depression-help-resource, a website providing information about types of depression, treatment options and depression related articles and resources.


depression-help-resource

Physiological Markers For Cutting, Other Self-harming Behaviors By Teenage Girls Found

Non-fatal, self-inflicted injuries by adolescent and young adult females are major public health problems and researchers have found physiological evidence that this behavior may lead to a more serious psychological condition called borderline personality disorder.



University of Washington psychologists have discovered that adolescent girls who engage in behaviors such as cutting themselves have lower levels of serotonin, a hormone and brain chemical, in their blood. They also have reduced levels in the parasympathetic nervous system of what is called respiratory sinus arrhythmia, a measure of the ebb and flow of heart rate along with breathing.



"A low level of this measure of the parasympathetic nervous system is characteristic of people who are anxious and depressed and among boys who are delinquent. But this is the first study to show it among adolescent girls who engage in self-harming behavior," said Theodore Beauchaine, UW associate professor of psychology.



The findings come from a study that also uncovered sharp disparities in the number of self-harming events and suicide attempts reported by the girls and their parents.



The research, headed by Sheila Crowell, a UW psychology doctoral student, focused on girls because self-harming behavior affects females far more often than it does males. The study included 23 girls, ages 14 to 18, who engaged in what psychologists call parasuicidal behavior. Participants were included if they had engaged in three or more self-harming behaviors in the previous six months or five or more such behaviors in their lifetime. An equal number of girls of the same ages who did not engage this behavior were enrolled as a comparison group.



The adolescents in the parasuicide group reported far more incidents of self-harming behavior than did their parents. Individuals engaged in this kind of behavior between 11 and 839 times. Their parents, however, reported a range of 0 to 205 incidents.



Similarly, the girls reported more than three times the number self-harming behaviors with intent to die, 310 events versus 90, than their parents did. However, the girls and their parents were very close on the number of times an adolescent required medical attention.



Twenty of the girls, or 87 percent, reported at least one attempted suicide, but Crowell said this number is not that surprising in this population.



"You need to understand a person's intent and the lethality of their attempts," she said. "Did they take a small number of Tylenol or were they holding a loaded gun to their head?"



She noted cutting was the most common self-harming behavior in which the girls engaged. Eight-two percent of girls used instruments ranging from paper clips to kitchen knives and razors with the intent of hurting themselves.
















"These attempts have to be taken seriously," said Beauchaine. "These girls may be really at risk for later suicide, and in the long term there needs to be studies of the progression of self-harm attempts."



To find physiological markers of self-harming behavior, the UW researchers showed both groups of adolescents a three-minute film clip from the movie "The Champ" depicting a boy with his dying father. Previous studies have shown the film can induce sadness. A number of different psychophysiological measures were collected from each of the girls before, while and after viewing the film clip. Following the viewing a small blood sample was taken to measure whole-blood serotonin.



The girls who engaged in self-harming behavior had lower levels of respiratory sinus arrhythmia in their parasympathetic nervous system while watching the film clip. These measures, the researchers argue, support the idea that the inability to regulate emotions and impulsivity can trigger self-harming behavior.



"This research supports the primary theory that borderline personality disorder is caused by an inability to manage emotions. These girls have an excessively strong emotional reactions and they have extreme difficulty in controlling those emotions," said Beauchaine. "Their self-harming behavior serves to distract them from these emotions."



Borderline Personality Disorder is far more serious than self-harming behavior and people with the condition have a very high suicide rate. An estimated 5.8 million to 8.7 million Americans, mostly women, suffer from borderline personality disorder. People with the condition have a multiple spectrum of disorders that are marked by emotional instability, difficulty in maintaining close relationships, eating disorders, impulsivity, chronic uncertainty about life goals and addictive behaviors such as using drugs and alcohol. They also have major impact on the medical system by being among the highest users of emergency and in-patient medical services.







Co-authors of the study are Elizabeth McCauley, UW professor of psychiatry and behavioral science; Cindy Smith a former psychiatrist at Children's Hospital who is now in private practice; Adrianne Stevens, an incoming UW psychology graduate student, and Patrick Sylvers, a former UW student who is now a graduate student at Emory University. The study, published in the journal Development and Psychopathology, was funded by Seattle Children's Hospital, the National Foundation for Suicide Prevention and the National Institute of Mental Health.



For more information, contact Crowell at mailto:crowellu.washington or Beauchaine at mailto:tbeauchau.washington



Contact: Joel Schwarz



University of Washington

Local Charity Soldiers Of Love Launches Peer Specialist Program To Aid Mental Health Crisis In New Orleans

Local non-profit organization Soldiers of Love is partnering with the Depression and Bipolar Support Alliance (DBSA) to launch a peer specialist training program to help mitigate the mental health crisis in New Orleans. The training program is an innovative concept for treating patients with mental health disorders through coaching and support from recovering mental health patients. Soldiers of Love and DBSA are currently seeking applicants to join the program, which will begin in early February 2008.


"Having lived with bipolar disorder for years, and seeing the dire need for mental health support in New Orleans, I am extremely excited to launch this training program," says John E. Wade II, founder of Soldiers of Love. "I participated in DBSA's peer specialist program and have seen how support from recovering patients to patients currently living with mental illnesses can make a difference."


DBSA will conduct a five-day/28-hour peer specialist training and post-training certification testing for up to 30 individuals on-site in New Orleans. Location is to be determined. The program is comprised of a peer specialist curriculum customized for the mental health needs in the city. The training is strongly focused on hope and recovery from the initial stage of diagnosis and symptoms to recovery as defined by the patient, not others. Following completion of the training and certification, DBSA and Soldiers of Love will consult with area patients, doctors, clinicians, hospitals, and community centers in order to facilitate full integration of peer support services throughout the community.


"When Soldiers of Love approached us about starting a peer program in New Orleans, we were more than thrilled," comments Sue Bergeson, President of DBSA. "We are aware of the current mental health crisis in New Orleans and feel our partnership with Soldiers of Love will help those suffering with mental illness."


Soldiers of Love and DBSA are conducting a search for applicants who are interested in participating in the program and, upon graduating and passing the program, want to put their peer training to use.


Soldiers of Love, a non-profit organization based in New Orleans, but with an international scope, supports three major areas in the New Orleans community: (1) mental health; (2) education; and (3) entrepreneurial education. It is currently partnering with Desire Street Ministries, Junior Achievement, and DBSA. As the organization grows, it will expand its programming to include other initiatives that will help meet its goal of achieving a heaven on earth.


The Depression and Bipolar Support Alliance is the nation's leading patient-directed organization focusing on depression and bipolar disorder. The organization, which has more than 1,000 support groups nationwide, fosters an understanding about the impact and management of these life-threatening illnesses by providing up-to-date, scientifically-based tools and information. Assisted by a 65-member scientific advisory board, comprised of the leading researchers and clinicians in the field of mood disorders, DBSA supports research to promote more timely diagnosis, develop more effective and tolerable treatments and discover a cure. More than 4 million people receive information and assistance each year.


For more information on Soldiers of Love, please visit soldiersoflove. For more information on the Depression and Bipolar Support Alliance, please visit DBSAlliance.

Teva Announces Tentative Approval For Generic Risperdal (Reg) Oral Solution

Teva Pharmaceutical Industries Ltd. (Nasdaq: TEVA) announced today that the U.S. Food and Drug Administration has granted tentative approval for the Company's Abbreviated New Drug Application (ANDA) to market its generic version of Janssen's Risperdal® (Risperidone) Oral Solution, 1 mg/mL. Final approval is expected upon expiry of patent protection for the brand product on December 29, 2007.


Upon final approval, Teva's Risperidone Oral Solution will be the AA-rated generic equivalent of Risperdal® Oral Solution, a product indicated for treatment of schizophrenia and acute manic or mixed episodes associated with Bipolar I Disorder.


Annual brand product sales in the U.S. were approximately $66 million for the twelve months ended June 2006, based on IMS data.


Teva Pharmaceutical Industries Ltd., headquartered in Israel, is among the top 20 pharmaceutical companies in the world and is the leading generic pharmaceutical company. The company develops, manufactures and markets generic and innovative human pharmaceuticals and active pharmaceutical ingredients, as well as animal health pharmaceutical products. Over 80 percent of Teva's sales are in North America and Europe.


Teva Pharmaceutical Industries Ltd

tevapharm/media/


View drug information on Risperdal Oral Formulation.

Scientists Identify A Bipolar Risk Gene, It Is Called FAT

A collaboration, led by scientists at the Garvan Institute of Medical Research and the University of New South Wales (UNSW) in Sydney, has discovered the first risk gene specifically for bipolar disorder, also known as manic-depressive illness. This means that people who have a particular form of this gene are twice as likely to develop the disease.


Lead author, Dr Ian Blair, says: "We are the first group in the world to take a multi-faceted approach to identify a bipolar risk gene - we used a number of families, unrelated patients, and therapeutic drug mouse models. Each of these three lines of investigation led us to a gene called FAT."


Contributing author Professor Phil Mitchell, Head of Psychiatry at UNSW, says: "Over the last twenty years we have collected blood samples from 67 families right across Australia. This amounts to hundreds of family members (904), some of whom are spread across four generations. This was a strong starting point in our hunt for a Bipolar gene."


"We know that the FAT gene codes for a protein that is involved in connecting brain cells together, what we need to do now is find out exactly how it contributes to the increased risk of bipolar disorder," explains Dr Blair.


While other scientists have found genes associated with Bipolar, most of them haven't stood up to scrutiny. The Sydney discovery has been verified in four independent study groups: two in the UK, one in Australia, and one in Bulgaria.


Bipolar disorder is a major psychiatric illness affecting around two people in every 100. Tragically, around one in six people suffering from the condition will commit suicide.


Mood-stabilising medications are typically prescribed to help control bipolar disorder. Lithium was the first mood-stabilising medication approved by the U.S. Food and Drug Administration (FDA) for treatment of mania. For decades it has been widely prescribed for the treatment bipolar disorder, yet no one knows for sure why it works.


"Lithium has a number of severe side effects that include tremor and weight gain. Kidney dysfunction may develop in a small proportion of patients when it is administered for long periods of time," says Professor Mitchell.


This new research has raised the possibility that lithium exerts its therapeutic affect by altering FAT gene expression, as well as the expression of genes encoding FAT's protein partners.


"Once we understand exactly what the FAT gene does, we will be able to develop better diagnostic tests for bipolar disorder. In the future, we hope our research will lead to new, targeted medicines specifically for bipolar disorder that don't have the unpleasant side effects that lithium has," says Dr Blair.


Background:


The bipolar project team has been a collaborative endeavour over the last decade involving Sydney-based scientists and clinicians from the Garvan Institute of Medical Research, the University of New South Wales and Macquarie University. Additional collaborations provided critical supporting data.


This research was E-published ahead of print on 10 January 2006 in Molecular Psychiatry


nature/doifinder/10.1038/sj.mp.4001784

Positional cloning, association analysis, and expression studies provide convergent evidence that the cadherin gene FAT contains a bipolar disorder susceptibility allele.
IP Blair, AF Chetcuti, RF Badenhop, A Scimone, MJ Moses, LJ Adams, N Craddock, E Green, G Kirov, MJ Owen, JBJ Kwok, JA Donald, PB Mitchell, PR Schofield


Dr. Branwen Morgan

b.morgangarvan.au

University of New South Wales

unsw.au

Scientists Discover Chemical Signature Of Manic Depression

People with manic depression have a distinct chemical signature in their brains, according to a new study. The research, published in the journal Molecular Psychiatry, may also indicate how the mood stabilisers used to treat the disorder counteract the changes in the brain that it appears to cause.



Manic depression, which is also known as bipolar disorder, is a debilitating psychiatric condition characterised by alternating mania and depression, affecting about one in every hundred people worldwide. Although it is known that the condition can be treated relatively effectively using the mood-stabilising drugs lithium and valproic acid, the reasons why these treatments work are poorly understood.



The authors of the new study, from Imperial College London, the University of Cambridge, and the National Institutes of Mental Health in the US, hope that their research will enable a better understanding of the condition and of how it can be treated.



The researchers compared postmortem brain tissue samples of people with manic depression with those of age and gender matched controls. The samples were taken from the dorsolateral prefrontal cortex, which controls the processes involved in higher cognitive functioning. The researchers analysed these samples using Nuclear Magnetic Resonance spectroscopy and found that people with manic depression had different concentrations of chemicals in this area of the brain than those without.



The researchers also used rat models to see the effects of lithium and valproic acid on the metabolite makeup of non-bipolar brain tissue. They found that these drugs caused the opposite chemical changes to those seen in the bipolar brain tissue samples. Chemicals that were increased in the bipolar brain tissue were decreased in rats given the mood stabilising drugs, and vice versa.



The researchers' findings lead them to believe that an upset in the balance of different neurotransmitters known as excitatory and inhibitory neurotransmitters, which are involved in sending signals in the brain, may be central to the disorder. The study also suggests that lithium and valproic acid work by restoring the balance of these neurotransmitters in the brain.



Levels of glutamate, an amino acid which acts as a neurotransmitter in the central nervous system, were increased in post mortem bipolar brain but glutamate / glutamine ratios were decreased following valproate treatment. Levels of another neurotransmitter, gamma-aminobutyric acid, were increased after lithium treatment and decreased in the bipolar brain. Both creatine and myo-inositol were increased in the post-mortem brain but depleted with the medications.



Dr Tsz Tsang, one of the authors of the study from the Department of Biomolecular Medicine at Imperial College London, said: "By identifying a distinct biochemical profile in patients with bipolar disorder, our new research provides a valuable insight into the origins and causes of the disease. Moreover, the changes we see in people's metabolic signatures may give a target for drug therapy, allowing us to see how effective a drug is at correcting these changes.
















"In this instance, we have already shown that the biochemical changes which valproic acid and lithium bring about in mammalian models represent almost a mirror image of the perturbations in bipolar disorder. This may provide a useful insight to the actions of these treatments and a basis for which to improve therapy in the future," added Dr Tsang.






1. "Metabonomic Analysis Identifies Molecular Changes Associated with the Pathophysiology and Drug Treatment of Bipolar Disorder" Molecular Psychiatry, 5 February 2007



Lan, M.J.(1),(3); and McLoughlin, G. A.(2); Griffin, J. L.(1); Tsang, T. M.(2); Huang, J. T. J.(1); Yuan, P.(3); Manji, H.(3); Holmes, E.(2) and Bahn S.(1)



(1) University of Cambridge, UK (2) Imperial College, London, UK (3) National Institutes of Mental Health, USA



2. About Imperial College London



Imperial College London - rated the world's fifth best university in the 2007 Times Higher Education Supplement University Rankings - is a science-based institution with a reputation for excellence in teaching and research that attracts 12,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.
Website: eurekalert/pub_releases/2008-02/imperial.ac.uk



Source: Abigail Smith


Imperial College London

Researchers Refine DNA Testing For Predisposition To Bipolar Disorder

Genetic testing may rise to a new level with the findings of Indiana University School of Medicine researchers whose "prototype" for laboratory testing for bipolar disorder appears today in the online edition of the American Journal of Medical Genetics Part B: Neuropsychiatric Genetics.


"This is an important advance in the development of a prototype for lab tests for bipolar disorder, and can serve as a model for developing tests in other complex disorders," said lead author Alexander B. Niculescu III, M.D., Ph.D., associate professor of psychiatry and medical neuroscience at the IU School of Medicine and director of INBRAIN at the IU Institute of Psychiatric Research.


Dr. Niculescu and colleagues used two different populations from large scale genetic studies and compared those individuals' genes to a small panel of 56 genes implicated in bipolar disorder by their work, to predict who has a predisposition to the disease.


The analysis resulted in a genetic risk prediction score that indicates high or low potential for developing bipolar disorder. "The coupling of a high score with certain environmental factors may be a predictor, not a certainty, that the individual will develop bipolar disorder" said Dr. Niculescu, who also is a staff psychiatrist at the Indianapolis Roudebush VA Medical Center.


"Genes explain a small portion of the risk of developing the illness," said Dr. Niculescu. "Unlike some genetic predisposition to diseases like Huntington's or cystic fibrosis, the variances in genes that can predispose people to mood disorders are found in all of us. What we are learning is that it may take a combination of factors - too many gene variances in the wrong environment and you are at higher risk."


The predictive value of the genetic risk factors could be useful in screening before the disorder manifests itself clinically, and the implementation of interventions to lower stress, adjust regular sleep hours and other life style factors that could serve as an environmental deterrent for developing bipolar disorder. Closer follow-up and earlier therapeutic intervention may be useful for individuals who are at higher risk.


Authors on the study include Sagar D. Patel, Dr. Helen Le-Niculescu, Dr. Daniel Koller, Stephen D. Green, Dr. Debomoy K. Lahiri, Dr. Francis J. McMahon and Dr. John I. Nurnberger, Jr.


The research was funded by the Veterans Administration as well as the National Institute of Mental Health.


In a corresponding editorial in the American Journal of Medical Genetics, Dr. Alexander B. Niculescu and Dr. Helen Le-Niculescu advocate for a more efficient way to identify genes involved with mental disorders.


"Coming to Grips With Complex Disorders: Genetic Risk Prediction in Bipolar Disorder Using Panels of Genes Identified Through Convergent Functional Genomics," by Patel SD, Le-Niculescu H, Koller DL, Green SD, Lahiri DK, McMahon FJ, Nurnberger JI, and Niculescu AB. American Journal of Medical Genetics Part B (Neuropsychiatric Genetics). 2010. Epub April 9.

Source
Indiana University

Shedding Light On How Psychiatric Risk Gene Disrupts Brain Development

Scientists are making progress towards a better understanding of the neuropathology associated with debilitating psychiatric illnesses like bipolar disorder and schizophrenia. New research, published by Cell Press in the July 15 issue of the journal Neuron, reveals mechanisms that connect a known psychiatric risk gene to disruptions in brain cell proliferation and migration during development.



A research group led by Dr. Li-Huei Tsai from the Massachusetts Institute of Technology had recently discovered that the psychiatric risk gene, Disrupted in Schizophrenia-1 (DISC1), is an essential regulator of the proliferation of early brain cells (known as neural progenitor cells) via inhibition of a molecule called GSK3? and modulation of the Wnt signaling pathway. Disruptions in the Wnt pathway, which is critical for embryonic development, have previously been linked with developmental defects and with various human diseases.



"Our recent finding was particularly interesting because one of the actions of lithium, the most common mood disorder drug, is to inhibit GSK3?." explains Dr. Tsai. "Although DISC1 was one of the first psychiatric illness risk genes to be identified and we know that it plays a key role in brain development, the mechanisms by which DISC1 is regulated remain unknown." In this study, Dr. Tsai and colleagues built on earlier work and investigated how DISC1 is regulated during cortical development by looking for novel DISC1-interacting proteins.



The researchers discovered a key interaction between DISC1 and a protein called Dixdc1 which is the mammalian version of a nonmammalian Wnt signaling molecule. Dixdc1 and DISC1 interacted to regulate neural progenitor proliferation via modulation of Wnt/GSK3? signaling. Interestingly, although DISC1 and Dixdc1 were both essential for neural migration, the Wnt/GSK3? pathway was not required for migration. It appears as if Dixdc1 integrates DISC1 into Wnt-dependent and -independent signaling pathways.



"Our findings identify the novel Wnt signaling pathway gene, Dixdc1, as a critical regulator of DISC1 function during cortical development. This discovery suggests that Dixdc1 and DISC1 are involved in Wnt signaling at many levels in the nervous system and that mutations in DISC1 likely contribute to disease pathology by disrupting Wnt signaling during neural development and in the adult brain," concludes Dr. Tsai. "Future studies are needed to determine whether other candidate psychiatric risk genes also interact with Wnt signaling."



The researchers include Karun K. Singh, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, Broad Institute, Cambridge, MA; Xuecai Ge, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA Yingwei Mao, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, Broad Institute, Cambridge, MA; Laurel Drane, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, Broad Institute, Cambridge, MA; Konstantinos Meletis, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, Broad Institute, Cambridge, MA; Benjamin A. Samuels, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, Columbia University, New York, NY; and Li-Huei Tsai, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, Broad Institute, Cambridge, MA.



Source:

Cathleen Genova

Cell Press

Borderline Personality Disorder: Advances In Science And Treatment

The National Education Alliance for Borderline Personality Disorder (NEA-BPD), the Department of Psychiatry, Mount Sinai School of Medicine, and the National Alliance on Mental Illness New York City Metro are co-sponsoring a one-day conference on Friday, September 29th at The Mount Sinai Medical Center, Hatch Auditorium, Madison Avenue at East 100th Street, from 8 am to 5:00 pm. Registration starts at 7:30 am. The conference title is: Borderline Personality Disorder: Advances in Science and Treatment.



Experts in borderline personality disorder (BPD), including leading professionals, family members and consumers, will present on topics including: new directions on BPD causes and treatments, affective instability (the difference between BPD and bipolar disorder), update on neurobiology, a panel on family research and family and consumer perspectives, suicide and self-injury, impulsivity and medication, and a case study that will be used to discuss and highlight the differences and complementary aspects of two treatment options: transference focused therapy (TFT) and dialectical behavior therapy (DBT). The conference is geared to mental health professionals, allied professionals, family members and recipients of service. This program has been approved by NASW-New York State for 6 contact hours under approval number A-896.



Perry D. Hoffman, Ph.D., President of NEA-BPD and Charlotte M. Fischman, Esq., President of the NAMI-NYC Metro Board will welcome conference attendees. Eric Hollander, M.D., Esther and Joseph Klingenstein Professor and Chair of Psychiatry, Director, Seaver and New York Autism Center, will introduce the all-day conference and will present the plenary session on impulsivity and medication. Other plenary presentations will be given by Larry Siever, M.D., Harold Koenigsberg, M.D., Antonia New, M.D., and Beth Brodsky, Ph.D., Marianne Goodman, M.D., Frank Yeomans, M.D., Ph.D., and Christine Foertsch. Participants in the panel include Perry Hoffman, Ph.D., Dixianne Penney, Dr.P.H., Charlotte M. Fischman, Esq., Coleen Bocuso, and Hillary Eaton, M.Ed.



Borderline personality disorder is a serious mental illness characterized by pervasive instability in moods, interpersonal relationships, self-image, and behavior. This instability often disrupts family and work life, long-term planning, and the individual's sense of self-identity. While less known than schizophrenia or bipolar disorder (manic-depressive illness), BPD is estimated to be at least as common, affecting one percent of adults. Up to 73% of those diagnosed with the disorder have made at least one suicide attempt. Further, approximately 10% of patients with BPD eventually do commit suicide. Thus, persons with BPD are a public health concern of significant magnitude.







Contact: Mount Sinai Press Office


The Mount Sinai Hospital / Mount Sinai School of Medicine

Efficacy Similar Among Antidepressants, Side Effects Drive Multiple Prescriptions

A review of 293 studies that assessed 12 commonly prescribed second-generation antidepressants found no significant differences between the drugs for the treatment of acute-phase depression, according to a report by the RTI International-University of North Carolina at Chapel Hill Evidence-based Practice Center.


However, side effects among the drugs varied, causing many patients to have to try more than one before settling on long-term therapy.


The drugs reviewed were bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone and venlafaxine. The studies included randomized controlled trials with active or placebo controls, observational studies and systematic reviews.


"Based on our review of the available research, we found very little difference in the effectiveness of various antidepressants," said Dr. Gerald Gartlehner, lead author of the report and a research associate at UNC's Sheps Center for Health Services Research.


Despite their similarities, the drugs create different side effects that lead only about 60 percent of patients to respond to an initial treatment regimen, said Linda Lux, an RTI researcher. And, she said, 61 percent of patients in efficacy trials experienced at least one adverse side effect, including constipation, diarrhea, dizziness, headache, insomnia and vomiting.


"Because of the high incidence of side effects, many patients try more than one medication before finding an effective treatment," Lux said. "Predicting which one will be most effective or best tolerated by any individual is not yet possible."


"This study highlights the important issue that side effects happen to patients, not doctors, and we need to take them a bit more seriously," said Dr Howard McLeod, director of the UNC's Institute for Pharmacogenomics and Individualized Therapy.


McLeod, who was not part of this study, and others at UNC are trying to solve this drug-prescribing dilemma by using a patient's DNA to help direct the selection of treatment.


Gartlehner and Lux said more research is also needed to determine the effects that dosage and duration of second-generation antidepressant treatment have on efficacy, and to see if efficacy differs in patients who also suffer from anxiety, insomnia, pain or fatigue.


The project was supported by the Agency for Healthcare Quality Research, and is posted on the agency's Web site: ahrq.


University of North Carolina at Chapel Hill

210 Pittsboro St. Campus Box 6210

Chapel Hill, NC 27514

United States

unc/

Study Sheds Light On Medication Treatment Options For Bipolar Disorder

For depressed people with bipolar disorder who are taking a mood stabilizer, adding an antidepressant medication is no more effective than a placebo (sugar pill), according to results published online on March 28, 2007 in the New England Journal of Medicine. The results are part of the large-scale, multi-site Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), a $26.8 million clinical trial funded by the National Institutes of Health's National Institute of Mental Health (NIMH).



Bipolar disorder, a sometimes debilitating illness marked by severe mood swings between depression and mania, is usually treated with mood stabilizers such as lithium, valproate, carbamazepine or other medications that reduce mania. However, depression is more common than mania in bipolar disorder, and depressive episodes tend to last longer than episodes of mania. Antidepressant medications are often used in addition to a mood stabilizer for treating bipolar depression, but they are thought to confer a serious risk of a switch from a depressive episode to a manic episode.



Finding the right treatment balance for people with bipolar disorder is a constant challenge; STEP-BD aims to identify the best treatment options. "Treating depression in people with bipolar disorder is notoriously difficult," said NIMH Director Thomas R. Insel. "STEP-BD sought to determine if adding an antidepressant to a mood stabilizer is effective and safe in treating depressive episodes. The results suggest that antidepressants are safe but not more effective than placebo as assessed in a large number of people with bipolar disorder. "



Lead author Gary Sachs, M.D., of Massachusetts General Hospital and colleagues studied 366 participants at 22 sites across the country. Unlike most clinical studies, participants were recruited from clinical settings and were included in the study even if they were being treated for co-existing disorders such as substance abuse, anxiety or psychotic symptoms. Such open recruitment criteria allows the study's results to have broader applicability than a tightly controlled trial in which people are excluded from participating if they have co-existing disorders.



Before participants were randomized to one of two antidepressants-bupropion (Wellbutrin) or paroxetine (Paxil)-or to a placebo, doctors trained in the treatment of bipolar disorder adjusted participants' mood stabilizer doses to optimal levels, ensuring that they were receiving the most appropriate amount.



After about 26 weeks, Sachs and colleagues found that 24 percent of those who had been randomized to the antidepressants stayed well for at least eight consecutive weeks-the study's stringent standard for recovery; 27 percent of those randomized to a placebo stayed well long enough to meet the eight-week recovery standard, indicating no difference between adding an antidepressant or adding placebo. In addition, about 10 percent of each group experienced emerging symptoms of mania, indicating that the antidepressants did not trigger a manic switch any more than placebo. Finally, when comparing the two antidepressants to each other, both showed similar rates of response and manic switch.



"Results of STEP-BD indicate that careful management of mood stabilizer medications is a reasonable alternative to adding an antidepressant medication for treating bipolar depression," said Dr. Sachs.



Future STEP-BD results will shed light on other treatment options for bipolar disorder, including psychotherapeutic treatments.







The National Institute of Mental Health (NIMH) mission is to reduce the burden of mental and behavioral disorders through research on mind, brain, and behavior. More information is available at the NIMH website, nimh.nih/.



The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih/.



Sachs G, et al. Effectiveness of Adjunctive Antidepressant Treatment for Bipolar Depression: A Double-blind Placebo-controlled Study. New England Journal of Medicine. online 28 Mar 2007.



Contact: Colleen Labbe

NIH/National Institute of Mental Health



View drug information on Paxil CR.

CeNeRx BioPharma Initiates Human Trials Of RIMA Antidepressant

CeNeRx BioPharma,
Inc., a clinical stage company developing and commercializing innovative
treatments for diseases of the central nervous system, today announced the
initiation of human clinical trials of Tyrima(TM), CeNeRx's new drug
candidate with a triple mechanism of action for the treatment of depression
and anxiety. Tyrima (formerly CX157) is a member of a novel class of drugs
known as reversible inhibitors of monoamine oxidase A, or RIMA. The Phase I
safety trials began this month following a successful review of the
Investigational New Drug (IND) application for Tyrima by the U.S. Food and
Drug Administration.


"Initiation of human trials for Tyrima is an important milestone for
CeNeRx, marking our transition to a clinical stage company," said Barry
Brand, chief executive officer of CeNeRx. "Our third generation RIMA series
of antidepressant compounds combine a known and effective triple action
mechanism that is novel to the U.S., along with an improved safety profile
that has been demonstrated in pre-clinical studies. The fact that a first
generation RIMA antidepressant is already marketed in Europe significantly
decreases the clinical risk associated with this approach, and we look
forward to rapidly advancing Tyrima to Phase II trials after successful
completion of these initial safety studies."



RIMA antidepressants elevate the levels of three key neurotransmitters
that affect mood and anxiety (serotonin, norepinephrine and dopamine), in
contrast to the leading antidepressants available today that affect the
single neurotransmitter serotonin. This triple mechanism has the potential
for enhanced efficacy and an improved therapeutic index compared to current
therapies. Tyrima could be the first RIMA antidepressant available in the
U.S. market, and it has patent protection through 2026. CeNeRx has
worldwide rights to develop and commercialize Tyrima.



Alan Schatzberg, M.D., Kenneth T. Norris, Jr. professor and chairman,
Department of Psychiatry and Behavioral Sciences at the Stanford University
School of Medicine and a member of the CeNeRx scientific advisory board,
noted, "Unlike other inhibitors of monoamine oxidase (MAOI), CeNeRx's RIMA
agent Tyrima acts selectively and reversibly, thereby significantly
reducing the cardiovascular risks historically associated with the MAOI
approach. Tyrima therefore has the potential to be the first safe and
well-tolerated oral antidepressant that works on all three key
neurotransmitters known to play a role in mood disorders, offering the 30%
of patients who currently do not receive adequate relief of their symptoms
a safe option with the potential for enhanced efficacy."



The National Institute of Mental Health reports that major depressive
disorders affect approximately 14.8 million American adults in a given
year, or about 6.7 percent of the U.S. population aged 18 and older.
Currently, major depressive disorder is the leading cause of disability in
the U.S. for individuals aged 15-44. Many patients do not respond
satisfactorily to current therapies, reinforcing the need for a range of
safe and effective treatments.



CeNeRx has raised approximately $25 million to fund development of
Tyrima and the RIMA antidepressant series. The company plans to enter Phase
II trials later this year.



For more information about depression, please visit the National
Institute of Mental Health (NIMH) web site at:
nimh.nih/healthinformation/depressionmenu.cfm.



About CeNeRx BioPharma



CeNeRx (SEN-er-ex) is a privately held clinical stage company
developing and commercializing innovative and improved treatments for
diseases of the central nervous system. The company focuses on identifying
and developing promising therapeutics to treat diseases related to
neurotransmitters, including anxiety, bipolar disorder, dementia,
depression, epilepsy, neuropathic pain, schizophrenia, and Parkinson's and
Alzheimer's diseases. CeNeRx's most advanced compounds, reversible
inhibitors of monoamine oxidase, or RIMAs, are in Phase I and late
pre-clinical development for the treatment of major depressive disorder.
More information about CeNeRx BioPharma can be found at
cenerx.


CeNeRx BioPharma, Inc.

cenerx

Mind: Public Must Be Able To Have Trust In Medicines, Says Mental Health Charity 'Mind', UK

Mental health charity Mind responds to the MHRA's ruling on GlaxoSmithKline.


Paul Farmer, chief executive of Mind, said:


"Mind welcomes news that the Government is to increase drug companies' responsibility to pass on clinical trials information. We look forward to discussions with ministers to ensure that patients' interests are best served. We hope that the legislation will pass quickly through Parliament; this is far too important to be delayed any longer.


"There can be no excuses from the pharmaceutical industry. The public must be able to have trust and confidence in the medicines they are taking. We need to be sure that the tragedies associated with Seroxat can never happen again. The best way to achieve this is for drug companies to publish all clinical trials data, making it available for scrutiny and review, and to inform prescribing decisions.


"The Health Committee's 2005 report on the influence of the pharmaceutical industry made powerful recommendations. We hope that both the Health Committee and the Government will be able to revisit those recommendations soon."


Mind first drew attention to the problems of Seroxat in the 1990s. View our Seroxat timeline.



Further Seroxat background.


Mind is the leading mental health charity in England and Wales. We work to create a better life for everyone with experience of mental distress.
Mind values its independence, and accepts no funding or donations from pharmaceutical companies.


mind.uk

A Combination Of Common Genetic Variations Can Lead To Schizophrenia

A multi-national group of investigators, including a scientist at the University of North Carolina at Chapel Hill, has discovered that nearly a third of the genetic basis of schizophrenia may be attributed to the cumulative actions of thousands of common genetic variants. The effects of each of these genetic changes, innocuous on its own, add up to a significant risk for developing both schizophrenia and bipolar disorder.


The finding, published online July 1, 2009, in the journal Nature, suggests that schizophrenia is much more complex than previously thought, and can arise not only from both rare genetic variants but also from a significant number of common ones.


"This is an enormous first for our field," said co-author Patrick Sullivan, M.D., Ray M. Hayworth and Family Distinguished Professor of Psychiatry in the department of genetics at the UNC School of Medicine. "You could say that we now have the outline of the puzzle, and we just need to take all of these pieces that we have identified and see how they fit them together."


Schizophrenia is a chronic and often devastating mental illness that affects one person in every 100 in the course of their lives. Scientists have long recognized that the disease which can run in families -- has a strong genetic component. However, only recently have they begun to pinpoint the exact spots in our genetic material that contribute to the illness. Last year, the International Schizophrenia Consortium found that rare chromosomal structural variants elevate the risk of developing schizophrenia.


In this study, Sullivan and other investigators in the Consortium used "genechip" technology to identify 30,000 genetic variants (single nucleotide polymorphisms or "SNPs") that were more common in 3,000 individuals with schizophrenia than in 3,000 comparison subjects without schizophrenia. This pattern was found in three separate samples of individuals with schizophrenia and two samples with bipolar disorder indicating a previously unrecognized overlap between the two diseases. These risk variants were not present in patients with other non-psychiatric diseases, such as hypertension or diabetes.


"While our study finds a surprising number of genetic effects, we fully expect that future work will assemble them into meaningful pathways that will teach us about the biology of schizophrenia and bipolar disorder," says senior author Pamela Sklar, MD, PhD, associate director of the Department of Psychiatry and Center for Human Genetic Research at Massachusetts General Hospital (MGH) and a senior associate member of the Broad Institute of MIT and Harvard.


The researchers are also investigating how genes and environment interact to cause the disease. One additional finding of their study was the identification of the human leukocyte antigen (HLA) locus as a possible risk factor. Because this region plays an important role in immune response to infection, it could suggest that exposure to an infectious agent increases risk of developing psychiatric disease.


Funding for the studies led at UNC came from the National Institutes of Mental Health, the Sylvan C. Herman Foundation and the Stanley Medical Research Institute.


In addition to those from UNC, the consortium includes investigators from the University of Aberdeen, Cardiff University, University of Edinburgh, Karolinska Institutet, Massachusetts General Hospital, the Queensland Institute of Medical Research, University of Southern California, Stanley Center for Psychiatric Research at the Broad Institute of Harvard and MIT, Trinity College Dublin and University College London.


Source: University of North Carolina

New York Times Examines Eli Lilly Program Aimed At Reducing Unnecessary Medicaid Prescriptions For Antipsychotic Drug Zyprexa

The New York Times on Friday examined an Eli Lilly program that offers state Medicaid programs assistance in monitoring physicians' prescribing practices for Zyprexa, a treatment for schizophrenia and bipolar disorder that is the single largest drug cost in state Medicaid budgets. Under the program, which Lilly has implemented in two dozen states since 2003, the company pays New York-based Comprehensive NeuroScience an undisclosed amount to monitor physicians' prescribing practices. When physicians prescribe doses that are too high or treat patients with too many similar drugs, "Dear Doctor" letters are sent notifying them that their prescribing patterns are outside of normal practices. Compliance is voluntary. Physicians also are notified if patients are not renewing their prescriptions. While Medicaid administrators in Michigan, Missouri and some other states say that the program has saved them money, others criticize Lilly for offering the program only in exchange for certain concessions. For example, Medicaid officials in at least four states say that Lilly offered them the program as an alternative to placing Zyprexa on a restricted-drug list. Lilly spokesperson Janice Chavers said that the program is not operating in any state where Zyprexa's use is restricted, although the company says that it generally does not require unrestricted access to operate the program. Lilly "acknowledges that it decided to finance the programs in response to state efforts to cut costs" through the use of preferred-drug lists and other measures, the Times reports. Lilly says it opposes restricted access to mental health drugs because physicians need the ability to prescribe any appropriate drug for serious mental illness.

Other Experiences with Program
David Beshara, chief pharmacy officer for Tennessee's Medicaid program, said that his state declined Lilly's offer to implement the program in exchange for placing Zyprexa on its preferred-drug list. Beshara said the offer was rejected because the potential savings were uncertain and because the program was offered on the basis that the state would not receive rebates for placing the drug on its preferred list, as is common industry practice. James Hardy, former deputy secretary for medical assistance in Pennsylvania, said that his state also declined Lilly's offer to provide the program in lieu of rebates. Hardy said, "I didn't like that commingling of service and rebates," adding, "I want to manage the benefit, and I want to get the best rebate deal I can." However, Joseph Parks, medical director of the Missouri Department of Mental Health, said, "I think they are honestly trying to improve their image by doing the right thing and by doing something about inappropriate overutilization." Parks has served as a paid consultant to Comprehensive NeuroScience (Saul, New York Times, 3/23).

"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.


View drug information on Zyprexa.

Schizophrenia-Linked Gene Controls The Birth Of New Neurons

A gene that is arguably the most studied "schizophrenia gene" plays an unanticipated role in the brain: It controls the birth of new neurons in addition to their integration into existing brain circuitry, according to a report in the March 20th issue of the journal Cell, a Cell Press publication. The finding suggests that loss of the gene, as occurs in some cases of schizophrenia as well as bipolar disorder and major depression, may "tip the balance" in the brain, leading to an increased risk of compromised cognition and behavioral abnormalities, the researchers said.



What's more, the protein encoded by the gene aptly known as Disrupted in Schizophrenia 1 (DISC1) exerts its influence through a well-studied molecular pathway. Specifically, it interacts directly with and blocks the activity of GSK3b, a protein that is the target of the lithium treatments that doctors have used for decades in the treatment of bipolar disorder.



"Lithium is still the most reliable [medication] for bipolar disorder," said Li-Huei Tsai of the Howard Hughes Medical Institute and the Massachusetts Institute of Technology. "This shows that DISC1 is almost like an endogenous lithium."



The findings are part of a larger picture of the genetic and developmental causes of psychiatric disorders that has recently begun to emerge and may point the way to new approaches for therapeutic intervention, Tsai said. Although people diagnosed with schizophrenia are typically resistant to treatment with lithium, she added, their observations should encourage scientists to "think creatively" about new and more powerful strategies for targeting GSK3b.



Schizophrenia is a severe brain illness that affects 0.5% of the world population, the researchers said. While its causes are poorly understood, accumulating evidence suggests that neurodevelopmental defects are involved and recent studies have identified many risk genes associated with schizophrenia, DISC1 among them. Studies of a very large Scottish family with a high incidence of schizophrenia, bipolar disorder and major depression over several generations also found that those family members who develop psychiatric disorders carry a mutation in DISC1.



Biochemical evidence later showed that DISC1 interacts with a growing number of binding partners, Tsai said, and functional studies have revealed a role for the gene in the growth and migration of neurons and in the integration of neurons into the brain. Mice with the abnormal version of the gene also develop behaviors that are reminiscent of human psychiatric disorders, including schizophrenia and depression.



Now, Tsai's team has begun to connect the genetic and biochemical evidence with the behavior in studies of mice.
















In addition to the known role of DISC1 in the function of existing neurons, the gene is also highly expressed in neural progenitor cells and is required for their proliferation, they report. This function of DISC1 involves regulation of the so-called b-catenin/GSK3b pathway.



In the adult mouse brain, loss of DISC1 function in the dentate gyrus, a portion of the brain that is important to the formation of new memories, led to reduced neural progenitor proliferation and elicited hyperactive and depressive behaviors in mice. Importantly, they found, those behavioral abnormalities were reversed when the DISC1-deficient animals were treated with a chemical that blocked GSK3b.



"These findings provide compelling evidence that DISC1 is a central player in the GSK3b/b-catenin signaling pathway that impinges on neural progenitor proliferation," the researchers concluded. Together with earlier findings, the new results suggest that behavioral abnormalities resulting from DISC1 loss of function in the dentate gyrus likely involve a combination of reduced numbers of newly born neurons and their aberrant integration into the existing circuitry, as well as effects on mature neurons.



"In the end, the human lesions may result in subtle functional changes that have an effect on the eventual size of the brain and the progenitor pool," Tsai said. While those changes might not be sufficient to cause psychiatric disorders on their own, she added, they may leave individuals more vulnerable to getting "pushed over the edge."



Notes:


The researchers include Yingwei Mao, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA ; Xuecai Ge, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, Harvard Medical School, Boston, MA; Christopher L. Frank, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA; Jon M. Madison, Massachusetts Institute of Technology, Cambridge, MA; Angela N. Koehler, Massachusetts General Hospital, Boston, MA; Mary Kathryn Doud, Massachusetts General Hospital, Boston, MA; Carlos Tassa, Massachusetts General Hospital, Boston, MA; Erin M. Berry, Massachusetts General Hospital, Boston, MA, Massachusetts Institute of Technology, Cambridge, MA; Takahiro Soda, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, Harvard Medical School, Boston, MA; Karun K. Singh, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA; Travis Biechele, Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, WA; Tracey L. Petryshen, Massachusetts General Hospital, Boston, MA, Massachusetts Institute of Technology, Cambridge, MA; Randall T. Moon, Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, WA; Stephen J. Haggarty, Massachusetts General Hospital, Boston, MA, Massachusetts Institute of Technology, Cambridge, MA ; and Li-Huei Tsai, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, Massachusetts Institute of Technology, Cambridge, MA.



Source: Cathleen Genova


Cell Press

Prepared Patient: Managing Mental And Medical Illness

In her 1984 boot camp graduation photo, Adrienne Fitts is smiling. Her hair is neatly groomed, her Navy cap and dress whites are spotless and she is regulation fit and trim.


Flash forward to 2001. Fitts, now a retired Gulf War veteran, struggles with a mental illness called schizoaffective disorder. She is 90 pounds heavier and has developed type 2 diabetes. She is certain her regimen of antipsychotic drugs ("there are so many") caused the diabetes as well as high blood pressure.


In April 2006, Adrienne Fitts suffers a stroke.


And there's Gloria, a 56-year-old legislative advocacy worker, who also deals with both a major mental and medical condition. Gloria,has long-term clinical depression, neurological problems and on top of that, partial kidney failure.


"Multiple conditions are not rare and they become even more common as people get older," says Dennis Freeman, Ph.D., the CEO of Cherokee Health Systems in Tennessee.


"Twenty-five percent of people in a primary care practice have a psychiatric illness," says Wayne Katon, M.D., vice chair of the department of psychiatry and behavioral science at the University of Washington School of Medicine.


Children are vulnerable, too. "Kids with asthma are more likely to have every kind of anxiety and depressive disorder," Katon says. "This makes more of an impact on school performance and the ability to make and keep friends. Parents and schools have to be especially watchful for the additive effects of having two conditions."


For many people, physical conditions can contribute to problems with their mental health problems that are often ignored and untreated. But your emotional health and physical health affect each other. Here's what you should know.


The stakes are high.


When recovering from a heart attack, it's natural to be focused on your physical recovery rather than your state of mind, but the two are intertwined, says Eric Goplerud, Ph.D.


"A heart attack produces large amounts of cortisol that precipitates depression," explains Goplerud, the director of the Center for Integrated Behavioral Health Policy at George Washington University Medical Center.















"At least twenty percent with heart attacks have severe depression and these people are three times more likely to die if the depression is not dealt with promptly," he says.


"People who have mental problems often have other health problems and they come together in legion," Goplerud says.


Drugs that help your mind can harm your body.


In a health care Catch-22, the same drugs that help people manage bipolar disorder, schizophrenia and depression can have serious physical side effects.


As part of her treatment, Fitts has received some heavy-duty drugs, including olanzapine.


"Clozapine and olanzapine are the two antipsychotic drugs that the American Diabetes Association found the highest risk of causing weight gain and poor lipid control." Goplerud says. As for drugs to combat depression, "some SSRIs are associated with weight gain and may contribute to diabetes. So you may be developing life-threatening illnesses from appropriate treatment of your mental illness."


The dilemma works both ways, Goplerud adds: "Sometimes treatment we prescribe for in medical care end up causing mental health problems." For instance, "People who have been legitimately prescribed powerful pain meds can become addicted."


If you are ever prescribed antidepressants, or given medication to help you sleep, doses often need to be fine-tuned and you might need to try several drugs before to find one that works for you. Although primary care practitioners or clinic doctors can prescribe these drugs, follow-up can fall through the cracks. Let someone know if your treatment isn't helping.


Patients have options, Goplerud says. "Talk to your physician about other medicines that might be used."


Speaking up is vital to your mental health.


Fear of the stigma of mental illness can keep patients from speaking up, says Chris Koyanagi, policy director of the Bazelon Center for Mental Health Law. Some "are reluctant to tell primary care doctors about their psychiatric medicines: 'I just don't want my regular doctor to know.'"


Recalls Gloria: "As a teenager I had aches and pains and my parents took me to the Mayo clinic. They wanted me to see a psychiatrist. My father said fine, as long as they could come with me. The psychiatrist asked, 'Are you depressed?' Dad answered, 'No, she's not.'"


Meanwhile, physical conditions arose that could not be brushed aside. It was only years later, when she had an emotional collapse on the job that Gloria began treatment for depression.


Your health care is usually scattered across different settings.


"Health systems are fragmented, people are integrated," says Dennis Freeman, Ph.D., the CEO of Cherokee Health Systems in Tennessee.


People are often are forced to work with an array of health care providers. "It's daunting to go to three different clinics; it's hard for anyone," Katon says. "Fragmentation is even worse for people with mental health issues."


Dangerous drug interactions are possible when no single health professional has a handle on all the medications you take: you could receive heart pills from one doctor and an antidepressant from another doctor without either being aware of what the other prescribes.


"At the least, one single person or entity needs to know all the medications you take and all the diagnoses you have," Koyanagi says. "This can be your primary care physician, your mental health practitioner, your pharmacist."


Some mental health care is "nested" with medical care.


Katon, who brings his psychiatric expertise to a medical practice one day a week, says, "It's ideal if psychiatric care can be merged into medical care,"
"We found that mental health care programs with primary care onsite sometimes provided by a nurse practitioner or physician assistant who can do regular and effective screens, can link people to community services [work best]," Koyanagi agrees.


Federally qualified health centers, like Freeman's Cherokee Health System in Tennessee, provide a full range of services from professionals who communicate daily with one another and have access to a single, unified medical record for each patient.


Unfortunately, it can be hard to find mental health care at all, much less integrated medical-mental care. "Half of counties in the United States don't have mental health providers," Freeman says.


In those areas, "You probably go to a primary care physician. They will do the very best they can. They're not psychotherapists or behaviorists, but psychiatrists are in short supply every place, even among insured," he says. "So you go to see your primary care physician, talk to your minister, if you're in school it may be your teacher and guidance counselor."


We're all vulnerable at various times in our lives.


Just as we have ups and downs of physical health, everyone also deals with challenges that affect our moods and stability. It helps to know your baseline: What's your usual mental state? How do you know when things are out of control?


"We all have times we're not as resilient and not managing as well," Freeman says. "That's when the team needs to support you, help you through the rough times."


You might need additional support, not only from mental health professionals but also the people in your life. Sharing confidences and concerns with trusted friends and family or joining a support group can help restore your mental balance.


Fitts has found and given support through the Depression and Bipolar Support Alliance, a peer group for people with mood disorders. Earlier, when she developed substance abuse issues which often go along with mental illness and can complicate medical treatment she looked outside herself for help. "I just made some decisions. It's a process. I use a 12-step approach. I have a group in my church. It's helped me to get my thoughts together."


If you've been diagnosed with a medical illness and you don't feel right emotionally: "Talk to your physician, tell your nurse." Goplerud says. "Misery is not necessary. You don't have to live with feeling physically miserable or mentally miserable."


Source: Health Behavior News Service

ACADIA Announces Presentation Of Data On Pimavanserin Co-Therapy At The 14th Biennial Winter Workshop On On Schizophrenia And Bipolar Disorders

ACADIA Pharmaceuticals Inc. (Nasdaq:ACAD), a biopharmaceutical company utilizing innovative technology to fuel drug discovery and clinical development of novel treatments for central nervous system disorders, today announced that Murray Rosenthal, D.O., a Fellow of the American Psychiatric Association, will present data from ACADIA's pimavanserin Phase II schizophrenia co-therapy trial at the 14th Biennial Winter Workshop on Schizophrenia and Bipolar Disorders in Montreux, Switzerland on February 5, 2008. Dr. Rosenthal was one of the lead investigators in ACADIA's Phase II co-therapy clinical trial with pimavanserin and has extensive experience conducting clinical studies for patients with schizophrenia.


In an oral presentation titled "Co-Therapy with Pimavanserin and Risperidone 2 mg Provides an Improved Clinical Profile," Dr. Rosenthal will discuss data from the Phase II trial demonstrating several advantages of co-therapy with pimavanserin, which include an enhanced efficacy, a faster onset of antipsychotic action, and an improved side effect profile, including less weight gain. Dr. Rosenthal also will present new data from this study showing that patients in the co-therapy arm combining pimavanserin with risperidone (2 mg) had significantly less increase from baseline in serum glucose levels after treatment compared to patients in the risperidone (6 mg) plus placebo arm (p=0.024). Taken together, the reductions in weight gain and glucose increase seen after effective antipsychotic treatment with pimavanserin and a sub-maximal dose of risperidone suggest that this co-therapy approach has the potential to reduce the metabolic problems commonly associated with atypical antipsychotics.


About Schizophrenia


Schizophrenia is a chronic, debilitating mental illness characterized by disturbances in thinking, emotional reaction, and behavior. Approximately one percent of the population develops schizophrenia during their lifetime and more than two million people in the United States suffer from this disease. Disturbances in schizophrenia may include positive symptoms, such as hallucinations and delusions, and a range of negative symptoms, including loss of interest, emotional withdrawal and cognitive disturbances.


About Pimavanserin


Pimavanserin is a novel, potent and selective 5-HT2A inverse agonist that ACADIA discovered and is developing as a co-therapy for patients with schizophrenia. ACADIA announced positive results in 2007 from its Phase II schizophrenia co-therapy trial, demonstrating several advantages of pimavanserin when combined with a sub-maximal dose of risperidone, including enhanced efficacy, a faster onset of antipsychotic action, and an improved side-effect profile. ACADIA also is in Phase III development with pimavanserin for the treatment of Parkinson's disease psychosis.















About ACADIA Pharmaceuticals


ACADIA is a biopharmaceutical company utilizing innovative technology to fuel drug discovery and clinical development of novel treatments for central nervous system disorders. ACADIA currently has five mid-to-late stage clinical programs as well as a portfolio of preclinical and discovery assets directed at diseases with large unmet medical needs, including schizophrenia, Parkinson's disease psychosis, sleep maintenance insomnia, and neuropathic pain. All of the drug candidates in ACADIA's product pipeline emanate from discoveries made using its proprietary drug discovery platform. ACADIA's corporate headquarters is located in San Diego, California and it maintains research and development operations in both San Diego and Malmö, Sweden.

acadia-pharm/


Forward-Looking Statements


Statements in this press release that are not strictly historical in nature are forward-looking statements. These statements include but are not limited to statements related to benefits to be derived from ACADIA's drug development programs, including the potential advantages of the use of pimavanserin as a co-therapy for schizophrenia with risperidone or other antipsychotics. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. Actual events or results may differ materially from those projected in any of such statements due to various factors, including the risks and uncertainties inherent in clinical trials, and drug development and commercialization, including the uncertainty of whether results in testing of pimavanserin to date will be predictive of results in later stages of development. For a discussion of these and other factors, please refer to ACADIA's annual report on Form 10-K for the year ended December 31, 2006 as well as other subsequent filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All forward-looking statements are qualified in their entirety by this cautionary statement and ACADIA undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof.

ACADIA Pharmaceuticals

Bipolar Disorder 'misdiagnosed In A Quarter Of Cases'

Bipolar disorder is misdiagnosed as depression in over a quarter of cases, a new study suggests. The research is presented today at the Royal College of Psychiatrists' 2009 Annual Meeting in Liverpool.



Psychiatrists Dr Krishna Gangineni and Dr Richard Annear, who work in Wales, reviewed the medical notes of people referred to psychiatric services for assessment.



They found that over 25% of the patients with bipolar disorder had initially had their condition misdiagnosed as unipolar depression.



Misdiagnosis often occurs because the symptoms of bipolar disorder overlap with depression and other psychiatric disorders. However, misdiagnosis can cause serious problems. For example, if people are wrongly prescribed antidepressants this can make their bipolar illness worse.



Dr Gangineni and Dr Annear said: "Our study found that bipolar disorder was misdiagnosed as unipolar disorder in more than 25% of the patients who first see a mental health professional.



"Recognition of bipolar disorder and its adequate treatment is paramount because bipolar disorder exacts such as a high personal and societal toll, with high rates of suicide and interpersonal problems and a substantial economic burden."



Reference:

Annual Meeting of the Royal College of Psychiatrists, BT Convention Centre, Liverpool, 2 -5 June 2009



Source
Royal College of Psychiatrists

New Drive To Improve Employers' Attitude To The Mentally Ill Launched In UK

A new initiative encouraging employers to improve the way they deal with mental health in the workplace has been launched by Health Minister Rosie Winterton to mark World Mental Health Day.



The three year initiative, called 'Action on Stigma', urges employers to sign up to a set of anti-stigma principles - for example, demonstrating that they have made changes in their work environment and employment practices to ensure that people with mental health problems are treated fairly and equally with others.



To mark World Mental Health Day, the Department of Health today published a document setting out these principles, highlighting existing best practice and the vision for the 'Action on Stigma' initiative. It also announced the start of a listening exercise to find out the views of employers and what support they will need to meet these principles.



Many employers who have taken part in projects to make their workplace culture more 'mental health friendly' have reported reduced staff turnover and sickness absences. Despite this:



Only about 20% of people with severe mental health problems are employed, compared to 65% of people with physical health problems and 75% for the whole adult population



Even for people with more common types of mental illness, such as depression, only about half are competitively employed



However, people with mental health problems have the highest 'want to work rate' with up to 90% wanting to work, compared to 52% for disabled people generally.



Although some of the principles are voluntary, adopting them will help public sector organisations, including local councils, government departments and hospitals, to meet the requirements of a new duty under the Disability Discrimination Act which comes into force in December 2006. This will require them to set out precisely how they intend to eliminate unlawful discrimination and promote equality of opportunity.



Speaking at a visit to a programme run by Oxleas Mental Health Trust in South East London to encourage businesses to employ people with mental health problems, Rosie Winterton said: "There is no better time than World Mental Health day to remind people that one in four of us will suffer from a mental health problem at some point in our lives and the cost to business and society is substantial. Ignorance and stigma still surrounds the issue of mental ill-health and when someone does develop a problem, they often do not get the support they need from society to help them recover. We all have a role to play in helping to tackle this issue. Employers can help by raising awareness of mental health issues amongst staff, supporting those affected and combating discrimination against staff and customers. This is good for staff and good for employers, who we know will benefit from reduced staff turnover and sickness absences. I am delighted to launch this new initiative and I urge employers to take the problem of mental health in the workplace seriously. We want employers to own this initiative and so we intend to spend the next few months listening to businesses about the support they need and discussing the set of principles we are proposing. Our priority must be to get our own house in order, so the first target of this drive will be the NHS and other public service organisations."
















Service user Emma Lindley, 27, of Manchester, said she was "ostracised" after she being off sick from an adminstrative job at a college of higher education for two months while being treated for bipolar disorder.



She added: "Some colleagues avoided me and dropped their eyes rather than have to greet me. Others began to patronise me even though they had always given me professional respect previously. People talked about me as though I wasn't there or fell out with me for no reason. I began applying for jobs very soon after returning because of the way I was treated. I left the post a few months later."



Department of Work and Pensions Minister, Lord Hunt, said: "Work is important and beneficial to our physical and mental well-being. Because of this, it is essential that we remove the barriers that prevent people starting, returning to, or remaining in work. I welcome this initiative, which will make an important contribution to the Government's strategy to improve health and well-being of the working age population."



Bill Callaghan, Chair of the Health and Safety Commission said: "I fully support the 'Action on Stigma' campaign. It's important that our organisations raise awareness of mental health issues amongst our staff and we support those affected. Being 'mental health friendly' is good for our businesses, helps our employees and customers and improves the health and wellbeing of all."



Hugh Taylor, Acting Permanent Secretary for the Department of Health, said: "Mental ill-health has an impact on both individuals and the organisations that employ them. We have a key role to play, by creating a work culture where staff are more aware of causes of mental illness, are not scared to ask for help and where discrimination is deemed unacceptable. I welcome this initiative and look forward to seeing how the Department of Health can, as an employer, play its part."



David Nicholson CBE, NHS Chief Executive, said:"People with mental health problems are often excluded from jobs, public services and playing a full part in our communities. The NHS is already doing a lot to increase social inclusion, promote mental wellbeing and support patients into employment. I welcome this initiative which will build on this good work and urge NHS organisations to get involved in changing the way we deal with mental health in the workplace."







The document is available on shift.uk/employment



In Scotland, the national anti-stigma campaign, 'see me', was launched in October 2002. It is run by five mental health organisations and is funded by the Scottish Executive. For further information, contact Katrina Beaton or Rebecca Charles at IAS Smarts on 0131 555 0425



For further information please go to:
UK Department of Health

Merck Receives Approval From FDA For Expanded Indications For Atypical Antipsychotic Medication SAPHRIS® (asenapine) Sublingual Tablets

Merck announced that the U.S. Food and Drug Administration (FDA) has approved two supplemental new drug applications (sNDA's) for SAPHRIS® (asenapine) sublingual tablets to expand the product's indications. SAPHRIS is now indicated for the treatment of schizophrenia in adults, as monotherapy for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults, and as adjunctive therapy with either lithium or valproate for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults. SAPHRIS was initially approved in the United States on August 13, 2009 for the acute treatment of schizophrenia in adults and as monotherapy for the acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features in adults.


"These FDA approvals demonstrate our active commitment to further understand how our medicines can be used to help physicians help their patients, and we look forward to discussing these new uses for SAPHRIS with the mental health community," said David Michelson, M.D., vice president of Neuroscience Clinical Research, Merck.


Important Safety Information about SAPHRIS


WARNING: INCREASED MORTALITY IN


ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS


Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in the drug-treated patients of between 1.6 to 1.7 times that seen in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5 percent, compared to a rate of about 2.6 percent in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. SAPHRIS® (asenapine) is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions (5.1)].


Cerebrovascular Adverse Events: In placebo-controlled trials with risperidone, aripiprazole, and olanzapine in elderly subjects with dementia, there was a higher incidence of cerebrovascular adverse reactions (cerebrovascular accidents and transient ischemic attacks) including fatalities compared to placebo-treated subjects. SAPHRIS is not approved for the treatment of patients with dementia-related psychosis.















Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported with administration of antipsychotic drugs, including SAPHRIS. NMS can cause hyperpyrexia, muscle rigidity, altered mental status, irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure. Management should include immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, intensive symptomatic treatment and medical monitoring, and treatment of any concomitant serious medical problems.


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. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses. Prescribing should be consistent with the need to minimize TD. If signs and symptoms appear, discontinuation should be considered.


Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases associated with ketoacidosis, hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. Patients with risk factors for diabetes mellitus who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of and during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should also undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the antipsychotic drug.


Weight Gain: Patients receiving SAPHRIS should receive regular monitoring of weight. There were differences in mean weight gain between SAPHRIS-treated and placebo-treated patients in short-term schizophrenia trials (1.1 kg vs. 0.1 kg) and in bipolar mania trials (1.3 kg vs. 0.2 kg). In a 52 week study, the proportion of patients with an equal to or greater than 7 percent increase in body weight was 14.7 percent.


Orthostatic Hypotension and Syncope and Other Hemodynamic Effects: SAPHRIS may induce orthostatic hypotension and syncope. SAPHRIS should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, conditions which would predispose them to hypotension and in the elderly. SAPHRIS should be used cautiously when treating patients who receive treatment with other drugs that can induce hypotension, bradycardia, respiratory or central nervous system depression. Monitoring of orthostatic vital signs should be considered in all such patients, and a dose reduction should be considered if hypotension occurs.


Leukopenia, Neutropenia, and Agranulocytosis: In clinical trial and postmarketing experience, events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents, including SAPHRIS. Patients with a pre-existing low white blood cell count (WBC) or a history of leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy, and SAPHRIS should be discontinued at the first sign of a decline in WBC in the absence of other causative factors.


QT Prolongation: SAPHRIS was associated with increases in QTc interval ranging from 2 to 5 msec compared to placebo. No patients treated with SAPHRIS experienced QTc increases of equal to or greater than 60 msec from baseline measurements, nor did any experience a QTc of equal to or greater than 500 msec. SAPHRIS should be avoided in combination with other drugs known to prolong QTc interval, in patients with congenital prolongation of QT interval or a history of cardiac arrhythmias, and in circumstances that may increase the occurrence of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval.


Hyperprolactinemia: Like other drugs that antagonize dopamine D2 receptors, SAPHRIS can elevate prolactin levels, and the elevation can persist during chronic administration. Galactorrhea, amenorrhea, gynecomastia and impotence have been reported in patients receiving prolactin-elevating compounds.


Seizures: SAPHRIS should be used cautiously in patients with a history of seizures or with conditions that lower seizure threshold, e.g., Alzheimer's dementia.


Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Aspiration pneumonia is a common cause of morbidity and mortality in elderly patients, in particular those with advanced Alzheimer's dementia. SAPHRIS is not indicated for the treatment of dementia-related psychosis, and should not be used in patients at risk for aspiration pneumonia.


Potential for Cognitive and Motor Impairment: Somnolence was reported in patients treated with SAPHRIS. Patients should be cautioned about performing activities requiring mental alertness, such as operating hazardous machinery or operating a motor vehicle, until they are reasonably certain that SAPHRIS therapy does not affect them adversely.


Body Temperature Regulation: Appropriate care is advised when prescribing SAPHRIS for patients who will be experiencing conditions that may contribute to an elevation in core body temperature, e.g., exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration.


Suicide: The possibility of suicide attempt is inherent in psychotic illnesses and bipolar disorder. Close supervision of high-risk patients should accompany drug therapy. Prescriptions for SAPHRIS should be written for the smallest quantity of tablets in order to reduce the risk of overdose.


Hepatic Impairment: SAPHRIS is not recommended in patients with severe hepatic impairment.


Drug Interactions: The risks of using SAPHRIS in combination with other drugs have not been extensively evaluated. Given the primary CNS effects of SAPHRIS, caution should be used when it is taken in combination with other centrally-acting drugs or alcohol. Co-administration of SAPHRIS with strong CYP1A2 inhibitors (fluvoxamine) or compounds which are both CYP2D6 substrates and inhibitors (paroxetine) should be done with caution.


Commonly Observed Adverse Reactions (incidence equal to or greater than five percent and at least twice that for placebo) were:



-- In short-term schizophrenia trials with SAPHRIS 5 or 10 mg BID vs. placebo: akathisia (6% vs. 3%), oral hypoesthesia (numbing of the tongue [5% vs. 1%]), and somnolence (13% vs. 7%). The safety profile of SAPHRIS in the maintenance treatment of schizophrenia was similar to that seen with acute treatment.



-- In short-term bipolar mania (monotherapy) trials with SAPHRIS 5 or 10 mg BID vs. placebo: somnolence (24% vs. 6%), dizziness (11% vs. 3%), extrapyramidal symptoms other than akathisia (7% vs. 2%) and weight increase (5% vs. less than 1%).



-- In the short term bipolar mania (adjunctive) therapy trial with SAPHRIS 5 or 10 mg BID vs. placebo: somnolence (22% vs. 10%) and oral hypoesthesia (5% vs. 0%).


About Bipolar I Disorder and Schizophrenia


Bipolar I disorder (also known as manic-depressive disorder) 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.


Schizophrenia is an often chronic and disabling brain disorder. It's characterized by various symptom domains, such as so-called positive symptoms (including hallucinations, delusions and disordered thinking) as well as negative symptoms, cognitive impairment and other general psychopathological symptoms (such as anxiety or depression).


Forward-Looking Statement


This news release includes "forward-looking statements" within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Such statements may include, but are not limited to, statements about the benefits of the merger between Merck and Schering-Plough, including future financial and operating results, the combined company's plans, objectives, expectations and intentions and other statements that are not historical facts. Such statements are based upon the current beliefs and expectations of Merck's management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements.


The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck's ability to accurately predict future market conditions; dependence on the effectiveness of Merck's patents and other protections for innovative products; the risk of new and changing regulation and health policies in the United States and internationally and the exposure to litigation and/or regulatory actions.


Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck's 2009 Annual Report on Form 10-K and the company's other filings with the Securities and Exchange Commission (SEC)


SAPHRIS® is a registered trademark of N.V. Organon, a subsidiary of Merck & Co., Inc., Whitehouse Station, N.J., U.S.A.


Source: Merck


View drug information on Saphris.