The medication tamoxifen, best known as a treatment for breast cancer, dramatically reduces symptoms of the manic phase of bipolar disorder more quickly than many standard medications for the mental illness, a new study shows. Researchers at the National Institutes of Health's National Institute of Mental Health (NIMH) who conducted the study also explained how: Tamoxifen blocks an enzyme called protein kinase C (PKC) that regulates activities in brain cells. The enzyme is thought to be over-active during the manic phase of bipolar disorder.

By pointing to PKC as a target for new medications, the study raises the possibility of developing faster-acting treatments for the manic phase of the illness. Current medications for the manic phase generally take more than a week to begin working, and not everyone responds to them. Tamoxifen itself might not become a treatment of choice, though, because it also blocks estrogen — the property that makes it useful as a treatment for breast cancer — and because it may cause endometrial cancer if taken over long periods of time. Currently, tamoxifen is approved by the Food and Drug Administration for treatment of some kinds of cancer and infertility, for example. It was used experimentally in this study because it both blocks PKC and is able to enter the brain.

Results of the study were published online in the September issue of Bipolar Disorders by Husseini K. Manji, MD, Carlos A. Zarate Jr., MD, and colleagues.

Almost 6 million American adults have bipolar disorder, whose symptoms can be disabling. They include profound mood swings, from depression to vastly overblown excitement, energy, and elation, often accompanied by severe irritability. Children also can develop the illness.

During the manic phase of bipolar disorder, patients are in "overdrive" and may throw themselves intensely into harmful behaviors they might not otherwise engage in. They might indulge in risky pleasure-seeking behaviors with potentially serious health consequences, for example, or lavish spending sprees they can't afford. The symptoms sometimes are severe enough to require hospitalization.

"People think of the depressive phase of this brain disorder as the time of risk, but the manic phase has its own dangers," said NIMH Director Thomas R. Insel, MD. "Being able to treat the manic phase more quickly would be a great asset to patients, not just for restoring balance in mood, but also because it could help stop harmful behaviors before they start or get out of control."

The three-week study included eight patients who were given tamoxifen and eight who were given a placebo (a sugar pill); all were adults and all were having a manic episode at the time of the study. Neither the patients nor the researchers knew which of the substances the patients were getting.

By the end of the study, 63 percent of the patients taking tamoxifen had reduced manic symptoms, compared with only 13 percent of those taking a placebo. Patients taking tamoxifen responded by the fifth day — which corresponds with the amount of time needed to build up enough tamoxifen in the brain to dampen PKC activity.

The researchers decided to test tamoxifen's effects on the manic phase of bipolar disorder because standard medications used to treat this phase, specifically, are known to lower PKC activity — but they do it through a roundabout biochemical route that takes time. Tamoxifen is known instead to block PKC directly. As the researchers suspected would happen, tamoxifen's direct actions on PKC resulted in much faster relief of manic symptoms, compared with some of the standard medications available today.

"We now have proof of principle. Our results show that targeting PKC directly, rather than through the trickle-down mechanisms of current medications, is a feasible strategy for developing faster-acting medications for mania," said Manji. "This is a major step toward developing new kinds of medications."

Findings from another recent NIMH study strengthen the results. This previous study showed that the risk of developing bipolar disorder is influenced by a variation in a gene called DGKH. The gene makes a PKC-regulating protein known to be active in the biochemical pathway through which standard medications for bipolar disorder exert their effects - another sign that PKC is a promising direct target at which to aim new medications for the illness.

"Mania isn't just your average mood swing, where any of us might feel upbeat in response to something that happens. It's part of a brain disorder whose behavioral manifestations can severely undermine people's jobs, relationships, and health," said Zarate. "The sooner we can help patients get back on an even keel, the more we can help them avoid major disruptions to their lives and the lives of people around them."

Reference

Zarate Jr. CA, Singh JB, Carlson PJ, Quiroz J, Jolkovsky L, Luckenbaugh DA, Manji HK. Efficiency of a Protein Kinase C Inhibitor (Tamoxifen) in the Treatment of Acute Mania: A Pilot Study. Bipolar Disorders, online ahead of print, September 2007.

Psychotherapy Combined with Antidepressant Medication Most Effective

A combination of psychotherapy and antidepressant medication appears to be the most effective treatment for adolescents with major depressive disorder—more than medication alone or psychotherapy alone, according to results from a major clinical trial funded by the National Institutes of Health’s National Institute of Mental Health (NIMH). The study was published in the October 2007 issue of the Archives of General Psychiatry.

The long-term results of the Treatment for Adolescents with Depression Study (TADS) found that when adolescents received fluoxetine (Prozac) alone or in combination with cognitive behavioral therapy (CBT) over the course of 36 weeks, they recovered faster than those who were receiving CBT alone.  

However, taking fluoxetine alone appeared to pose some safety concerns for the teens.  During treatment, those taking fluoxetine alone had higher rates of suicidal thinking (15 percent) than those in combination treatment (8 percent) and those in CBT alone (6 percent), particularly in the early stages of treatment.  This suggests that while treatment with fluoxetine may speed recovery, adding CBT provides additional safeguards for those vulnerable to suicide, according to the researchers.

“Depression in teens is a serious illness that can and should be treated aggressively,” said NIMH Director Thomas R. Insel, M.D. “TADS provides compelling evidence for families and clinicians that the most effective way to treat depression in teens is with a two-pronged approach. It reassures us that antidepressant medication combined with psychotherapy is an effective and safe way to help teens recover from this disabling illness.”

Results at 36 weeks of treatment were consistent with those found at 12 weeks in the 439-person study, when NIMH reported that combination treatment produced the greatest improvement in teenagers with major depression. At 18 weeks (results not previously reported), combination treatment still outpaced the other treatments with an 85 percent response rate, compared to 69 percent for fluoxetine alone and 65 percent for CBT alone. By 36 weeks, the response rate to combination treatment still remained the highest (86 percent), while response rates to fluoxetine and CBT essentially caught up, at 81 percent each. 

“In the combination approach, the two treatments complemented each other,” said John March, M.D, MPH, of Duke University and lead author of the study. "The fluoxetine can help dissipate the physical symptoms of major depression relatively quickly, and CBT can help patients develop new skills to contend with difficult, negative emotions.” 

Because the trial sample included a mix of younger and older teens, both genders, substantial minority representation and variable socioeconomic status, the TADS results can be applied broadly to the adolescent population.

Reference

The TADS Team. The Treatment for Adolescents with Depression Study (TADS): Long-term Effectiveness and Safety Outcomes. Archives of General Psychiatry. Oct 2007; VOL 64(10).

Depression can strike anyone at any time. The mental illness afflicts more than 20 million Americans each year, making it the leading cause of disability in the United States.

The Pain of Depression: A Journey through the Darkness explores the physical and psychological challenges of depression, whose symptoms range from insomnia to debilitating fatigue. Compelling stories from depression sufferers capture the illness’ devastating impact on their families, friends and communities.

This informative documentary has aired on over 250 public television stations nationwide (visit http://www.painofdepression.org) and takes viewers on a journey to understand depression through the first-hand experiences of three people. Their family members and friends express their early misconceptions about the illness and recall how their loved ones fought depression with counseling, medication and lifestyle changes. 

John, a self-described "macho man” first became depressed at the age of 40. He stayed in bed, felt sick and lost interest in playing with his children. John’s denial and resistance to treatment prevented him from seeking help. Once he did, John regained the rewarding family life he once enjoyed.

By: Stanley Popovich

Everybody deals with anxiety and depression, however some people have a hard time in managing it. As a result, here is a brief list of techniques that a person can use to help manage their most persistent fears and every day anxieties.

When facing a current or upcoming task that overwhelms you with a lot of
anxiety, the first thing you can do is to divide the task into a series of
smaller steps. Completing these smaller tasks one at a time will make the
stress more manageable and increases your chances of success.

Sometimes we get stressed out when everything happens all at once. When this happens, a person should take a deep breath and try to find something to do for a few minutes to get their mind off of the problem. A person could get some fresh air, listen to some music, or do an activity that will give them a fresh perspective on things.

A person should visualize a red stop sign in their mind when they encounter
a fear provoking thought. When the negative thought comes, a person should
think of a red stop sign that serves as a reminder to stop focusing on that
thought and to think of something else. A person can then try to think of
something positive to replace the negative thought.

Another technique that is very helpful is to have a small notebook of
positive statements that makes you feel good. Whenever you come across an
affirmation that makes you feel good, write it down in a small notebook that
you can carry around with you in your pocket. Whenever you feel depressed
or frustrated, open up your small notebook and read those statements. This
will help to manage your negative thinking.

Learn to take it one day at a time. Instead of worrying about how you will
get through the rest of the week, try to focus on today. Each day can
provide us with different opportunities to learn new things and that
includes learning how to deal with your problems. You never know when the
answers you are looking for will come to your doorstep. We may be
ninety-nine percent correct in predicting the future, but all it takes is
for that one percent to make a world of difference.

Take advantage of the help that is available around you. If possible, talk
to a professional who can help you manage your depression and anxieties.
They will be able to provide you with additional advice and insights on how
to deal with your current problem. By talking to a professional, a person
will be helping themselves in the long run because they will become better
able to deal with their problems in the future. Remember that it never
hurts to ask for help.

Dealing with our persistent fears is not easy. Remember that all you can do
is to do your best each day, hope for the best, and take things in stride.
Patience, persistence, education, and being committed in trying to solve
your problem will go along way in fixing your problems.

BIOGRAPHY:

Stan Popovich is the author of "A Layman's Guide to Managing Fear Using
Psychology, Christianity and Non Resistant Methods" - an easy to read book
that presents a general overview of techniques that are effective in
managing persistent fears and anxieties. For additional information go to:
http://www.managingfear.com/

New Jersey teenager hopes new initiative will help teens with mental illness.

Out of the Silence, a new web-based non-profit organization (http://stepoutofthesilence.org/) that aims to offer a safe venue in which young people with mental health problems can express their emotions through artwork, prose, poetry, photography, and graphic art; will be launched on September 9 to coincide with National Suicide Prevention Week. The initiative and web site was created by 16 year-old Caitlin Carey of New Jersey to assist teens dealing with mental health problems but who feel they have no place to express their thoughts and feelings.

“It’s no secret that thousands of teens today suffer in silence, not knowing where they can voice their concerns and experiences with mental illness,” said Caitlin Carey, founder of the project. “Young people tend to rely on their peers for support in everyday situations. However, the stigma attached to mental illness makes it difficult to reach out to friends; so many teenagers who are trying to cope with an illness such as depression or anxiety feel isolated.”

Carey, who has struggled with obsessive compulsive disorder for nearly a decade, added, “I felt like I was the only girl in the world who experienced these horrible emotions and isolation. No one should have to feel the way I did.”

Carey’s hope is that Out of the Silence will provide a community of advocates for teenagers dealing with mental illness. She plans to eventually hold empowering events such as sponsored writing and art contests.

“While there are many networking opportunities available for adults with mental health disorders, there are very few resources that are targeted and accessible to young people who are suffering,” added Carey. “I felt the time was right for me and my peers to become more vocal and proactive in the fight against the stigma associated with mental illness. Our voice has to count.”

“Caitlin Carey’s commitment to fighting the stigma surrounding mental health issues is truly remarkable. Her courageous efforts will no doubt help countless teens and young adults navigate the many challenges of living with mental illness,” said Jeff Bell, author of Rewind, Replay, Repeat: A Memoir of Obsessive Compulsive Disorder and advocate for mental health. “The mental health community is most fortunate to have Caitlin join its ranks!”

To learn more about the web site and Caitlin, visit us at http://stepoutofthesilence.org/.

A decision to treat bereavement-related depression should be based on considerations used for nonbereavement depression, rather than on the time since the death of a loved one.

For some time now, psychiatric scientists have been making forays into the nether world of bereavement, and their efforts seem to be leading to some clarification of what grief for a loved one is and what it is not.

Normal grief for a loved one, for example, does not seem to be the same as complicated or traumatic grief. The latter is characterized by persistent difficulty in accepting the death, recurrent pangs of intense grief, preoccupation with thoughts and images of the deceased, and avoidance of reminders of the loss (Psychiatric News, July 6, 2005; April 6).

Also, the depression stemming from complicated grief does not seem to be the same as major depression.

On the other hand, depression stemming from normal grief seems to be very closely related to major depression, two psychiatrists now conclude. Sidney Zisook, M.D., a professor of psychiatry at the University of California at San Diego, and Kenneth Kendler, M.D., a professor of psychiatry and human genetics at Virginia Commonwealth University, presented data backing their theory in the June Psychological Medicine.

Zisook and Kendler searched all English-language reports in Medline up to November 2006 to identify published data about key characteristics that define bereavement depression and standard major depression. They then compared characteristics for both types of depression.

Several of their results indicated that bereavement depression might be a separate disorder from major depression. For example, although women are more vulnerable to major depression, men may be equally as vulnerable to bereavement depression.

Most of their analysis, however, suggested that bereavement depression is closely related to major depression. For instance, bereavement depression, like major depression, is more common in younger adults than in older ones, more likely to occur in individuals with a personal or family history of major depression, more likely to occur in persons in poor health than in good health, and more likely to occur in those with little social support.

Furthermore, both bereavement depression and major depression are accompanied by heightened adrenocortical activity, impaired immune responses, and sleep disturbances. And bereavement depression has clinical characteristics similar to those of major depression—impaired psychosocial function, comorbidity with a number of anxiety disorders, and symptoms of worthlessness and suicidality.

"Overall, the prevailing evidence more strongly supports similarities than differences between bereavement-related depression and standard major depression," Zisook and Kendler concluded.

These findings have important clinical implications, Zisook and Kendler believe. For example, DSM-IV-TR guidelines for diagnosing depression indicate that bereavement depression can only be diagnosed as major depression if it exceeds two months or if specific symptoms, such as suicidal ideation, morbid preoccupation with worthlessness, or psychomotor retardation, are present. Yet if bereavement depression is the same as major depression these guidelines may be invalid.

On the other hand, if depression following the death of a loved one should be largely excluded from the definition of major depression, then should depression following other types of losses, say a divorce or bankruptcy, also be excluded from it? Currently, "DSM-IV-TR singles out bereavement as the only stressful life event that excludes the diagnosis of major depressive episode when all other features are present," Zisook and Kendler noted.

"The ideal study to test the validity of the bereavement exclusion," they pointed out, "would compare individuals with depressive syndromes beginning within two months of the loss of a loved one...[to individuals with] major depressive episodes of similar duration and symptom profile whose onset is unrelated to the death of a loved one." But "Unfortunately, we found no such studies in the literature," they said.

What about treatment? "The ultimate decision of when, whether, and how to treat the depression," Zisook told Psychiatric News, "should be made on the basis of considerations generally used for other, nonbereavement-related depressions, such as past history of depression and response to treatment, severity and chronicity of the episode, comorbidity, anxiety level, suicidal ideation, effects on functioning, supports, et cetera. The decision should not be based on time since the death of a loved one."

Zisook and Kendler's review was not supported by outside funding.

The birth of a new baby is often a joyous and exciting time. However, for about 400,000 women each year in the U.S., this is a time filled with physical and emotional symptoms that can adversely affect the new mother’s mental health and subsequently may also affect growth and development of her child.

The effect of rapid hormonal changed that occur during and immediately after childbirth often causes women to encounter what is called “baby blues” or “maternal blues”, characterized by mood swings that occur three to five days after delivery and begin to stabilize within a few weeks. Up to 80% of new moms experience these transient symptoms. Typically, this temporary mood shift does not require treatment.

Unfortunately for about 10% to 20% of women, severe and persistent symptoms eveolve into a syndrome known as postpartum depression (PPD). PPD is a form of major depressive disorder. It is a significant public health issue that is under-recognized and under-treated in the medical community. Because women who have PPD often do not understand their symptoms and feel ashamed of being unable to experience the “joy” they feel is expected of them, they continue to silently suffer without seeking professional care.

A rare and serious medical condition, postpartum psychosis affects only about 1 in 1,000 mothers. Some women have delusions or hallucinations and may become irrational, incoherent or paranoid. The potentially devastating effects, including child abuse, suicide and infanticide, put it in the category of a psychiatric emergency that requires immediate intervention.

Postpartum depression disorders have “biopsychosocial” components. Women experience biological symptoms that may include exhaustion or fatigue, sleep or appetite disturbances, or headaches, chest pains or heart palpitations. Psychological reactions may include increased crying or irritability, feelings of sadness and hopelessness, mood swings, inability to cope or feeling overwhelmed, fears of being alone or frightened thoughts about harming the baby, her partner or herself. Social presentation of this condition may include poor self-care, a lack or interest or an excessive concern for the baby, loss of pleasure in previously enjoyable activities, withdrawal and isolation, or an inability to concentrate or make decisions.

In addition to the postpartum depressive disorder, many women endure a variety of anxiety disorders either alone or co-existing with depression. Childbirth is a major life change that can increase the likelihood of developing panic disorder. Intense fear of losing control, dizziness, hot or cold flashes may signal this postpartum complication, however, chest pains and sensations that feel like a heart attack are the two most commonly reported symptoms. Other anxiety disorders that may sidetrack a new mom are obsessive-compulsive disorder that includes irrational thoughts (obsessions) and repeated behaviors (compulsions) performed in an attempt to combat a persistent fear. Post-traumatic stress disorder causes women to experience intrusive memories of pat or present trauma exhibited in nightmares and/or flashbacks that consequently causes avoidance, anger or hyper-vigilance about the baby.

There are risk factors in the mother’s environment that can increase or decrease the potential for developing any of these postpartum disorders. Often postpartum disorders are preventable and early detection that leads to early intervention produces a more positive outcome for the women and her child.

The first step to decreasing maternal depression is education for women, their families and their physicians. In addition, although more pediatricians do not treat the mothers of their infant patients, awareness of the prevalence and risk factors as well as the signs and symptoms will enable them to ask the appropriate questions about their patient’s mom and family functioning.

Another possibility for obstetrician/gynecologists, pediatricians and even primary care physicians is to routinely screen for the symptoms of depression and anxiety. There are advantages to using a screening too; as it is quick and easy and has been validated to detect depression and/or anxiety symptoms. Doctors and patients may feel more confident talking about the women’s feelings, using the screening instrument to open up the dialogue.

The good news is that treatment works! Medication and/or psychotherapy are extremely effective in treatment of depressive and anxiety disorders. Support groups are a valuable adjunct to the medical and psychological treatment plan. The most important message that you can share with a woman experiencing any of these disorders is: You are not alone. You are not to blame. Your feelings are real. This is a treatable illness. There is help and hope.

The Broward Healthy Start Coalition’s Maternal Depression Task Force has developed a screening tool that is used in its intake process. You can obtain a copy of this screening, along with other literature and a Maternal Depression Resource Guide by calling Healthy Start at (954) 563-7583 or online at www.browardhealthystart.org.

This article was submitted by Marcia Pinck of the Mental Health Association of Broward County. She is the chair of the Broward Healthy Start Coalition’s Maternal Depression Task Force and can be reached at (954) 746-2055.

Roy Perlis, M.D., of Massachusetts General Hospital, and colleagues analyzed DNA samples of 1,447 STAR*D participants who reported no suicidal thinking or behavior prior to treatment and who received up to 12 weeks of the antidepressant citalopram (Celexa®). Perlis and colleagues focused on the participants' genetic variations—known as single nucleotide polymorphisms (SNPs)—that reside within or nearby the CREB1 gene, which scientists suspect is linked with major depression and possibly related to suicidal thinking and behavior, and also may be involved in how antidepressants work. SNPs are responsible for many of the variations in human genetics, and most scientists believe they may predispose people to certain diseases or influence their response to a medication.

Among the participants, 124 (8.6 percent) developed suicidal thinking after starting treatment, including 54 men. Two of the five SNPs studied were significantly and strongly associated with the onset of suicidal thinking in the men, but not in the women. In previous studies, the same two SNPs appear to be associated with anger among men with major depression—a symptom commonly associated with suicide. Further analyses indicated that none of the five SNPs were linked to suicidal thought and behaviors in men before they began treatment.

The authors conclude that if the results can be replicated, they will have tremendous potential for identifying a subset of people at greater suicidal risk during initial antidepressant treatment.

Perlis R, et al. Association between treatment-emergent suicidal ideation with citalopram and polymorphisms near cyclic adenosine monophosphate response element binding protein in the STAR*D study. Archives of General Psychiatry. 2007 Jun. 64(6):689-697.

A new study supports earlier estimates of the prevalence of bipolar disorder in the U.S. population, and suggests the illness may be more accurately characterized as a spectrum disorder. It also finds that many people with the illness are not receiving appropriate treatment. The study, published in the May 2007 issue of Archives of General Psychiatry, analyzed data from the National Comorbidity Survey Replication (NCS-R), a nationwide survey of mental disorders among 9,282 Americans ages 18 and older. The NCS-R was funded by the National Institutes of Health's National Institute of Mental Health (NIMH).

NIMH researcher Kathleen Merikangas, Ph.D. and colleagues identified prevalence rates of three subtypes of bipolar spectrum disorder among adults. Bipolar I is considered the classic form of the illness, in which a person experiences recurrent episodes of mania and depression. People with bipolar II experience a milder form of mania called hypomania that alternates with depressive episodes. People with bipolar disorder not otherwise specified (BD-NOS), sometimes called subthreshold bipolar disorder, have manic and depressive symptoms as well, but they do not meet strict criteria for any specific type of bipolar disorder noted in the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV), the reference manual for psychiatric disorders. Nonetheless, BD-NOS still can significantly impair those who have it.

The results indicate that bipolar I and bipolar II each occur in about 1 percent of the population; BD-NOS occurs in about 2.4 percent of the population. The findings support international studies suggesting that, given its multi-dimensional nature, bipolar disorder may be better characterized as a spectrum disorder.

"Bipolar disorder can manifest itself in several different ways. But regardless of type, the illness takes a huge toll," said NIMH Director Thomas R. Insel, M.D. "The survey's findings reiterate the need for a more refined understanding of bipolar symptoms, so we can better target treatment."

Most respondents with bipolar disorder reported receiving treatment. Nearly everyone who had bipolar I or II (89 to 95 percent) received some type of treatment, while 69 percent of those with BD-NOS were getting treatment. Those with bipolar I or II were more commonly treated by psychiatric specialists, while those with BD-NOS were more commonly treated by general medical professionals.

However, not everyone received treatment considered optimal for bipolar disorder. Up to 97 percent of those who had some type of bipolar illness said they had coexisting psychiatric conditions, such as anxiety, depression or substance abuse disorders, and many were in treatment for those conditions rather than bipolar disorder. The researchers found that many were receiving medication treatment considered "inappropriate" for bipolar disorder, e.g., they were taking an antidepressant or other psychotropic medication in the absence of a mood stabilizing medication such as lithium, valproate, or carbamazepine. Only about 40 percent were receiving appropriate medication, considered a mood stabilizer, anticonvulsant or antipsychotic medication.

"Such a high rate of inappropriate medication use among people with bipolar spectrum disorder is a concern," said Dr. Merikangas. "It is potentially dangerous because use of an antidepressant without the benefit of a mood stabilizer may actually worsen the condition."

Merikangas and colleagues speculate that as people seek treatment for anxiety, depression or substance abuse disorders, their doctors, especially if they are not mental health specialists, may not be detecting an underlying bipolar condition in their patients.

"Because bipolar spectrum disorder commonly coexists with other illnesses, it is likely underrecognized, and therefore, undertreated. We need better screening tools and procedures for identifying bipolar spectrum disorder, and work with clinicians to help them better spot these bipolar symptoms," concluded Dr. Merikangas.

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.

Merikangas KR, et al. Lifetime and 12-Month Prevalence of Bipolar Spectrum Disorder in the National Comorbidity Survey Replication. Archives of General Psychiatry. May 2007; 64.

Each year more than 17 million Americans will suffer from an anxiety disorder and more than 19 million Americans will suffer with a depressive illness. Often these illnesses manifest with not only emotional symptoms but physical symptoms as well. Individuals often believe the cause of their discomfort and pain is an undiagnosed physical illness. Anxiety and depression can happen to anyone at anytime.

The following are symptoms of anxiety and depression:

• Constant uncontrollable worrying
• Feeling blue, sad, or hopeless
• Sleeping problems, poor concentration
• Anxiety attacks, nervousness, or tension
• Feelings of intense anxiety in social situations
• Loss of pleasure
• Phobias