CABF policy director on the importance of properly diagnosing bipolar disorder in children and the antidepressants-suicide controversy.

Comments by CABF Research Policy Director, Martha Hellander at American Academy of Child & Adolescent Psychiatry, Town Meeting, Washington, DC. (AACAP 2004 Annual Meeting)

Hello, and thank you for inviting me today. I should start by saying that I have no conflicts of interest other than being a mom. I am also the Research Policy Director and co-founder of the Child & Adolescent Bipolar Foundation, a nonprofit advocacy group of nearly 25,000 families raising children diagnosed with, or at risk for, bipolar disorder. Over half of our children are under the age of 12, more than half of them have been hospitalized anywhere from 1 to 10 times, and about a third of them take antidepressants along with mood stabilizers. Many of our members reported in an informal poll last January, as we testified before the FDA, that their children had been suicidal from a very young age, often before taking any medications; others were never observed by their parents to be suicidal until soon after taking antidepressants, and among those families, about half report that the suicidal behavior stopped when the medication was removed.

CABF does not take a position on whether individual cases were or were not caused by antidepressants. Our position is that mood disorders in children are a major public health crisis, and antidepressants are an essential part of treatment for SOME, but not all, of those kids. CABF welcomes the FDA attention, and increased warnings, being added to the labeling of these medications. As we say at CABF, these are powerful and potentially dangerous drugs that are used of necessity to treat powerful and extremely dangerous illnesses.

Doctors and parents must keep in mind that symptoms of depression in a child may not be a one-time episode, but a manifestation of a developmental stage of a lifelong, hereditary illness such as bipolar disorder in which more time is typically spent depressed than manic or schizophrenia. Parents need to know that depression is often the first sign of bipolar disorder, and is also the most common symptom seen in adolescents during the five years prior to the first psychotic break in schizophrenia. So how can we tell which kid presenting with depression is likely to respond well, or have an adverse reaction to, a particular medication? We can't at this time. We can recognize depression in even preschoolers now, but we don't yet know how to match up which kids with which treatments.

To parents demanding an answer, and God knows how badly we want answers, you must stand firm and say "I don't know." We need you to be honest and tell us frankly that if you conclude that our children are depressed, you have no way of telling whether it is the type of depression likely to respond to an antidepressant, or to psychotherapy, or whether the medication might provoke the child to become manic, or go into a mixed state (which is the highest period of risk for suicide in those with bipolar disorder). And until we have a major federal investment into research on these questions, you will have no answers. To quote the Dali Lama, "Wisdom is the ability to tolerate ambiguity." In other words, don't give us false assurances.

Many parents aren't going to like this ambiguity, of course. They want you to reassure them that it is probably nothing serious, that you're confident the child will grow out of it, and they will look back in a couple of years and laugh at how worried they are now. Please do not sugar-coat the implications of depression in a child. You must deliver the bad news, unvarnished, and lay out the worst case scenario, as well as the best case scenario, and admit to parents that you don't know whether this or that treatment will help the child. It is essential that parents hear from you, and from advocacy groups such as CABF, that suicide is a possible outcome of depression itself in children. This fact is not widely known, and until it is, the public will continue to assume that suicides that occur while a patient is on antidepressants were caused by the drug. Large clinical trials were not designed to tell, in individual cases, what happened. Large group statistics do not identify the lives lost, or the lives saved, at an individual level.

Screen the child for mania. Use the Young Mania Rating Scale - Parent Version on our web site; a group led by Mani Pavuluri is presenting a child mania rating scale at this conference on Saturday afternoon. CABF will encourage parents to do this screening at home, so you may find parents coming in more educated than before. This is good. Parents ignorant of the symptoms of mania will not call manic behaviors to your attention unless you ask; we tend to be proud of our young kids who stay up late writing poetry, or plays, or making art projects, and admire their bravery and adventuresome nature as they climb to the top of the tallest tree or go fearlessly headfirst down the slide over and over again. We are not likely to mention that our kids rarely sleep at night, or won't stop talking from morning until night, unless you ask us.

Take a family history. You may discover that this child's family, on both sides, has many individuals with bipolar illness or schizophrenia. Educate parents as to why it might make sense to starting a depressed child with some manic tendencies and a family history of bipolar disorder on one of the mood stabilizers known to reduce the risk of suicide, such as lithium, before starting the child on an antidepressant.

Monitoring. This is the latest intervention to prevent suicide by children on antidepressants that has taken the country by storm - it is called "monitoring." Is there evidence about how effective it is, of what it consists? In what environment? Is the concept of monitoring likely to induce a false sense of security?

I have asked several parents whose children took their lives what sort of "monitoring" might have saved them. I was told about the teenage boy just out of the hospital whose parents pleaded with the doctor and insurance company to keep him over the weekend. He was started on medication, discharged over their objections, and told by the doctor to just "go home and have a low-key weekend" and report for day hospital on Monday. They made it through Friday night, and Saturday, and Saturday night, one or the other of them always by his side, even sleeping with him at night. Come Sunday, the father had to run an errand, and the mother needed to use the bathroom. During a few moments alone, the boy stole the car keys and the car, disabled the family phone, and drove off to end his life. Does this mean that during monitoring, parents should not leave the house to buy food, or go to the bathroom? And how many adults must be present; what options are there for single parents, or with other young children to care for, or working parents?

---

Another mom told me that her daughter got into the medicine cabinet in the family bathroom, and took all the aspirin and Tylenol she could find. The doctor treating her child had not told her to "suicide proof" the house, had not, in fact, told her at all that a depressed child may attempt suicide. Had she known, she told me, she would have locked up the medicine cabinet. Must the house be "suicide-proofed?" I question whether this is even possible, unless one puts grates over windows, removes closet rods and belts, and locks the doors with deadbolt locks from the inside.

Other parents have told me of how in a moment when their back was turned, their depressed children took kitchen knives and cut their wrists, or got up in the middle of the night when the parents were sleeping, wandering the house to find objects with which to injure themselves. During monitoring, are parents to stay awake round-the-clock? Perhaps "monitoring," to be adequate, means constant supervision, literally round the clock, in a secure environment (so the child cannot run off and head for the railroad tracks to throw himself in front of a train, as one boy did), and in which the cupboards, drawers, utensils, doorknobs, indeed, any object, substance, or opportunity by which to harm themselves or attempt suicide has been removed. I don't know of any such place, except for a locked inpatient hospital unit or locked residential treatment center. What are the implications of that, when insurance companies refuse to cover hospital or residential treatment for so-called "mental" illnesses beyond a few days, and even there, hospitals often use one-on-one continuous observation or check patients every 15 minutes, with round-the-clock staffing. So there is a huge need for some guidance to parents of what exactly does "monitoring" mean for them, and we question whether it is really possible for most families to do it at home.

I want to thank each of you for devoting your careers to studying and healing a particularly painful type of suffering endured by too many children. As times change and we learn more about the brain and how it is molded both by genes and environment, we look to you to identify the illness that is attacking their brains and destroying their will to live and sometimes ending their lives. We look to you to provide healing treatment and advice to help us return them to a normal path of development. It seems ironic that at a time when your services are in such great demand, with your appointment books filled for months into the future, that you are often portrayed in the media as carelessly eager to drug America's children. That's just not true. Please don't be discouraged. We parents whose children's lives have been saved by modern medicine and appropriate psychotherapy wisely administered are grateful to you, and to your colleagues who do the research, and to those who develop and produce medication and other treatments.

We need to stand together and insist upon more federal funding and investment in research on these important questions.

Thank you.

Martha Hellander
CABF Research Policy Director
October 21, 2004

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Many patients receive multiple psychiatric medications for a mental health condition, but there's little scientific evidence to back the practice.

Mixing mental illness drug 'cocktails' is still more art than science.

They call them drug cocktails. They're becoming the vogue for mental illnesses such as bipolar disorder and schizophrenia. But mixing drugs is still more art than science.

If you have a serious mental illness, it's becoming more likely that you'll be treated with multiple drugs. Doctors call this polypharmacy. Polypharmacy is common for conditions such as heart disease, cancer, and HIV infection. The basic idea is to attack the mental illness on multiple fronts, using different drugs with different actions.

That's the upside. It can offer mental illness patients tremendous benefits when doctors have a careful, rational plan for trying multiple drugs. But there's a downside, too, says Andrew C. Furman, MD, director of clinical services for psychiatry at Atlanta's Grady Memorial Hospital and associate professor of psychiatry at Emory University.

"Unfortunately, in the majority of cases doctors are just throwing everything they possibly can at a mental illness in hopes that something will get better," says Furman.

That happens too often, agrees Alan J. Gelenberg, MD, head of psychiatry at the University of Arizona and editor-in-chief of the Journal of Clinical Psychiatry.

"What often happens in busy practices, both private and public, is that medications are thrown on without adequate information," according to Gelenberg. "Patients can end up with regimens that include multiple drugs without a rationale for using them all. It is not uncommon to look at a medical chart and say, 'I can't figure out why a patient is on this combination regimen.'"

That can be bad news for mental illness patients, says Beth Murphy, MD, PhD, a psychiatric drug researcher at McLean Hospital in Belmont, Mass., and instructor in clinical psychiatry at Harvard University.

"The bad news is it costs more. And the more medicines you take, the more likely it is you will have an adverse response," says Murphy. "Moreover, it increases the chance your medicines will [harmfully] interact with one another."

Mental Illness: Much to Learn About Drugs

When they prescribe drugs for physical diseases, doctors usually know exactly how each drug acts on the body. What is more, they have a precise idea of how this helps treat disease. Drugs for mental illness work on the brain -- by far the most complex and least understood part of the body. That makes prescribing mental illness drugs far different from prescribing drugs for heart disease, Gelenberg says.

"Definitely the increase in psychiatric polypharmacy is not coming from a better understanding of disease," remarks Gelenberg. "Psychiatry isn't the same as cardiology in our understanding of the exact mechanisms of illness."

"This being the decade of the brain, there has been a burgeoning of understanding. But even with these incredible advances, the understanding of the brain is not at the same place as the understanding of the heart," says Murphy. "We don't have enough understanding to know exactly which medicines a given individual will respond to. We have increased our understanding of the biochemistry that underlies these illnesses, but we don't know all we would like to know."

Multiple drug treatment is becoming state-of-the-art treatment for bipolar disorder, notes Mark A. Frye, MD, director of the UCLA bipolar disorder research program and associate professor of psychiatry at UCLA's David Geffen School of Medicine. But he emphasizes the word "art."

"We have little clinical trial data on which to base this, so it is still more an art than a science," Frye says. "This is a painful contrast to other areas of medicine where doctors have large-scale clinical trial data to guide them. That is only just happening now in psychiatry."

Mental Illness: A Delicate Balance

If they don't know exactly what they are doing -- and there are no large clinical trials to guide them -- why prescribe multiple drugs for mental illness?

"This is part of a trend not to accept anything less than wellness," Murphy says. "Years ago, if a psychiatric patient was not in the hospital, that was good enough. Now, because of advances in our understanding of mental illness and mental wellness, health is the goal. So often multiple treatments are an attempt to reach that goal."

In the right patient at the right time, one mental illness drug can enhance the action of another, Frye suggests.

"There is a trend to maximize outcome, to use medications that enhance one another," he says. "We can clinically show that often when there is [enhancement], we get lower doses of both drugs and better adherence and fewer side effects."

What's needed, Gelenberg says, is balance.

"I talk about a balance of caution and the appropriate need to be aggressive in therapy," he says.

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The Example of Bipolar Disorder

Bipolar disorder is perhaps the best example of a mental illness in which different drugs may be effective. These patients cycle between deep depression and mania or euphoria.

"People with bipolar disorder need different things at different times," Murphy says. "At some point they might need an antidepressant, at others they may need additional help to maintain their sleep cycles. So I think polypharmacy today is more of a fluid and responsive regimen than it would have been in the past."

That's a far cry from simply piling one mental illness drug on top of another.

"Most psychiatrists in the bipolar world start with one medication, then see how you do, then add a second or a third drug as needed," Frye says. "Should we start treatment with two or three drugs? I think it is an important theoretical question. I generally start with one drug now for bipolar patients, but that may change. If a clinical trial shows that new, first-break bipolar patients do better beginning with two drugs rather than one, I would change my practice. For now, a doctor will start with a single medication and go from there."

Mental Illness: What Patients Should Know

Rule No. 1: Don't stop taking your medication. If your doctor has prescribed multiple mental illness drugs for you and you aren't sure why, ask. Suddenly stopping any of your medications could seriously affect your treatment.

"Do not stop your medicine," Furman warns. "But it is always reasonable to discuss with your mental health provider what you are on and reappraise what medications you should take. By no means should you stop any medicine without talking to your doctor. You may be on three or four medications for very good reasons."

Rule No. 2: Find a doctor qualified to treat mental illness that you can talk to. Then, talk.

"The patient needs to ask, 'Why are we adding this drug? Should we subtract another drug? Is this the best dose? Is this really needed?" Gelenberg advises.

"Accurate reporting of your symptoms really will allow your psychiatrist to tailor your medical regimens to your needs," Murphy says. "There is a burden on the consumer to be aware of things like sleep cycles, to notice when a couple of nights in a row go by when you didn't seem to need any sleep, and to take this kind of information to your doctor."

Sources: Mark A. Frye, MD, associate professor of psychiatry, David Geffen School of Medicine, UCLA; director, Bipolar Disorder Research Program, UCLA. Andrew C. Furman, MD, associate professor of psychiatry, Emory University; director of clinical services for psychiatry, Grady Memorial Hospital, Atlanta. Alan J. Gelenberg, MD, professor and head of psychiatry, University of Arizona; editor-in-chief, Journal of Clinical Psychiatry. Beth Murphy, MD, PhD, assistant director, clinical evaluation center, and co-investigator, psychopharmacology clinical research unit, McLean Hospital, Belmont, Mass.; clinical instructor of psychiatry, Harvard University. Gelenberg, A.J. Annals of Clinical Psychiatry, September-December 2003; vol 15: pp 203-216. Zarate, C.A. Jr., Bipolar Disorder, June 2003; vol 37: pp 12-17. Frye, M.A. Journal of Clinical Psychiatry, January 2000; vol 61: pp 9-15.

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Pauley's Book: Steroid Treatment, Antidepressants Unmasked Mood-Swing Illness

Treatment with steroids and antidepressants unmasked Jane Pauley's bipolar disorder, the TV news personality reveals in her new autobiography.

Drug treatments do not cause bipolar disorder, according to experts. But they can make the symptoms much worse. And this may be the first time people with the disorder find out they have the mental illness.

Fortunately, USA Today reports, Pauley says treatment with lithium keeps her symptoms under control. But in the spring of 2001, Pauley writes, she spent three weeks in a New York psychiatric hospital.

"I mourned 'Janie,' the person I had thought I was - the 'most normal girl on TV' - the girl who never was," Pauley writes in Skywriting: A Life Out of the Blue. An excerpt from the book, scheduled for release later this month, is available on the Barnes & Noble web site.

Bipolar disorder is a serious psychiatric disease, once known as manic-depressive disorder. It greatly increases a person's risk of suicide, says Charles Raison, MD, assistant professor of psychiatry and behavioral science at Atlanta's Emory University.

The illness may begin with either a depression or a manic episode. This may be followed years later by another episode, either of depression or of mania. Left untreated, the interval between these mood swings gets shorter and shorter. A particularly bad sign is called "rapid cycling," in which a person has four or more mood swings in a single year.

"These people become less responsive to treatment and more disabled in their lives," says Raison. "One month they are full of energy and making all kinds of unrealistic plans. The next month they can't get out of bed and all their plans are dashed. It is devastating to a person's life. It's more common in women, more common to see what we call 'bipolar II disorder,' characterized by depression and minor manias."

How can such a serious illness go undiagnosed? Raison says that many patients suffer "hypomania" during their manic swings. This may be experienced as irritability or as a euphoric, energetic "high."

A Case of Hives

Pauley writes that her bipolar diagnosis came a year after treatment for a bad case of hives. Doctors treated her with steroids, often used to relieve the painful swelling and itching of this allergic skin condition.

After her first steroid treatment, Pauley says she was "revved." But a second treatment left her depressed. Treatment with antidepressants threw her into a manic state. At age 50 -- a year after her first treatment for hives -- Pauley was diagnosed as having bipolar disorder.

"It is unusual to be diagnosed with bipolar disorder so late in life," Raison says. "Fifty is definitely old, but the average time from a first episode of bipolar disorder to a correct diagnosis averages eight to 10 years. So most people are not diagnosed, or are diagnosed with unipolar depression. This is more likely for women, who are more likely to have their first episode of bipolar disorder as depression."

And when bipolar disorder goes unrecognized, an experience like Pauley's is not uncommon.

"There is no doubt that steroids can make people manic," Raison says. "Sometimes they make people depressed, sometimes they make people irritable and wired, and sometimes they make them euphorically manic. ... It is not just steroids, but antidepressants, too. All of us in psychiatry have seen first-episode mania after putting a person on antidepressants. Most people with antidepressant-induced mania will go on to have the disease spontaneously generate itself in future mood swings. Whether it is just a canary in the coal mine signaling a person's vulnerability, or whether the drugs cause harm, is not known."

That's why it's important for doctors to find out whether a patient's depression is bipolar before putting them on antidepressants, says Dorothy K.Y. Sit, MD, assistant professor at the University of Pittsburgh's Western Psychiatric Institute and Women's Behavioral Health Care clinic.

"If we have a patient who has, in fact, an [unrecognized] underlying bipolar disorder, the patient is treated with a single agent antidepressant without properly addressing the bipolar component of the illness," Sit says. "It may help at first. But the risk is we can induce not just mania but mixed mania with symptoms of both mania and depression."

Multiple Treatments Available

Lithium -- to which Pauley is reported to be responding -- is the initial treatment for bipolar disorder. If patients can tolerate the drug, it can exert a powerful mood-stabilizing effect. It works for up to half of all patients with bipolar disorder, Sit says.

Some patients may get better results with valproate than with lithium.

Controlling manic episodes often requires another drug. For this, the seizure drug Depakote can be useful. Recently, doctors have begun to prescribe a class of drugs known as atypical antipsychotics: Zyprexa, Abilify, Risperidal, and Geodon.

"They started as anti-schizophrenia treatments but now appear to work very well for bipolar disorder," Raison says. "And they work very well for acute manias and for maintenance. They all have different side effect profiles. So there is a growing armamentarium of useful agents."

After getting psychiatric drugs, patients generally benefit from psychotherapy to help manage the illness and associated difficulties.

The important thing is for people with bipolar disorder to get diagnosed and treated. There's no cure for bipolar disorder, so patients must remain on treatment for the rest of their lives.

"The most important thing is finding a treatment that works, one you can tolerate, that you can commit to taking for an extended period," Raison says. "It is like diabetes. If you want to avoid these devastating episodes, you will be on these drugs for an indefinite period. It is a lifetime condition. And as a person gets older, there is a tendency to have more episodes, with more depressions and fewer manias. It is a bad deal. And there is growing social dysfunction. If left untreated, bipolar disorder causes alterations in the brain not conducive to optimal functioning in life. So it is important to find a drug that works and that one can stay on."

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Some antipsychotics, antidepressants and other prescription drugs can lead patients to pack on pounds

The pills millions of people take every day for diabetes, clinical depression, psychotic disorders, high blood pressure, and other illnesses are small, weigh almost nothing, and aren't packed with calories.

Stacked up against a super-sized restaurant meal, a bucket of butter-laced popcorn, or a jumbo cola, pills usually don't raise red flags when people worry about putting on pounds.

Although it may seem hard to swallow, certain prescription drugs can cause people to gain weight - sometimes a pound a week - they get little attention when experts search for causes of the national epidemic of obesity.

Both doctors and patients overlook the possibility that weight gain can originate in the medicine chest, as well as fast food restaurants and couch-potato lifestyles, according to Dr. Lawrence J. Cheskin. He directs the weight management center at Johns Hopkins University in Baltimore.

"While obesity is being more widely recognized, I'm not sure the same can be said for patients and physicians recognition of the possible contributing role of prescription medicines," he said in an interview.

Dr. Cheskin and his associates first warned about the problem in a medical report published in the 1990s. They realized that many patients seeking help for obesity at the center gained large amounts of weight after starting antipsychotics, antidepressants and other prescription drugs.

One 42-year-old woman, for instance, gained 42 pounds after taking lithium, a drug for mood swings. A 36-year-old supermarket worker gained 240 pounds while taking prednisone, a steroid drug.

"This is a really important subject," said Dr. Madelyn H. Fernstrom, director of the Weight Management Center at the University of Pittsburgh Medical Center.

Weight gain is among side effects listed in official information sheets for some of the most frequently prescribed drugs in the United States. They include drugs taken by tens of millions of people for diabetes, clinical depression, high blood pressure, gastric reflux and heartburn, and serious mental disorders like schizophrenia and bipolar disorder.

Among them are top-selling medications like the antidepressants Prozac (Fluoxetine), and Paxil (Paroxetine); heartburn drugs such as Nexium and Prevacid; Clozaril and Zypexa, used to treat serious mental disorders; diabetes drugs like Glucotrol, Diabeta, and Diabinese; and the high blood pressure drugs Minipress, Cardura, and Inderal. Some, like Inderal, are prescribed for several different health problems.

"Weight-gain drugs" is how Dr. George A. Bray, an obesity expert at Louisiana State University, described such medications.

Dr. Fernstrom emphasized that although many prescription drugs may list weight gain among the potential side effects, relatively few are known to cause large weight gains. "We have to be careful not to give the impression that all drugs cause weight gain," she said. "A few groups of medicines are associated with a lot of weight gain. Others really don't cause much."

Nobody knows exactly how many prescription drugs fall into those categories. Lists published in medical journals vary from one to another. One provided by Dr. George L. Blackburn, an obesity authority at Harvard University, includes more than 50 common drugs.

Internet drug discussion sites carry accounts from patients who say they got fat after starting anti-cholesterol and other drugs not thought to cause heavy weight gain.

Nonprescription may also cause weight gain. The antihistamine, diphenhydramine, for instance, is on Dr. Blackburn's list. It is an ingredient in dozens of popular cold and allergy remedies; sleep aids; and drugs to prevent motion sickness. An increasing number of prescription drugs, including some linked to weight gain, also become available for sale without a prescription.

In some cases, it takes years for weight-gain to emerge as a troublesome drug side effect.

When the Prozac--Paxil family of popular antidepressants hit the market, doctors thought the drugs caused weight loss. They were even prescribed for obese people trying to lose weight. Later, doctors realized that any weight loss is brief, with the drugs often causing long-term weight gain.

Weight gain is bad because it puts people at risk for a variety of health problems, including Type 2 diabetes and heart disease. Unexpected weight gain also ranks among the main reasons why patients stop taking some medicines, Dr. Fernstrom noted, including those urgently needed to treat health problems far more dangerous than extra pounds.

Studies show that weight-gain drugs can cause obesity in individual patients. However, researchers can't tell how much medicines contribute to the society-wide epidemic of overweight and obesity.

Dr. Bray has studied why obesity skyrocketed in the United States between 1970 and the 1990s. The number of obese people remained fairly steady - about 20 percent of men and 15 percent of women - until the mid-1970s. Then it took off on an upward spiral that by 2000 meant a 100 percent increase in obesity in men and a 50 percent rise in women.

Use of prescription drugs rose during that period and exploded in the 1990s. In 1993, the number of prescriptions written each year edged over the 2 billion mark for the first time. It reached 3 billion by 2001, and will top 4 billion by the end of 2004, according to the Association of Chain Drug Stores.

Almost every person in the United States now takes at least one prescription drug a year. Factor in people who take multiple drugs, and doctors write an average of 12 prescriptions annually for every person in the country.

"For some, weight gain drugs may play a role," Dr. Bray said. But he thinks that dietary changes probably had a bigger role in the obesity epidemic.

New ways of using drugs also are contributing to patients' weight gain.

Doctors have known for decades, for instance, that insulin makes some diabetes patients gain weight. About 1 million people with Type 1 diabetics take insulin injections, as do some of the 15 million with Type 2 diabetes.

Until the 1990s, patients almost always took just one insulin shot a day. Then, however, a landmark clinical trial showed that "intensive insulin therapy" -- multiple injections each day -- did a better job of controlling the disease's complications. Those include a high risk of heart attacks, vision loss, and other serious health problems.

Patients on intensive therapy, however, gain an average of 10.5 pounds more than those taking one insulin shot daily, according to a major 2001 study.

Consumers who would never suspect to look in the medicine chest for the cause of their weight gain have few sources of information.

Package inserts (which include the official description of a drug's side effects) usually give weight gain short shrift, including those for widely used weight-gain medicines like antidepressants.

About 19 million adults and 11 million children in the United States take drugs for clinical depression. Long-term use of certain antidepressants often causes weight gain.

Consider, however, the package insert for Paxil (Paroxetine), an antidepressant linked to some of the biggest weight gains. Weight gain gets 3 words, which appear in a listing of Paxil's (Paroxetine) adverse effects. "Frequent: Weight gain." There is no hint that about 1 in 4 patients add at least 7 percent to their body weight. That's about 9 pounds for a 130-pound person. Some report much larger gains in the double-digit range.

Package inserts for the four other top-selling antidepressants -- Zoloft, Prozac, Celexa, and Luvox -- use the same approach, without detailing the amounts that patients may gain.

Weight gain side effects get similar treatment at online consumer-health sites, including the National Institutes of Health's popular "MedlinePlus" web site (www.medlineplus.gov). It lists weight gain as a "frequent" side effect for such drugs without specifics.

Experts say that doctors and patients are aware of those side effects for certain drugs, especially those to treat serious psychiatric illnesses.

"Increased weight gain is a potential side effect of a number of different classes of medications," said Dr. Neal D. Ryan, a professor of psychiatry at the University of Pittsburgh Medical Center. "Because many patients and many physicians are careful about their weight, this side effect is probably less likely to be overlooked than others."

Dr. Fernstrom said there's major recognition for steroids like prednisone; older clinical depression drugs like Elavil and Tofranil; and a new family of antipsychotic drugs termed the SGAs. Less recognition exists for other drugs, including the new family of antidepressants that includes drugs like Paxil and Zoloft.

"There is a general recognition among physicians that certain medications can promote weight gain," she said. "But it is not often considered as a reason not to use a medication."

Nobody, however, knows exactly why certain medicines make people gain weight. Patients who gain weight on such drugs often say they feel hungrier, or develop intense cravings for sweets or high-carbohydrate foods.

Drugs for clinical depression and other mental conditions work by altering levels of brain chemicals, including ones that make people feel hungry and full. Even a slight shift in the balance could cause big weight gains. An extra candy bar and soda a day, or one extra ice cream snack, could easily make a patient gain one pound a week one study found.

Poor appetite and weight loss are symptoms of some diseases, and weight gain also may be a sign that the drug is working.

Weight gain and diabetes became such a serious problem in patients taking atypical antipsychotics (SGAs) that several medical organizations issued a joint report early in 2004. It identified drugs that cause weight gain and alternative medicines and detailed what doctors and patients can do to keep off the pounds.

SGAs are "second-generation antipsychotics," which became popular in the 1980s to treat serious mental conditions like schizophrenia, bipolar disorder or "manic depression," and psychotic depression.

About 3 million people in the United States have schizophrenia and 2 million have bipolar disorder. Psychotic depression, which involves hallucinations, affects about 2 million of the 18 million people with depression.

Use of the drugs, however, has expanded to include other disorders, including aggressive behavior, posttraumatic stress syndrome, and autism.

The American Diabetes Association, the American Psychiatric Association, the American Association of Clinical Endocrinologists, and the North American Association for the Study of Obesity convened an expert panel to study the side effects.

It concluded that some SGAs do cause rapid weight gain, with many patients putting on a pound a week - mostly fat -- after treatment starts. Weight gain may continue even after a year of treatment.

The panel also found a documented link between SGAs and the development of prediabetes (a condition that involves abnormally high levels of sugar in the blood), diabetes, and elevated levels of fats in the blood. Those are risk factors for heart attacks.

However, the panel also emphasized the benefits of antipsychotic drugs.

"These medications have helped millions of people manage their symptoms," the report said. "For people who respond well, antipsychotics can mean the difference between leading an engaged, fulfilling community life and being severely disabled."

The panel recommended that doctors check on each patient's body weight and risk for obesity, diabetes, and high blood fats before prescribing a SGA and during treatment. It noted that some SGAs have a lower risk of weight-related side effects, and gave doctors information they need to pick low-risk drugs for patients with weight problems.

The SGA panel could be a model for gathering and spreading reliable information about other weight-gain drugs, according to some experts.

"I think it would be a good idea to develop an expert panel to review weight gain from specific drugs," said Dr. Samuel Klein. He is an authority on obesity at Washington University in St. Louis who served on the SGA panel.

"Once such a panel reaches some conclusions, a decision could be made on whether the information is important enough to include in package inserts or patient information sheets."

Dr. Lawrence Blonde said studies should provide specific information on the whole topic of prescription medication and weight gain. An authority on diabetes at the Oschner Clinic Foundation in New Orleans, he also served on the SGA panel.

He cited a need for information on the drugs most likely to cause weight gain, the percentage of patients who gain weight, how much weight gain is likely to occur, and how long it will last.

"I think it would be useful to provide patients and caregivers with some additional information on potential weight gain from prescription drugs," he noted.

Some of the existing information is from clinical trials that may exaggerate the seriousness of drug-related weight gain, he pointed out. In those experiments, patients were told not to make any changes in diet or lifestyle while taking the medicine.

"It may well be that patients could have avoided or reduced the weight gain if they had implemented appropriate nutritional and physical activity lifestyle changes," he said.

There are hints that patients can lose the weight with changes in lifestyle, switching to alternative medicines that don't cause weight gain, or adding new medicines to control appetite.

A 2003 study at Dartmouth Medical School, for instance, focused on patients who gained an average of 65 pounds while taking SGAs. Lifestyle and medication changes enabled them to shed about two-thirds of the weight.

"Physicians and their patients need to choose drugs after assessing both the risks and the benefits that a particular medication might have for the condition. Depending on the clinical situation, the benefits of taking a medication may exceed the risks of weight gain.

"Before prescribing such a drug, the physician should discuss the potential risks of weight gain, and attempt to minimize it by recommending appropriate lifestyle changes," Dr. Blonde added.

"But it shouldn't be given in isolation. Patients should understand that the benefits of taking the medication may far exceed the risks of weight gain. For patients who already are overweight, there may be alternative medicines that do not seem to be associated with weight gain."

Dr. Fernstrom cautioned that patients who gain weight while taking a medication should not stop. Rather, she suggested that they talk with the doctor. Changes in lifestyle, rather than the drug, may be the real cause. In addition, there may be an alternative medicine not linked to weight gain.

Likewise, possible weight gain should not discourage patients from taking needed drugs.

"Raise the issue with your doctor," Dr. Fernstrom added. "Say that you are concerned about weight gain as a side effect and ask if there are other medications available. If the drug of choice is the only option, and you do notice weight gain, you can make some lifestyle changes."

That means steps like getting more exercise, reducing food intake, and drinking only non-calorie beverages. Even 30 minutes of walking can burn about 150 calories, she noted.

May 15, 2004 - Eating steamed potatoes could be more effective than anti-depressant drugs in treating winter depression, new research has found.

Winter depression, also known as Seasonal Affective Disorder (SAD) is believed to develop from a lack of bright light during the winter months.

Bright light changes the chemicals in the brain but how this occurs and its effects are still being studied.

Serotonin, dubbed the happy hormone, and other nutrients such as folate are generally deficient in people who suffer depression.

The Australian Centre of Neuropsycotherapy has found that steam cooked potatoes could provide greater use of serotonin for treating the disorder than taking anti-depressants.

Steam cooking potatoes resulted in the highest retention of amino acids compared to other cooking methods studied.

The centre found nutritional factors played a key role in the onset of depression, and eating more foods containing necessary vitamins could ease symptoms.

The centre's director Rod Markham said the best time to eat steamed potatoes was three hours after a protein dinner to make the best use of tryptophan which can boost serotonin levels.

"If people exercise, have enough bright light exposure during the day and have a good social network and nutrition intake, they could actually perhaps, if not totally, give up anti-depressants such as Prozac," he said.

A range of factors contribute to depression including child abuse and poverty.

"Factors contributing to different types of mental depression is irrational thinking, ... cold winters, possible child abuse, feelings of alienation from others, poverty, genetics, pregnancy, deficiencies in nutrients and the utilisation of these nutrients such as tryptophan and folate," Mr Markham said.

"Cognitive behaviour therapy is also very useful when combined with bright light or sunlight therapy, some exercise and nutrition."

Eating more complex carbohydrates like potatoes, broccoli, pasta and brown rice could boost serotonin activity in the brain.

Depressed people also often lack folic acid and should eat more asparagus, beetroot, avocado, cabbage, beans, lentils and oranges.

Magnesium, contained in spinach, chocolate, oysters and some nuts, could also ease symptoms of depression by acting as a muscle relaxant, the centre said.

Depression is currently the fifth leading cause of death and disability, according to World Health Organisation figures.

It is often genetic and affects about twice as many women as men.

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Teens who binge and purge less frequently than full-blown bulimics resemble bulimics in many ways, and should therefore be treated as if they had the condition, researchers argue in a new report.

The investigators compared the characteristics of teens with "partial-syndrome" bulimia nervosa, in which they exhibited the typical characteristics of bulimia-binge eating followed by a purge. Partial-syndrome progresses to bulimia when binging and purging occurs at least twice per week for 3 months.

The researchers found that teens with bulimia and partial-syndrome bulimia showed similar levels of self-esteem and depression (extensive information in the HealthyPlace Depression Community Center).

The findings suggest that doctors should treat partial-syndrome bulimia as seriously as they do full-blown bulimia, study author Dr. Daniel le Grange of the University of Chicago told Reuters Health.

"We shouldn't 'wait' for someone with a partial syndrome presentation to develop the full syndrome before we intervene," he said.

An estimated 1 to 5 percent of teen girls develop full-blown bulimia. The partial form of the condition is even more common, with recent research estimating that between 10 and 50 percent of teen girls and boys binge eat and purge on a frequent basis.

To investigate how partial bulimia differs from bulimia, le Grange and his colleagues surveyed a sample of 120 teens in an eating disorder program. All teens were diagnosed with anorexia, bulimia or partial-syndrome bulimia.

Reporting in the Archives of Pediatrics & Adolescent Medicine, the researchers found "more similarities than differences" between bulimics and partial-syndrome bulimics. In contrast, teens with either form of bulimia differed from those with anorexia on "almost every variable examined," the authors note.

For instance, compared with bulimic teens, those with anorexia nervosa tended to weigh less and be younger, and were more likely to come from intact families.

Partial-syndrome bulimics were asked how many times each week they binged--meaning, how many times they overate and felt as if they lost control over food.

Using established guidelines, interviewers estimated that partial bulimics binged less than once per week. However, teens themselves said they felt like they had binged around 5 times each week, even if they had only eaten a normal or small amount.

Although binging often goes hand-in-hand with purging, partial bulimics purged more than 4 times per week, which more closely matches their perception of how many times they had binged, rather than the actual number of episodes.

"It would appear that the size of the binge does not matter to the adolescent--it is the perception of being out of control and the concomitant distress that lead to purging," le Grange explained.

SOURCE: Archives of Pediatrics & Adolescent Medicine, May 2004

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A new study conducted at the University Hospital in Zurich, Switzerland has revealed that women with anorexia are more likely to have suicidal thoughts than those with bulimia or other disorders.

The researchers led by Gabriella Milos found that 84 percent of the women in the study had at least one other psychiatric disorder besides an eating disorder, including depression, drug or alcohol abuse or fearfulness or anxiety.

The two-year study included 288 patients diagnosed with some form of eating disorder. 26 percent of the women said that they had attempted suicide at least once in the past.

This rate is four times higher than in the general female population of Western states, the researchers said. Also, about 26 percent of the patients said they were having current thoughts about suicide.

Women in the study who reported suicidal thoughts tended to be much younger when their eating disorder appeared and were more fixated on their appearance and fearful of weight gain than those without suicidal thoughts.

"Anorexia nervosa patients' starvation is a form of chronic self-harming behavior and continuously maintaining underweight generates considerable distress," Milos said. (ANI)

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Presented at the American Psychiatric Association 2004 Annual Meeting

The appropriate administration of antidepressants in patients with bipolar disorder is a challenging clinical problem. Antidepressants can, even in the presence of the administration of an adequate dose of a mood stabilizer, induce mania and cycling. Since there are now several clinical alternatives to antidepressant use in patients with cycling mood, these questions are of great clinical relevance in this difficult-to-treat population. Three studies were presented at the American Psychiatric Association 2004 Annual Meeting that attempted to address these questions.

The current studies were part of a large STEP-BD (Systemic Treatment Enhancement Program for Bipolar Disorder) study being conducted at numerous study sites nationally.[1] In a study by Pardo and colleagues,[2] 33 patients who had responded to a mood stabilizer and adjunctive antidepressant were included. Subjects were openly randomized to either discontinue the antidepressant (short-term [ST] group) or continue on the medication (long-term [LT] group). Patients were rated using the Life Chart Methodology as well as the Clinical Monitoring Form, and they were followed for a period of 1 year. The antidepressants utilized included selective serotonin reuptake inhibitors (64%), bupropion (Wellbutrin XL) (21%), venlafaxine (Effexor) (7%), and methylphenidate (Ritalin) (7%). The mood stabilizers included lithium (Eskalith) (55%), divalproex (Depakote) (12%), lamotrigine (24%), and others (70%).

The findings were as follows:

1. Subjects were rated as euthymic 58.6% of the time, depressed 30.3% of the time, and manic 4.88% of the time.
2. The time in remission was similar in the ST group (74.2%) compared with the LT group (67.3%). Remission was defined as <!--= 2 DSM-IV mood criteria for 2 or more months.
3. The number of mood episodes was similar in the ST group (1.0 ± 1.6) compared with the LT group (1.1 ± 1.3).
4. A history of rapid cycling, substance abuse, and psychotic features were associated with poorer outcome.
5. Females remained well longer than males.

Although clinical courses vary widely in this disorder, many patients with bipolar disorder suffer more frequently from depression than from manic episodes. This was true in these studies; the patients were rated as being in a depressed mood 30.3% of the time and in a manic state only 4.88% of the time. Serious adverse events such as suicide are more common during depressive episodes. Therefore, rigorous treatment of depressive episodes is essential to optimally treat the patient with bipolar disorder. There have been numerous reports and studies concerning the risk of antidepressant use in bipolar disorder. In work by Altshuler and colleagues,^[3] it was estimated that 35% of patients with treatment-refractory bipolar disorder experienced a manic episode that was rated likely to be antidepressant-induced. Cycle acceleration was thought likely to be associated with antidepressants in 26% of the patients assessed. Forty-six percent of patients who demonstrated antidepressant mania had a prior history of this. This compared with a history of antidepressant mania in only 14% of patients who did not currently show antidepressant cycling.

In a study by Post and associates,^[4] 258 outpatients with bipolar disorder were followed prospectively and rated on the National Institute of Mental Health-Life Chart Method (NIMH-LCM) for a period of 1 year. In the second part of the study, 127 bipolar depressed patients were randomized to receive a 10-week trial of , bupropion, or venlafaxine as adjunctive treatment to mood stabilizers. Patients who did not respond to this regimen were rerandomized and responders were offered a year of continuation treatment.

The number of days spent depressed among the 258 outpatients was 3 times the rate of manic symptoms. These symptoms persisted even with intensive outpatient treatment provided in the study. During the 10-week antidepressant trial, 18.2% experienced switches into hypomania or mania or exacerbation of manic symptoms. In the 73 patients who were continued on the antidepressants, 35.6% experienced switches or exacerbation of hypomanic or manic symptoms.

Alternative options now available for the treatment of the depressed phase of bipolar disorder include lamotrigine, more aggressive treatment with mood stabilizers, and/or use of adjunctive treatment with atypical agents. The risks vs the benefits of sustained treatment with antidepressants must be weighed to make a rational decision as to continued use of these agents.^[5] Data from a study by Hsu and colleagues^[6] suggest that antidepressant continuation does not lead to increased time in remission in bipolar disorder, compared with antidepressant discontinuation.

Bipolar Disorder and Comorbid Conditions

The purpose of a study by Simon and colleagues^[7] was to determine to what extent comorbid conditions are linked to the adequate use of mood stabilizers and other pharmacologic interventions. The first 1000 patients enrolled into a large 20-site study on bipolar disorder (STEP-BD) were included in this study. The treatments were rated for adequacy based on predecided criteria for mood stabilizer use as well as treatment of associated specific disorders (eg, attention-deficit/hyperactivity disorder [ADHD], substance abuse, anxiety disorders).

The rates of comorbidity were as follows: current anxiety disorder in 32%; lifetime substance abuse disorder in 48%; current alcohol use in 8%; current ADHD in 6%; current eating disorder in 2%; and past eating disorder in 8%.

With regard to pharmacologic interventions:

1. A total of 7.5% of the sample were not treated with any psychotropic medications.
2. A total of 59% were not on adequate mood stabilizers. The extent of adequate mood stabilizer treatment was not related to comorbid diagnosis or bipolar I or II status.
3. Only 42% of individuals with a current anxiety diagnosis were receiving adequate treatment for this disorder.
4. The presence of comorbid conditions was only minimally associated with the appropriateness or extent of psychopharmacologic intervention.

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This as well as other studies have noted a high rate of comorbidity among patients with bipolar disorder.^[8] Patients with manic depression and comorbid conditions have been found to have higher levels of ongoing subsyndromal symptoms.^[9] The findings from this study indicate that these associated symptoms and syndromes are not being addressed adequately by the clinician, and they may not be detecting them at all. Alternatively, the clinician may have concerns about adding medications such as stimulants, benzodiazepines, or antidepressants in someone with bipolar disorder.

Lack of treatment of these associated conditions may lead to significantly poorer outcome. Panic and anxiety, for example, have been associated with increased risk of suicide and violence.^[10] Substance abuse has consistently been associated with more difficult course of treatment and worse outcomes.^[11] Thus, "treatment resistance" in some patients may not be due to the difficulties inherent in treating the bipolar syndrome but rather to the lack of comprehensive and aggressive treatment of the associated comorbid conditions. Furthermore, a very large proportion of patients (59%) were not receiving adequate mood stabilization and 7.5% were on no psychotropic agents. The lack of adequate treatment of both the mood instability as well as the lack of attention to other associated conditions indicates that a large majority of patients were being treated suboptimally.

Using Ziprasidone as Adjunctive Treatment in Bipolar Disorder

Atypical neuroleptics are increasingly being utilized in the treatment of bipolar disorder as both stand-alone agents as well as adjunctively. Weisler and colleagues^[12] reported on the long- and short-term effectiveness of ziprasidone as an add-on agent. A total of 205 adult inpatients with bipolar I disorder, most recent episode manic or mixed, who were being treated with lithium were randomized to receive ziprasidone or placebo. Subjects were given 80 mg on day 1 and 160 mg on day 2. Doses were then adjusted to between 80 and 160 mg as tolerated by the patient. Significant improvement was noted as early as day 4 compared with placebo, and the improvement continued throughout the 21-day period of the acute study. A total of 82 subjects continued in a 52-week open-label extension study, and continued improvement occurred on several measures through the extension period. There were no increases noted in weight or cholesterol, while mean triglyceride levels dropped significantly. Thus, employing this atypical agent early in treatment is helpful in accelerating the response time.

Body Weight and the Impact of Mood Stabilizers

A study to evaluate weight changes and their negative effects on patient compliance and the effective treatment of bipolar disorder was presented by Sachs and colleagues.^[13] Weight gain is a specific area of concern for both clinicians and patients. Previous studies have shown that weight gain is associated with lithium, valproate, carbamazepine, gabapentin, and olanzapine. This study focused on the use of lamotrigine and its effects on maintenance treatment of bipolar I disorder utilizing data from 2 studies of bipolar disorder I patients who recently experienced a depressive or manic episode. Patients were enrolled into 1 of 2 different protocols. Each protocol consisted of an 8- to 16-week, open-label study where lamotrigine was added to the "existing psychotropic regimen prior to gradual transition to lamotrigine monotherapy."

A total of 583 patients were randomized to up to 18 months of double-blind lamotrigine treatment (n = 227; 100-400 mg/day fixed and flexible dosing), lithium (n = 166; 0.8-1.1 mEq/L), or placebo (n = 190). Mean age was 43 years, and 55% of participants were female. Mean weight at randomization was similar among treatment groups: lamotrigine = 79.8 kg; lithium = 80.4 kg; and placebo = 80.9 kg. One third had previously attempted suicide, while the other two thirds had been hospitalized for psychiatric reasons.

This study showed that lamotrigine patients lost an average of 2.6 kg over the 18 months of treatment while patients treated with placebo and lithium gained 1.2 kg and 4.2 kg, respectively. Other results showed no statistically significant differences between lamotrigine and placebo in the number of patients experiencing >/= 7% weight change, >/= 7% weight gain, or >/= 7% weight loss. Patients taking lamotrigine experienced a > 7% weight loss (12.1%) compared with patients taking lithium (5.1%; 95% confidence interval [-13.68, -0.17]). Patients taking lamotrigine stayed in the trial for longer periods of time, increasing the chance of observing differences in weight in the lamotrigine group (lamotrigine, lithium, and placebo treatment groups: 101, 70, and 57 patient years, respectively). Lithium patients experienced statistically significant weight changes from randomization at week 28 compared with the placebo group (lithium: +0.8 kg ; lithium placebo: -0.6 kg). Statistically significant differences between lithium and lamotrigine were seen at week 28 through week 52 (lamotrigine: up to -1.2 kg; lithium: up to +2.2kg). This study concluded that patients with bipolar I disorder taking lamotrigine did not experience relevant changes in weight.

Bipolar Disorder and the Burden of Depression

A study by Fu and colleagues^[14] was conducted to examine the frequency and economic burden to a managed care payer of depressive and main episodes in a bipolar population. Utilizing claims data between 1998 and 2002 for bipolar patients (ICD-9:296.4-296.8), episodes of care of depression and mania were characterized based on ICD-9 codes. Using t-tests and multivariate linear regression, these were compared with outpatient, pharmacy, and inpatient costs. Data were taken from a large US managed care database with medical and pharmacy administrative claims data from more than 30 health plans. Samples were gathered of 1 or more claims for bipolar disorder for patients aged 18-60 years with no comorbid diagnosis of epilepsy (ICD-9: 345.xx) with a continuous enrollment of at least 6 months prior to first episode and 1 year after the start of episode. Episodes were defined as started by the first claim for bipolar disorder preceded by a 2-month period without any bipolar-related healthcare claims and ended when there was a gap of greater than 60 days between prescription refills of bipolar medication. Episodes were classified as depressive or manic if more than 70% of the medical claims were related to depression or mania.

A total of 38,280 subjects were included with a mean age of 39 years; 62% of subjects were female. More than 70% of resource utilization was accounted for by hospitalizations and outpatient visits. The length of stay for mania (10.6 days) was higher (P < .001) than for depression (7 days). A total of 14,069 episodes were defined for 13,119 patients by applying continuous inclusion criteria and an episode definition algorithm. Episodes of depression occurred 3 times more frequently than manic episodes (n = 1236). Average outpatient ($1426), pharmacy ($1721), and inpatient ($1646) costs of a depressive episode were compared with outpatient ($863 [P < .0001]), pharmacy ($1248 [P < .0001]), and inpatient ($1736 [P = 0.54]) costs for a manic episode. It was shown that the cost of a depressive episode ($5503) was approximately double the cost of a manic episode ($2842) after controlling for age, gender, site of visit, and healthcare costs prior to the start of the episode. Bipolar depression appears to be a greater burden than mania. The prevention or delay of bipolar depression could result in cost savings to managed care providers.

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Predicting Relapse in Bipolar Disorder

Because bipolar disorder is a recurrent and cyclic disease, early prediction of subsequent episodes is essential for optimal treatment. In a study by Tohen and associates,^[15] a post-hoc analysis was conducted based on the pooled data from 2 bipolar maintenance studies. A total of 779 patients who were in a state of remission from manic or mixed episodes were followed for up to 48 weeks. Patients were treated with olanzapine (n = 434), lithium (n = 213), or placebo (n = 132) after completion of an acute open-label treatment study comparing lithium monotherapy with olanzapine-lithium combination therapy. There were several predictors of early relapse, including a history of rapid cycling, a mixed-index episode, frequency of episodes in the previous year, age of onset younger than 20 years, family history of bipolar disorder, female gender, and the lack of a hospitalization in the past year. The strongest predictors were a history of rapid cycling and a mixed-index episode. The identification of risk factors might help the clinician to identify those individuals most at risk for relapse and aid in the development of early intervention strategies.

A Decade of Pharmacologic Trends in Bipolar Disorder

There have been many new treatments for bipolar disorder introduced in the past decade. The most important development has been the introduction of numerous atypical agents and the numerous studies documenting their effectiveness. A study by Cooper and colleagues^[16] looked at the trends in medication use between 1992 and 2002. Data were derived from a pharmacy prescription database of 11,813 patients. The findings were as follows:

• The percentage of patients treated with a mood stabilizer has remained stable through the 10-year period at approximately 75%. The percentage of patients on lithium has decreased steadily, a trend paralleled by the increase in valproate (Depakene). In 1999, valproate became the most widely prescribed mood stabilizer. Lamotrigine (Lamictal) and topiramate (Topamax) have been increasing steadily since 1997 to 1998, while the use of carbamazepine (Tegretol) has been decreasing steadily.
• Antidepressant use has been relatively stable, varying between 56.9% and 64.3%.
• Atypical neuroleptics were utilized in 47.8% of patients in 2002. Olanzapine was the most prescribed atypical medication in 2002, followed by risperidone, quetiapine, and ziprasidone. Clozaril use has decreased dramatically.

The overall trend indicates that mood stabilizing is still the mainstay of treatment; the atypical agents are becoming much more accepted as integral to the treatment of the bipolar patient.

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References

1. Perlis RH, Miyahara S, Marangell LB, et al. Long-term implications of early onset in bipolar disorder: data from the first 1000 participants in the systematic treatment enhancement program for bipolar disorder (STEP-BD). Biol Psychiatry. 2004;55:875-881. Abstract
2. Pardo TB, Ghaemi SN, El-Mallak RS, et al. Do antidepressants improve remission in patients with bipolar disorder? Program and abstracts of the American Psychiatric Association 2004 Annual Meeting; May 1-6, 2004; New York, NY. Abstract NR25.
3. Altshuler LL, Post RM, Leverich GS, Mikalauskas K, Rosoff A, Ackerman L. Antidepressant-induced mania and cycle acceleration: a controversy revisited. Am J Psychiatry. 1995;152:1130-1138. Abstract
4. Post RM, Leverich GS, Nolen WA, et al. A re-evaluation of the role of antidepressants in the treatment of bipolar depression: data from the Stanley Foundation Bipolar Network. Bipolar Disord. 2003;5:396-406. Abstract
5. Ghaemi SN, El-Mallakh RS, Baldassano CF, et al. Effect of antidepressants on long-term mood morbidity in bipolar disorder. Program and abstracts of the American Psychiatric Association 2004 Annual Meeting; May 1-6, 2004; New York, NY. Abstract NR771.
6. Hsu DJ, Ghaemi SN, El-Mallakh RS, et al. Antidepressant discontinuation and mood episode relapse in bipolar disorder. Program and abstracts of the American Psychiatric Association 2004 Annual Meeting; May 1-6, 2004; New York, NY. Abstract NR26.
7. Simon NS, Otto MW, Weiss RD, et al. Pharmacotherapy for bipolar disorder and comorbid conditions: baseline data from STEP-BD. Program and abstracts of the American Psychiatric Association 2004 Annual Meeting; May 1-6, 2004; New York, NY. Abstract NR394
8. Sasson Y, Chopra M, Harrari E, Amitai K, Zohar J. Bipolar comorbidity: from diagnostic dilemmas to therapeutic challenge. Int J Neuropsychopharmacol. 2003;6:139-144. Abstract
9. MacQueen GM, Marriott M, Begin H, Robb J, Joffe RT, Young LT. Subsyndromal symptoms assessed in longitudinal, prospective follow-up of a cohort of patients with bipolar disorder. Bipolar Disord. 2003;5:349-355. Abstract
10. Korn ML, Plutchik R, Van Praag HM. Panic-associated suicidal and aggressive ideation and behavior. J Psychiatr Res. 1997;31:481-487. Abstract
11. Salloum IM, Thase ME. Impact of substance abuse on the course and treatment of bipolar disorder. Bipolar Disord. 2000;2(3 Pt 2):269-280.
12. Weisler R, Warrington L, Dunn J, Giller EL, Mandel FS. Adjunctive ziprasidone in bipolar mania: short and long-term data. Program and abstracts of the American Psychiatric Association 2004 Annual Meeting; May 1-6, 2004; New York, NY. Abstract NR358.
13. Sachs G, Merideth C, Ginsburg L, et al. The long-term impact of mood stabilizers on body weight. Program and abstracts of the American Psychiatric Association 2004 Annual Meeting; May 1-6, 2004; New York, NY. Abstract NR74.
14. Fu AZ, Krishnan AA, Harris SD. The burden of depression patients with bipolar disorder. Program and abstracts of the American Psychiatric Association 2004 Annual Meeting; May 1-6, 2004; New York, NY. Abstract NR556.
15. Tohen M, Bowden CL, Calabrese JR, et al. Predictors of time to relapse in bipolar I disorder. Program and abstracts of the American Psychiatric Association 2004 Annual Meeting; May 1-6, 2004; New York, NY. Abstract NR800
16. Cooper LM, Zhao Z, Zhu B. Trends in pharmacologic treatment of patients with bipolar: 1992-2002. Program and abstracts of the American Psychiatric Association 2004 Annual Meeting; May 1-6, 2004; New York, NY. Abstract NR749.

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Once associated mainly with hyper kids, attention deficit disorder is now widely diagnosed in adults. But drugs aren't the only answer.

A teacher for more than three decades, Terri Mangravite, 56, has seen her share of attention deficit/hyperactivity disorder (ADHD) in students. She has also seen it at home. Her husband and two adopted children were diagnosed with it. So when her primary-care physician told her she had it as well, she could hardly believe it. "I laughed when he told me," she remembers.

On reflection, she says the diagnosis makes sense. Growing up, she was constantly distracted, and as an adult, she continued to find it hard to focus, she admits. Mangravite may not be unusual say experts, who estimate that some 8 million to 9 million adults have ADHD. These people either weren't diagnosed as children or had been treated but didn't outgrow the condition.

Now, as awareness among both the general public and the medical community has risen, more adults are being diagnosed with ADHD. Also known as adult ADD, ADHD includes inattention, hyperactivity, and impulsivity among its primary symptoms. While about 30% of children diagnosed with ADHD are treated, a mere 5% of adults with the condition are, says Ginger Johnson, senior consultant at Defined Health, a pharmaceutical strategy consulting firm. All this adds up to a potentially huge market for pharmaceutical companies making ADHD medications.

HUGE MARKET. It's tricky to know whether the drug industry's aggressive marketing campaign is a catalyst or a response to a rapidly growing market. Even if a significant portion of those with the disease remain undiagnosed and/or treated, the total market for ADHD drugs -- now about $2 billion annually and consisting mainly of children -- ultimately could be closer to $10 billion, says Johnson. Many experts say more research is needed to educate doctors about diagnosing and prescribing drugs for adult ADHD.

Depression was one of the top 10 leading diagnoses by doctors in the U.S. in 2003, according to market researcher IMS Health. Antidepressants -- such as Eli Lilly's Prozac (Fluoxetine), Pfizer's , and Wyeth's Effexor (Venlafaxine) -- racked up $13.5 billion in revenues in 2003. As use increases among children, teens, and even pets, these drugs should continue to be among the industry's fastest and most reliable growers.

"LITTLE BIT MESSY." For ADHD, Lilly has been heavily promoting Strattera, which was approved for use in adults and children in late 2002. Lilly has told investors that the "adult market is important to future growth" for the drug. Shire Pharmaceuticals, maker of stimulant Adderall XR, which is used with children, expects approval this summer from the Food & Drug Administration for adult use of the drug.

Some companies are taking a more cautious approach and sticking to treating ADHD only in children, at least for now. Johnson & Johnson recently canceled its Phase III trials of Concerta in adults, deciding to focus its research on children and adolescents, for whom the drug is already approved.

Strattera, Adderall, and Concerta could potentially be as widely used as some big-selling antidepressants. But such spectacular growth won't be unfettered -- or without controversy. Even though a battery of drugs can interact with brain chemistry and create a desirable effect, an understanding of the basic science of ADHD is still sketchy at best. The mechanisms of mental-health disorders in general "are a little bit messy," says consultant Johnson.

RELATED CONDITIONS. In the case of depression, the availability of treatment increased public awareness, which in turn generated a profound demand and ongoing debate about whether drugs are being used too often for mild cases of the disease. The same could happen with adult ADHD, which makes some people uneasy.

"I wonder whether we're dealing with a social fashion, as opposed to a disease condition," says Daniel Hoffman, an analyst at Pharmaceutical Business Research Associates. He notes that the impact of long-term treatments for ADHD hasn't been well studied. "It's incumbent upon companies to do the long-term outcome studies," Hoffman says, especially if ADHD is indeed a life-long struggle for so many.

OTHER APPROACHES. Surman is encouraged that research in the field is active and diverse because that should lead to better understanding of the disorder. Some researchers are looking for common genes in ADHD sufferers. Neuroimaging with functional MRI scans aim to clarify how normal and ADHD brains work differently. Others are researching the high rate of other mental illnesses that come alongside the disorder.

And it turns out that medication isn't the answer for everyone. It wasn't for Terri Mangravite. Her doctor believed that she had developed effective ways to compensate for the condition. Mangravite says she's comforted that drug therapy is available, but she has instead focused on changing her behavior. For example, she forces herself to complete challenging projects instead of abandoning them midway through, as she used to.

Still, as ADHD's profile increases, so will the questions about it. Millions of ADHD adults and children are benefiting from medication for the disease. And more awareness will almost certainly mean more prescriptions, but research and healthy public debate over this issue are also needed.

Source: Business Week magazine

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Women with eating disorders who have attempted suicide may have had a depressive disorder long before their problems with food began, the results of a small study suggest.

Researchers found that among 27 eating-disorder patients with a history of suicide attempts, two thirds had major depression before the onset of the eating disorder. That compares with just one of 27 patients who had never attempted suicide.

Women in the suicidal group also developed depression and anxiety disorders at a younger age than the other women did.

A substantial number of people with eating disorders purposely injure themselves or attempt to take their lives, according to the study authors, led by Dr. Lisa R. R. Lilenfeld of Georgia State University in Atlanta.

The new findings show that for these women, "the eating disorder may be secondary to a mood disturbance," the researchers report in the International Journal of Eating Disorders.

That stands in contrast to some past research suggesting that depression typically arises after a woman develops an eating disorder like anorexia or bulimia. According to Lilenfeld and her colleagues, depression may often be a consequence of the eating disorder, but this may not be true of suicidal patients.

They say that understanding such differences between eating-disorder patients who do or do not attempt suicide should aid in treatment.

For the study, the researchers interviewed 54 women with anorexia, bulimia, or other eating disorder, half of whom had a history of suicide attempts and self-inflicted injuries such as cuts and burns.

The authors found that while suicidal and non-suicidal women did not differ much in their rates of depression--most women in both groups had a history of major depression--those with a history of attempted suicide developed depression at a younger age.

Excluding the subjects who developed an eating disorder and major depression in the same year, more suicidal women developed major depression before they developed the eating disorder.

In addition, women in the suicidal group had a higher rate of anxiety disorders--93 percent versus 56 percent--and, on average, developed anxiety at a younger age.

According to the researchers, the findings suggest that for most women with eating disorders and no history of suicidal behavior, depression may be a consequence of the eating disorder. But for those who are suicidal, the first and perhaps most "central" psychological problem may often be major depression.

Therefore, the authors write, women with eating disorders and a history of depression may be at increased risk for suicide. This, they note, suggests the need to put more emphasis on regulating emotion and mood in treating these patients.

SOURCE: International Journal of Eating Disorders, March 2004.

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