New Treatments to Fight Depression
by Christina Frank
For Diane Benson Harrington, being depressed feels like being trapped at the bottom of a deep, dark hole. “It makes me feel heavy, weighed down by dirt and blackness,” says Harrington, 42, of Madison, WI. “I have trouble getting through the day; brushing my teeth is too much of a chore. I forget basic things, like what you do when the traffic light turns yellow--and I constantly think of ways to kill myself.”
The kind of profound despair Harrington describes may sound melodramatic, but for millions of people it is all too real. Approximately 18.8 million Americans over age 18 experience a depressive disorder each year, according to the National Institutes of Mental Health (NIMH). Depression is the leading medical cause of disability in the United States, resulting in workplace costs of over $34 billion per year in sick days, absenteeism and decreased productivity.
Still, odd as it sounds, it’s not such a bad time to be depressed. The “second generation” antidepressants, including Selective Serotonin Reuptake Inhibitors (SSRIs) like Prozac, Lexapro, and Zoloft, along with drugs like Wellbutrin and Effexor, have made radical inroads in the treatment of depression since they were introduced in the late 1980s, proving safer and more easily tolerated than their predecessors (known as tricyclics and MAOI inhibitors). And new, fine-tuned versions of these drugs are being created all the time. According to PhRMA, the trade association for U.S. pharmaceutical companies, there are currently 30 antidepressants on the market and 23 more in development. Even the 20 percent of patients with so-called “treatment-resistant” depression, which stubbornly resists medications and psychotherapy, have some promising new treatments to contemplate. One, a surgical-implant procedure known as Vagus Nerve Stimulation (VNS), was approved for clinical use by the FDA in July, with encouraging results so far. More focused, less intense versions of electro-convulsive therapy (ECT), known as Transcranial Magnetic Stimulation (TMS) and Magnetic Seizure Therapy (MST), are also being investigated.
But perhaps the most heartening breakthrough is the slow but steady peeling away of the stigma surrounding depression, which is now firmly recognized as a true biochemical illness and not a sign of weak character or laziness. A recent survey by the American Psychiatric Association (APA) showed that 90 percent of respondents believe that people with mental illness can lead healthy lives, 80 percent think that mental-health treatments work and 70 percent view seeking psychiatric help as a sign of strength. Younger adults are significantly more positive than those over age 65 about mental illness issues. Helping to further demystify depression are the many celebrities--including Brooke Shields, Lorraine Bracco, Dick Cavett and Alex Rodriguez -- who have gone public about their own battles with the disease.
WHO GETS DEPRESSION AND WHY
Depression is actually a term covering several specific disorders, all of which differ from run-of-the-mill sadness. “It’s a human response to feel down or blue at times,” explains Marcia Goin, MD, PhD, a psychiatrist at the University of Southern California Keck School of Medicine. “But that’s different from a true depressive illness, which is persistent and can include symptoms like lack of pleasure in anything, excessive or reduced sleeping, physical ailments like stomach aches, headaches and loss of appetite or suicidal thoughts.
The most severe form of depression, called unipolar or major depression, is characterized by a significant change in mood and behavior that lasts for at least two weeks and interferes with normal functioning. Another type, dysthymia, manifests itself as a chronic, low-grade melancholy, often lasting for years, and frequently unrecognized by sufferers or doctors. Then there are “situational” depressions, induced by a specific event, such as a life crisis or post-holiday letdown. Seasonal affective disorder (SAD) and Post-partum depression (PPD) also fall into this category; the situations cause biochemical changes in the brain, resulting in depression. Often, when the situation improves, the depression lifts—but not always. People with bipolar disorder, also called manic depression, experience depressive episodes that alternate with periods of mania.
About three-fourths of those who experience depression will have at least one other episode in their lives. Untreated, episodes commonly last anywhere from six months to a year, bringing with them a high risk of suicide in severe cases; up to 15 percent of people with major depression end up committing suicide, according to The National Alliance for the Mentally Ill (NAMI).
While depression has no single cause, certain factors put people at higher risk of developing it. Women are more than twice as likely as men to experience depression. Children of depressed parents are three times more likely to become depressed than children of non-depressed parents. And certain life events, such as the death of a loved one, a major loss or change, or chronic stress, can also trigger a depressive episode. New research is looking at whether a certain genetic variation predisposes some people to depression.
In the brain, depression manifests itself as an imbalance in three neurotransmitters—serotonin, norepinephrine and dopamine; these chemicals transmit electrical signals between brain cells and help regulate emotions, mood, reactions to stress, appetite, sleep and sexuality.
THE PILL / THERAPY DEBATE
Before the SSRIs came on the scene, talk therapy was the first-line treatment for depression. Tricyclic antidepressants and MAOI inhibitors were often effective, but they had unpleasant, sometimes dangerous, side effects, and it was all too easy to fatally overdose on them. Today’s antidepressants are safer because the risk of overdosing on them is very low, and, while they do have side effects (a notorious one being sexual difficulties), most tend to be mild and diminish over time. The new medications work by increasing the availability of neurotransmitters or by changing the sensitivity of the receptors for these chemical messengers in the brain. Because of their safety and efficacy, along with decreasing stigma surrounding depression, they are now considered a first-line treatment. But there is ongoing controversy about the ease with which doctors prescribe these medications, and who is prescribing them. (NUMBER OF ANTIDEPRESSANT PRESCRIPTIONS DISPENSED ANNUALLY TK) Up to 80 percent of these are written by primary-care doctors, who don’t necessarily have an extensive background in mental illness.
Then there is the question of whether psychotherapy has taken a back seat to medications because the “quick fix” of a pill is more appealing to most people than months of self-examination. Another issue is how much of an influence managed-care companies have over this shift, considering that they tend to provide better coverage for prescription medications than for psychotherapy.
In fact, the latest research shows that the most effective way to treat major depression is with a combination of drugs and psychotherapy. “Therapy really helps people and deserves a place alongside medications,” says Erik Nelson, MD, director of the Mood Disorders Research Program at The University of Cincinnati College of Medicine. “Talk therapies have been shown to provoke neurological and biological changes in the brain, much as antidepressants do. Both treatments cause rebalancing in the brain, but from different angles.” What a good therapist does that a medication can’t is to help a patient deal with specific life stressors, to organize their lives, develop coping techniques—and, perhaps most important—help them use their medications properly. Nonadherence is a big problem among patients will mental illnesses; most antidepressants take up to 6 weeks to work optimally and people are frequently discouraged by temporary side effects or perceived ineffectiveness, and stop taking them or take them incorrectly. A recent study by NAMI showed that 91 percent of people surveyed said it was very important to take their medication exactly as prescribed—yet 40 percent stopped taking their medication without the advice of a healthcare professional.
“This is why it is important for patients to meet regularly with a psychiatrist, so that if they are on medication they will have a chance to discuss their reactions before abruptly stopping,” says Nelson.
Realizing the talk-therapy component of the equation, however, is becoming increasingly challenging. Managed-care companies often balk at covering psychotherapy, or have stringent limitations on who can be seen and how often.
“Trying to get help for depression is enough to make you depressed in and of itself, says Tracy Needham, 35, of Arlington, VA. “When I called my managed-care company to get information about providers, they couldn’t tell me a darn thing about the providers, what they specialized in, or even what type of therapy they did. So I called a laundry list of numbers they gave me and found that the providers' phone numbers had changed, or they no longer took insurance, or weren't taking new patients, or just never bothered to return the calls.”
Insurance companies commonly create lists of providers who don’t actually participate in the plan, says Deborah Serani, Psy. D., a psychologist in New York who specializes in depressive disorders. She says she’s listed with one managed care company for whom she does not work, and has had no luck when she’s tried to be removed from their list. “It’s called a ghost or phantom network,” she explains. “It helps insurance companies sell themselves to employers. A lot of psychologists have stopped participating in managed care because of the way they control things.” (Needham eventually went with a psychiatrist who doesn’t take insurance.)
In comparison, filling a prescription can seem far less daunting. Since it’s more cost-efficient for insurance companies to cover medications than for psychotherapy, psychiatrists themselves benefit from going the pill route. One 2003 APA study found that psychiatrists could earn around $263 per hour by doing 3 “medication management” sessions per hour versus $156 for a single 45-50 minutes session of therapy. This may also also account for the recent rise in “psychopharmacologists,” doctors who focus exclusively on medications for treating mental illnesses. According to the APA, the percentage of patients who see psychiatrists just for medication rose from 20 percent to 30 percent between 1988-2002.
“Talk therapies have been essentially denigrated with these concurrent forces of pharmaceutical marketing, insurance companies having no mental health benefits, or coverage being rationed out a few sessions at a time,” says David Byrom, Ph.D, president of the National Coalition of Mental Health Professionals and Consumers.
Byrom says this phenomenon has spread to hospitals as well, resulting in a quick and often questionable rush to treat people with medications. “Commonly, when someone is admitted to a hospital due to mental illness, they are likely to be handed a prescription and discharged, rather than given a full psychiatric evaluation, due to limited coverage of hospital stays,” he says. “Say an adolescent is hospitalized for a suicide attempt. Ideally, the kid would stay in the hospital for about two weeks. He would be thoroughly evaluated, family members would be interviewed, and a treatment plan would be made after a full assessment. These days, most hospitals would have to fight on a daily basis and have some very effective staff on hand to argue with insurance company reps to make this happen. Instead, a stay of 3-4 days is usual, and instead of an adequate assessment and treatment plan, the kid is given a prescription and sent out the door.”
PROBLEMS WITH TREATMENT
Sadly, many people who are suffering from depression don’t know it, and even doctors can fail to recognize it in patients; up to 60 percent of depression goes unrecognized, according to the APA.
Goin blames this on several factors. “Vague symptoms like ‘feeling down’ or having trouble concentrating are feelings that the person doesn’t realize represent a real illness,” she says. “And of course, there’s the stigma, so people feel like they’re just being weak and should pull themselves up by their bootstraps.”
Studies also show that up to 50 percent of people don’t display depression in emotional terms, but instead report somatic symptoms, like headaches or stomach problems or fatigue. “Unfortunately, many medical schools do not spend a great deal of time educating their students about psychiatric illness,” says Goin. “So, the internist or primary care physician doesn't have it front and center in their minds when someone comes in complaining of physical symptoms.” Consequently, educating primary-care physicians and pediatricians about all aspects of depression has become a major goal of the APA.
Among minority groups, unrecognized depression looms especially large. For people who often feel stigmatized already, getting a diagnosis of mental illness feels like one more label, explains Annelle B. Primm, MD, MPH, Director of Minority and National Affairs for the American Psychiatric Association.
Or, they describe their feelings in physical terms, which can confuse doctors. Among Arabs and Native Americans, it is not uncommon to complain of ‘heart problems,” says Primm. “This might get someone sent to a cardiologist.” African- Americans tend to convey symptoms like fatigue, headaches or changes in appetite. “It’s so important for clinicians to understand some of these cultural differences,” says Primm. “The standard criteria for major depression is a list of 9 symptoms, but that doesn’t mean that every single patient has them. We need to get into the mindset of being able to see beyond the DSM-IV diagnostic criteria.”
Non-white groups also tend to be more skeptical of medication, preferring counseling or religious guidance instead. When they do take antidepressants, they sometimes respond differently than Caucasians. A growing area of study called ethnopsychopharmacology looks at how people of different racial and ethnic groups metabolize and respond to psychotropic medications. Genetic differences can affect how quickly or slowly medications are metabolized, although not every person of a certain racial group metabolizes at the same rate—but the risk is greater. “This is important for clinicians to be aware of because if you give someone a medication and they have side effects, you risk the person not coming back,” says Primm. “In the absence of being able to measure metabolism, a safer approach is to start low and go slow and to inform the patient what you’re doing and why.”
WHEN STANDARD TREATMENTS FAIL
Then there are those on whom medications and therapy have no effect at all—like Karmen McGuffee. McGuffee had tried just about everything to relieve her depression since being diagnosed at age 19. “I had been hospitalized 5 times and had tried about 15 different medications,” says McGuffee, now 36. “I’d been in individual psychotherapy, group therapy, you name it—but nothing ever helped.”
McGuffee is among the 20 percent of people with depression who fail to respond to standard treatments; recent research suggests that people with treatment-resistant depression (TRD) may have a genetic variation that causes them to be less responsive to SSRIs.
It was during a group therapy meeting in 1999 that McGuffee learned about a study being conducted at a nearby hospital for a new surgical treatment for people like her. “At that point, I felt I had nothing to lose,” recalls McGuffee. “I weighed about 400 pounds and if I had died on the operating table, I wouldn’t have cared.”
During the outpatient procedure, a battery-operated device—called a Vagus Nerve Stimulator (VNS)--was surgically implanted into McGuffee’s (chest wall). Thin, flexible wires are tunneled through the neck and send intermittent pulses to the left vague nerve, which in turn delivers a pulse about every five minutes to the areas of the brain involved in the regulation of mood, motivation, sleep, appetite and other areas related to depression. Originally used to treat epilepsy, VNS Therapy has been approved for TRD in parts of Europe and Canada since 2001; this past July, the FDA approved it for such use in people with depression who failed to respond to at least four other therapies. (Currently, VNS Therapy is intended to be used in conjunction with medication.) The device and surgery cost approximately $20,000- $25,000, according to Cyberonics, Inc, the manufacturer; insurance companies are now considering whether they will cover this cost.
McGuffee says her entire life has turned around since the procedure. “I’ve changed careers, had weight-loss surgery and had a baby girl,” she says.
Yet, while preliminary data shows that VNS Therapy holds promise, the most effective treatment currently available for TRD remains electro-convulsive therapy (ECT), in which electric currents are delivered to certain areas of the brain via electrodes, causing a seizure and affecting areas of the brain unreachable by medications.
ECT has been shown to relieve depression in up to 80 percent of those with TRD, and vast improvements have been made in the procedure. It is now done under general anesthesia and uses less electricity --which results in less memory loss, one of the most distressing side effects. And instead of being delivered on both sides of the brain, as was once standard, it can be delivered on one side only—again, resulting in dramatically fewer side effects.
Still, despite being safe and effective, ECT has not shed its image as barbaric. “There remains a gap between the reality of what ECT really involves today and the stigma that surrounds it,” says Sarah Lisanby, MD, chair of the APA committee on ECT and related brain-stimulation techniques. “This prevents many people from considering it as an option, even when their suffering is tremendous.” Lisanby is encouraged by a new form of brain stimulation, known as transcranial magnetic stimulation (TMS), which uses magnetic fields to stimulate the brain, does not cause seizures and has fewer side effects than ECT. A major trial of TMS was recently completed and submitted to the FDA, which will decide whether to approve it within a year or two. Another treatment, called magnetic seizure therapy (MST)—which uses magnetic fields to cause seizures-- is also in preliminary trials.
As bleak and seemingly intractable as depression can be, 80-90 percent of sufferers eventually find relief with treatment of one kind or another, according to NAMI. Currently, there is no permanent cure for depression; for most sufferers, it is a chronic, recurrent illness.
“It was important to realize that depression may always be a part of me,” says Diane Benson Harrington, who currently takes medication for her illness and is doing well. “When you know this, when you stop fighting it or wishing it away, then you'll be much more successful in coping with it.” She recalls a suicide attempt she made many years ago. “If I had succeeded, I'd never have learned what it's like to be married, what it's like to have kids and see how goofy and fun they can be, what it's like to renovate a house or to have fun coaching my 6-year-old's soccer team, or to have new people in my life tell me just last week how happy they are that I recently moved to this town.”
Harrington even wonders if being prone to depression is a peculiar sort of blessing. “It’s a cliché, but there’s truth to it: If you never experience the lowest of the lows, you'll never know how high those highs can be.”
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BOX: NATURAL REMEDIES FOR DEPRESSION
For those who gravitate to natural remedies, there are a couple worth considering. A study in the October 2005 Journal of Clinical Psychopharmacology found St. John’s Wort to be more effective in treating depression than either fluoxetine (Prozac) or a placebo. Still, just like pharmaceutical medications, St John’s Wort can have side effects and can interact dangerously with certain medications, so seek advice from a healthcare professional before using it. The FDA does not test herbal remedies for safety or efficacy.
Fish oil, touted for its role in preventing other forms of disease, has also been shown in studies to improve depression symptoms when taken with medication. The Omega-3 fatty acids found in fish oil contain DHA, a critical component of the brain. Though it’s not known exactly how fish oil works, “it can have a pretty phenomenal effect and can even replace medication in some patients,” says Jerry Cott, PhD, former chief of the psychopharmacology program at the NIMH. “It’s not possible to predict who will most benefit from it, but there’s no downside to taking it.”
BOX: DO SSRI’s INCREASE THE RISK OF SUICIDE?
Reading recent reports linking SSRIs—Paxil in particular—with an increased risk of suicide could scare anyone off of trying antidepressants. Yet. there is so far no evidence that something in these medications themselves actually cause suicidal behavior. Instead, it seems to be an result of unfortunate timing.
When a depressed, potentially suicidal patient starts taking antidepressants, often the sense of lethargy is relieved first. “If a patient’s energy and ability to concentrate are improving, but their suicidal thoughts have not yet receded, they are at particular risk to act on those thoughts,” says David Fassler, MD, a child psychiatrist. “Psychiatrists have long known that this is a particularly dangerous time and that is why patients must be carefully monitored throughout the illness.”
Experts agree that risk for suicidal behavior is far greater among people whose depression remains untreated.
BOX: GETTING THE HELP YOU NEED
You don’t have to blindly accept your insurance-company’s mental health care limitations. Here’s how to act on your own behalf to get the type of care you want--and deserve:
1. Learn exactly what your health plan allows and doesn’t allow. This information is available through your employer or on the plan’s website. Save all correspondence between yourself and the company, in case you need proof that you were denied care.
2. Learn what your rights are as a healthcare consumer. Each state has an attorney general and an insurance department that can provide this information. The National Coalition of Mental Health Professionals and Consumers (www.nomanagedcare.org or 1-866-8-COALITION) is another resource.
3. If you think your rights aren’t being recognized by your health care plan, file a grievance with the company. Most healthcare companies outline grievance procedures on their websites. If necessary, you can then appeal the company’s decision.
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