Get Active Subscribe Support Us

DEPRESSION: THE NEXT EPIDEMIC

Better Treatment Is On The Way.  Will It Get Here In Time?

Editor's note: Last month Madison Magazine reported on medical advances in treating drug addiction.  Now, in the second of a two-part series, we look at where science is taking treatment of depression, a mental illness that afflicts one in three people during their lifetimes.

Emotions have a biology all their own.  Scientists have mapped it.  Drug companies have made a six-billion dollar industry of it.  And Jennifer M., a 20-something Madison native, came face to face with it a couple of years ago.  "I was going through a horrible, rocky relationship time," she recalls, "and I just could not get out of a funk.  A friend called me up one weekend and said, 'Maybe you really should talk to your doctor.'" A self-described "queen of the self-help books," Jennifer was reluctant to see a physician for such a non-physical problem.

But when her doctor explained that the depression that had laid siege to her brain was indeed chemical - and treatable - Jennifer followed her doctor's orders faithfully.  For a year, she saw a counselor regularly and took an anti-depressant daily.  Her self-confidence and naturally even-keeled disposition gradually returned, and she has sailed on with her life.  Today she looks back on that time as "the year that saved my life."

About 21,500 Dane County adults suffer from depression, according to National Institute of Mental Health estimates.  The bad news is that far too few of them are Jennifer-type success stories.  They don't seek help to begin with, and only one in 10 sees a psychiatrist.  Or the drugs they're prescribed don't work - experts say the symptoms of one-third of depressed people don't respond to any medications currently available.  Or their insurance coverage runs out midway through psychotherapy.  They struggle in stigmatized silence, costing their employers hundreds of thousands of dollars in sick time and putting themselves at risk for all kinds of other illnesses and even death - depression remains the leading cause of suicide.

Yet, what's also true is that depression is more treatable than ever.  The newest drugs are more effective and have fewer side effects.  Physicians like Jennifer's are more informed on how to diagnose depression and recommend treatment.  The stigma is - slowly - fading, and more people who need help are more likely to seek it.  Without a doubt, there have been remarkable advances in understanding and treating depression during the past two decades.

But, say researchers, a lot of that progress will soon fall away like a used-up booster rocket, thanks to explosive new discoveries in what causes - really causes - depression.  At sophisticated labs all over the country, and especially here at the University of Wisconsin Health Emotions Research Institute, hard-charging investigations unlock more of the brain's emotional puzzles daily, suggesting that there are new and vastly better ways to treat depression - and possibly cure or even prevent it - than those currently considered state-of-the-art.  Now researchers are racing time to translate those findings into treatments that will be available when people need them most.

Consider once again, for example, the Baby Boomers.  The largest population swell the nation has ever seen, the Boomers have been in a medical version of the right place at the right time for most of their lives; an amazing variety of their diseases have been cured and disabilities eased.  Even as they begin to age - one-fifth of the population will be 65 and older by the year 2020 - their doctors stand ready with artificial hips, angioplasties, arthroscopic surgery and more.  But the Boomers will also become more susceptible to geriatric depression as they age, and it's not clear whether the innovative research will coalesce in time to be of much use to them.

"This gets particularly interesting in the presence of an aging population," says Dr.  Ned Kalin, University of Wisconsin Medical School Hedberg Professor of Psychiatry and Psychology, of the research he directs as head of HealthEmotions.  "Certainly as people age they have more likelihood of having medical problems, disabilities, loss of function.  They're more likely to face the loss of a spouse or partner.  All these things contribute to depression.  There are going to be more people who are getting older and who will be more likely to be depressed."

And, because mental health and physical well-being are linked more closely than even Norman Vincent Peale might have imagined, the health care consequences of depression could reverberate ever louder in the coming years.  Depression occurs, for example, in only about 5 percent of the healthy adult population, but in people with old-age illnesses, such as arthritis and heart disease, that figure jumps to anywhere from 25 to 50 percent.  Researchers have discovered that depression may symbiotically worsen or even help cause such conditions as well.

"These are very important issues in an aging population," says Kalin, "because not only do you want to be thinking about preventing illness, you also want to prevent depression because it increases medical problems.  It's a chicken-and-egg thing."

Building A Better Pill

According to a 1999 report published by Bergen Record Corp., the most popular anti-depressants available today - Prozac, Zoloft and Paxil - target the way the brain processes serotonin, an emotion-governing chemical long known to figure prominently in depression.  The newest drugs, like Vestra, target norepinephrine, on the hunch that some 20 percent of depression is related to this particular neurotransmitter.  While another 20 percent of depression is serotonin-related, the drug industry has theorized that the remaining 60 percent of people suffer from a depression that has to do with a mixture of the two.  As a result, physicians are beginning to prescribe medications in combination as a first treatment step rather than trying them sequentially to see which one, if any, will work.

Meanwhile, research at Health Emotions is showing that the current drugs may actually work harder on the symptoms of depression than they do on the cause itself.

"Serotonin is important," says Kalin, "but not the essential element.  CRH is a brain chemical that is much more closely related to the cause of depression, and that likely is at the heart of the problem, than is serotonin.  "A medication to adjust the stress-related CRH," says Kalin, "would work much faster and better to bring relief from depression."

Will such a drug be invented? We're working on it, say the experts.  "There are a number of projects under way to see if you can develop specific medications to block the effects of the hormone that starts the stress cascade," says Dr.  John F.  Greden, who runs the University of Michigan Depression Center.  "So instead of trying to treat the depression that comes later by changing neurotransmitters that have already been altered, this would be a strategy to alter things at the front end."

Even when it does arrive, though, it's certain to be a cure - but not a cure-all.  Researchers have picked up many of the threads of how depression forms and festers, but they're still in the process of unraveling this tangled knowledge.  Scientists have known for years, for instance, that there are different types of depression, which in turn have different causes and results.  Pinning them down and developing the right therapy for each is a different matter.

Depression can be caused by alcohol abuse or drug addiction, for example, but it will differ in how it changes the workings of the brain from the depression that may have actually sparked the "self-medicating" addiction in the first place.  The symbiotic relationship between depression and addiction is increasingly understood as a profound one.  "It's pretty straightforward," says Sherry Martin, a top-level certified alcohol and drug counselor who assesses the severity of teen-age substance abuse as part of her work at the UW Adolescent Intervention Program.  "Of my caseload, probably 25 percent to 33 percent are people who are clinically depressed and self-medicating with substances."

Drug-related depressions, in turn, differ from hormonally linked post-partum depressions and from the post-adolescent depressions that strike girls three times as often as boys.  There is also the depression that is thought to be caused by age related changes in the brain's hippocampus and the stress-related depression that strikes with illness or loss.

"The work that's going to be crucial is in parsing the homogeneity of depression," says Richard Davidson, a UW-Madison psychologist who directs the W.M.  Keck Laboratory for Functional Brain Imaging and Behavior.  "Saying depression is a single disorder would be like saying cancer is a single disorder.  It's very clear from the research that depression has subtypes."

That's the reason pills or psychotherapy make some depressed people feel better but not others.  It has also led to some serendipitous breakthroughs on what does work, if not why it works.  One of these occurred a few years ago when doctors noticed that certain epilepsy medications seemed to relieve depression in some of their patients, even when the patients' seizures weren't prevented.  As a result, the drugs are currently being given in clinical trials to people diagnosed with depression but not with epilepsy, and the early results indicate that it is actually quite an effective treatment.  It may prove especially important for Boomers in light of a recent study showing that clinically depressed older adults are six times as likely to have a seizure as their non-depressed peers.

Finding The Cranial Sore Spot

What's on the horizon - and Kalin, Davidson, Greden and others say they can already see it from where they stand - are increasingly fine-tuned medications and increasingly high-tech diagnostic tools and treatments, thanks to breakthroughs in computerized technology.

MRI and PET scans let researchers actually watch computerized images of the brains of people who are depressed.  Researchers can see metabolism and blood flow.  They can track electrical impulses.  Soon, they'll even be able to tell how much serotonin or CRH is concentrated and in which part of the brain.  And, thanks to the mapping of the human genome, scientists can see more clearly than ever the genetic links to depression.

"I think we're going to be able to develop more specific interventions that are based upon what we know is wrong with the brain," says Davidson.  "Drugs, for example, affect chemical systems throughout the brain.  They're not terribly specific." As scientists learn more about the different components of emotional circuitry, Davidson envisions the development of medication that will act only upon a given sore spot in the brain.  A pacemaker-like device that uses electrical pulses to stabilize people with epilepsy is already being investigated for use in treating depression.  The therapy is called vagus nerve stimulation, and in a recent pilot study it helped 40 percent of the patients who tried it.  It may be reviewed and approved for treatment of depression by the end of this year.

Transcranial magnetic stimulation is a high-tech answer to traditional electric shock therapy, which has always shown some promise in treating severe depression but requires anesthesia and has serious side effects.  TMS, though, uses an electric current and an electromagnetic coil to depolarize neurons in the brain, so it's painless and has no known side effects.  Presently being evaluated as a treatment for depression in several studies worldwide, TMS will be in use here, Greden estimates, within a year or two.

Much of the research will also improve low-tech treatments for depression, such as cognitive behavioral therapy and talk therapy, predicts Davidson.  "It will help us to better design behavioral interventions that may affect very specific areas of the brain," he explains.  "We shouldn't think of behavioral treatments as any less biological." Indeed, psychotherapy is expected to remain an important treatment component; not only is it a drug-free way to create healthy biological and chemical change in the brain, it is crucial in helping reduce the impact of stress-related depression.

The other promise of technology lies in diagnosing depression; advancing research may well allow doctors of the future to find it in a patient just by performing a simple lab test.  Technology will undoubtedly create the ability to screen for depression - Kalin has said he'd like to see this done in childhood - as well as to predict it and possibly prevent it.

"Inevitably, we'll have medications that attempt to turn off certain genes that get and keep depression going," says Greden," and to turn on certain genes that actually promote well being."

Along with the coming bulge in depression rates that the aging Boomers will cause, overall rates of depression are expected to rise - not because more people are expected to become depressed but because more of the ones who already are will be diagnosed.

A key aspect of whether any of them will get the help they need, though, will be their willingness to seek it.  "Most people don't start with the viewpoint that it's an illness," says Greden.  "They don't necessarily believe that it's treatable." With research-driven advances in dealing with depression approaching warp speed, says Greden and others, it's a good time for people to start changing their minds.

Mary Feingold is a senior writer for Madison Magazine.