Climbing out of the dark
Sunday, June 27, 2004
by Anne Rueter, Ann Arbor News

Bonnie Hagerty and Reg Williams' patients say it over and over, as they crawl out of the pit of a deep depression that keeps them from sleeping, eating, working and relating to others normally: They never want to feel that low again. And they don't have to, say the two depression experts at the University of Michigan nursing school.

People prone to depression can learn to spot early signs and promptly take steps to manage a depressive episode, Hagerty and Williams say. Patients can stave off the worst results - inability to work or even get off the couch, feelings of worthlessness and suicidal thoughts - by using self-management techniques Hagerty and Williams have developed.

Those techniques are a lot like ones that people with asthma or chronic pain use successfully to control their illnesses and get on with their lives.

It's a major step forward for patients, and society in general, to view depression as another manageable chronic illness, says John Greden, executive director of the University of Michigan Depression Center. "The stigma is disappearing."

People are getting the picture that depression is indeed a physical illness in which brain chemistry and the hormones governing stress go awry. Many are familiar with drugs such as Zoloft and Prozac that doctors now widely prescribe to adjust levels of certain brain neurotransmitters.

Though drug therapy is a well-established approach to halting or muting the worst symptoms, it alone is no panacea for an illness as complex as depression, says Greden. He hopes the new U-M center he heads is the first of a series of depression centers nationwide to focus on causes and treatments.

Several researchers affiliated with the center are working on new ways to treat depression. A handful of promising drug and nondrug treatments have come to the fore recently, with an even wider array of methods in the pipeline.

"What's hopeful about depression is that patients really have several options," says U-M psychiatry professor Heather Flynn, who works with a team testing drug and nondrug strategies to help pregnant women at risk of depression.

Besides Hagerty and Williams' self-management model, other emerging strategies that interest Depression Center researchers and others nationwide include:
o Two types of short-term, results-oriented talk therapy, cognitive behavior therapy and interpersonal psychotherapy.
o New antidepressant drugs and ways to better match drugs to individual patients.
o Electrical brain stimulation techniques designed to help people for whom other methods don't work.

Some U-M researchers are part of a burgeoning scientific movement to understand the brain. They say the work is beginning to shed needed light on what happens in the brains of depressed people. That fundamental knowledge, it's hoped, will reveal precisely how antidepressants and other treatments help or fail to help.

The goal down the road is to tailor treatment to each person's needs. There's a growing sense that people with depression tend to experience periodic episodes tied to the interplay between difficult life experiences and physical factors, such as low levels of mood-regulating brain agents and an overabundance of stress hormones. Research at U-M and elsewhere suggests some people have genetic variants that make them prone to depression if life delivers big stresses such as job loss, grief or marital conflict.

Here's a sampling of next-generation thinking about treatments and ways to manage the illness:

Training patients to be managers
"Even depressed persons can make decisions about their care," Hagerty told colleagues at a recent U-M depression symposium. She and Williams, both psychiatric nursing professors, got together with focus groups of people with depression to see the stages of a depressive episode through their eyes. The resulting self-management model has helped many of their patients identify first signs - such as withdrawing from others and feeling overwhelmed - and to identify what helps bring them out again, such as upping medications and seeking therapy. Patients also figure out what helps them stay well between episodes, such as regular exercise.

A patient who's a pharmacist realized he had to get help for his depression when he found himself counting pills incorrectly and putting them in the wrong container - cognitive impairment is a common depression symptom.

"That's the self-management part: You don't allow it to go on and on and get into a worse place," says Williams. Many patients guided by the model have had less severe episodes and in some cases have prevented them, he says.

Therapy to build a toolbox
The long-standing rift in psychiatry between those who think drugs are the best treatment for depression vs. those who espouse psychotherapy is "a dumb fight," says Greden. "Almost every study that's been done shows it's the combination that has the very best effect."

Two methods, cognitive behavior therapy and interpersonal psychotherapy, are getting increased attention because they "have evidence-based research showing they work," Greden says.

In contrast to more traditional psychotherapy methods, both aim to teach recovery tools within a limited time, one that health insurance may cover: typically one to two sessions a week for about 12 weeks, with occasional booster sessions if needed later. Both methods prepare people to get along on their own by developing a maintenance plan.

In cognitive behavior therapy, people learn to spot recurring habits of thought that mire them in their depressed state and to redirect their thoughts toward healthier pursuits such as exercise or helping others. U-M psychology professor Susan Nolen-Hoeksema suggests several cognitive behavior therapy techniques in her popular 2003 self-help book, "Women Who Think Too Much", which addresses the needs of women who tend to brood over problems and become depressed.

In interpersonal psychotherapy, people focus on changing how they deal with troubling relationships at work or home that contribute to their depression, or on handling grief and difficult role transitions such as divorce or retirement.

"The focus is very much on the here and now," says Flynn. She wants to promote better access to the therapy, known better in research circles than it is to the public. "You don't delve a lot in the past. The goal is to change your current relationships and make those work for you."

Nolen-Hoeksema sees potential in a third type of therapy emerging in England, where there's evidence that meditation-based techniques can help depressed people step back from chronic negative thoughts. It's outlined in a book, "Mindfulness-based Cognitive Therapy for Depression", by Zindel Segal, Mark Williams and John Teasdale.

Drugs that fit
Most of the widely used antidepressants on the market, the class known as SSRIs, regulate serotonin - one of the handful of neurotransmitters, or chemical messengers, in the brain known to govern mood, says Greden. A new class of drugs, SNRIs, is emerging to regulate both serotonin and another neurotransmitter, norepinephrine. One drug, venlafaxine (brand name Effexor) is on the market. Another, duloxetine (Cymbalta) may win Food and Drug Administration approval later this year.

Greden sees particular promise in these new drugs for people who suffer both from depression and chronic pain. He's optimistic that with about 40 new medications under development that target depression and related illnesses, there will be better ways to tailor medications to people with different types of depression and bipolar illness relatively soon.

At U-M, researchers have been working on a different type of drug that holds promise for depression. The body produces stress hormones that normally wax and wane. In many depressed people, though, these hormones get stuck in overdrive. The new drugs, which Greden estimates are about 10 years away, try to block the effects of stress hormones in the brain.

More choices - plus a better sense of how they work - are important, because many family physicians now are swinging in the dark where depression's concerned. When a physician first prescribes an antidepressant for a patient, the drug fails to help in about 50 percent of cases. So what should the doctor try next?

A large 14-center national study in which the U-M is engaged, "Sequenced Treatment Alternatives to Relieve Depression," is trying to sort out what other options physicians should try and when, with an eye to finding cost-effective ones that work with the fewest side effects.

The strategies under study include a variety of antidepressants drawn from the 20 currently on the market, other medications and several types of psychotherapy. The 5-year, $26 million study runs through this September.

Electrical-stimulation approaches
U-M psychiatrist Dan Maixner is lining up participants for a company-sponsored clinical trial of transcranial magnetic stimulation, a new treatment that may help people with moderate to severe depression who don't get better with medications. The company, Neuronetics, is testing the technique at 18 centers, with results due in 2005, when it plans to apply for FDA approval.

The method has been moderately successful in previous studies, Maixner says.

As head of the U-M Electroconvulsive Therapy Program, he sees many patients who are still depressed or have repeat episodes despite taking medications. He would welcome a proven new treatment without the stigma electroconvulsive therapy carries. "We try extra hard not to give up on people," he says.

With the magnetic method, a small electrical coil is placed on the patient's head in the left frontal area. It produces a pulsing magnetic field that generates an electric current when it reaches tissue. The current stimulates an area of the brain about the size of a quarter, a zone where "we believe depression circuits have connections," Maixner says.

Electrical stimulation in this method is confined and milder compared to electroconvulsive therapy, which Maixner's clinical unit provides to about 100 patients a year. Patients undergoing transcranial magnetic stimulation sit awake in a chair for 30- to 40-minute sessions, five days a week for six weeks.

Several other makers of magnetic stimulation devices are pursuing transcranial magnetic stimulation; a related method, stimulation of the vagus cranial nerve, is also getting attention.

Inside the depressed brain
How do treatments work? Who's vulnerable to depression? What role do cycles of sleep and light play?

In the chase after better treatments, Jon-Kar Zubieta argues it's essential to understand the disease better. He directs psychiatric programs at the Depression Center. He takes the interdisciplinary approach the center is striving for in one in-depth project using advanced brain-imaging techniques. He and others measure genetic factors, stressors, hormonal factors and brain transmitters in 60 depressed patients and 60 controls to get an integrated picture of the illness. He wants more than isolated clues. "We are complex systems," he says.

But who will pay?
With a promising picture of emerging treatments, there's a big caveat: People won't have access to them if health insurance continues to cover mental health at a lower level than physical health. A federal parity law to close this gap is stalled in Congress, but 39 states have enacted parity laws of their own, Greden says. Michigan has not.

Greden says data from states with parity contradict the argument opponents often use, that expanded mental health coverage would be too expensive.

"There is a 1 percent increase in cost or none, and other costs go down," he says. "By treating things like depression you actually reduce other health care costs, increase productivity, stop hospitalizations and decrease absenteeism. ...Everybody functions better, so the long-term costs aren't there."