For years, Martha, a 54-year-old mental health professional, suffered from severe bouts of depression. To mask her feelings of despair, she began drinking heavily. Over time her depressive episodes got worse—so severe, in fact, that in 1979 she contemplated suicide. That’s when Martha (a pseudonym to protect her privacy) decided to seek help from a psychiatrist, who diagnosed her with mild bipolar II disorder.

“There is a denial that comes with the two illnesses—you don’t want to believe that you are an alcoholic, and you don’t want to see how depressed you are,” she admits.

Placed on the mood stabilizer lithium, Martha felt better but had gained weight and was tired all of the time. “Although the drug helped with my depression, it had many side effects. And I didn’t feel like myself. I felt sort of blah,” she recalls.

Today Martha is off of lithium and taking newer, more effective drugs—a combination of the mood stabilizer Lamictal with the antidepressant Prozac. “I feel really well now. I work, I have a life, and I’m happy most of the time.”

Treatment in the form of a pill was unthinkable just 50 years ago. The Department of Psychiatry and Behavioral Sciences at the Miller School of Medicine, under the direction of professor and chair Julio Licinio, M.D., seeks to improve medication for depressive disorders by focusing on biological and genetic factors. Before arriving last year at the University of Miami, Licinio served as director of the UCLA Semel Institute Center for Pharmacogenomics and Clinical Pharmacology and associate program director of the UCLA General Clinical Research Center. The pharmacogenomics of antidepressants—examining a person’s genetic markers to predict whether he or she will respond to a specific drug—is one of Licinio’s main areas of research.

According to the National Institute of Mental Health, 9.5 percent of the population, or about 20.9 million American adults, will suffer from a depressive illness in any given one-year period. Depression alone costs the economy approximately $44 billion a year in productivity loss, according to the U.S. Department of Health and Human Services’ Center for Mental Health Services.

Electroshock therapy was used for decades to treat severe depression. The 1963 autobiographical novel The Bell Jar gave readers a glimpse into this treatment. Here, Sylvia Plath recounts the troubled teenage years of Ester Greenwood, a talented young writer whose ongoing battle with depression, subsequent treatment with electroshock therapy, and eventual suicide opened the nation’s eyes to the debilitating disease.

Electroshock therapy is no longer the standard of care for depressive disorders, though it is sometimes used today when drugs are not effective. For years much of the research focused on the brain’s neurotransmitters serotonin and norepinephrine, which fueled the development of SSRIs, or selective serotonin reuptake inhibitors. These antidepressants work by increasing the level of these neurotransmitters in the brain.

“The introduction of SSRIs, specifically Prozac in 1986, was a big leap forward in treating depression,” Licinio says. “SSRIs have fewer side effects, especially life-threatening ones, than the earlier class of antidepressants (known as tricyclics). Since then, getting treatment for the disease has become more mainstream.”

In a June 2006 study published in the journal PLoS Medicine, Licinio and his colleagues found that U.S. suicide rates have fallen dramatically since the introduction of SSRIs, specifically Prozac, for treatment of depression. These findings do not preclude the possibility of an increased risk of suicide among small populations of individuals, Licinio notes.

Today, about 20 SSRIs are on the market, but little difference exists between them. “If you came to me with depression today, I would pick one of those drugs out of a hat; there is no specific reason to prescribe one over another,” Licinio says, noting that physicians eventually do find what works best through trial and error. “We just don’t know which person will respond better to which drug.”

SSRIs are the product of scientific discoveries that were made many years ago, so why has nothing remarkably new hit the market since? The new Miami Institute for Medical Discovery and Health Disparities at the Miller School of Medicine may help answer questions like this.

“This is a new paradigm,” says Licinio, who leads the institute. “What we’re trying to do is to foster the discovery of more drugs and new treatment. By joining forces with various departments at the Miller School, other colleges and schools from the University, as well as our community partners, we hope to speed up this process and make it more efficient.”

Peter (not his real name), a 33-year-old patient with bipolar disorder, hopes the drug combination he is now taking will work. Bipolar disorder, also known as manic-depressive disorder, is characterized by dramatic mood swings ranging from feelings of extreme euphoria or irritability (mania) to deep despair. These episodes can last hours, days, or even months. By comparison, bipolar II, the disorder that Martha has, is characterized by one or more major depressive episodes along with at least one hypomanic episode, which is less severe than a traditional manic episode.

When he was first diagnosed 18 months ago, Peter took Lamictal to control both his depressive episodes as well as his mania, but it failed to treat his mania. His psychiatrist has since added another drug, Abilify, which seems to be working.

“I am banking that this combination will work because my life got pretty messed up,” Peter says. “With my last two episodes I screwed up relationships and lost a job in each case, so I hope not to go through that again because it’s very traumatic.”

This wait-and-see approach to treating depressive disorders will soon change, thanks to promising new research focusing on how the brain can be permanently damaged by overactive stress responses. In the case of depression, such responses can be caused by prolonged exposure to inescapable stress (such as what soldiers in Iraq are facing), extended periods of chronic stress (such as at a high-stress job), a single traumatic event, or a genetic predisposition to the disease, Licinio explains.

“Many people with depression stay depressed for years, and the biggest predictor of someone becoming a chronic patient is failure in the first treatment,” says Licinio. “That’s why pharmacogenetics is so important. It can identify a drug that is going to work so that you don’t give up on the treatment.”

Knowing who is at risk for depression can also help patients incorporate preventive interventions. A person with a predisposition to depression, for example, could benefit from learning how to better handle stress or avoiding high-stress situations altogether.

These scientific breakthroughs will be especially helpful to those with bipolar disorder. Due to the various phases of the disease—the range from mania to depression—many individuals are often misdiagnosed. On average it takes ten years and four doctors to properly diagnose the disorder.

“Currently there is no biological test for any psychiatric disease, so you can see how badly off we are,” says Samuel Gershon, M.D., vice chairman of academic affairs in the Department of Psychiatry and Behavioral Sciences. An expert on bipolar disorder, Gershon is known for his groundbreaking work on lithium, which helped pave the way for the understanding of mood stabilizers. His research influenced the way bipolar disorder is treated throughout the world. “So the field of pharmacogenetics has a big future. It could help a doctor properly diagnose the disorder in a patient more quickly—not to mention the amount of money you would save.”

Despite all of the recent advancements in treating depressive disorders, negative stereotypes still persist. “I don’t think the stigma is gone,” Peter says. “Most people hear the words ‘mental illness’ and they automatically freak out.”

Educating the public about depressive disorders is the first step to shattering negative perceptions. The Science of the Mind Initiative, a campaign Licinio is spearheading at the Miller School, is aimed at bringing new knowledge, global awareness, and dynamic treatment to illnesses of the brain—from depression to Post-Traumatic Stress Disorder to Alzheimer’s disease. “The stigma must be lifted if we are ever going to truly help the people who need our help most,” Licinio announced at the campaign kickoff last spring.

Licinio also plans to launch a regional grassroots Stop Depression Campaign and to create a University-based mood disorders unit that will specialize in such disorders as schizophrenia, hyperactivity disorder, depression, and bipolar disorder. Licinio is presently recruiting clinicians and researchers from the various specialties to head up these units.

“People in regular practice see everybody who comes through the door, but if patients could be referred to professionals who have the clinical acumen and specialized knowledge of such disorders, ultimately patients are going to get better treatment,” Gershon says.

Even with all of the suffering depressive illnesses can bring, those who have found solace in modern-day treatments rarely take for granted being able to live a normal life.

“We’re all waiting for that cure that will make this go away, but the gains in the last 25 years have certainly been tremendous,” Martha says. “There are times when I really hate this illness, but then there are times that I am grateful to have it. I’ve learned so much about myself, and it’s made me more compassionate toward others. In a way, I think I am a better person for it.”

Lisa Sedelnik, M.A.’00, is a freelance writer in Miami, Florida.