Many Shades of Blues

Myriad forms of depression complicate diagnosis and treatment.

By Daniel DeNoon WebMD Feature

Reviewed By Brunilda  Nazario, MD

Who's depressed?

The man who eats too little, or the man who eats too much? The woman who can't sleep, or the woman who can't stay awake? The sad sack that doesn't react to what others say or do, or the flighty one who overreacts to everything? The man who was fine until his mid-30s, or the man who's suffered since childhood?

Each of these people shows signs of depression. That may seem odd because we've come to think of depression as one thing. It's not.

And pretending that it is one thing is bad for patients. It's bad for therapists. And it's bad for clinical trials of antidepressant drugs, says Jonathan W. Stewart, MD, professor of clinical psychiatry at Columbia University and research psychiatrist at New York State Psychiatric Institute.

"The fact is, we don't know what the different illnesses are, all of which we call depression," Stewart tells WebMD.

Depression Many Things for Many People

Depression turns out to be a very general term.

"You come into the doctor's office and you say, 'I think I've got a fever.' He takes your temperature and says, 'By golly, you do have a fever.' It's the same with depression," Stewart says. "Someone comes to my office and tells me he feels depressed. I ask him to tell me about it and then I say, 'Yes, you have major depression.' It is like saying, 'You've got a fever all right.' We don't know -- just as the doctor with the fever patient doesn't know -- the actual cause of the problem."

That's a startling admission, given that Stewart is widely considered an expert in the diagnosis and medical treatment of depression.

But other experts say the same thing. One is David D. Burns, MD, clinical professor of psychiatry and behavioral sciences at the Stanford University School of Medicine and visiting scholar at Harvard Medical School. Burns' best-selling book, Feeling Good: The New Mood Therapy, and the more recent Feeling Good Handbook are the books most often recommended to depressed patients by psychologists and psychiatrists.

Burns notes that there's recently been a lot of interest in defining the different types of depression, particularly a diagnosis called "atypical depression." It's part of an effort, he says, to link different aspects of depression to specific brain disorders. Perhaps one day that effort will bear fruit, but Burns isn't optimistic about that.

"I am worried that our field is moving in the wrong direction," he tells WebMD.

Burns worries that there's a trend to put people into categories and then to treat the category, not the person.

"It is a question of what is right for that individual, not what is right for that diagnosis," Burns says. "Human beings suffer in many different ways and will fit into many diagnostic categories. So how do we treat the human being in front of us who is suffering?"

That's true, says psychotherapist Andrew Elmore, PhD, assistant clinical professor at Mt. Sinai School of Medicine in New York.

"There is too much emphasis on giving a person a label, rather than what is really important to the patient," Elmore tells WebMD.

The Many Faces of Depression

Doctors and psychologists don't just make up diagnoses. There's a standard guide called the Diagnostic and Statistical Manual, Fourth Edition -- the DSM IV.

Burns, Elmore, and Stewart all say a DSM IV diagnosis is important.

"I am not saying we shouldn't do thorough, competent intakes and diagnoses," Burns says. "That is a part of good, competent, professional work. You can't ignore the importance of properly assessing problems. If people have a problem with drug abuse and you diagnose them with depression, their depression treatment is not going to be helpful. But the idea we can impose treatment formulas based on diagnostic categories is wrongheaded."

What are the categories of depression? There's bipolar depression, in which a person may be manic one day and depressed the next. This article, however, deals with unipolar depression -- that is, with people who suffer long-lasting or episodic depression without manic swings.

"Bipolar disorder is clearly biologically and genetically determined," Burns says. "But we don't know the cause of depression. It is not outside the range of human experience. These are, in a sense, normal human experiences."

Some of these experiences fit the DSM IV definition of major depression. Some don't.

"It is interesting to think about how what really exists fits into the DSM IV definition," Stewart says. "I don't know how many different causes of depression there are. There is atypical depression, melancholia, seasonal affective disorder or SAD, and something else -- whatever that is, I am not sure. Obviously, the DSM IV has atypical depression in it, it has melancholia in it, it has SAD in it, and it has a couple of others as well, which may also be different disorders. Psychotic depression, for example. But if people don't meet the specific DSM IV criteria for any of these, what is it?"

Burns agrees that patients don't always fit into the specific DSM IV criteria.

"Now psychiatrists are trying to take certain parts of the pattern of depression and make them essential for a diagnosis -- but it is totally arbitrary," he says. "For major depressive disorder, you have to have so many items on a list every day for 14 days. So on midnight on the 14th day you suddenly have a major depressive episode? The reduction of human emotions to a series of disorders and biological and psychological formulae is minimally useful -- but that utility has a big downside to it."

Diagnosis: Melancholia

Hippocrates described what he called "melancholia" in the fifth century B.C. It's still what most of us think of when we hear the word "depression."

"The classic picture is somebody doing well in life who then gets depressed. They just lose all interest in doing things: they stop eating, lose weight, can't sleep," Stewart says. "They may be agitated, pace about, say 'Woe is me,' 'The world has ended,' 'There is nothing but darkness on my horizon,' 'It is all my fault,' 'I have ruined my and everyone else's life,' and you can't talk them out of it."

Melancholic depression comes in distinct episodes and tends to appear later in life. While it's seen in people in their 20s and even younger, it's more likely to appear -- mysteriously -- from the 30s on.

"So it is a late-onset activity typically characterized by loss of interest in activities and eating," Stewart says. "Food becomes tasteless. I have had people go to gourmet restaurants and say the food tastes like cardboard. They wake up early in the morning worrying about things like, 'If I had given enough money to the Red Cross, there wouldn't be starvation in Somalia.' It is reverse omnipotence."

Historically, people with severe melancholic depression tend to respond to treatment with the older tricyclic antidepressants and to electroconvulsive therapy. But while a person's diagnosis might influence his third- or fourth-line treatment, Stewart doesn't think it's helpful to make a person's specific depressive diagnosis the basis of medical treatment. Diagnosis, he says, simply doesn't predict drug response.

"It is wishful thinking that we can make those kinds of predictions and that these medications have those kinds of differences," he says.

Diagnosis: Atypical Depression

Atypical depression is atypical only in the sense that it isn't like melancholic depression. It's actually the most common form of depression.

"Atypical depression tends to be early onset; chronic, not episodic; characterized by overeating and oversleeping; and an awful lethargy called leaden paralysis," Stewart says. "They care what people think of them. The melancholic doesn't care whether you say good morning or slap them in the face, whereas the atypical over-responds to either: They're ecstatic if you throw them a birthday party, despondent if you slap them in the face. They're over-reactive, the opposite of melancholia."

People with atypical depression also are supposed to have more "comorbidity." That means they have lots of other psychiatric problems in addition to depression. But Stewart says that's what one might expect from someone whose illness began early in life.

"The true atypical has early-onset, chronic depression," he notes. "This means that person has more general problems in life than someone who is fine until age 30 or 40. The melancholics have plenty of time to get their act together then, boom, they are depressed. Whereas the atypicals have been depressed since age 15 or so, and have not been free from it very long -- if at all -- so when did they have time to get their act together? That is gong to create problems. And those problems that get created may look like this or that or other comorbid problems or disorders."

Historically, people with atypical depression get better when treated with a class of drugs called MAO inhibitors. But most doctors are reluctant to prescribe these drugs because they can cause serious, possibly deadly side effects when combined with certain foods or medications.

The Distribution of Depression

Since so many people don't fit neatly into categories of depression, it's hard to say how many have what.

"It turns out that depressed people haven't by and large been appropriately diagnosed," Stewart says. "How many are out there in the community? I think about a third of depressed people have that atypical depression. A third have melancholia, but a lot of them don't meet the DSM IV criteria."

If one went strictly according to DSM IV criteria, Stewart says, about 10% of depressed people are melancholic, about 25% have atypical depression, about 10% have SAD, and another 5% have psychotic depression. That adds up to just half of people with depression.

"My pretty strong feeling is that for melancholia, it looks to me that the people the DSM IV criteria identify, almost all have what I want to call melancholia," Stewart notes. "But there are also at least an equal number of people who have that illness but don't meet the DSM IV criteria. It is too narrow. It actually affects more people than the criteria identify."

For atypical depression, the diagnostic situation is different.

"With atypical depression, the diagnostic category is both too narrow and too broad," Stewart says. "So indeed the criteria in DSM IV capture a bunch of people who actually have the illness, but they also capture a bunch who don't have it and miss a bunch who do have it."

A Working Definition of Depression

Burns prefers a definition of depression based more on a person's experience than on symptoms. He lists five key elements of depression:

• A feeling of despair and sadness, of being down in the dumps, of gloominess that won't lift. "Obviously that is the necessary, the essential aspect of depression," Burns says.
• A feeling of helplessness or discouragement. "It's the illogical belief that nothing will change, that there's nothing that can be done," Burns says. "This causes most of the pain of depression."
• Loss of self-esteem. "It's the feeling you are no good or bad, that you deserve to suffer for some screw-up you have made," Burns says. "You feel guilty, worthless, inadequate."
• Loss of pleasure or satisfaction. Nothing seems worth doing.
• Loss of interest in life at the motivational level. Life becomes one big procrastination.

"When you measure those symptoms, you can get a test with a reliability of 95%," Burns says.

But the job of diagnosing a person's problem doesn't stop there. Burn's agrees that just knowing a person has a major depression doesn't cure anybody.

"People who are depressed are also anxious or angry," he says. "We should give up on the idea they have depression and not something else."

Treating Depression in All Its Forms

So how does a doctor or therapist treat depression? It's a complicated question.

It's generally thought that people with depression should receive psychotherapy, but few insurance plans pay for it. Nearly all of them pay for medication, however. That's why general practitioners -- not psychiatrists -- prescribe most antidepressant drugs. The upside is that at least people get treated. The downside is that it may not be the most effective treatment.

Most experts agree that cognitive behavioral therapy, in which people learn to identify and correct misinterpreted events and negative thoughts, is useful in treating people with depression. Elmore says the treatment is uniquely suited to the kinds of problems people with depression face.

"Depression is existentially giving up hope -- failing to take responsibility for the things you don't take responsibility for, and the sense that you can't do it, that you are just spiritually incapable of doing it," he says. "So cognitive behavioral therapy is the same approach, which is just 'Let me give you the skills to overcome the problem.' In depression, the problem is what is going on in the people's lives that makes them feel life is not worth living or that they are not capable of dealing with life."

Burns says that treatment begins with the recognition that a person's depression is part of an individual pattern of suffering.

"There is nobody with just depression, there are just human beings," he says. "Human beings suffer in many different ways. So how do we treat the human being in front of us who is suffering?"

Burns says that different things work for different people -- and that no therapist or doctor can predict what will work.

"Just because someone has a diagnosis of melancholia, you don't impose that on them," he says. "Instead you ask, 'When was the last time you were suffering? What was going on, what were you feeling, what were you thinking?' Then you individualize your approach to what is their unique problem."

How does this work? Burns is famous for his pioneering work in cognitive therapy. Here's his approach.

"Once I've done an intake, got to know them, done a thorough screening, then I would ask the patient if today is a therapy session," Burns says. "We would empathize for a while, then I would say, 'What would you like to work on today? Was there any time last week or in your life you were upset and want to work with?' You have to empathize first. You have to say, 'Gosh that must feel horrible, tell me about it.' That person has to be accepted as who they are, and then you can work on it."

If patients can't focus on a specific problem to work on, Burns says, it means they aren't yet ready to move on to the treatment stage of their therapy. When they do come up with specific problems, Burns invites them to help come up with a solution. The idea is to negotiate around their resistance to dealing with the problem and to motivate them to move forward.

"I say, 'Give me a particular time of day you were upset. What were you feeling? What were you thinking?' Then I see what they are struggling with," he says. "It could be anything, not necessarily related to all these diagnoses. I'll say, 'If I tell you I can cure this, how hard are you willing to work? How much homework are you willing to do?' So if it's a person suffering from depression, we might work with the symptom, say, of thinking he or she is worthless. Then I run through treatment techniques until I find the one that will be helpful. I do this very quickly. The idea is that if a treatment isn't going to work, you want to fail quickly so you can try something else, and then something else until something works. Then once the patient is symptom free, we move on to preventing the depression from coming back."

Stewart, on the other hand, is not a psychotherapist. While he believes that psychotherapy can be very helpful, he believes that medication is crucial to the treatment of depression. But finding the right treatment is complicated.

"It is complicated because you have 25 antidepressants on the market," he says. "You have at least three psychotherapies that have at least somewhat reasonable demonstration they work for depression. And you have various herbal remedies that help some."

Depression, Stewart says, remains a black box. Until more is known, the treatment of depression will remain more of an art than a science.

"We need to get at what is going on in that black box better," Stewart says. "We need to identify what the meaningful differences are between different people with depression, and then correlate those meaningful differences with treatment outcomes. But that takes a lot of patients -- and a lot of patience. And we are not there yet."

Published April 7, 2004.