New Weapons in the Assault on Depression : Medicine: Some new drugs and short-term therapies offer relief to the problem that afflicts one person in five.

It afflicts one person in five at some time in their lives, leaving them feeling more than just the occasional blues that can descend on everyone, even, say, during the just past holidays.

For some, it’s like a constant veil over experience, a shadow that never darkens but never lifts.

For others, it’s an even grimmer, socially stigmatizing concern that lingers and often worsens with time.

Depression.

“The pain is unrelenting, and what makes the condition intolerable is the foreknowledge that no remedy will come--not in a day, an hour, a month or a minute. It is hopelessness even more than pain that crushes the soul,” author William Styron wrote in December’s Vanity Fair, describing his own struggles with depression and his downward spiral to near suicide four years ago.

But a new generation of psychotherapeutic drugs--as well as new short-term approaches to psychotherapy--make it unnecessary for people to endure depression without hope, experts say.

Still, even this optimism must be tempered by the continued limits in treatment: Drugs and psychotherapy can take weeks to give relief; patients and doctors sometimes give up on therapies too early; and depressions often recur.

In the war on depression, one of the newest weapons in the drug arsenal is Prozac, which was approved for widespread use two years ago and has shot to the top of the market.

Prozac, which represents a third-generation effort to employ drugs to correct the biochemical imbalances thought to underlie depression, is also being used to treat bulimia, obsessive-compulsive disorders, obesity, phobias and smoking addiction.

“It is a wonderful drug, a very effective drug,” said Dr. John P. Feighner, director of a La Mesa center that conducts clinical trials of psychiatric drugs and has tested Prozac. “Lots of people tolerate it extremely well. And if clinicians are knowledgeable about the dosage range . . . most patients can take it without a lot of trouble from side effects.”

Eli Lilly & Co.’s annual U.S. sales of Prozac were expected to hit $280 million by 1989’s end--a sum roughly equal to the total American sales of all other antidepressants, a Dean Witter Reynolds analyst reports.

That makes Prozac the undisputed market king, although sales volume figures alone are misleading because Prozac costs about $1.50 a tablet, more than 10 times the price of most other antidepressants.

As a drug, Prozac has proved effective in affecting levels of serotonin, a key mood-enhancing chemical in the brain. Many researchers theorize that depression’s biochemical basis can be traced to abnormal brain concentrations of serotonin and the stress hormone, norepinephrine.

When administered, Prozac, which plays a role in preventing brain cells from reabsorbing serotonin, has fewer negative side effects than earlier drugs. It acts as a mild stimulant rather than making patients drowsy.

In waist-conscious America, it also has what many consider another beneficial side effect--it causes people to lose weight, the reverse of what most other antidepressants do.

But Dr. Michael Gitlin, director of UCLA’s affective disorders clinic, expressed concern about Prozac’s popularity.

“I think people are using it in the way they would use a gentle amphetamine,” he said. “I hear all the time at parties people saying, ‘Well, I was feeling a little sluggish so my doctor gave me some Prozac.’ Luckily, it seems so far that Prozac is safe enough that nothing bad has happened. But that kind of thoughtless use of powerful medicines is not the best way to use them.”

If there is blithe prescription of mood-enhancing drugs like Prozac, women seem to get more than their share of them, experts said. The American Psychological Assn. has reported that women account for 58% of all physician visits but get 73% of all psychotropic drug prescriptions.

And if Prozac and other antidepressants are being prescribed inappropriately, there may be even more reason for concern ahead as pharmaceutical firms release more state-of-the-art mood-enhancing drugs, which now are in clinical trials and still would require approval by the U.S. Food and Drug Administration.

Venlafexine, for example, will, like Prozac, inaugurate a new class of antidepressants. But it shows promise of working faster and being easier to tolerate, Feighner said.

Three other drugs--paroxetine, sertraline and fluvoxamine--also act like Prozac in tests but don’t linger as long in the body, he said. One of Prozac’s chief drawbacks is that, if patients cannot tolerate it, they must wait at least five weeks before they can safely take certain other antidepressants. There have been at least three American deaths from Prozac cross-reactions, Feighner said.

The growing use of antidepressants, in general, also has generated its own professional controversy between doctors and some mental health practitioners.

Because drugs are relatively easy to give, some clinicians fear that doctors may slight the need for psychotherapy.

“At best, medication is only an adjunct to psychotherapy,” said Harriet Braiker, a Los Angeles psychologist. “The answer does not appear in a pill bottle. And that’s one of the biggest dangers.”

There’s also a worry, however, that some psychotherapists may not accept medication as a valid way to treat depression, said Dr. Stephen Shuchter, director of outpatient mental health programs at UC San Diego. Psychotherapists, he said, must let go of their traditional views, “borne out of psychoanalytic theory, that depression is simply conflict manifesting itself,” which should only be treated by therapy.

Recent research does show that some 12- to 16-week psychotherapies can be just as useful as drugs in mild and moderate depressions. These include:

* Cognitive therapy, which aims at changing negative thought patterns in a depressed person.

* Behavioral therapy, which tries to change behaviors that cause conflicts in one’s life.

* Interpersonal therapy, which focuses on improving the relationships in a person’s life.

As for long-term, insight-oriented psychotherapy, there is little research on its effectiveness, said Robin Post, a Denver psychologist. She and other psychologists wonder if it isn’t better than short-term therapies at preventing future depressions. Braiker agreed but acknowledged that it probably is “an expensive luxury” for most people.

Consensus, then, seems to be building for a compromise approach: short-term psychotherapy in milder depressions, with drugs added if results aren’t shown in a few weeks; drugs to provide a “chemical floor” for more intense depressions, with short-term psychotherapy as a necessary adjunct.

But how can patients begin to discern differences between garden-variety blues and clinical depression requiring treatment?

The difference between them, experts said, is like that between a cold and pneumonia.

“Everybody feels depressed now and then,” said psychologist Post. “It’s just that beyond a certain level the cost is high, either in the way of dysfunction or pain or in relationships that don’t work or in feeling inadequate.”

To be a true clinical or major depression, a blue mood must be virtually continuous over at least two weeks and include several symptoms such as: tearfulness; loss of interest in normal activities; weight loss or gain; fatigue; sleep disruption; loss of self-esteem; inability to concentrate; restlessness or extreme inactivity; feelings of emotional numbness.

Even among the more serious manifestations of depression, there also are sub-types, including:

* Bipolar or manic depression, in which an individual alternates between agitated highs and deep lows. An equal number of men and women have this illness.

* Unipolar depression, in which the mood’s only direction is down. Women outnumber men 2-to-1 in this type.

* Dysthymic disorder, a low-level unipolar depression lasting at least two years. This type can easily go undetected, since it lets people function in the everyday world, although they’re often labeled as “personality problems.”

* Seasonal affective disorder, a unipolar depression seen in northern latitudes in winter. Exposure to bright lights (2,500 lux, about 10 times as bright as normal indoor light) for several hours a day is effective in some people. Others require drug therapy.

Many nonpsychiatric illnesses can bring on or intensify depression, including diabetes, metabolic disorders, thyroid trouble, severe anemia, mononucleosis, hypertension and cancer. So, too, can certain drugs--most notably the benzodiazepene tranquilizers such as Valium, which are sometimes mistakenly given to depressed patients to help them sleep better but end up making their condition worse.

Consequently, doctors must conduct complete physicals and take patients’ drug histories before treating them for depression symptoms, experts said.

There is strong agreement on a genetic basis for depression, although a major study released in November failed to find a specific genetic defect. If one identical twin is depressed, the other has an 80% chance of suffering depression, too; for fraternal twins the chance is 60%; for non-twin siblings the correlation is 35%.

But the genetic predisposition doesn’t always result in depression, making the case for the role of the psychosocial environment. As in other illnesses, stress is seen as the probable trigger.

“People have varying genetically predetermined areas of vulnerability in their bodies,” Shuchter said. “For some it is their blood pressure, and some have headaches, and some get ulcers, and for some it affects the brain--with a predisposition to depression.”

The theory is that a combination of genetics and environment can disrupt normal mechanisms for the brain’s regulating of its internal levels of norepinephrine and serotonin. Antidepressants may artificially restore the biological balance of these neurotransmitters while the brain’s own regulatory mechanisms recuperate, suggested Dr. Floyd Bloom, a neurotransmitters expert at Scripps Clinic in La Jolla.

The role of psychotherapy, then, would be to prepare the psychosocial environment so the imbalance isn’t triggered again after the medication is withdrawn.

Bloom said he suspects that some of depression recurrences occur because medications are stopped before the brain can reset its regulators. Indeed, the rule of thumb is that medication should be continued for at least six months, even if symptoms have disappeared. And there will be some people who must stay on medications indefinitely, because their depression returns without them.

But methods learned in psychotherapy and “refresher courses” may help many others get through subsequent episodes without drugs, psychologists say.

For depressed people, the complexities of treating the disorder are dizzying to evaluate when their organ of perception and analysis--the brain--already isn’t working well.

“The best you can do is ask other people (for referrals), consult your internist and call your local university,” suggested UCLA’s Gitlin.

Patients should seek a good “fit” with the psychotherapist, not only personally but also in approaches to therapy. For instance, patient and therapist should have compatible attitudes toward use of antidepressant drugs.

And a no-nonsense patient would prefer a therapist who favors cognitive or behavioral therapies, rather than one who favors insight-oriented psychoanalysis that could take years.

People react differently to drugs and to psychotherapeutic approaches and it may take months before the right combination is found. Psychiatrists said patients should take a drug for 4-8 weeks before asking to try another one; psychotherapies, other experts advised, should show initial results in a month.

And if one or two antidepressants prescribed by a family doctor don’t work, consider seeing a psychiatrist knowledgeable in psychopharmacology; different drugs or dosages often can make a difference.

Seeking help early in a depression is important because it can make a difference whether an individual grows suicidal while waiting for treatments to take effect, experts said, adding that the ultimate test of the success of a particular drug or psychotherapy regimen is simple: It should work.

“Depression is a disruptive enough and painful enough experience that people should expect to get better and to ‘be themselves’ again,” said UC San Diego’s Shuchter. “And if that’s not happening they should be pressing to have that happen.”

THE DRUGS TRI-CYCLIC

ANTIDEPRESSANTS

Amitryptyline (Elavil and others); amoxapine (Asendin); clomipramine (Anafranil); desipramine (Norpramin, Pertofrane); doxepin (Adapin and others); imipramine (Tofranil and others); nortriptyline (Aventil, Pamelor).

Advantages: Most have been used for many years, so their actions are well documented.

Disadvantages: Side effects include sleepiness, dry mouth, constipation and weight gain.

MONOAMINE OXIDASE

(MAO) INHIBITORS.

Isocarboxazid (Marplan); phenelzine (Nardil); tranylcypromine (Parnate and others).

Disadvantages: Dangerous if mixed with decongestants and certain foods, including aged cheeses and red wine.

NEWER

ANTIDEPRESSANTS

Fluoxetine (Prozac); maprotiline (Ludiomil and others); trazodone (Desyrel and others); bupropion (Wellbutrin).

Advantages: Tend to have fewer side effects.

Disadvantages: Doctors aren’t as familiar with precautions or dosages. If Prozac isn’t tolerated, patient must be unmedicated for at least five weeks before taking another drug.

ON THE HORIZON

Sertraline , paroxetine , fluvoxamine (similar to Prozac, but appear better tolerated and don’t remain in the body as long). Venlafexine (appears to have more rapid onset and better toleration than Prozac). BuSpar (appears useful for depression that includes anxiety). Moclobemide (a quickly reversible MAO inhibitor).

Sources: The Medical Letter; Dr. John Feighner.