New depression treatments are extremely effective – use of medications and psychotherapy – includes related information on depression myths – Special Report: Helping Employees Overcome Depression
The majority of sufferers can obtain relief from medication alone. Adding psychotherapy helps even more.
The high incidence of depressive illness, along with the enormous financial and emotional costs that it generates, has provided strong impetus for scientists to develop new ways of treating the disease.
Researchers have learned that psychoactive drugs can combat depression in the majority of patients. In addition, new, short-term psychotherapies (See “The role of psychotherapy,” page 25), used in conjunction with antidepressant medications, are providing relief for more than 80% of those individuals who suffer from mild to moderate depression.  For patients whose depression is more severe, resistant to medication, or even life-threatening, electroconvulsive therapy (ECT) may offer additional hope.
When someone is diagnosed with clinical depression, chances are that his or her doctor will prescribe an antidepressant medication. “If I diag-nose a major depression, medication is absolutely the treatment,” says Edward Shahady, M.D., professor of family medicine at the University of North Carolina in Chapel Hill.
According to Stewart H. Reiter, M.D., clinical director of Summit Psychiatric and Counseling Associates in Summit, N.J., antidepressant medications alone are capable of treating more than 70% of all cases. 
Brain chemistry is the culprit
The number of available antidepressant medications is growing as scientists understand more about the chemical changes that take place in the brain and that apparently cause depression.
Investigation in this area stems from breakthrough research performed by Julius Axelrod, a researcher for the National Institute of Mental Health (NIMH) in Bethesda, Md. In 1960, Axelrod discovered that the neurons within the brain communicate via specific chemicals, or neurotransmitters, that flow across the synapses, as the gaps between neurons are called.
Axelrod’s landmark work, for which he received a Nobel Prize, paved the way for extensive study into how psychotropic drugs–including antidepressants–can be used to alter this communication in ways that are beneficial.
Basically, antidepressants change the level of the brain’s neurotransmitters in either one or both of two ways. They may increase the amount of time it takes for these chemicals to be taken up by brain cells, and they may slow the rate at which chemical neurotransmitters break down. Both actions result in an increased level of neurotransmitters in the brain, thereby correcting any chemical imbalance and relieving symptoms of depression in most patients.
Most of the antidepressants available today fit into one of three general classifications: tricyclics, monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitors (SSRIs).
Tricyclics: the first antidepressants–
For more than 25 years, tricyclics have been used to treat depression. These drugs slow the rate at which neurotransmitters are taken up by the brain’s neurons. For many patients, this correlates with a reduction in depression symptoms.
On the other hand, tricyclics can have several drawbacks. “Probably the most common and troubling side effect is that patients feel drugged, sedated. They have trouble thinking,” says Robert Robinson, M.D., chairman of the department of psychiatry at the University of Iowa College of Medicine, in Iowa City.
Other side effects include: dry mouth; blurred vision; tachycardia (excessively rapid heartbeat); constipation; urinary hesitancy and blockage; memory and cognitive difficulties; and paralytic ileus (intestinal blockage).
Weight gain and lowered blood pressure are other side effects of some tricyclics, notes Shahady. While some of the effects show up only rarely, others appear almost universally. Referring to his own experiences with patients, Shahady explains, “I think almost everybody who takes tricyclics gets the dry mouth and blurred vision.”
MAOIs: rarely used–
Medications in the MAOI category inhibit one enzyme that breaks down neurotransmitters. This indirectly increases the quantity of neurotransmitters in the brain, also resulting in a shift in chemical balance.
Due to the severity of potential side effects that can result from interactions with foods and other drags, however, MAOIs are the most rarely used drugs to treat depression. For example, when combined with certain foods or drinks containing tyramine–such as aged cheeses, beer or wine, or pickled foods–MAOIs can potentially cause severe hypertension or fatal circulatory problems in some people.
Andrew A. Nierenberg, M.D., is associate director of the depression research program of the chemical psychopharmacology unit at Massachusetts General Hospital, in Boston. Nierenberg estimates that because of these serious potential interactions, fewer than 1% of physicians now prescribe MAOI drags for their patients. 
SSRIs: Effectiveness, with fewer side effects
These drags inhibit the reuptake of a single type of chemical neurotransmitter–serotonin–by brain cell receptors. The result is a net increase in the level of serotonin.
Because SSRIs affect just one type of neurotransmitter, the potential for adverse side effects is minimized. SSRIs do not usually make a patient feel sedated. Nor do they usually result in weight gain, notes Robinson, citing another factor that has contributed to the popularity of SSRIs.
SSRIs also offer a safety advantage in cases of accidental—or intentional-overdose. The sobering truth, Shahady reports, is that some subset of all depression sufferers will attempt suicide. Shahady says that he is extremely cautious about prescribing tricyclics to those patients he suspects may be at greater risk of suicide. “When I treat someone with a sedating tricyclic who is potentially suicidal, I only give that person one week’s worth of tricyclic medication at a time,” he says.
Michael Thase, M.D., is director of the mood disorders program of the department of psychiatry at the University of Pittsburgh School of Medicine. Thase says that SSRIs, by contrast, can be prescribed with greater confidence than tricyclics.
A few mild and usually short-lived side effects are associated with SSRIs. They include nausea, diarrhea, nervousness, and insomnia. Despite these side effects, and given the fact that SSRIs offer the same high degree of efficacy as the other antidepressants, SSRIs are becoming increasingly popular.
Short- and long-term treatment
While antidepressants are highly effective, patients usually have to wait several weeks for the medication to take effect. If the results aren’t satisfactory after that time, says Shahady, the physician might increase the dosage or consider switching to another antidepressant. However, more than half of all patients taking antidepressants show noticeable improvement by about the sixth week, according to the Agency for Health Care Policy and Research (AHCPR) in Rockville, Md.  The AHCPR recently issued guidelines for the treatment of depression.
The fact that depression may involve several chemical pathways means that even if one drug doesn’t work for a particular patient, the odds of finding relief through another one are still very good. Or, instead of switching medications, doctors may find that a combination of medications is the most effective treatment.
Currently, the initial course of treatment lasts from four to nine months. Typically, patients take antidepressants for at least six months.
However, taking the medication just long enough to resolve a single episode of depression is not usually advisable, doctors maintain. Virtually all studies of this illness indicate that once a person has experienced a major depressive episode, the likelihood of having a recurrence increases dramatically
Based on two studies [17-19] that they conducted over a seven-year period (as reported in the October 1992 issue of Archives of General Psychiatry), Thase and several other researchers found that “when people have had several bouts of depression, they remain at high risk for further bouts unless they stay on longer-term treatment.”
The studies on recurrence included patients who had had at least two prior depressive episodes, Thase says. In the first study, the three-year depression recurrence rate for patients who did not receive any continuing treatment was a startlingly high 85%. By contrast, the rate of relapse for patients who received either maintenance medication (regular doses) or medication plus psychotherapy was only about 20%.
The study also evaluated the effectiveness of interpersonal psychotherapy alone. This form of treatment focuses on the way in which the depressed person relates to others. Thase reports that the result of using psychotherapy alone “was about midway between doing nothing and staying on medication.”
In a follow-up blind study, half of the patients who had remained well agreed to go off medication. Within two years, depressive episodes recurred in about 80% of those who were no longer taking medication. None of those who had remained on antidepressants for those same two years suffered a relapse.
According to this and other research, continued treatment with antidepressants may help prevent recurrence of the disease. Moreover, it appears that patients who have already suffered repeated episodes of depression and who are thus more likely to suffer relapses in the future may benefit not only from continued short-term treatment, but possibly long-term treatment with antidepressants.
The role of psychotherapy
The efficacy of antidepressant medication for most depressed patients is undeniable. However, some experts feel that medication alone is not the answer. “There’s an enormous emphasis on the biological aspects of depression,” notes Harold Goldstein, training director for the NIMH-sponsored Depression Awareness, Recognition and Treatment (D/ART) Program. “And while no one would really argue that there aren’t chemical imbalances, the real question is, `What triggers those imbalances?’
“It’s very hard to determine the precise cause,” Goldstein concedes. “But there are a variety of therapies that address both the psychosocial and cultural aspects of depression.”
Today, psychotherapeutic treatment methods used by practitioners vary along a continuum. However, many of the courses of treatment are relatively short-term and highly focused and require the active involvement of both therapist and patient. The short-term approach focuses on identifying single, specific, current problematic thoughts and behaviors and attempting to modify them.
Cognitive behavioral therapy (CBT), for example, is directed at modifying the automatic negative thinking that is often typical of depressed patients, explains Reiter.
Goldstein offers a workplace-related example of how depressed people may possibly react: A manager walks past an employee without acknowledging him or her. If the employee has a tendency toward depression, he or she might interpret that event by thinking, “The boss is angry at me. I’ve done something wrong. I didn’t do a good job.”
Responses such as these “are so ingrained in this person’s way of operating that they occur instantaneously, without the person’s stopping to think that maybe the boss was busy or that he or she was in a hurry–anything other than ‘I did a terrible job,'” explains Goldstein.
One technique often used in CBT and variants of cognitive therapy is giving the patient written homework assignments. The patient may be asked to keep a formal record of moods and thoughts during the day
Those thoughts, logged in writing by the patient, would be the subject of discussion during the next therapy session. The objective is to help the person become aware of and control these types of negative responses and to get the patient involved in examining his or her thought processes.
Interpersonal therapy (IPT), on the other hand, “focuses on the real-adaptive ways in which people relate to each other when they’re depressed,” he explains. This type of therapy emphasizes improving the depressed patient’s interpersonal functioning. IPT is short-term and usually concentrates on one or two problems.
An employee going through a divorce, for example, may become profoundly upset at the prospect of being single again. The therapist’s strategy in this situation might include encouraging the patient to develop both a support system and social skills.
Research indicates that psychotherapies such as CBT and IPT are about as effective as some antidepressants in patients who have not been diagnosed with major or severe depression. In a study  conducted over 18 months, researchers at the NIMH Treatment of Depression Collaborative Research Program found these psychotherapies about as effective as imipramine, a tricyclic medication. Neither type of psychotherapy was found to be superior to the other for patients with mild to moderate depression.
However, for those patients with severe depression, antidepressants are still usually considered the first course of treatment. “Sometimes I have to get patients on antidepressants before they can even think about going for psychotherapy,” says Shahady
Treating the most severe cases
Medication and/or psychotherapy can alleviate depressive symptoms for most patients. But for the minority of patients who don’t respond to such treatment or for the patient who is severely depressed, profoundly incapacitated, suicidal, or who has a medical condition that precludes use of antidepressant medication, ECT may be the treatment of choice.
“ECT is probably given to less than 10% of the patients we treat, simply because the other treatments are effective in most patients,” Thase notes. The only serious drawback of ECT, he says, is that like taking a single course of antidepressant medication, receiving a single ECT treatment doesn’t minimize the chance that the patient will have another depressive episode in the future. The severely depressed patient who is not taking antidepressant medication may require yearly or bi-yearly courses of ECT. Despite its limitations, however, ECT can be helpful in intractable cases of depression. “ECT is the most efficacious short-term treatment known for severe depression,” says Thase.
Research efforts in depression treatment are now aimed at discovering new medications that have fewer side effects as well as antidepressants that will work for the small percentage of patients who aren’t responsive to current medication.
More drags in the SSRI category are coming to market. Among them are drugs that affect a specific serotonin receptor (referred to as the 5HT receptor) located in the brain. Other research addresses the possibility that depression may be associated with a specific area of the brain. During 1992, at least four reports were released that linked primary mood disorders with abnormalities of function in the left prefrontal cortex of the brain. [20-24]
Robinson’s work at the University of Iowa College of Medicine supports these suppositions. “Since 1984, we have been reporting that injury to the left prefrontal cortex produces a very high frequency of depression,” he asserts. It’s too soon to tell the effect of targeting therapies toward the left prefrontal cortex brain area, he concedes. However, he adds, “We are at the beginning stages of making those kinds of inferences.”
Certain questions still need answers, Robinson points out. Among them: Are biochemical changes that occur in the left prefrontal cortex different from those that occur in other parts of the brain? Does the left prefrontal cortex have different connections that make it particularly important in depression?
“When those questions are answered,” he says, “we can begin to identify how we might be able to more specifically target treatment?
Considering the rapid developments taking place in drug research, the millions of people who now suffer from depression have reason to be optimistic. Today’s treatments are highly effective. Tomorrow’s may be even better.
Misinformation and myth
Over the years, physicians and patients alike have contended with inaccurate and misleading information about antidepressant medications. Patients sometimes must deal with negative advice from well-meaning but uninformed family members and friends about staying with their medications for an extended period. “They actually have relatives counsel them about getting ‘hooked’ on antidepressants,” says Michael Thase, M.D., director of the mood disorders program of the department of psychiatry at the University of Pittsburgh School of Medicine.
The idea that antidepressants are addictive is commonplace. “It’s a myth that a lot of people believe,” adds Edward J. Shahady, professor of family medicine at the University of North Carolina in Charlotte.
Some practical evidence also exists that antidepressants aren’t physically addictive. That evidence, according to Shahady, is the lack of popularity of antidepressants in illicit street trade. “Antidepressants aren’t like the uppers and downers used by drug addicts. You don’t get kicks with them,” stresses Shahady.
Some recent evidence indicates that patients taking tricyclics regularly over a period of years may have some withdrawal symptoms if the medication is stopped abruptly. The risk of withdrawal symptoms upon abrupt discontinuation of SSRIs, however, is significantly lower than with tricyclics.
Another myth that received attention in the lay press a few years ago centered around the claim that some antidepressants could cause mental disturbances, possibly leading to suicide. Robert Robinson, M.D., chairman of the department of psychiatry at the University of Iowa College of Medicine in Iowa City, contends that it was simply the rapid popular acceptance of SSRIs that led to the exaggerated media attention that was given to sporadic reports of suicidal tendencies in patients taking the drug.
In the meantime, extensive investigations, including an evaluation by the FDA, have been conducted. No evidence of a link between antidepressants and an increased risk of suicide has been found.
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