For decades, the public and most mental health professionals have felt
that antidepressant medications are a magic bullet for depression.
Beginning in the late 1950s, antidepressants ushered in an era of safe,
reliable and reasonably affordable treatment that often produced better
results than the psychotherapies of the day. As the compounds rose in
popularity, many physicians came to view psychotherapy alone as
ineffective and as little more than a minor adjunct when combined with
medication.
This is no longer the case, if it was ever true. Contrary to
prevailing wisdom, recent research suggests that several focused forms
of psychotherapy may be as effective as medication, even when treating
more severe depressions. Moreover, the newer psychotherapies may
provide advantages beyond what antidepressants alone can achieve.
Nevertheless, pharmaceutical therapy remains the current standard of
treatment, and effective new options are being added all the time.
These trends are important to examine because depression exacts
a significant toll on society as well as individuals. Depression is one
of the most common psychiatric disorders and is a leading cause of
disability worldwide. The impact of mood disorders on quality of life
and economic productivity matches that of heart disease. Depression
also accounts for at least half of all suicides.
The efficacy of antidepressants has been established in thousands of
placebo-controlled trials. The newer ones are safer and have fewer
noxious side effects than earlier compounds. About 50 percent of all
patients will respond to any given medication, and many of those who do
not will be helped by another agent or a combination of them.
Not everyone responds, however, and many who do would prefer not to
have to take the pills. Quietly over the years, newer psychotherapeutic
techniques have been introduced that may be just as good at alleviating
acute distress in all but the most severely depressed patients. And
some of the therapies provide advantages over medication alone, such as
improving the quality of relationships or reducing the risk that
symptoms will return after treatment is over.
This last revelation is significant because many people who
recover from depression are prone to succumb again. The illness is
often chronic, comparable to diabetes or hypertension, and patients
treated with medication alone may have to remain on it for years, if
not for life, to prevent symptoms from returning. Moreover, combining
treatments--prescriptions to reduce acute symptoms quickly and
psychotherapy to broaden their effects and to prevent symptoms from
returning after treatment terminates--may offer the best chance for a
full recovery without recurring problems.
Remission or Relapse
Our conclusions refer mainly to the condition termed unipolar
disorder. Depression comes in two basic forms: The unipolar type
involves the occurrence of negative moods or loss of interest in daily
activities. In the bipolar form, commonly known as manic-depression,
patients also experience manic states that may involve euphoria,
sleeplessness, grandiosity or recklessness that can lead to everything
from buying sprees to impulsive sexual adventures that later bring
regret.
Bipolar disorder shows up in only 1 to 2 percent of the
population and is usually treated with mood-stabilizing medication such
as lithium. In contrast, about 20 percent of women and 10 percent of
men suffer from unipolar depression at some time in their lives.
The treatment of unipolar depression typically progresses
through three phases, determined by changes in the patient's intensity
of symptoms. These are usually measured by clinical ratings such as the
Hamilton Rating Scale for Depression. Seriously depressed patients in
the acute phase often report feeling down much of the time. They have
lost interest in formerly pleasurable activities, and they may have
difficulty sleeping, changed appetite, and diminished libido. They may
feel fatigued or worthless, and they may entertain recurrent thoughts
of death or suicide. The goal of treatment is to relieve symptoms.
"Remission" is reached when someone is fully well.
Even when in remission, however, patients may still have an elevated
risk for the return of symptoms. It is common practice to encourage
patients to stay on medication for at least six months following the
initial remission. The return of symptoms soon after remission is
called a relapse. In this sense, treating depression with drugs may be
like treating an infection with antibiotics; a patient must take the
medication beyond the point of first feeling better, to fully prevent
the original problem from coming back. This effort to forestall relapse
is called continuation treatment and typically lasts at least six to
nine months beyond the point of remission.
Those who pass the point at which the treated episode is likely
to return are said to have recovered. But even then, they might
experience a new episode; people with a history of depression are three
to five times more likely to have an episode than those with no such
history. A new episode is considered a recurrence. To protect against
recurrence, many patients are kept in ongoing maintenance treatment,
typically medication but sometimes with psychotherapy. But once
patients are off medication, having been on it does nothing to reduce
subsequent risk for recurrence. Therefore, patients with a history of
multiple episodes are usually advised to stay on medication
indefinitely.
Although the scope of depression can vary widely, there are
only a few prevailing treatments. Most of the leading antidepressants
fall into three main classes: monoamine oxidase inhibitors (MAOIs),
tricyclic antidepressants (TCAs), and selective serotonin reuptake
inhibitors (SSRIs), such as Prozac and Paxil. Each class has a slightly
different action and different side effects and is prescribed based on
a patient's history, the likelihood of certain complications, and cost.
Although about equally effective in a general population, some
medications are more efficacious than others for specific types of
depression. In general, the older MAOIs and TCAs carry greater risk of
side effects than the SSRIs. But the SSRIs do not always work,
especially for more severely depressed patients, and they are more
expensive.
Despite the widespread use of antidepressants, their actions
are not fully understood. They work in part by affecting the
neurotransmitters (signaling molecules in the brain) norepinephrine,
serotonin and dopamine, which are involved in regulating mood,
primarily by blocking the reuptake of these neurotransmitters into the
neurons that secrete them. Yet this action cannot fully explain the
effects, and it is quite likely that the compounds drive a subsequent
cascade of biochemical events. Many people who do not respond to one
antidepressant will respond to another or to a combination.
New psychotherapy methods have proved as effective as
medication, although they are still not as extensively tested. The
programs include interpersonal psychotherapy (IPT), which focuses on
problems in relationships and helps patients lift the self-blame common
in depression. Developed in the 1970s, IPT has performed well in trials
but has only begun to enter clinical practice. Studies do show,
however, that when IPT is paired with medication, patients receive the
best of both worlds: the quick results of pharmaceutical intervention
and greater breadth in improving the quality of their interpersonal
lives.
Cognitive and behavioral therapies, collectively known as CBT,
also compare well with medication in all but the most severely
depressed patients--and they can benefit even those people if they are
administered by experienced therapists. Most exciting is that CBT
appears to have an enduring effect that reduces risk of relapse and
perhaps recurrence. Even the most effective of the other treatments
rarely have this type of long-lasting benefit. Cognitive therapy is
perhaps the most well established CBT approach. It teaches patients to
examine the validity of their dysfunctional depressive beliefs and to
alter how they process information about themselves. Behavioral therapy
had lost favor to the cognitive approaches, but it, too, has done well
in recent trials and is undergoing a revival.
Which Way to Turn
It is not possible to simply say whether medication or psychotherapy is
"better" for depressed patients. But many studies have reached
interesting conclusions about the approaches when they are applied
across the illness's three phases: the acute symptoms at onset, the
months of continuation treatment to forestall relapse, and the
maintenance of health for years to come.
Among patients who take antidepressants during treatment for
acute symptoms, about half show a 50 percent drop in symptom scores on
rating tests over the first four to eight weeks. About one third of
those patients become fully well (remission). Not all the improvement
can be attributed to pharmacology, however. In pill-placebo control
experiments, placebos can achieve up to 80 percent of the success rate
of active medication, probably by instilling in patients hope and the
expectation for change. The placebo effect does tend to be less stable
over time and smaller in magnitude in more severe or chronic
depressions. A major problem with acute-phase therapy, however, is that
many stop taking their medication--primarily because of side
effects--before therapists can clearly tell if the agents are working.
Attrition rates from clinical trials are often 30 percent or higher for
older medications such as the TCAs and around 15 percent for newer
options such as the SSRIs.
The newer psychotherapies appear to do as well as medication
during the acute depression phase, although the number of studies is
fewer and the findings are not always consistent. One typical study
found that IPT alone was about as effective as medication alone (with
each better than a control condition) and that the combination was
better still. In general, medication relieved symptoms more quickly,
but IPT produced more improvement in social functioning and quality of
relationships. The combined treatment retained the independent benefits
of each.
IPT also fared well in the 1989 National Institute of Mental
Health Treatment of Depression Collaborative Research Program. The
TDCRP, as it is known, is perhaps the most influential study to date
that compared medication and psychotherapy. In that trial, patients
with major depression were randomly assigned to 16 weeks of IPT, CBT or
the TCA imipramine, combined with meetings with a psychiatrist or a
placebo plus meetings. Patients with less severe depression improved
equally across conditions. Among more severely depressed patients,
imipramine worked faster than IPT, but both were comparable by the end
of treatment and both were superior to a placebo.
As for CBT, most of the published trials have found it to be as
effective as medication in the acute phase. The most notable
exception--the TDCRP--did find that cognitive therapy was less
efficacious than either medication or IPT (and no better than a
placebo) in the treatment of more severely depressed patients. Because
the study was large and was the first major comparison to include a
pill-placebo control, its results considerably dampened enthusiasm for
cognitive therapy, even though no other study had produced such a
negative finding.
Today this conclusion appears to have been premature. More
recent studies have found that CBT is superior to pill-placebos and is
as good as an SSRI for more severely depressed outpatients. These
studies suggest that cognitive therapy's success depends greatly on the
level of a therapist's training and experience with it, especially for
patients with more serious or complicated symptoms.
Continuing the Fight
The best treatments for reducing acute
distress also seem to work as well for reducing relapse when they are
carried into the continuation phase. Antidepressants appear to reduce
the risk for relapse by at least half. It is unclear exactly how long
patients must keep taking medication to pass from remission into full
recovery, but current convention is to go for at least six to nine
months.
IPT during the continuation phase appears to prevent relapse nearly as
well as medication, although studies in this regard are few. Recent
investigations also suggest that if cognitive therapy is continued past
the point of remission, it can reduce the risk for relapse. To date, no
studies have compared continuation CBT to continuation IPT or
medication.
During the maintenance phase, medication is usually recommended
for high-risk patients, especially those with multiple prior episodes.
Therapy can go on for years. It does protect against recurrence. Even
among recovered patients, though, the risk of recurrence off medication
is at least two to three times greater. Given that there is no evidence
that prior medication use does anything to reduce subsequent risk for
recurrence, most physicians will encourage their high-risk patients to
stay on medication indefinitely.
Studies of maintenance IPT are few, but they generally support
the notion that it, too, reduces risk of recurrence. It has not been as
efficacious as keeping people on medication, but the handful of studies
have typically cut back the frequency of IPT to monthly sessions while
maintaining medication at full, acute-treatment dosages. It would be
interesting to see how maintenance IPT compares when the psychotherapy
sessions are also kept at "full strength."
Several studies have shown that CBT has an enduring protective
benefit that extends beyond the end of treatment. Patients treated to
remission with CBT were only about half as likely to relapse after
treatment termination as patients treated to remission with medication,
and the CBT patients were no more likely to relapse than patients who
continued on the prescriptions. CBT appears to produce this enduring
effect regardless of whether it is provided alone or in combination
with medication during acute treatment and even if it is added only
after medication has reduced acute symptoms. Further, indications are
that this enduring effect may even prevent wholly new episodes
(recurrence), although findings are still far from conclusive.
Given these trends, CBT may ultimately prove more
cost-effective than medication. Psychotherapy usually costs at least
twice as much as medication over the first several months, but if the
enduring effect of CBT truly extends over time, it may prove less
costly for patients to learn the skills involved and discontinue
treatment than to stay on medication indefinitely. It remains unclear
whether other interventions such as IPT have an enduring effect, but
this possibility should certainly be explored.
Our review of the treatment literature indicates that some
forms of psychotherapy can work as well as medication in alleviating
acute distress. IPT may enhance the breadth of response, and CBT may
enhance its stability. Combined treatment, though more costly, appears
to retain the advantages of each approach. Good medical care can be
hard to find, and the psychotherapies that have garnered the most
empirical support are still not widely practiced. Nevertheless, some
kind of treatment is almost always better than none for a person facing
depression. The real tragedy is that even as alternatives expand, too
few people seek help.