Depression is a chronic illness with recurring episodes. So should
we deploy antidepressants battle by battle, or order them in for the long
war?
When Sheila Singleton, 45, filled her first prescription for an
antidepressant, she assumed it would also be her last. "I thought OK,
when the pills work and get myself straightened out, I'll go back to
taking nothing but my vitamins," she says. Seventeen years later,
Singleton still pops a pill every day. During the brief intervals when
she's gone off medication, or when the ones she was on stopped working,
the depression returned with a vengeance.
Among the newer antidepressants, options range from SSRIs
(selective serotonin reuptake inhibitors) such as Prozac, Paxil, and
Zoloft, to those—Wellbutrin and Effexor, for example—that target
different or combined neurotransmitters. Most satisfied patients claim
they provide highly effective relief with few side effects.
But there is one notorious downside: roughly 70% of SSRI users are
plagued by sexual difficulty. "It's a big problem," acknowledges Donald
Klein, M.D., professor of psychiatry at Columbia University and director
of research at the New York State Psychiatric Institute. "There are no
hard data on how many people actually discontinue treatment due to the
sexual side effects; it largely depends on how they are handled by the
specific doctor. Zoloft, for example, is short-acting and can be stopped
for a couple of days, restoring sexual function for that period. Adding
Wellbutrin to an SSRI is another way to restore libido. But not all
doctors may try these adjustments; they may just say that's the price you
have to pay."
Another fly in the psychiatric salve is that that these drugs have
been officially approved only for short-term use—six to 12 months—yet
are routinely prescribed for indefinite periods, in order to prevent
future depressive episodes. It's not that the drugs are contraindicated
for long-term use, it's just been impossible to conduct long-term
studies. Americans move or drop out.
"So you have this disparity between the length of time for which
the medications are approved and the length of time you might have to
take them in order to have a good interval without depression," says
Peter D. Kramer, M.D. "No one has really bridged that gap and figured out
just what is appropriate for long-term treatment. It does seem that
recurrences are prevented. On the other hand, do the medications lose
their effectiveness? Are there long-term side effects? These are just not
known."
What is known is that although many individual depressive episodes
can be temporarily "fixed" by antidepressants, the drugs are not
curative, no more than insulin cures diabetes or anti-hypertensives cure
high blood pressure. The demon almost always returns at some
point.
"We're increasingly recognizing something our European colleagues,
who've been able to do longitudinal studies on depression, have known for
some time: That major depression is predominantly a recurrent illness,"
says Fred Goodwin, M.D., professor of psychiatry at George Washington
University, former director of the National Institute of Mental Health,
and host of "The Infinite Mind" on National Public Radio. "Eighty percent
of people who have had one episode will eventually have another one, one
year or many years down the road."
So why not just stop the medication after one episode is cured and
wait until the next one hits before resuming treatment? Kramer points to
a phenomenon known as kindling: the more episodes you have, the worse
they get—and the less stress it takes to trigger them. Anecdotal
evidence also suggests that going on and off medications may increase the
dose needed next time to achieve the same benefit as last time. In the
long run, stopping and starting doesn't reduce overall drug
exposure.
Untreated, some depressive episodes eventually resolve themselves,
on average, says Goodwin, in less than a year, though there is
considerable variation from person to person. What antidepressants do is
speed recovery by eliminating symptoms and enhancing motivation and
energy.
Klein points out that of 100 depressed patients given any
antidepressant, only 66 will show improvement. However, half of these
positive responses are a placebo effect. Thus, only a third of patients
are truly responding to the specific drug.
In Klein's estimation, the vast majority of sufferers—85% to
90%—can find substantial relief with one or a combination of drugs
within six to eight weeks, assuming they faithfully follow the prescribed
drug regimen ("total compliance" in medical jargon). Most people with
depression, he says, can find relief with the first or second
antidepressant they try. Only about 10% to 15% of patients, unipolar and
bipolar, are truly resistant to treatment.
A study of 161 outpatients, reported in the Journal of the
American Medical Association, demonstrated that long-term treatment with
sertraline (Zoloft) prevents recurrence of chronic severe depression. In
the study, conducted for 76 weeks, 50% (42) of 84 placebo-treated
patients experienced recurrence of significant depressive symptoms,
versus only 26% (20) of 77 patients given sertraline.
