It's one of the most missed diagnoses in psychiatry.
Bipolar disorder, involving moods that swing between the highs of
mania and the lows of depression, is typically confused with
everything from unipolar depression to schizophrenia to substance
abuse, to borderline personality disorder, with just about all stops
in between. Patients themselves often resist diagnosis, because they
may not see as pathologic the surge in energy that accompanies the
mania or hypomania that distinguishes the condition.
But on a few points consensus is emerging. Bipolar disorder is a
chronically recurring illness. And the age of onset is dropping--in
less than one generation it has gone from age 32 to 19. Whether
there is a genuine increase in prevalence of the disorder is a
matter of some debate, but there does seem to be a genuine increase
among the young.
What's more, the depression of manic-depression is emerging as a
particularly thorny problem for both patients and their doctors.
"Depression is the bane of treatment of bipolar disorder," says
Robert M.A. Hirschfeld, M.D., head of psychiatry at the University
of Texas Medical Branch in Galveston.
It's what is most likely to motivate patients to accept care.
People spend more time in the depression phase of the disorder. And
unlike unipolar depression, the depression of bipolar illness tends
to be treatment-resistant.
"Antidepressants don't work very well in bipolar depression,"
says Dr. Hirschfeld. "They are underwhelming in their ability to
treat the depression." In fact, a shift away from antidepressants is
formally recognized in new treatment guidelines for bipolar disorder
just released by the American Psychiatric Association.
As physicians gain experience in treating the disorder, they are
discovering that antidepressants have two negative effects on the
course of the disorder. Used by themselves, antidepressants can
induce manic episodes. And over time they can accelerate mood
cycling, increasing the frequency of episodes of depression or of
mania followed by depression.
Instead, research points to the value of drugs that work as mood
stabilizers for the depression of bipolar disorder, either alone or
in combination with antidepressants. If antidepressants have any use
at all in bipolar disorder, it may be as acute treatment for bouts
of severe depression before mood stabilizers are added or
Even in cases of severe depression, the new guidelines favor
increasing the dosage of mood stabilizers over other strategies.
Until recently, mood stabilizers could be summed up in a single
word--lithium, in use since the 1960s to tame mania. But over the
past decade research has additionally demonstrated the effectiveness
of divalproex sodium (Depakote) and lamotrigine (Lamictal), drugs
that were initially developed for use as anticonvulsants in seizure
disorders. Divalproex sodium has been approved for use as a mood
stabilizer in bipolar disorder for several years, while lamotrigine
is currently undergoing clinical trials for such an application.
"Optimizing the dose of lithium or divalproex has good
antidepressant effects," reports Dr. Hirschfeld. "We also now know
that divalproex and lamotrigine are very good for preventing
recurrence in bipolar patients." A recent study showed that
lamotrigine not only delays the time to any mood events but is
notably effective against the depressive lows of bipolar
No one knows for sure exactly how anticonvulsants work in bipolar
disorder. For that matter, the condition has been described since
the time of Hippocrates, but it is still not clear what goes awry in
Despite the unknowns, medications for treating the disorder are
proliferating. In contrast to downplaying antidepressants in the
depressive phase of the disorder, clinical research is ramping up
the value of antipsychotic drugs for combating the manic phase,
albeit a new generation of such drugs, collectively called atypical
antipsychotics. Chief among them are olanzapine (Zyprexa) and
risperidone (Risperdal). They are now considered a first-line
approach to acute mania, and adjuncts for long-term therapy along
with mood stabilizers.
In the long term, however, observes Nassir Ghaemi, M.D.,
assistant professor of psychiatry at Harvard and head of bipolar
research at Cambridge Hospital, medication goes only so far. "Drugs
are not effective enough. It may have to do with the overuse of
antidepressants; they interfere with the benefits of mood
"Medications don't take you to the finish line." There seem to be
residual symptoms of depression that don't clear. Even when patients
stabilize into a normal, or euthymic, mood state, he says, some
troubling signs can appear.
"Sometimes we see in euthymic patients cognitive dysfunction that
we didn't expect in the past--word-finding difficulties, trouble
maintaining concentration," Dr. Ghaemi explains. "Cumulative
cognitive impairment seems to emerge with time. It may be related to
findings of decreased size of the hippocampus, a brain structure
that serves memory. We are on the verge of recognizing long-term
cognitive impairment as a result of bipolar disorder."
He believes there is a role for aggressive psychotherapy for
keeping patients well, for keeping everyday ups and downs from
becoming full-blown episodes. At the very least, he finds,
psychotherapy can help patients resolve the work and relationship
problems that often outlast symptoms.
In addition, psychotherapy can help patients learn new coping
styles and interpersonal habits. "Many of the ways patients deal
with their illness are not relevant when they are well," explains
For example, he says, many people develop the habit of staying up
late as a way of coping with the manic symptoms. "What they couldn't
change before because of the illness needs to be changed after
treatment if, for example, it bothers a spouse. People have to learn
to change. But the longer one is ill, the harder it is to become
completely well, because the harder it is to change the habits of
And for young people diagnosed with bipolar illness, he considers
psychotherapy essential. "The younger patients are, the less
convinced they are that they have bipolar disorder," he says. "They
have impaired insight. They're especially concerned about the need
to take medications. They should be in psychotherapy to get educated
about the illness and medication."
He also stresses the value of support groups, especially for
young people. "It's another, important layer of