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 substituted.

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 illness.

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 manic-depression.

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 stabilizers.

“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 Dr. Ghaemi.

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 one’s life.”

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 validation.”