Sachs, director of the clinical psychopharmacology unit of the Massachusetts General Hospital's Bipolar Mood Disorder Program, spoke in a symposium on "Current Treatment Approach in Managing Bipolar Disorder" organized by GlaxoSmithKline Philippines. He discussed various aspects of bipolar disorder, including diagnostic classification, evidence-based treatment algorithms, prevention of recurrences, and the need for treatment to reduce mortality risks.

Misdiagnosis, mistreatment

    In 2000, Angst et al. reported that standardized mortality ratios showed a 30-fold higher risk of suicide among untreated bipolar patients than in the general population. With appropriate treatment, this risk was brought down by 80 percent.

    The problem is that prompt management of bipolar disorder is complicated by time. On average, it takes about a decade from onset before patients are correctly diagnosed, said Sachs. "During that decade, there is not only considerable stigma and impairment; misdiagnosis is [also] often linked with mistreatment."

    Bipolar disorder is a lifelong condition with recurrent episodes, apparently triggered more with mania than depression. Sachs explained: "If you have had one episode of mania, you can see that almost always you'll have another....Bipolar disorder, by its very nature, is recurrent."

A STEP better

    Patient participation is important in the management of bipolar disorder, Sachs stressed, relating a scheme adopted under the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) of the United States National Institute for Mental Health. The program educates patients and lets them choose from evidence-based treatment options.

    "We offer the patients a menu of reasonable choices….We educate them about the profile and adverse effects, rate the evidence for efficacy of these options, and let them choose," said Sachs.

    Patients are also classified into one of eight mutually exclusive clinical states. Recognizing the appropriate clinical status is key because it is the link to a particular treatment pathway. Mania, depression, hypomania, and mixed episode (mania + depression) are four "full syndromal" bipolar states defined in DSM-IV.

    "Subsyndromal states" are also recognized. Continued symptomatic patients would have just three or four symptoms of depression, while "euthymic" patients for a week or two are necessarily recovering (partial remission). Recovered means being well for eight consecutive weeks. Roughening is a "new subsyndromal" state occuring after a patient has recovered.

    A roughening patient may be headed for a recurrence. Sachs said roughening provides the opportunity for preventing a new full episode from recurring. When the roughening is towards depression, 25 percent of the patients are likely to meet the criteria for major depression within four weeks. But if the roughening is toward hypomania or mania, two-thirds of patients would be manic within four weeks.

    The manner of treatment is also vital. The "sequential care" approach would involve selecting the most benign treatment like low-dose monotherapy for better tolerability. An "urgent care" situation, on the other hand, is necessary for patients acutely manic, suicidal, or depressed with psychotic features.

    Sachs said it is also important to recognize that patients with bipolar disorder more often suffer from depression than mania.

    In the treatment of depression-dominated bipolar disorder, only three monotherapies--lamotrigine, olanzapine, and quetiapine--have conclusive evidence of efficacy, said Sachs. Olanzapine and fluoxetine is the only combination that show benefits. Category A evidence exists for lamotrigine, he said, citing a study by Calabrese et al. where lamotrigine monotherapy achieved significant reduction in MADRS score from baseline.

    In the maintenance phase, five agents have been shown to work: lithium, valproate, lamotrigine, olanzapine, and aripiprazole. Two of the most rigorous trials involve lamotrigine and lithium. Citing studies by Bowden, et al., Sachs said lamotrigine had lower recurrence rate for depression compared with lithium, although lithium was slightly better in preventing recurrence of mania, but the difference was not statistically significant.

    Concluded Sachs: "This is why the FDA (Food and Drug Administration) approved Lamictal (lamotrigine) for the prevention of recurrence of episodes of depression as well as mania. You could see clearly where the edge is for lamotrigine, [which] is on the depressed side, and where the edge for lithium is, the high side. Lamotrigine was also well tolerated and not associated with weight gain." R. Badillo, MD