New Studies Help Patients With Treatment-Resistant Bipolar Disorder

Main Category: Bipolar
Article Date: 01 Feb 2006 - 23:00 PDT

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The initial results of two of the "Sequenced Treatment Enhancement Program for Bipolar Disorder" (STEP-BD) studies are being released in the February 2006 edition of the AMERICAN JOURNAL OF PSYCHIATRY (AJP), the official journal of the American Psychiatric Association (APA).

STEP-BD, supported by the National Institute of Mental Health (NIMH), is the largest federally-funded treatment study ever conducted for bipolar disorder, also known as manic depression. In its entirety the study, conducted over five years with more than 4,000 participants in real world clinical settings, will evaluate all the best-evidence treatment options used for the disease. These two papers report initial results on treatment outcomes and recurrence characteristics.

The AJP article, "Predictors of Recurrence in Bipolar Disorder: Primary Outcomes From the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)" authored by Roy H. Perlis, M.D., evaluates 1469 participants who were in the trial for up to two years. The study reports that 58 percent of participants experienced a significant period of recovery in response to evidence-based treatment for bipolar disorder including contemporary medications and psychosocial interventions. However, about half of the recovered patients had recurrences during the following two years.

Recurrence was more likely to take the form of depression than mania and was more common among patients who had residual mood symptoms despite being considered recovered. The authors conclude that more vigorous treatment of each episode is required to minimize the possibility of relapse.

"STEP-BD's purpose is to provide information to give doctors and patients guidance about the relative effectiveness of treatment options. Because bipolar disorder affects over one percent of the population, we expect a number of people to benefit from this clinical guidance," said Robert Freedman, M.D., AJP editor-in-chief.

A companion AJP article, "Treatment-Resistant Bipolar Depression: A STEP-BD Equipoise Randomized Effectiveness Trial of Antidepressant Augmentation With Lamotrigine, Inositol, or Risperidone" led by Andrew A. Nierenberg, M.D., compares three possible supplementary treatments for those patients who have treatment-resistant bipolar depression and finds some advantages for lamotrigine as an addition to other mood stabilizers and antidepressants.

The 66 patients in the study were already receiving a mood stabilizer plus at least one antidepressant, as is widely recommended. What to do if this combination fails is not clear, and so in this trial one of three agents was added: lamotrigine (another mood stabilizer), inositol (a sugar derivative with effects on intracellular signaling) or risperidone (an atypical antipsychotic).

The choice of these three agents was dictated by preliminary evidence for their possible effectiveness for patients who have failed to respond to initial treatment. The three treatments represent quite different mechanisms of drug action. Lamotrigine is an antiseizure medication; many such medications have effectiveness in bipolar disorder. Inositol affects hormone signaling inside nerve cells, a mechanism of effect that is similar to that of lithium ion, the oldest treatment for mania. Risperidone is a drug that is effective in schizophrenia; many antischizophrenic drugs are also effective in bipolar disorder.

Although the recovery rates were modest to low and did not differ significantly among treatments, lamotrigine was better for treating depressive symptoms, improving functioning and increasing willingness to continue treatment. Longer treatment duration is considered a key element of real-world effectiveness. "We commend the National Institute of Mental Health for undertaking this lengthy, costly, and complex study. Trials such as STEP-BD are indispensable for understanding the effectiveness of treatments in the diverse array of patients who are seen in everyday treatment settings," said Darrel A. Regier, M.D., M.P.H., director of APA's Division of Research.

"The availability of research-based information about the strengths and weaknesses of various treatment combinations will be of great benefit to clinicians who necessarily must tailor treatment to each patient's particular needs," Dr. Regier said.

(Am J Psychiatry. 2006; 163: 210-224).

About the American Psychiatric Association

The American Psychiatric Association is a national medical specialty society whose more than 36,000 physician members specialize in diagnosis, treatment, prevention and research of mental illnesses including substance use disorders.
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