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Augmenting Strategies for Bipolar Depression

They’re not created equal — but none are very effective, anyway.

Bipolar depression is notoriously difficult to treat. Usual strategies include combining a mood stabilizer with a tricyclic antidepressant or with an SSRI; adding ECT; switching mood stabilizers; switching to monoamine oxidase inhibitors, to quetiapine, or to olanzapine combined with fluoxetine; or adding novel treatments such as pramipexole (a dopamine agonist) or riluzole (an NMDA-receptor antagonist). However, evidence supporting these strategies varies in quality.

As part of the NIMH-sponsored Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), 66 patients with treatment-resistant bipolar depression received open-label lamotrigine (starting dosage, 50 mg/day; increased to 150–250 mg/day), inositol (starting dosage, 2.5–5.0 g/day; increased to 10–25 g/day) or risperidone (starting dosage, 0.5–1.0 mg/day; increased, as tolerated, to 6.0 mg/day). Treatments were given via equipoise randomization, where patients could choose to be randomized to two or to three competing drugs. All patients continued their mood stabilizer and antidepressant treatments.

In a series of head-to-head comparisons, treatment response at 16 weeks did not differ among the groups, but lamotrigine yielded the best outcomes on two secondary measures and in post hoc analyses. Overall rates of recovery (i.e., no more than two symptoms meeting DSM-IV threshold criteria for a mood episode and no significant symptoms for 8 weeks) were 24% for lamotrigine, 17% for inositol and 5% for risperidone — but these differences were not statistically significant. Lamotrigine recipients generally elected to stay on the study medication longer than did inositol or risperidone recipients.

Comment: Regardless of treatment assignment to lamotrigine, inositol, or risperidone, the rates of sustained recovery were low. A much larger study population would be required to find significant differences. The search for better therapies for treatment-resistant bipolar depression clearly has a long way to go.

— Joel Yager, MD

Published in Journal Watch Psychiatry March 22, 2006

Citation(s):

Nierenberg AA et al. Treatment-resistant bipolar depression: A STEP-BD equipoise randomized effectiveness trial of antidepressant augmentation with lamotrigine, inositol, or risperidone. Am J Psychiatry 2006 Feb; 163:210-6.

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