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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…