Treatment Resistent Depression

Q: Augmenting fluoxetine with olanzapine may provide a successful treatment for resistant major depression, while causing only minimal side effects, researchers conclude in a report published in the January 1st issue of the American Journal of Psychiatry.

A:In an 8-week, randomized double-blind trial, Dr. Richard C. Shelton of the Vanderbilt Medical Center in Nashville, Tennessee, and colleagues studied 28 patients diagnosed with recurrent, treatment-resistant, unipolar depression without psychotic features. Each patient had previously failed to respond to at least 4 weeks of treatment with two separate classes of antidepressants. During the trial, conducted in three phases, patients were initially screened for non-response to fluoxetine over 6 weeks. The initial dose of fluoxetine was started at 20 mg/day and was titrated up to the highest dose tolerated, up to a maximum of 60 mg/day. Patients were then randomly assigned to fluoxetine plus placebo, olanzapine plus placebo or olanzapine plus fluoxetine, for 8 weeks. The fluoxetine dose remained the same during the trial, while the olanzapine dose varied between 5 mg and 20 mg/day, depending on individual response and tolerance of side effects. Patients who completed this phase received another 8 weeks of combination therapy with fluoxetine and olanzapine. "The combination group (n=10) achieved greater improvement from baseline on the Montgomery-Asberg Depression Rating Scale than either monotherapy group," the authors report. "In contrast with the significant response observed with the combined therapy, neither fluoxetine nor olanzapine alone was effective in this resistant population." Using the Hamilton Depression Scale, the investigators also noted greater improvement in the patients receiving combination therapy compared with those receiving olanzapine alone, but the difference was not statistically significant from the results obtained with patient on fluoxetine alone. The authors point out that widespread treatment of resistant depression with antipsychotics has been "largely precluded by the high risk of extrapyramidal symptoms and/or tardive dyskinesia." Both fluoxetine and olanzapine were well tolerated, and no significant differences in acute extrapyramidal symptoms were observed during the study period. Dr. Shelton's group concludes that "combined olanzapine and fluoxetine appears to be an effective and well tolerated treatment for treatment-resistant depression," but that due to the small number of patients studied, the results should be "considered preliminary."

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