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