A novel augmentation strategy for treating resistant major depression.
OBJECTIVE
Treatment-resistant depression is a significant public health concern; drug switching or augmentation often produce limited results. The authors hypothesized that fluoxetine could be augmented with olanzapine to successfully treat resistant depression.


METHODS
An 8-week double-blind study was conducted with 28 patients who were diagnosed with recurrent, nonbipolar, treatment-resistant depression without psychotic features. Subjects were randomly assigned to one of three groups: olanzapine plus placebo, fluoxetine plus placebo, or olanzapine plus fluoxetine.


RESULTS
Fluoxetine monotherapy produced minimal improvement on various scales that rate severity of depression. The benefits of olanzapine monotherapy were modest. Olanzapine plus fluoxetine produced significantly greater improvement than either monotherapy on one measure and significantly greater improvement than olanzapine monotherapy on the other measures after 1 week. There were no significant differences between treatment groups on extrapyramidal measures nor significant adverse drug interactions.


CONCLUSIONS
Olanzapine plus fluoxetine demonstrated superior efficacy for treating resistant depression compared to either agent alone.
Shelton
R C
RC
Department of Psychiatry, Vanderbilt University Medical Center, Nashville, TN 37212, USA. richard.shelton@mcmail.vanderbilt.edu
Tollefson
G D
GD
Tohen
M
M
Stahl
S
S
Gannon
K S
KS
Jacobs
T G
TG
Buras
W R
WR
Bymaster
F P
FP
Zhang
W
W
Spencer
K A
KA
Feldman
P D
PD
Meltzer
H Y
HY
D000553:Ambulatory Care; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000453:epidemiology; D001569:Benzodiazepines; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005473:Fluoxetine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D000077152:Olanzapine; D010890:Pirenzepine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D001569:Benzodiazepines; D005473:Fluoxetine; D000077152:Olanzapine; D010890:Pirenzepine; D017367:Selective Serotonin Reuptake Inhibitors