The objective of this study is to develop a rapid treatment for major depression. Although a variety of effective antidepressants are currently available, all are associated with delayed response. A recent neuropharmacologic study in animals provided a rationale for more rapid treatment. Baron and associates found that the combination of fluoxetine and desipramine (DMI) down regulated beta-adrenergic receptors more rapidly than either drug alone. Since beta-receptor down regulation has been proposed as a theory of antidepressant action, these findings suggest that this drug combination might be clinically useful. A preliminary uncontrolled clinical study, which we conducted, indicated that this combination was substantially more rapidly acting than DMI alone.
the specific aim of the current proposal is to determine, with a controlled study in patients hospitalized for major depression, if the combination of fluoxetine and DMI is more rapidly acting than either drug alone and if the difference is both statistically significant and clinically meaningful. Our hypothesis is that combined drug treatment will be substantially more effective than either drug alone and that the differences will be observable in one week. The study will be a 4-week, double-blind, random assignment, parallel comparison of the drug combination with each drug individually in 81 patients hospitalized for nonpsychotic major depression. Assignment to treatment will follow a one week period of hospitalization without antidepressant drugs during which patients who respond to hospitalization will be identified and excluded. 24-hour DMI plasma levels will be used to rapidly achieve adequate DMI levels and to obtain comparable DMI blood levels in the combined treatment and DMI treatment groups. The duration of the study will be 3 years.
| Nelson, J Craig; Mazure, Carolyn M; Jatlow, Peter I et al. (2004) Combining norepinephrine and serotonin reuptake inhibition mechanisms for treatment of depression: a double-blind, randomized study. Biol Psychiatry 55:296-300 |
