NR557
Wednesday, May 25, 12:00 p.m.-2:00 p.m.

Adjunctive Eszopiclone and Fluoxetine in MDD and Insomnia: Depression Effects

Supported by Sepracor Inc. W. Vaughn McCall, M.S., Department of Psychiatry, Wake Forest University, Medical Center Boulevard, 8th Floor, Winston-Salem, NC 27157; Maurizio Fava, M.D., Thomas Wessel, M.D., Robert Rubens, M.D., Judith Caron, Ph.D., David Amato, Ph.D., Thomas Roth, Ph.D.

Educational Objectives:
At the conclusion of this presentation, the participant should be able to evaluate the effects of adjunctive eszopiclone treatment in patients with insomnia associated with MDD during concurrent
fluoxetine treatment on clinician-rated measures of depression.

Summary:
Objective: Insomnia frequently coexists with depression. This study evaluated eszopiclone and fluoxetine coadministration in depressed patients with comorbid insomnia.
Methods: Patients who met the DSM-IV criteria for new major depressive disorder (MDD) and insomnia received fluoxetine 20mg qam plus either eszopiclone 3 mg (N = 275) or placebo (N = 270) nightly for eight weeks. Efficacy was assessed with the 17-item Hamilton Depression Rating Scale (HAMD17) and Clinical Global Impression Improvement (CGI-I) and Severity (CGI-S).
Response = 50% decrease from baseline HAMD17; remission =HAMD17 - 7.
Results: Eszopiclone coadministration resulted in significantly greater changes in HAMD17 scores at week 4 (-9.9 vs -8.5 for placebo, p = 0.02), with progressive improvement at week 8 (-13.8 vs -　11.8, p < 0.001). At week 8, significantly more eszopiclone patients were responders (74% vs 61%, p < 0.009) and remitters (54% vs 41%, p < 0.02). Even after removing insomnia items, significant changes in HAMD17 were found at week 8 (p < 0.03). HAMD17 differences were greater in patients with more severe depression (baseline HAMD17 - 22). CGI-I and CGI-S scores were significantly greater with eszopiclone coadministration (p < 0.05). Fewer eszopiclone patients required fluoxetine dose increases (44% vs 54%, p < 0.05). Treatment was well tolerated; dropouts due to adverse events were comparable.
Conclusions: Eszopiclone/fluoxetine coadministration significantly augmented the antidepressant response in patients with MDD and insomnia. The sleep response occurred immediately, followed by augmentation of the antidepressant response.

References:
1. Krystal AD, et al: Sustained efficacy of eszopiclone over 6 months of nightly treatment: results of a randomized, doubleblind, placebo-controlled study in adults with chronic insomnia. Sleep 2003; 26:793-9.
2. Breslau N, Roth T, Rosenthal L, Andreski P; Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry 1996; 39:411-418.