Evaluation of eszopiclone discontinuation after cotherapy with fluoxetine for insomnia with coexisting depression.
BACKGROUND
Insomnia and major depressive disorder (MDD) may coexist. This study evaluated hypnotic discontinuation effects following an 8-week placebo-controlled study of eszopiclone/fluoxetine cotherapy in patients with insomnia and comorbid MDD.


METHODS
Patients meeting DSM-IV criteria for MDD and insomnia received fluoxetine each morning for 8 weeks and were randomized to concomitant treatment with nightly eszopiclone 3 mg (cotherapy) or placebo (monotherapy). Thereafter, patients received 2 weeks of continued fluoxetine plus single-blind placebo.


RESULTS
Incidence rates of central nervous system (CNS) and potentially CNS-related adverse events (AEs) during the run-out period were similar between treatment groups (8.8% with monotherapy vs 9.8% with cotherapy), and there was no evidence of benzodiazepine withdrawal AEs. Physician-assessed Clinical Global Impression improvements in depressive symptoms were maintained after eszopiclone discontinuation. Improvements in 17-item Hamilton-Depression Rating Scale (HAMD-17) scores with cotherapy versus monotherapy seen at Week 8 (p = .0004) were maintained at Week 10 (p < .0001) and significantly higher depression response and remission rates were observed after cotherapy at Week 10 (p < .02). Patients discontinued from eszopiclone maintained improvements in SL (sleep latency), WASO (wake after sleep onset), and TST (total sleep time) during the 2 weeks following discontinuation (p < .05).


CONCLUSIONS
In this study, eszopiclone discontinuation did not result in significant CNS or benzodiazepine withdrawal AEs, rebound insomnia, or rebound depression; and improvements in sleep and depressive symptoms were maintained.
Krystal
Andrew
A
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. krystal@phy.duke.edu
Fava
Maurizio
M
Rubens
Robert
R
Wessel
Thomas
T
Caron
Judy
J
Wilson
Phebe
P
Roth
Thomas
T
McCall
W Vaughn
WV
D000328:Adult; D053961:Azabicyclo Compounds; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016037:Single-Blind Method; D007319:Sleep Initiation and Maintenance Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D013997:Time Factors; D028761:Withholding Treatment / Q000706:statistics & numerical data*
D053961:Azabicyclo Compounds; D005473:Fluoxetine; D006993:Hypnotics and Sedatives; D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors; C515050:zopiclone