Comparative effects of duloxetine and desipramine on sleep EEG in healthy subjects.
BACKGROUND
Antidepressants are known to modify human sleep patterns.


OBJECTIVE
Duloxetine is a new antidepressant with a mechanism of action involving reuptake inhibition of both serotonin (5-HT) and norepinephrine (NE). In this study, the effects of two dosing regimens of duloxetine on sleep electroencephalography (EEG) were investigated at steady-state plasma concentrations in young, healthy, male subjects.


METHODS
Placebo (n=12), desipramine (50 mg BID; n=12) and two regimens of duloxetine (80 mg QD, n=6; or 60 mg BID, n=6) were compared in a randomized, double-blind, three-period crossover study, each treatment being administered from day 1 to day 7. Sleep polygraphic recordings took place at baseline (day -1) and day 6 of each period. The Leeds sleep evaluation questionnaire (LSEQ) was also administered on the morning of day 7.


RESULTS
Both regimens of duloxetine produced a significant increase in the onset latency of REM sleep as well as a significant mean decrease in total REM sleep duration. Desipramine exhibited comparable effects. When compared to placebo, sleep continuity was significantly reduced with desipramine and duloxetine 60 mg BID whereas a significant improvement was observed with duloxetine 80 mg QD. On the LSEQ, duloxetine 80 mg QD produced a significant improvement in the "getting to sleep" subscale compared to placebo, whereas desipramine demonstrated a significant reduction (worsening) in the "quality of sleep" score versus placebo.


CONCLUSIONS
The two dose regimens of duloxetine (80 mg QD and 60 mg BID) produced a REM sleep pattern comparable to that of most antidepressant medications. Duloxetine 80 mg QD appeared to exhibit less impact upon sleep quality than duloxetine 60 mg BID in healthy subjects.
Lilly Research Laboratories, Indianapolis, IN 46285, USA. chalon_stephane_a@lilly.com
Stephan
S
Chalon
Alvaro
A
Pereira
Eric
E
Lainey
François
F
Vandenhende
John G
JG
Watkin
Luc
L
Staner
Luc-André
LA
Granier
D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003891:Desipramine / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D004311:Double-Blind Method; D000068736:Duloxetine Hydrochloride; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D017286:Polysomnography; D012701:Serotonin / Q000378:metabolism; D012890:Sleep / Q000187:drug effects*; D012894:Sleep Stages / Q000187:drug effects; D011795:Surveys and Questionnaires; D013876:Thiophenes / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D013876:Thiophenes; D012701:Serotonin; D000068736:Duloxetine Hydrochloride; D003891:Desipramine; D009638:Norepinephrine