The efficacy and safety of a new enteric-coated formulation of fluoxetine given once weekly during the continuation treatment of major depressive disorder
Me. Schmidt et al., The efficacy and safety of a new enteric-coated formulation of fluoxetine given once weekly during the continuation treatment of major depressive disorder, J CLIN PSY, 61(11), 2000, pp. 851-857
Background: A simple, once-weekly dosing regimen could be a convenient alte
rnative for many patients during long-term treatment of depression. Such a
strategy might also be effective for improving medication compliance and th
e outcome of continuation treatment. The safety and effectiveness of a new
formulation of enteric-coated fluoxetine (90 mg) given once weekly was test
ed during the continuation treatment of major depressive disorder.
Method: Patients meeting DSM-IV criteria for major depressive disorder with
modified 17-item Hamilton Rating Scale for Depression (HAM-D-17) scores gr
eater than or equal to 18 and Clinical Global Impressions-Severity of Illne
ss scale (CGI-S) scores greater than or equal to 4 were treated 13 weeks wi
th open-label 20 mg/day of fluoxetine in a multicenter U.S. study. Responde
rs (N = 501) were randomly assigned to receive 20 mg of fluoxetine daily, p
lacebo, or 90 mg of enteric-coated fluoxetine weekly for 25 weeks of double
-blind continuation treatment. The primary efficacy measure was the percent
age of patients who relapsed. Time to relapse was tested over the 25-week c
ontinuation period using log-rank analyses of the Kaplan-Meier estimates of
relapse rates. Additional analyses of efficacy included comparison of chan
ge from baseline to endpoint for the HAM-D-17, CGI-S, and HAM-D-28 subscale
s by last observation carried forward (LOCF). Safety measures included comp
arison of treatment-emergent adverse events, both spontaneous and solicited
(using the Association for Methodology of Documentation in Psychiatry-Modu
le 5), vital signs, and laboratory measures.
Results: Relapse rates for patients assigned to fluoxetine, either 20 mg da
ily or 90 mg weekly, were significantly lower than for placebo by log-rank
analysis and LOCF analyses of secondary efficacy measures. Efficacy did not
significantly differ between the 2 active drug groups by these measures. E
nteric-coated fluoxetine at a once-weekly dose of 90 mg was well tolerated,
and its safety profile was similar to that of daily 20 mg of fluoxetine.
Conclusion: The formulation of enteric-coated fluoxetine taken once weekly
is effective, safe, and well tolerated for continuation treatment of depres
sion in patients who responded to acute treatment with 20 mg/day of fluoxet
ine. Monitoring during long-term treatment fur evidence of sustained remiss
ion is important regardless of dosing regimen.