The efficacy and safety of a new enteric-coated formulation of fluoxetine given once weekly during the continuation treatment of major depressive disorder.
BACKGROUND
A simple, once-weekly dosing regimen could be a convenient alternative for many patients during long-term treatment of depression. Such a strategy might also be effective for improving medication compliance and the outcome of continuation treatment. The safety and effectiveness of a new formulation of enteric-coated fluoxetine (90 mg) given once weekly was tested during the continuation treatment of major depressive disorder.


METHODS
Patients meeting DSM-IV criteria for major depressive disorder with modified 17-item Hamilton Rating Scale for Depression (HAM-D-17) scores > or = 18 and Clinical Global Impressions-Severity of Illness scale (CGI-S) scores > or = 4 were treated 13 weeks with open-label 20 mg/day of fluoxetine in a multicenter U.S. study. Responders (N = 501) were randomly assigned to receive 20 mg of fluoxetine daily, placebo, or 90 mg of enteric-coated fluoxetine weekly for 25 weeks of double-blind continuation treatment. The primary efficacy measure was the percentage of patients who relapsed. Time to relapse was tested over the 25-week continuation period using log-rank analyses of the Kaplan-Meier estimates of relapse rates. Additional analyses of efficacy included comparison of change from baseline to endpoint for the HAM-D-17, CGI-S, and HAM-D-28 subscales by last observation carried forward (LOCF). Safety measures included comparison of treatment-emergent adverse events, both spontaneous and solicited (using the Association for Methodology of Documentation in Psychiatry-Module 5), vital signs, and laboratory measures.


RESULTS
Relapse rates for patients assigned to fluoxetine, either 20 mg daily 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. Enteric-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.


CONCLUSIONS
The formulation of enteric-coated fluoxetine taken once weekly is effective, safe, and well tolerated for continuation treatment of depression in patients who responded to acute treatment with 20 mg/day of fluoxetine. Monitoring during long-term treatment for evidence of sustained remission is important regardless of dosing regimen.
Schmidt
M E
ME
Lilly Research Laboratories, Indianapolis, Ind 46285, USA.
Fava
M
M
Robinson
J M
JM
Judge
R
R
D000293:Adolescent; D000328:Adult; D003866:Depressive Disorder / Q000188:drug therapy* / Q000517:prevention & control / Q000523:psychology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012008:Recurrence; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013608:Tablets, Enteric-Coated; D016896:Treatment Outcome
D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors; D013608:Tablets, Enteric-Coated