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. Method: Patients meeting DSM-IV criteria for major depressive disorder with modified 17-item Hamilton Rating Scale for Depression (HAM-D-17) scores greater than or equal to 18 and Clinical Global Impressions-Severity of Illness scale (CGI-S) scores greater than or equal to 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. Conclusion: 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 fur evidence of sustained remission is important regardless of dosing regimen.