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 dosingregimen could be a convenient alternative for many patientsduring long-term treatment of depression. Such a strategy mightalso be effective for improving medication compliance and theoutcome of continuation treatment. The safety and effectivenessof a new formulation of enteric-coated fluoxetine (90 mg) givenonce weekly was tested during the continuation treatment of majordepressive disorder.

Method: Patients meeting DSM-IV criteriafor major depressive disorder with modified 17-item HamiltonRating Scale for Depression (HAM-D-17) scores >= 18and Clinical Global Impressions-Severity of Illness scale (CGI-S)scores >= 4 were treated 13 weeks with open-label 20 mg/day offluoxetine in a multicenter U.S. study. Responders (N = 501) wererandomly assigned to receive 20 mg of fluoxetine daily, placebo,or 90 mg of enteric-coated fluoxetine weekly for 25 weeks ofdouble-blind continuation treatment. The primary efficacy measurewas the percentage of patients who relapsed. Time to relapse wastested over the 25-week continuation period using log-rankanalyses of the Kaplan-Meier estimates of relapse rates.Additional analyses of efficacy included comparison of changefrom baseline to endpoint for the HAM-D-17, CGI-S, and HAM-D-28subscales by last observation carried forward (LOCF). Safetymeasures included comparison of treatment-emergent adverseevents, both spontaneous and solicited (using the Association forMethodology of Documentation in Psychiatry-Module 5), vitalsigns, and laboratory measures.

Results: Relapse rates for patientsassigned to fluoxetine, either 20 mg daily or 90 mg weekly, weresignificantly lower than for placebo by log-rank analysis andLOCF analyses of secondary efficacy measures. Efficacy did notsignificantly differ between the 2 active drug groups by thesemeasures. Enteric-coated fluoxetine at a once-weekly dose of 90mg was well tolerated, and its safety profile was similar to thatof daily 20 mg of fluoxetine.

Conclusion: The formulation ofenteric-coated fluoxetine taken once weekly is effective, safe,and well tolerated for continuation treatment of depression inpatients who responded to acute treatment with 20 mg/day offluoxetine. Monitoring during long-term treatment for evidence ofsustained remission is important regardless of dosing regimen.