NEW STATISTICAL PROPOSALS TO EVALUATE THE BENEFIT RISK RATIO OF LONG-TERM TREATMENT OF DEPRESSION - APPLICATION TO A ONE-YEAR DOUBLE-BLIND-STUDY COMPARING MEDIFOXAMINE WITH FLUOXETINE/

The aim of this study was to determine the benefit/risk ratio of long- term treatment with medifoxamine, a non-tricyclic, non-monoamine oxida se inhibitor agent, and fluoxetine in patients with acute depressive e pisode and at high risk of relapse and/or recurrence. The study involv ed a 12-month double-blind, randomised, parallel-group design with a m ulticentric trial setting conducted by 64 participating physicians. 15 5 and 158 patients of either gender, aged between 18 and 70 years, wer e allocated to fluoxetine and medifoxamine, respectively. All patients had an acute depressive episode defined by the presence of at least f ive of the DSM III-R criteria with a minimal score of 25 on the Montgo mery and Asberg Depression Rating Scale (MADRS). All subjects had at l east one previous documented depressive episode in their medical histo ry. The main outcome criterion consisted of good therapeutic response defined by a sustained 50% reduction of the Clinical Global Impression (CGI) score combined with the absence of any serious or troublesome ( i.e. intensity motivating study discontinuation) events. In the fluoxe tine and medifoxamine groups, respectively, 45.2% and 43% of the rando mised patients completed the 12-month follow-up period with no major d ifferences between groups regarding the reasons for treatment withdraw al. With each treatment 58% of the patients reached at least a 50% dec rease in their CGI score, with no differences on the evolution of the MADRS, Hamilton Anxiety Rating Scale (HARS), the Self Rating Depressio n Scale of Zung (Zung scale) and Scott depression visual analogue scal e (VAS) scores on average. According to the main efficacy criterion, 2 6% of the patients in the fluoxetine group were considered as responde rs compared with 36% in the medifoxamine group (p = 0.047). When only serious adverse effects were considered in combination with CGI scores to define response rates, the respective percentages were in favour o f medifoxamine but the difference (45 vs 53%) was not significant. Res ults with medifoxamine were better in the elderly whereas, with fluoxe tine, best responses were observed in younger patients. In conclusion, medifoxamine was an active and well tolerated drug in the continuatio n and maintenance treatment of depression. Its benefit/risk ratio appe ared to be superior to fluoxetine, but this difference was mainly base d on the occurrence of less minor adverse effects, a potential advanta ge not sufficient to favour better compliance with long-term therapy. Nevertheless, efficacy and tolerance of medifoxamine merits further ev aluation in specific elderly populations.