Therefore, for the majority of patients, there is no advantage in increasing the dose of paroxetine above 20 mg/day. In this study,19 there were no differences

between paroxetine 10 mg/day and placebo on change on the HAMD total score at the end of 6 weeks. Significant differences were seen between other doses of paroxetine of 20, 30, and 40 mg/day and placebo. There were no differences between the three higher dosages of paroxetine on visual inspection of the figures of the publication.19 Sertraline The SSRI sertraline did not show significant differences in terms of clinical Inhibitors,research,lifescience,medical efficacy across a dose range of 50 to 200 mg/day, according to a major study by Fabre and Putman (Table I). 20 Therefore, for the majority of patients, there is no advantage to increase the dose of sertraline above 50 mg/day. In the study by Fabre and Putman,20 sertraline 50 mg/day, but not 100 and 200 mg/day, was more effective than placebo at end-point analysis on change Inhibitors,research,lifescience,medical on the HAMD 17 items total score on ITT-LOCF at 6 weeks. There was no statistical analysis performed between the different doses, but inspection of the data in

the publication20 suggests no differences. Evaluable patients, defined as those who Inhibitors,research,lifescience,medical had taken study medication at least up to the 11th day of the double-blind phase, with efficacy assessment performed on or after this date. With this learn more population of 289 evaluable patients, all doses of sertraline were statistically Inhibitors,research,lifescience,medical superior to placebo on change on the HAMD total score with LOCF at the end of 6 weeks. There was no statistical analysis of the different doses, but inspection of the data in the publication20 suggests no differences; on the CGI, the percentage of responders was 58.5%, 62.7%, 58.9%, and 42.1% in the Inhibitors,research,lifescience,medical sertraline 50, 100, 200 mg/day and placebo groups, respectively. Inspection of the data in the publication20 for the 191 patients who completed

the study suggests no difference between the three doses of sertraline on change on the MADRS total score. Moreover, efficacy was similar in patients with moderate depression (HAMD score at baseline: 17 to 24) and with severe depression (HAMD score at baseline: 25 or more). A small part of this study with 30 patients had been released enough 6 years earlier in a short publication,28 with the same conclusions. In a very small study in 17 patients at the start of the study and 8 at the end, Guy et al29 could not demonstrate the efficacy of sertraline 50 and 100 mg/day over placebo on the HAMD 17 items at the end of 4 weeks. No symptomatic improvement was noted for sertraline 200 or 400 mg/day. Lower dosages were better tolerated than higher dosages. Milnacipran Three fixeddose studies30’32 and one doseranging study33 were identified for milnacipran (Table II), The studies showed flat dose-response relationship between 100 and 300 mg/day; milnacipran 50 mg/day was less effective than higher doses and even than placebo.