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Amlodipine and losartan brand of antidepressants, was the same as in placebo group. Patients assigned to the low-dose group were given two tablets of citalopram (30 mg) once daily. The low-dose patients also received sertraline (20–40 mg) plus either escitalopram (500–1,000 mg, 5 or 10 depending on the patient's response to treatment) or fluoxetine (30–60 mg, 3, 4, or 5 5–10 days, depending on the patient's response to treatment) for 10 days with a single dose of sertraline each night. These two doses were the same as in first-dose groups, and patients assigned to both groups received oral low-dose sertraline for six months. Statistical analysis Covariating variables were baseline values and treatment assignment. Because the response to antidepressants has a linear progression, linear-regression analysis was performed for the response rates to three antidepressant trials. Each of the two baseline variables was treated as a linear predictor variable with an ordinal response (0–1) and a continuous variable (0–5 or greater). Covariates were tested for interaction effects by the use of two-way ANOVAs. effects on the primary outcome were tested by a linear model using one set of data and a likelihood ratio test using an additional set of data (Supplemental Table 1). The primary efficacy variable, percentage of patients who achieved and maintained an Drug prices canada vs us antidepressant response, was based on the Kaplan–Meier survival analysis. primary analysis was performed on the patients who had longest response duration (≥12 weeks) and on the patients who had response rates of at least 50%, using data from each of the three trials. This outcome measure was used to compare two groups. The second outcome measure was a percentage of response (defined as a proportion of patients with response rate at least 50% in one of the three trials) for a subset of patients in each trial who had a response of less than 50% after six months of treatment. The secondary outcomes were proportion of patients with a response less than 50% in each of the three trials, percentage patients who achieved an antidepressant response for the first time at a median of 12 weeks, and the proportion of patients who did not achieve an antidepressant response as a secondary outcome after six months of treatment. The Kaplan–Meier survival analysis was also used to determine the median time a new response after 6 months of treatment and to evaluate the association between response rate and treatment duration. In addition, the Kaplan–Meier analysis was used to evaluate the effect of baseline risk disease and adverse events as well the effect of severity treatment-emergent adverse events. The primary and secondary outcomes were analyzed separately by sex and study were analyzed by using the Mantel–Haenszel test for continuous outcomes and the Friedman test for categorical outcomes and a Cox proportional hazards regression model for the analysis of Kaplan–Meier analysis. The use of Kaplan–Meier analysis is appropriate for the of a long-term follow-up study that includes patients with multiple comorbidities; the analysis was performed in three individual trials on the basis of initial study population in each trial. The proportion of patients still alive at the end of a median follow-up period 24 weeks was calculated as the percent who were alive at the endpoint of study (endpoint value minus baseline value). The distribution of Kaplan–Meier survival curve was tested for homogeneity of the distribution, assuming one-way analysis of variance, and results were assessed using Shapiro–Wilk tests. The effect of treatment duration on the primary outcome was tested by a two-way ANOVA in addition to the analysis of primary efficacy variable. The statistical model included a linear predictor for treatment duration and a covariate of time for each patient. The association was evaluated by use of Cox analysis. The baseline hazard of disease and the developing a new adverse event over time were modeled as continuous outcomes (endpoint vs. time) and categorical outcomes (baseline, 24 weeks, 48 or 1 year). The Kaplan–Meier curve showed no evidence of heterogeneity by treatment duration. In the analyses of primary outcome, Kaplan–Meier survival analysis was also used to determine the time a final response at the 24-week visit. main outcome was the proportion of patients who achieved a new response at one year in the treatment groups. Patients were defined as responding (defined a response in two of the three trials) or not responding (defined as a relapse in any trial) at one year based on the time of first response. As in this analysis, the Kaplan–Meier survival curve showed no evidence of heterogeneity by time.
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