The objective of this double-blind, placebo-controlled, multicentre randomized withdrawal study was to evaluate the efficacy and tolerability of sertraline for 16 weeks in treating Japanese patients with major depressive disorder (MDD) who had achieved a response to 8 weeks of sertraline treatment. Patients (n=361) were initially treated with 8 weeks of open-label sertraline treatment followed by 16 weeks of double-blind treatment with either sertraline (50-100 mg/day) or placebo. Responders during the open-label phase were eligible to be entered into the double-blind phase. A total of 235 patients (65.1%) were entered to the double-blind phase and randomly assigned to receive sertraline (n=117) or placebo (n=118). A significantly (P=0.016) lower relapse rate was found for sertraline (8.5%) compared to placebo (19.5%) during the double-blind phase. Examination of time-to-relapse showed that the relapse free rate curve was significantly higher for sertraline (log-rank test, P=0.026) than placebo. Mean changes from beginning to end of the double-blind phase on measure of depressive symptoms, quality of life and global improvement also significantly favoured sertraline over placebo. Sertraline was well-tolerated, with similar adverse events as found in previous studies. These results confirm the efficacy of sertraline in preventing the relapse of MDD in Japanese patients.

The objective of this double-blind, placebo-controlled randomized withdrawal study was to evaluate the efficacy and safety of sertraline for 8 weeks in treating Japanese patients with DSM-IV panic disorder. Patients (n=394) were initially treated with 8 weeks of open-label sertraline followed by 8 weeks of double-blind treatment with either sertraline (50-100 mg/day) or placebo. Responders during the open-label phase were eligible to be entered into the double-blind phase. Two hundred and forty patients were entered to the double-blind phase and randomly assigned to receive sertraline (n=119) or placebo (n=121). On the primary efficacy measure (relapse), there was no significant difference between the two treatment groups (sertraline 10.1%; placebo 13.2%). However, the frequency of panic attacks was significantly (P=0.012) lower for sertraline compared to placebo. The proportion of sertraline-treated patients who met response criteria (Clinical Global Impression-Improvement Scale score of 1 or 2) at the end of double-blind phase treatment was also significantly (P=0.003) higher for sertraline (89.9%) compared to placebo (74.4%). Panic Disorder Severity Scale total score was significantly (P=0.012) lower in the sertraline group compared to the placebo group. Adverse events during acute treatment were consistent with the known adverse event profile of sertraline, and the incidence of adverse events during the double-blind phase treatment was not different between sertraline and placebo.

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BackgroundSurvival analysis methods such as the Kaplan-Meier method, log-rank test, and Cox proportional hazards regression (Cox regression) are commonly used to analyze data from randomized withdrawal studies in patients with major depressive disorder. However, unfortunately, such common methods may be inappropriate when a long-term censored relapse-free time appears in data as the methods assume that if complete follow-up were possible for all individuals, each would eventually experience the event of interest.MethodsIn this paper, to analyse data including such a long-term censored relapse-free time, we discuss a semi-parametric cure regression (Cox cure regression), which combines a logistic formulation for the probability of occurrence of an event with a Cox proportional hazards specification for the time of occurrence of the event. In specifying the treatment's effect on disease-free survival, we consider the fraction of long-term survivors and the risks associated with a relapse of the disease. In addition, we develop a tree-based method for the time to event data to identify groups of patients with differing prognoses (cure survival CART). Although analysis methods typically adapt the log-rank statistic for recursive partitioning procedures, the method applied here used a likelihood ratio (LR) test statistic from a fitting of cure survival regression assuming exponential and Weibull distributions for the latency time of relapse.ResultsThe method is illustrated using data from a sertraline randomized withdrawal study in patients with major depressive disorder.ConclusionsWe concluded that Cox cure regression reveals facts on who may be cured, and how the treatment and other factors effect on the cured incidence and on the relapse time of uncured patients, and that cure survival CART output provides easily understandable and interpretable information, useful both in identifying groups of patients with differing prognoses and in utilizing Cox cure regression models leading to meaningful interpretations.