The effectiveness and safety of short-term and long-term use of antidepressants (ADs) for the treatment of patients with bipolar disorder (BD) remains controversial, and even less research has been done on the effectiveness and safety of long-term use of ADs for BD. With this in mind, Dr. V. hringer from Tufts University Medical Center and others published an article in the Journal of Clinical Psychopharmacology in October 2015 about the results of their secondary analysis of the results of a long-term controlled trial designed to examine the safety of ADs for type II BD (BD-II) compared to type I (BD-I). (BD-II) than type I (BD-I). ADs are the most commonly prescribed medications for the treatment of BD today and are commonly used in combination with long-term treatment. The authors conducted this non-blinded randomized trial in the Systematic Treatment Enhancement Program for BD (STEP-BD), in which subjects were randomly assigned to continue treatment with ADs under mood stabilizer therapy after recovery from an acute depressive episode and then analyzed for treatment The results were then analyzed. A total of 70 subjects were enrolled in the trial based on the DSM-IV diagnostic criteria for BD. Subjects experienced an acute depressive episode lasting 2-4 months with at least 2 typical depressive symptoms and recovered with AD and mood stabilizer treatment. Mood stabilizer treatment remained unchanged during the 3-year prospective follow-up, but subjects were randomized to the maintenance ADs group and to the ADs discontinuation group. The primary metric of the study was the Clinical Monitoring Form (CMF) of the STEP-BD, which measures the incidence of symptoms rather than the frequency of episodes for subjects at each clinical follow-up visit; the type and frequency of affective episodes, latency to first affective episode, and time to remission were systematically recorded according to DSM-IV criteria. Secondary indicators were recorded for affective episodes as the primary indicator of interest. The study showed that BD-I and BD-II subjects in the ADs discontinuation group had similar annual recurrence rates of affective episodes. The frequency of depressive phase relapse was slightly higher in BD-II subjects in the maintenance ADs group than in BD-I, but the former had fewer (mild) manic episodes. Overall, the 3-year follow-up showed fewer depressive episodes in both the BD-I and BD-II subtypes than in the discontinued ADs group, with more improvement in the BD-I subgroup than in the BD-II subgroup, with statistically significant differences. Cox regression models and survival analyses stratified by diagnostic type showed no statistically significant difference in the overall recurrence rate of (mild) mania and no difference in the number of weeks of latency for the first depressive or (mild) manic episode. In other words, BD-II subjects in the maintenance ADs group did not have a better regression in depressive episodes than BD-I. The authors concluded that the benefit for subjects in the maintenance ADs group was more a direct result of fewer depressive episodes in BD-I, and that no difference was found between subjects in the ADs discontinuation group across diagnostic groups. primary study indicators measured by CMF showed that maintenance AD treatment partially reduced the incidence of affective episodes and prolonged the latency to first recurrence of affective episodes. The authors give their opinion on the hypothesis that ADs may be more effective in BD-II than in type I. One, this hypothesis does not take into account the fact that ADs are more effective in BD-II than in type I. For one, this hypothesis does not take into account studies comparing head-to-head whether type I and type II subjects have been treated with ADs. In addition, the individual studies referenced by this hypothesis were limited to or primarily studied type I or type II BD cases, so that most randomized trials of ADs for bipolar depression enrolled mostly type I subjects, but most did not or barely studied the benefits of ADs for acute bipolar depressive episodes. In contrast, many studies examining only type II bipolar depression have reported benefits of various ADs compared with placebo (or lithium) for acute depressive episodes. On the other hand, the “rich” or randomized termination trial design may have influenced the differences shown in these studies. Previous studies have selected subjects who responded to one AD, often treated with AD alone or sometimes with a mood stabilizer. It is this “enriched” trial design that may tend to support the desired response outcome for the initial treatment. The authors note that the trial results reproduced in this study are notable for the increased rate of BD-I manic relapse with maintenance AD treatment, but the decreased rate of BD-II. To summarize the study limitations, the authors concluded that the unblinded trial design and the combined BD-II and BD-NOS cases made the study evidence limited. Although not statistically significant, the findings do not support the hypothesis that Type II BD on maintenance ADs is less beneficial than Type I. In addition, continued treatment with mood stabilizers may diminish potential differences in outcomes between diagnostic groups or reduce the effect of combined AD therapy. However, maintaining treatment with ADs without mood stabilizers, especially for BD-I patients, raises clinical and ethical issues.