We thank Juruena and colleagues for their comments and their interest in our work, ‘Efficacy and safety of bright light therapy for manic and depressive symptoms in patients with bipolar disorder: A systematic review and meta-analysis.’ We agree with most of their suggestions and provide answers to each of their comments below. The first point highlighted by Juruena et al. is that the high heterogeneity of the interventions and control conditions and an approach that differs from those of previous studies yielded conflicting results between our study and earlier publications. We strongly agree with this point. Our meta-analysis could not show a statistically significant antidepressant effect for bipolar depression because of the high heterogeneity of the interventions and control conditions and because of factors associated with our meta-analysis being limited to randomized controlled trials. However, our sensitivity analysis for studies with low overall indirectness showed a significant antidepressant effect for bipolar depression (Fig. 1), which is already illustrated in our meta-analysis in Figure S1. We therefore also believe that bright light therapy (BLT) is an effective treatment option for bipolar depression, as previously concluded by Tseng et al. and the International Society for Bipolar Disorders task force. The second point raised by Juruena and colleagues is the study durations included in our meta-analysis. Because our study evaluated only randomized controlled trials, more than half of the studies included in our analysis had an evaluation duration of less than 6 weeks. As Juruena et al. point out, the results of our meta-analysis might have been influenced by the studies with shorter durations, and the effect of BLT might thus not have been accurately evaluated. We agree that studies with longer durations will be needed to clarify the effectiveness of BLT for bipolar depression. The third point is the risk of bias assessment in our study. We judged the study conducted by Sit et al. as having a low risk of bias in blinding of participants and personnel, because the study had a doubleblind design and because the details of the blinding method were well described compared to other studies (e.g. ‘The active and placebo light boxes appeared identical when not illuminated’ and ‘personnel conducting the visits and performing the clinical ratings worked separately from the non-blinded personnel’). However, as Juruena et al. point out, there is a possibility that the participants may have detected the active light box because of differences in illuminance or contact with nonblinded personnel. Therefore, our risk of bias assessment might not have been strict enough. In conclusion, the results of our study do not clearly show an antidepressant effect of BLT for bipolar depression owing to several critical limitations, such as the high heterogeneity of conditions, short study durations, small sample sizes, and high risk of bias, which might have influenced our findings. We thus believe that the effectiveness of BLT for bipolar depression will be clarified by studies designed with low heterogeneity of interventions and control conditions, larger sample sizes, longer study durations, and lower risk of bias. Additionally, it is not clear whether BLT can be effective for all patients with bipolar depression. BLT may be more useful for treating cases of bipolar disorder with seasonal variations and/or circadian rhythm dysfunctions compared to those without these characteristics. It is also important to identify factors associated with treatment responses to BLT in patients with bipolar depression, which will be useful information for clinical practice.

中文翻译：

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对“双相抑郁症强光疗法的有效性和安全性”的反应

我们感谢 Juruena 及其同事对我们工作的评论和对我们工作的兴趣，“亮光疗法对双相情感障碍患者躁狂和抑郁症状的疗效和安全性：系统评价和荟萃分析”。我们同意他们的大部分建议，并在下面为他们的每条评论提供答案。Juruena 等人强调的第一点。是干预和控制条件的高度异质性以及与以前研究不同的方法在我们的研究和早期出版物之间产生了相互矛盾的结果。我们非常同意这一点。由于干预措施和控制条件的高度异质性以及与我们的荟萃分析相关的因素仅限于随机对照试验，我们的荟萃分析无法显示双相抑郁症的统计学显着抗抑郁作用。然而，我们对总体间接性较低的研究的敏感性分析显示，双相抑郁具有显着的抗抑郁作用（图 1），这已在我们图 S1 的荟萃分析中得到说明。因此，我们也相信强光疗法 (BLT) 是双相抑郁症的有效治疗选择，正如 Tseng 等人先前得出的结论。和国际躁郁症学会特别工作组。Juruena 及其同事提出的第二点是我们的荟萃分析中包含的研究持续时间。由于我们的研究仅评估了随机对照试验，因此我们分析中超过一半的研究的评估持续时间少于 6 周。正如 Juruena 等人。指出，我们的荟萃分析的结果可能受到持续时间较短的研究的影响，因此可能没有准确评估 BLT 的效果。我们同意需要更长时间的研究来阐明 BLT 对双相抑郁症的有效性。第三点是我们研究中偏倚评估的风险。我们判断了 Sit 等人进行的研究。对参与者和人员进行盲法的偏倚风险较低，因为该研究采用双盲设计，并且与其他研究相比，盲法方法的细节得到了很好的描述（例如 '主动和安慰剂灯箱在未点亮时看起来相同'和'进行访问和执行临床评级的人员与非盲人人员分开工作')。然而，正如 Juruena 等人。指出，参与者有可能因为照度差异或与非盲人接触而检测到活动灯箱。因此，我们的偏见风险评估可能不够严格。总之，我们的研究结果并没有清楚地显示 BLT 对双相抑郁症的抗抑郁作用，原因是几个关键的局限性，例如条件的高度异质性、研究持续时间短、样本量小和偏倚风险高，这可能影响了我们的发现。因此，我们相信 BLT 治疗双相抑郁症的有效性将通过干预和控制条件的低异质性、更大的样本量、更长的研究持续时间和更低的偏倚风险而设计的研究得到澄清。此外，尚不清楚 BLT 是否对所有双相抑郁患者有效。与没有这些特征的双相情感障碍相比，BLT 可能更有助于治疗具有季节性变化和/或昼夜节律功能障碍的双相情感障碍病例。确定与双相抑郁患者对 BLT 治疗反应相关的因素也很重要，这将是临床实践的有用信息。此外，尚不清楚 BLT 是否对所有双相抑郁患者有效。与没有这些特征的双相情感障碍相比，BLT 可能更有助于治疗具有季节性变化和/或昼夜节律功能障碍的双相情感障碍病例。确定与双相抑郁患者对 BLT 治疗反应相关的因素也很重要，这将是临床实践的有用信息。此外，尚不清楚 BLT 是否对所有双相抑郁患者有效。与没有这些特征的双相情感障碍相比，BLT 可能更有助于治疗具有季节性变化和/或昼夜节律功能障碍的双相情感障碍病例。确定与双相抑郁患者对 BLT 治疗反应相关的因素也很重要，这将是临床实践的有用信息。