加拿大多伦多总医院Alastair J. Flint团队取得一项新突破。他们发现持续服用奥氮平联合舍曲林，可降低缓解期精神病性抑郁症患者的复发风险。 2019年8月20日出版的《美国医学会杂志》发表了这项成果。

126名年龄超过18岁的患者出现精神性抑郁症发作，采用舍曲林联合奥氮平急性治疗12周后症状缓解，缓解期持续8周后进入为期36周的临床试验。随机分为两组，奥氮平组（64例）继续服用舍曲林加奥氮平，安慰剂组（62例）服用舍曲林加安慰剂。

奥氮平组中有13例（20.3%）患者复发，安慰剂组中有34例（54.8%）患者复发，差异显著，风险比为0.25。与安慰剂组相比，奥氮平组患者的平均体重多了0.13磅，平均腰围增长0.009英寸，总胆固醇增加0.29mg/dL，且差异显著。但低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酯、葡萄糖和糖化血红蛋白水平与安慰剂组相比差异无统计学意义。综上，处于缓解期的精神病性抑郁症患者，持续服用舍曲林联合奥氮平可有效降低复发的风险，但可能伴随体重增加等副作用。

据悉，精神病性抑郁症是一种严重致残并可能致命的疾病。但对缓解期精神病性抑郁症患者持续服用抗精神病药物的疗效和耐受性，仍知之甚少。

Title: Effect of Continuing Olanzapine vs Placebo on Relapse Among Patients With Psychotic Depression in Remission

Author:Alastair J. Flint, Barnett S. Meyers, Anthony J. Rothschild, Ellen M. Whyte, George S. Alexopoulos, Matthew V. Rudorfer, Patricia Marino, Samprit Banerjee, Cristina D. Pollari, Yiyuan Wu, Aristotle N. Voineskos, Benoit H. Mulsant, for the STOP-PD II Study Group

Issue&Volume: Vol 322 No 7

Abstract:

Importance  Psychotic depression is a severely disabling and potentially lethal disorder. Little is known about the efficacy and tolerability of continuing antipsychotic medication for patients with psychotic depression in remission.

Objective  To determine the clinical effects of continuing antipsychotic medication once an episode of psychotic depression has responded to combination treatment with an antidepressant and antipsychotic agent.

Design, Setting, and Participants  Thirty-six week randomized clinical trial conducted at 4 academic medical centers. Patients aged 18 years or older had an episode of psychotic depression acutely treated with sertraline plus olanzapine for up to 12 weeks and met criteria for remission of psychosis and remission or near-remission of depressive symptoms for 8 weeks before entering the clinical trial. The study was conducted from November 2011 to June 2017, and the final date of follow-up was June 13, 2017.

Interventions  Participants were randomized either to continue olanzapine (n = 64) or switch from olanzapine to placebo (n = 62). All participants continued sertraline.

Main Outcomes and Measures  The primary outcome was risk of relapse. Main secondary outcomes were change in weight, waist circumference, lipids, serum glucose, and hemoglobin A_1c (HbA_1c).

Results  Among 126 participants who were randomized (mean [SD] age, 55.3 years [14.9 years]; 78 women [61.9%]), 114 (90.5%) completed the trial. At the time of randomization, the median dosage of sertraline was 150 mg/d (interquartile range [IQR], 150-200 mg/d) and the median dosage of olanzapine was 15 mg/d (IQR, 10-20 mg/d). Thirteen participants (20.3%) randomized to olanzapine and 34 (54.8%) to placebo experienced a relapse (hazard ratio, 0.25; 95% CI, 0.13 to 0.48; P < .001). The effect of olanzapine on the daily rate of anthropometric and metabolic measures significantly differed from placebo for weight (0.13 lb; 95% CI, 0.11 to 0.15), waist circumference (0.009 inches; 95% CI, 0.004 to 0.014), and total cholesterol (0.29 mg/dL; 95% CI, 0.13 to 0.45) but was not significantly different for low-density lipoprotein cholesterol (0.04 mg/dL; 95% CI, −0.01 to 0.10), high-density lipoprotein cholesterol (−0.01 mg/dL; 95% CI, −0.03 to 0.01), triglyceride (−0.153 mg/dL; 95% CI, −0.306 to 0.004), glucose (−0.02 mg/dL; 95% CI, −0.12 to 0.08), or HbA_1c levels (−0.0002 mg/dL; 95% CI, −0.0021 to 0.0016).

Conclusions and Relevance  Among patients with psychotic depression in remission, continuing sertraline plus olanzapine compared with sertraline plus placebo reduced the risk of relapse over 36 weeks. This benefit needs to be balanced against potential adverse effects of olanzapine, including weight gain.

DOI: 10.1001/jama.2019.10517

Source: https://jamanetwork.com/journals/jama/article-abstract/2748508