From the Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA.
H. Lundbeck A/S, Valby, Denmark.
J Clin Psychopharmacol. 2020 Nov/Dec;40(6):560-567. doi: 10.1097/JCP.0000000000001297.
PURPOSE/BACKGROUND: Evidence supports use of adjunctive atypical antipsychotics in major depressive disorder (MDD). Impaired sexual functioning is common in MDD and may be worsened by antipsychotic adverse effects. We evaluated the effect of brexpiprazole on prolactin and sexual functioning in patients with MDD.
METHODS/PROCEDURES: In short-term studies, patients received adjunctive brexpiprazole 1, 2, or 3 mg or placebo. The long-term study was a flexible-dose (0.5-3 mg/d) open-label extension (OLE). Change from baseline and shifts in prolactin status and prolactin-related treatment-emergent adverse events (TEAEs) were assessed. Sexual functioning was assessed by the Massachusetts General Hospital Sexual Functioning Questionnaire.
FINDINGS/RESULTS: Median changes in prolactin levels from baseline to week 6 in short-term studies were as follows: brexpiprazole, 5.99 ng/mL (females) and 1.61 ng/mL (males); placebo, -0.15 ng/mL (females) and -0.08 ng/mL (males).Median changes from baseline to week 52 in the OLE were as follows: 0.27 ng/mL (females) and 0.27 ng/mL (males). Prolactin levels in patients with baseline prolactin greater than 1× upper limit of normal values tended to decrease over time.The proportion of brexpiprazole-treated patients with greater than 3× upper limit of normal postbaseline prolactin values in short-term studies for both sexes was low (0%-0.3%) and did not differ from placebo: OLE, 0.5% (females) and 0.8% (males).In short-term studies, the incidence of prolactin-related TEAEs was 3.1% for brexpiprazole and 0.7% for placebo (OLE, 3.1%). There were overall numerical improvements from baseline in sexual functioning for females and males after short- and long-term brexpiprazole treatment, with statistically significant improvements for brexpiprazole versus placebo in females on the items 'interest in sex' (-0.19; 95% confidence interval [CI], -0.33 to -0.05; P = 0.0074), 'sexually aroused' (-0.17; 95% CI, -0.30 to -0.03; P = 0.0154), and 'overall sexual satisfaction' (-0.16; 95% CI, -0.30 to -0.03; P = 0.0184).
IMPLICATIONS/CONCLUSIONS: There were small changes in prolactin levels, low proportions of patients with postbaseline elevated prolactin values, low incidences of prolactin-related TEAEs, and modest improvements in sexual functioning with adjunctive brexpiprazole in MDD.
目的/背景：有证据表明，在重度抑郁症（MDD）中使用辅助性非典型抗精神病药。在 MDD 中，性功能障碍很常见，并且可能会因抗精神病药的不良反应而加重。我们评估了布瑞哌唑对 MDD 患者催乳素和性功能的影响。
方法/程序：在短期研究中，患者接受了辅助性布瑞哌唑 1、2 或 3mg 或安慰剂治疗。长期研究是一项灵活剂量（0.5-3mg/d）的开放标签扩展（OLE）。评估从基线的变化以及催乳素状况的变化和催乳素相关的治疗出现的不良事件（TEAEs）。性功能通过麻省总医院性功能问卷进行评估。
结果/发现：短期研究中从基线到第 6 周催乳素水平的中位数变化如下：布瑞哌唑，女性为 5.99ng/mL，男性为 1.61ng/mL；安慰剂，女性为-0.15ng/mL，男性为-0.08ng/mL。OLE 中从基线到第 52 周的中位数变化如下：女性为 0.27ng/mL，男性为 0.27ng/mL。基线催乳素值大于正常上限 1 倍的患者，其催乳素水平随时间呈下降趋势。在短期研究中，男女患者中基线后催乳素值大于正常上限 3 倍的布瑞哌唑治疗患者比例较低（0%-0.3%），与安慰剂无差异：OLE，女性为 0.5%，男性为 0.8%。在短期研究中，布瑞哌唑的催乳素相关 TEAEs 发生率为 3.1%，安慰剂为 0.7%（OLE，女性为 3.1%，男性为 3.1%）。在接受短期和长期布瑞哌唑治疗后，女性和男性的性功能均有总体上的数值改善，与安慰剂相比，布瑞哌唑在女性的“性兴趣”（-0.19；95%置信区间[CI]，-0.33 至-0.05；P=0.0074）、“性唤起”（-0.17；95%CI，-0.30 至-0.03；P=0.0154）和“总体性满意度”（-0.16；95%CI，-0.30 至-0.03；P=0.0184）项目上均有统计学意义的改善。
意义/结论：在 MDD 中，辅助性布瑞哌唑治疗可导致催乳素水平出现轻微变化、患者基线后催乳素值升高比例较低、催乳素相关 TEAEs 发生率较低，以及性功能适度改善。
