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ENGLISH ABSTRACT
不同剂量阿立哌唑对氨磺必利和利培酮引起的高催乳素血症的影响
徐彩霞
黄炜
赵惜辉
梁震韬
邓文
作者及单位信息
·
DOI： 10.3760/cma.j.issn.1006-7884.2015.05.008
Effect of various doses aripiprazole on hyperprolactinemia induced by amisulpride and risperidone
Xu Caixia
Huang Wei
Zhao Xihui
Liang Zhentao
Deng Wen
Authors Info & Affiliations
Xu Caixia
Department of Psychology, the Third People Hospital of Foshan, Foshan 528041, China
Huang Wei
Zhao Xihui
Liang Zhentao
Deng Wen
·
DOI： 10.3760/cma.j.issn.1006-7884.2015.05.008
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摘要

目的探讨不同剂量阿立哌唑治疗氨磺必利和利培酮所致高催乳素血症的疗效及安全性。

方法采用随机数字表法将87例氨磺必利所致高催乳素血症患者随机分为氨磺必利联用5、10、15 mg阿立哌唑（Ami+5 mg、Ami+10 mg、Ami+15 mg）组，每组29例；将106例利培酮所致高催乳素血症患者随机分为利培酮联用5、10、15 mg阿立哌唑（Ris+5 mg、Ris+10 mg、Ris+15 mg）组，每组分别为36例、35例、35例。维持原有氨磺必利或利培酮剂量不变，联用相应剂量阿立哌唑进行12周对照研究。于治疗前、治疗后第4周、第8周及第12周检测患者催乳素水平，观察高催乳素血症患者的相关临床变化；以PANSS和治疗中需处理的不良反应症状量表评定联用不同剂量阿立哌唑对疗效和不良反应的影响。

结果在第4、8、12周末氨磺必利合并阿立哌唑不同剂量组催乳素水平在组内及组间差异无统计学意义。利培酮合并阿立哌唑不同剂量组在第4周起催乳素水平均有显著下降并持续到12周，与基线时相比，Ris+5 mg组[(38.9±19.0) nmol/L与（11.0±8.1）nmol/L]、Ris+10 mg组[(36.2±16.5) nmol/L与（8.8±7.3）nmol/L]、Ris+15 mg组[（35.6±14.8）nmol/L与（9.2±7.6）nmol/L]第12周催乳素水平差异有统计学意义（ t=4.129、4.798、4.506，均 P<0.01）。Ris+5 mg组、Ris+10 mg组、Ris+15 mg组高催乳素血症相关临床症状消失比率分别为66.67%（24/36）、62.86%（22/35）、51.43%（18/35），3组间高催乳素血症相关临床症状消失比率的差异无统计学意义。PANSS评分第12周末除Ami+15 mg组、Ris+10 mg组、Ris+15 mg组较基线有明显下降外（ t=2.419、2.406、2.631，均 P<0.05），其余差异均无统计学意义。Ami+15 mg组不良反应率[52%（15/29）]高于Ami+5 mg组[17%（5/29）， t=3.521， P<0.01]和Ami+10 mg组[24%（7/290）， t=2.348， P<0.05]，Ris+15 mg组不良反应率[34%（12/35）]高于Ris+5 mg组[11%（4/36）， t=2.203， P<0.05]和Ris+10 mg组[11%（4/35）， t=2.314， P<0.05]。

结论合并不同剂量阿立哌唑对氨磺必利所致高催乳素血症无改善作用，但可以降低由利培酮引起的高催乳素血症，且5 mg/d为合适的联用剂量。

高催乳素血症;精神分裂症;氨磺必利;利培酮;阿立哌唑
ABSTRACT

ObjectiveTo investigate the efficacy and safety of different doses of aripirazole on hyperlactinemia induced by amisulpride and risperidone.

Methods87 patients with hyperlactinemia induced by amisulpride were randomly assigned to three groups on the basis of original medication combined with aripiprazole 5 mg/d, 10 mg/d and 15 mg/d (Ami+5 mg, Ami+10 mg, Ami+15 mg) with 29 cases in each group.106 patients with hyperlactinemia induced by risperidone were randomly assigned to three groups on the basis of original medication combined with aripiprazole 5 mg/d (36 cases), 10 mg/d (35 cases) and 15 mg/d (35 cases). The plasma prolactin (PRL) level was measured before and after 4 th,8 th and 12 th week treatment. The Positive and Negative Syndrome Scale (PANSS) and Treatment Emergent Symptom Scale (TESS) were assessed for psychotic symptoms and adverse effects.

ResultsThe level of PRL of Ami+5 mg, Ami+10 mg and Ami+15 mg group had no statistical difference within and between groups at 4 th,8 th and 12 th week. The level of PRL of Ris+5 mg , Ris+10 mg and Ris+15 mg group were significantly lower than that of baseline at each visit after baseline. The level of PRL of Ris+5 mg group ((38.9±19.0) nmol/L vs. (11.0±8.1) nmol/L), Ris+ 10 mg group ((36.2±16.5) nmol/L vs. (8.8±7.3) nmol/L) and Ris+ 15 mg group((35.6 ± 14.8) nmol/L vs. (9.2±7.6) nmol/L) at baseline were significantly different from which at the 12 th week ( t=4.129, 4.798,4.506;all P<0.01). The remission rates of symptoms relevant with hyperlactinemia in Ris+5 mg group, Ris+10 mg group and Ris+15 mg group were 66.67% (24/36), 62.86% (22/35), 51.43% (18/35) respectively. There were no difference of the remission rate of symptoms relevant with hyperlactinemia among those three groups. There were no difference of PANSS score within groups at 12 th week except Ami+15 mg group, Ris+ 10 mg group and Ris+15 mg group( t=2.419, 2.406, 2.631, all P<0.05). The adverse effect rate of Ami+15 mg group (52%(15/29)) was significantly higher than that of Ami+5 mg group(17%(5/29), t=3.521, P<0.01) and Ami+10 mg group (24% (7/29), t=2.348, P<0.05). The adverse effect rate of Ris+15 mg group (34%(12/35)) was significantly higher than that of Ris+ 5 mg group (11%(4/36), t=2.203, P<0.05) and Ris+10 mg group (11% (4/35), t=2.314, P<0.05).

ConclusionVarious dose of aripiprazole did not show improvement in hyperprolactinemia induced by amisulpride, However that could significantly decrease PRL level in hyperprolactinemia induced by risperidone, and considering efficacy and safety, 5 mg/d aripirazole may be the best combination dose.

Hyperprolactinemia;Schizophrenia;Amisulpride;Risperidone;Aripiprazole
Xu Caixia,Email: mocdef.9ab3124899772831
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引用本文

徐彩霞,黄炜,赵惜辉,等. 不同剂量阿立哌唑对氨磺必利和利培酮引起的高催乳素血症的影响[J]. 中华精神科杂志,2015,48(5)：297-302.

DOI:10.3760/cma.j.issn.1006-7884.2015.05.008

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精神分裂症患者在应用第1代和第2代抗精神病药治疗时，均有引起高催乳素血症的可能。高催乳素血症对精神分裂症患者不仅存在短期的影响，如泌乳、性欲减退、月经紊乱、男性乳房发育等，也存在长期的影响，如骨质疏松、体重增加及肿瘤的发生等 [ 1 ]，这严重影响了患者的生活质量以及治疗依从性等。而在第2代抗精神病药中，氨磺必利 [ 2 ]和利培酮 [ 3 ]所致高催乳素血症较为常见。国际上的研究根据对催乳素的不同影响将抗精神病药分为两类：刺激催乳素水平升高和对催乳素无影响 [ 1 ]，前者包含氨磺必利和利培酮，后者包含阿立哌唑 [ 1 ]。目前有学者建议将阿立哌唑作为治疗抗精神病药所致高催乳素血症的一线药物 [ 4 ]。但国内外关于联用阿立哌唑分别对氨磺必利和利培酮所致高催乳素血症疗效研究结果不一 [ 5 ]，关于阿立哌唑联用剂量的研究较少，因此我们着重于探讨阿立哌唑对氨磺必利和利培酮所致高催乳素血症的影响，同时探索合适的联用剂量，从而为临床用药提供依据。
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备注信息
A
徐彩霞，Email： mocdef.9ab3124899772831
B
中南大学湘雅二医院精神科郝伟老师在文章撰写中给予的指导；西安杨森公司医学部在数据统计方面给予的支持
C
佛山市医学类科技攻关项目 (201008062)
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