非典型抗精神病药对男性精神分裂症患者勃起功能及血浆催乳素水平的影响

目的:探讨非典型抗精神病药(AAP)对恢复期男性精神分裂症患者勃起功能及血浆催乳素(PRL)水平的影响。方法:采用国际勃起功能指数-5问卷(IIEF-5)对以氯氮平、喹硫平、奥氮平、利培酮、阿立哌唑、氨磺必利、帕利哌酮及齐拉西酮单一治疗≥6个月、具有稳定性伴侣的恢复期男性精神分裂症患者各30例进行总体勃起功能障碍(ED)评定,以IIEF-5≤21分定义为ED;同时采用放免法检测患者的血浆PRL水平。结果:ED发生率氨磺必利组显著高于氯氮平组、喹硫平组及阿立哌唑组(P均0.001),利培酮组显著高于阿立哌唑组(P0.01)。血浆PRL水平氨磺必利组、齐拉西酮组及利培酮组显著高于氯氮平组、喹硫平组、奥氮平组及阿立哌唑组(P均0.001),帕利哌酮组显著高于阿立哌唑组(P0.001)。IIEF-5评分与全部患者及氨磺必利组、帕利哌酮组和齐拉西酮组血浆PRL水平呈正相关(P均0.001)。结论:AAP中氨磺必利较易导致ED,利培酮次之;且氨磺必利、齐拉西酮及利培酮可能导致血浆PRL水平增高。     

抗精神病药对男性精神分裂症患者性功能影响的相关性分析

目的 探讨抗精神病药喹硫平、利培酮、氯丙嗪及氯氮平对男性精神分裂症患者性功能影响的差异及相关因素分析.方法 将门诊就诊的男性精神分裂症患者120例,随机分为喹硫平组38例、利培酮组41例、氯丙嗪39例、氯氮平组42例.应用酶联免疫吸附法检测血清泌乳素、放射免疫法检测睾酮水平,检测各组患者治疗前及治疗第12周末的血清泌乳素(PRL)和睾酮水平.分别于基线及治疗第12周末使用简明男性性功能量表、阳性与阴性症状量表(PANSS)评估性功能及精神症状,于治疗第12周末用副反应量表(TESS)评估药物治疗的不良反应.结果 治疗第12周末,利培酮组、氯丙嗪组、氯氮平组的性功能量表总分较治疗前降低(P＜0.05).利培酮组和氯丙嗪组治疗第12周末的血清泌乳素水平高于基线水平[利培酮组:(12±5)ng/ml,(22±6)ng/ml,t=13.92,P＜0.01;氯丙嗪组:(13±6)ng/ml,(19±5)ng/ml,t=8.27,P＜0.01],喹硫平组和氯氮平组无明显变化.利培酮组和氯丙嗪组治疗第12周末的血睾酮水平低于基线水平:利培酮组:(0.77±0.21)ng/ml,(0.27±0.11)ng/ml,t=13.22,P＜0.01;氯丙嗪组:(0.90±0.11)ng/ml,(0.32±0.14)ng/ml,t=11.27,P＜0.01;喹硫平组和氯氮平组无明显变化.影响男性精神分裂症患者性功能的因素有泌乳素、睾酮、年龄及TESS分.结论 抗精神病药物中,利培酮和氯丙嗪易引起血清泌乳素升高和血清睾酮降低,氯氮平具有较多药物不良反应,这些可能造成男性精神分裂症患者的性功能减退.     

利培酮与氯氮平维持治疗精神分裂症三年随访对照研究

目的比较利培酮与氯氛平治疗精神分裂症的长期效果。方法对经利培酮与氯氮平治疗出院的精神分裂症患者各58例进行3年随访,以总体印象量表（CGI）、副反应量表（TESS）及社会功能缺陷量表（SDSS）评估两种药物长期维持治疗时的临床疗效、药物副反应及社会功能康复状况。结果CGI中的疗效指数EI：利培酮组高于氯氮平组,两者存在显著差异（P〈0．05）;TESS评分：利培酮组与氯氮平两者无显著差异;SDSS评分：利培酮组与氯氮平组存在显著差异（P〈0．001）。同时,利培酮与氯氮平治疗患者3年内复发率为25．9％和39．6％,再住院率分别为10．6％和53．1％,x2=8．3,P〈0．01,两者间具有显著性差异。结论利培酮比氯氮平更适合精神分裂症患者的长期维持治疗．     

抗精神病药对精神分裂症患者认知功能的影响

目的：比较非经典抗精神病药奎硫平、奥氮平、氯氮平与经典抗精神病药氯丙嗪对精神分裂症患者认知功能的影响。方法：对160例住院精神分裂症患者随机开放分配接受奎硫平、奥氮平、氯氮平和氯丙嗪药物治疗。12周的急性期治疗后,获得临床稳定期的患者[阳性与阴性量表（PANSS）总分≤60或减分率／〉50％]进入固定剂量的24周治疗。分别在基线、治疗12周和24周进行威斯康星卡片分类测验（WCST）、言语流畅性测验、霍普金斯词语学习测验（HVLT-R）、持续操作功能测验（CPT）、韦克斯勒记忆测定（WMS）、韦克斯勒智能测定（WAIS）、连线试验测定、手指叩击试验测定。结果：奎硫平组、奥氮平组、氯氮平组治疗12周和24周后认知功能均有不同程度的改善（P均〈0．05）,明显优于氯丙嗪,而氯丙嗪组无显著改善。治疗12周后奎硫平组在改善执行功能、言语流畅性和警觉性显著优于奥氮平组和氯氮平组（P〈0．05）。奥氮平组在数字特征和连线测定上明显优于氯氮平组（P〈0．05）。3种非经典抗精神病药在认知功能总分的改善与PANSS总分、阴性症状分的改善有显著相关性（r=-0．32,P〈0．05）。结论：3种非经典抗精神病药奎硫平、奥氮平、氯氮平可不同程度改善精神分裂症患者的认知功能。     

喹硫平与利培酮对血清催乳素影响的研究

目的了解喹硫平与利培酮对精神分裂症患者的疗效及对血清催乳素的影响。方法对71例符合CCMD-3诊断标准的精神分裂症患者随机分为喹硫平治疗组（33例）与利培酮治疗组（38例）,观察12周,分别于治疗前及治疗后4周、8周、12周予以阳性症状与阴性症状量表（PANSS）,副反应量表（TESS）及血清催乳素测定。结果喹硫平组和利培酮组疗效差异无显著性,两组治疗后4周、8周及12周PANSS总分及各因子分显著下降（P〈0.01）,利培酮组的不良反应高于喹硫平组,主要表现在肌强直、震颤、泌乳（χ^2=5.69,P〈0.01）及闭经（χ^2=6.74,P〈0.01）等不良反应上,利培酮组治疗后4周、8周及12周血清催乳素明显增加（t=13.48,P〈0.01）,而喹硫平组治疗前后无差异。结论喹硫平与利培酮对精神分裂症均有效,但利培酮不良反应大,明显升高血清催乳素,且有较高高血清催乳素不良反应,而喹硫平对血清催乳素影响较少。     

非典型抗精神病药对男性精神分裂症患者性功能影响的初步分析

目的 探讨喹硫平、利培酮、奥氮平及氯氮平对男性精神分裂症患者性功能影响的差异.方法 将门诊就诊的男性精神分裂症患者145例,分为喹硫平组 30 例、利培酮组 47 例、奥氮平组 31 例及氯氮平组 37 例.检测各组患者血清泌乳素水平.使用简明男性性功能量表、阳性与阴性综合征量表(PANSS)评估性功能及精神症状,用副反应量表(TESS)评估药物治疗的不良反应.共观察8周.结果 治疗第 8 周末,利培酮组的性功能量表总分及因子分均较治疗前降低,奥氮平组的性唤起因子及性功能因子得分有所下降,氯氮平组的性满意度因子及性功能因子得分有所下降.喹硫平组得分无明显变化.利培酮组和奥氮平组治疗第 8 周末的血清泌乳素水平高于基线水平[利培酮组:(12±5)ng/ml,(20±6)ng/ml,t=13.92,P＜0.01;奥氮平组:(13±6)ng/ml,(18±5)ng/ml,t=8.27,P＜0.01],喹硫平组和氯氮平组无明显变化.影响男性精神分裂症患者性功能的因素有泌乳素、年龄及TESS分.结论 常见非典型抗精神病药物对男性精神分裂症患者的性功能影响有所不同.     

奥氮平和利培酮治疗青年女性精神分裂症患者的骨密度及催乳素变化对照研究

目的探讨精神分裂症青年女性患者奥氮平或利培酮治疗后骨密度及催乳素的变化,分析其关联性。方法将60例青年女性精神分裂症住院患者随机分为奥氮平组（研究组）和利培酮组（对照组）,每组各30例,分别予以为期1年的奥氮平或利培酮治疗。在基线时及治疗后第3,6、12个月末进行骨密度及催乳素检测,观察两组间的差异,并对骨密度和催乳素进行相关分析。结果治疗后第6、12个月末,对照组骨密度显著低于研究组（P〈0．05）。对照组在治疗后第3、6、12个月末骨密度较基线时显著下降（P〈0．05）。对照组治疗后第12个月末的骨质疏松发生率显著高于研究组（P〈0．05）。在治疗后第3、6、12个月末,对照组催乳素水平均显著高于研究组（P〈0．05）,且骨密度和催乳素水平显著负相关（P〈0．05）。结论与利培酮比较,奥氮平较少影响青年女性精神分裂症患者的骨密度和催乳素,骨质疏松发生率较低。青年女性患者的高催乳素水平可导致骨密度下降。     

利培酮、氯氮平与氯丙嗪的疗效和不良反应及相关因素的研究

目的　比较利培酮、氯氮平与氯丙嗪的疗效和不良反应 ,探讨有关的实验室检查和药物浓度相互关系。方法　将符合CCMD 2 R诊断标准的精神分裂症患者 ,根据临床情况和入院顺序 ,分别进入利培酮组、氯氮平组与氯丙嗪组 ,观察 8周。以PANSS、CGI、TESS和ESRS量表评定药物的疗效和不良反应。同时测定血清泌乳素和药物浓度。结果　治疗 8周后 :①利培酮组、氯氮平线和氯丙嗪组的PANSS量表总分、阴性分量表、一般精神病理学分量表和CGI量表病情严重程度评分均下降 ,而利培酮组和氯氮平组减分较氯丙嗪组明显 (分别P <0 0 1,P <0 0 5 ) ,TESS及ESRS量表的评分也与氯丙嗪组有显著性差异 (分别为P <0 0 1,P <0 0 5 )。②利培酮组、氯氮平组与氯丙嗪组肝功能、心电图检查组间差异有非常显著意义 (均P <0 0 1)。③氯氮平的剂量与去甲氯氮平、氯氮平浓度呈显著相关 ,9 羟利培酮浓度与PRL、利培酮有效率呈显著性相关 ,氯丙嗪浓度与PRL呈显著性相关 (rs=0 .2 6 1,P =0 .0 15 )。结论　利培酮、氯氮平具有较强抗精神病作用 ,相对氯丙嗪更为有效和全面。利培酮的安全性相对较好。     

氯氮平和利培酮对催乳素、甲状腺素的影响

目的：比较氯氮平、利培酮对精神分裂症患者血清催乳素（PRL）、三碘甲状腺原氨酸（T3）、甲状腺素（T4）的影响。方法：将68例精神分裂症患者随机分为氯氮平组和利培酮组，治疗6周。用磁酶免疫法在治疗前后分别测定血清PRL、T3、T4水平。结果：氯氮平组治疗后血清PRL、T3、T4均增高，治疗前后差异有显著性；但血清PRL、T3、T4的改变无性别的差异；利培酮血清PRL治疗后较治疗前高，T3、T4较治疗前低，差异均有显著性，也无性别的差异。结论：氯氮平和利培酮治疗均明显增加血清催乳素水平，利培酮增加幅度更大。氯氮平增加T3、T4水平，而利培酮降低T3、T4水平。     

四种非典型抗精神病药对血清催乳素和血脂的影响

目的探讨四种非典型抗精神病药对精神分裂症患者血脂和血清催乳素（PRL）的影响,以及血清PRL水平与药物疗效的关系。方法118例精神分裂症患者分为4组,分别予以喹硫平（29例）、氯氮平（30例）、奥氮平（30例）和利培酮（29例）治疗12周。于治疗前及治疗4、8及12周末予以阳性与阴性症状量表（PANSS）评定,测定血总胆固醇（TC）、甘油三脂（TG）高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、阿朴脂蛋白A—I（ApoA-1）、阿朴脂蛋白-B（Apo—B）及血清PRL浓度。结果（1）喹硫平组TG、HDL在12周末有显著升高（P〈0．05）,氯氮平组Apo—B在4、12周末有显著升高（P〈0．05）、LDL在8、12周末有显著升高（P〈0．05）,利培酮组除TG外其余血脂指标在8、12周末有显著升高（P〈0．05）,奥氮平组TG、HDL、LDL、ApoA-1、Apo—B在12周末有显著升高（P〈0．05）,TC在8与12周有显著升高（P〈0．05）。（2）利培酮组治疗8、12周后血清PRL明显升高（P〈0．01）。（3）氯氮平组和利培酮组PANSS一般病理分的减分率分别与PRL、LDL有显著相关;氯氮平组PRL与LDL有显著相关。结论利培酮、奥氮平、喹硫平和氯氮平均影响血脂代谢;氯氮平疗效与血清催乳素及LDL有关,利培酮疗效与LDL有关。     

迟发性运动障碍与抗精神病药物治疗关系的研究

目的观察迟发性运动障的发生与长期应用抗精神病药物的关系。方法选取北京回龙观医院长期住院的患者,符合CCMD-3精神分裂症的诊断标准,抗精神病药剂量恒定维持治疗6个月。排除器质性疾病及其它神经精神疾患。先用Simpson迟发性运动专业量表进行全院患者筛选,最终选出合乎要求病例109例,再用AIMS量表评定,依据患者用药情况分为三组,典型抗精神病药组（包括氯丙嗪、奋乃静、氟哌啶醇、安棕酯）、氯氮平组、利培酮组,使用SPSS10.0,采用独立样本t检验、单因素方差分析,分析三组药物与TD的相关性。结果利培酮组的AIMS总分显著低于典型抗精神病药组（p=0.032）,与氯氮平组无显著差异（P=0.275）。结论利培酮组,氯氮平组致TD症状的严重程度偏低,或对TD症状有一定抑制或治疗作用。     

氨磺必利与利培酮对精神分裂症患者催乳素及糖脂代谢影响

目的:探讨氨磺必利与利培酮对精神分裂症患者催乳素及糖脂代谢的影响。方法:精神分裂症患者按治疗方案分为氨磺必利组(入组25例,完成20例)及利培酮组(入组20例,完成19例),分别在治疗前及治疗后4周、8周监测催乳素及糖脂代谢方面的各项指标,并分析治疗前后两组之间的差异。结果:两组治疗4周及治疗8周与治疗前相比,催乳素水平均有显著升高(P0.05);利培酮组较氨磺必利组催乳素升高更为显著。两组胰岛素抵抗指数及体质量指数均升高(P0.05)。结论:与利培酮相比,氨磺必利对催乳素的影响相对较轻,而两种药物对代谢方面的影响相当。     

Effect of risperidone and olanzapine on reproductive hormones, psychopathology and sexual functioning in male patients with schizophrenia

OBJECTIVE: To study the effect of drugs on the hypothalamo-pituitary-gonadal (HPG) axis we compared the endocrine actions of two neuroleptics with different receptor affinity profiles-risperidone and olanzapine in male schizophrenic patients. METHODS: We investigated the levels of prolactin, estradiol, testosterone, LH, FSH and testicular peptide hormone-inhibin B, and we assessed psychopathology (PANSS), sexual function (ASEX) and treatment adherence (DAI-10) in 89 male schizophrenic inpatients treated with olanzapine or risperidone administered orally. The initial and final evaluations were carried out at weeks 3 and 8 after the onset of treatment, respectively. RESULTS: At initial evaluation the mean serum prolactin and inhibin B levels were markedly higher, whereas testosterone level was lower in patients treated with risperidone, than in those treated with olanzapine. In 5 out of 50 subjects from risperidone group (10%) and in 1 from olanzapine group (2.6%) testosterone levels were below the lower limit (<241ng/ml), which reflected Leydig's cell impairment. In one patient receiving risperidone and in three receiving olanzapine, inhibin B level was below 80pg/ml, indicating Sertoli's cell dysfunction. At the final evaluation the mean serum prolactin level was markedly higher in patients taking risperidone, whereas their FSH levels were lower than in patients receiving olanzapine. In all investigated groups, except for the risperidone-hyperprolactinemic group inhibin B levels were negatively correlated with serum FSH. The mean LH, FSH, testosterone and estradiol levels were within the normal reference range at initial and final evaluation. The non-adherence to medications and ASEX scores were significantly higher in risperidone groups. Sexual dysfunction and medication non-adherence was not related to prolactin or gonadal hormone levels. CONCLUSIONS: Risperidone elicited higher PRL elevation than olanzapine. Treatment with this medication can be associated with disturbances in reproductive hormones (testosterone) and gonadotropins (FSH). The cause of olanzapine-elicited reduction of inhibin B level and the lack of negative correlation between FSH and inhibin B in patients with risperidone-induced hyperprolactinemia require further investigation. Patients receiving risperidone showed higher level of sexual dysfunction and treatment non-adherence than those treated with olanzapine.     

Elevation of prolactin levels by atypical antipsychotics.

OBJECTIVE: Atypical antipsychotics are thought not to elevate prolactin levels. The authors examined data suggesting that atypical antipsychotics do elevate prolactin levels but more transiently than typical antipsychotics. METHOD: Prolactin levels in 18 male patients with schizophrenia who were receiving atypical antipsychotics were monitored over the 24-hour period following administration of their daily oral dose of risperidone, olanzapine, or clozapine. RESULTS: The baseline prolactin levels in patients receiving risperidone (mean=27 ng/ml, SD=14) were abnormally high, but baseline prolactin levels in patients receiving olanzapine (mean=9 ng/ml, SD=5) and clozapine (mean=9 ng/ml, SD=5) were not high. All three atypical antipsychotics caused a doubling of prolactin levels over baseline levels 6 hours after medication administration. CONCLUSIONS: These data suggest that these atypical antipsychotics raise prolactin levels, although the increases with olanzapine did not reach statistical significance. This suggests that the differences in the effects on prolactin levels of atypical and typical antipsychotics are not categorical but lie in the degree and duration of dose-induced prolactin elevation, attributable to the differential binding properties of each drug on pituitary dopamine D(2) receptors.     

Sexual functioning associated with quetiapine switch vs. risperidone continuation in outpatients with schizophrenia or schizoaffective disorder: a randomized double-blind pilot trial

This study evaluated the effect of switching to quetiapine vs. risperidone continuation on sexual functioning in outpatients with risperidone-associated sexual dysfunction. Outpatients (n = 42, age ≥ 18 years) with schizophrenia or schizoaffective disorder who experienced risperidone-associated sexual dysfunction were randomized to 6 weeks of double-blind risperidone continuation (mean dose = 4.1 mg/day, S.D. = 1.2) or quetiapine switch (mean dose = 290.0 mg/day, S.D. = 55.2) treatment. The five-item Arizona Sexual Experience Scale (ASEX) assessed sexual functioning at baseline and subsequently at weeks 2, 4 and 6. A mixed-model analysis of repeated measures included gender and baseline ASEX and PANSS scores as covariates. There was no significant Treatment Group effect for ASEX total scores and ASEX sub-items, and no significant Treatment Group × Period interaction for ASEX total scores and ASEX sub-items. Treatment Group effects were not significantly different in any of the prospective weeks for ASEX total scores and ASEX sub-items. Adjusted mean ASEX total scores were slightly lower in the quetiapine switch group than in the risperidone continuation group at weeks 2 and 6 (21.27 vs. 22.18 and 18.51 vs. 20.53, respectively), but were nearly identical at week 4 (20.01 vs. 20.15). In this pilot trial, sexual functioning did not differ significantly between outpatients receiving quetiapine switch vs. risperidone continuation, although the quetiapine switch group had slightly lower adjusted mean ASEX total scores at weeks 2 and 6.     

Prolactin levels in schizophrenia and schizoaffective disorder patients treated with clozapine, olanzapine, risperidone, or haloperidol

BACKGROUND: Prolactin levels are elevated to varying degrees by antipsychotics. Prolactin elevations may result in sexual and other adverse effects, and they may be related to antipsychotic effects. We used the data collected in a trial of antipsychotics to study the differential effect of these drugs on prolactin level, to explore the relation between clinical effects and prolactin level, and to determine the relationship between plasma levels of antipsychotics and prolactin level. METHOD: Treatment-resistant patients (133 men, 24 women) diagnosed with DSM-IV schizophrenia or schizoaffective disorder participated in a double-blind, randomized, 14-week trial comparing clozapine (N = 40), olanzapine (N = 39), risperidone (N = 41), and haloperidol (N = 37). Plasma levels of prolactin and antipsychotics were determined at baseline and at weeks 5, 8, 10, 12, and 14 during the trial. Clinical effects were measured with the Positive and Negative Syndrome Scale and the Extrapyramidal Symptom Rating Scale. Statistical analyses were limited to the 75 men for whom repeated prolactin levels were available. Data were gathered from June 1996 to December 1999. RESULTS: Risperidone caused significant elevation of prolactin levels (p <.05) that appeared to be dose-dependent. Clozapine and olanzapine were associated with decreases of prolactin, whereas haloperidol led to a minor, nonsignificant increase. Plasma olanzapine and prolactin levels were correlated. Prolactin levels were not related to clinical improvement or extrapyramidal side effects. CONCLUSION: Antipsychotics show major differences in their effects on prolactin, and risperidone has clearly the most robust effect.     

注射用利培酮微球与口服利培酮对精神分裂症血浆催乳素及社会功能的影响

目的比较两种不同剂型的利培酮（注射用长效利培酮微球与口服利培酮）对精神分裂症患者血浆催乳素及社会功能的影响。方法 74例口服利培酮≤4mg/d达6周且病情稳定的门诊精神分裂症患者,被随机分为注射长效利培酮微球组（注射组,利培酮剂量每2周为25～50mg）和口服利培酮组（口服组,利培酮剂量≤4mg/d）。于分组前及分组后4周、8周、16周检测患者的血浆催乳素水平,于分组前和分组后8周、16周以个人和社会功能量表（Personal and Social Performance,PSP）评定患者的社会功能,以阳性和阴性症状量表（PANSS）、临床疗效总评量表中的病情严重程度（GGI-SI）及Simpson锥体外系副反应评定量表（SEPS）评定疗效和不良反应。结果注射组37例患者中,有30例（82.1%）完成研究,口服组37例患者中,有32例（85.7%）完成研究,将完成全部研究的患者的资料纳入统计分析。分组前两组的PNASS、CGI-SI及SEPS评分比较均无统计学差异。分组治疗16周后,两组的PANSS评分及CGI-SI评分均下降,但两组间比较无统计学差异;注射组、口服组的SEPS评分的均数（标准差）为3.7（2.5）和5.1（2.8）,（t=2.12,P=0.037）。分组治疗8周后,注射组与口服组的血浆催乳素均数（标准差）分别为48.2（15.7）μg/L及54.2（18.8）μg/L,（t=2.59,P=0.012）,两组的PSP评分的均数（标准差）分别为70.9（9.7）及65.3（11.1）,（t=2.01,P=0.049）;分组16周后,注射组与口服组的血浆催乳素浓度的均数（标准差）分别为31.5（17.1）μg/L及58.5（16.8）μg/L,（t=6.24,P〈0.001）,两组的PSP评分的均数（标准差）分别为79.3（6.0）及66.1（9.6）,（t=6.44,P〈0.001）。两组血浆催乳素水平的差异有统计学意义（F=4.79,P=0.033）,两组PSP分值的差异有统计学意义（F=8.70,P=0.005）。结论与口服利培酮相比,注射长效利培酮微球后患者出现的锥体外系不良反应较轻,高催乳素血症的程度较低,社会功能恢复较好。