利培酮和氟哌啶醇对精神分裂症患者超氧化物歧化酶及催乳素影响的临床对照研究

目的 探讨经第一、二代抗精神病药治疗的精神分裂症患者体内超氧化物歧化酶(SOD)、催乳素(PRL)与精神症状间的关系.方法 符合美国精神障碍诊断与统计手册第4版诊断标准的78例精神分裂症患者,随机分为利培酮组(41例),剂量为6 mg/d;氟哌啶醇组(37例),剂量为20mg/d;观察疗程均为12周.使用阳性和阴性症状量表(PANSS)评定临床疗效.采用放射免疫法在治疗前后分别测定患者血浆SOD及PRL浓度.以30名正常人为正常对照组.结果 利培酮组(40例)、氟哌啶醇组(33例)患者的基线SOD浓度[(794±126)ng/mg Hb,(750±101)ng/mg Hb]均明显高于正常对照组[(483±110)ng/mg Hb],而PRL浓度[(6±7)μg/L,(6±8)μg/L]均明显低于正常对照组[(18±12)μg/L],差异均有统计学意义(P均＜0.05).利培酮组和氟哌啶醇组患者的治疗前SOD与PRL间存在显著负相关(n=70,P＜0.05).治疗第12周末,利培酮组和氟哌啶醇组的SOD浓度[(499±98)ng/mg Hb,(482±76)ng/mg Hb]明显降低,而PRL浓度[(33±19)μg/L,(25±16)μg/L]则明显升高.利培酮组与氟哌啶醇组间治疗前后的SOD、PRL的差异均无统计学意义(P均＞0.05).治疗前后,阴性症状改善与SOD浓度差值(P＜0.05)、阳性症状改善与PRL浓度差值(n=70,P＜0.01)有相关性.结论 精神分裂症患者SOD及PRL浓度异常,两者间存在着相互作用,且对抗精神病药的临床疗效有影响.     

氟哌啶醇、利培酮及齐拉西酮对精神分裂症患者血清催乳素及认知功能影响的对照研究

目的 探讨氟哌啶醇、利培酮及齐拉西酮对精神分裂症患者血清催乳素及认知功能的影响.方法 选取精神分裂症患者120例,随机分为3组,分别予以氟哌啶醇、利培酮、齐拉西酮进行干预治疗.于治疗前及治疗后第4、8、12周末分别进行阳性和阴性综合征量表（PANSS）、精神分裂症认知功能评定量表（SCoRS）评定,并测定血清催乳素（PRL）水平.结果 （1）3组PANSS评分治疗后各时点均较治疗前下降（P＜0.01）.（2）3组患者各时点男性PRL水平均较治疗前升高（P＜0.01）,治疗后12周末齐拉西酮组PRL水平低于利培酮组（P＜0.05）;女性患者中氟哌啶醇组从第8周始、利培酮组从第4周始,PRL水平均较治疗前升高（P＜0.05）,治疗后第12周末齐拉西酮组PRL水平均低于氟哌啶醇组与利培酮组（P＜0.05）.（3）3组患者治疗后各时点SCoRS评分较治疗前下降（P＜0.01）,治疗后各时点SCoRS评分齐拉西酮组低于氟哌啶醇组（P＜0.05,P＜0.01）.结论 氟哌啶醇、利培酮、齐拉西酮均可造成催乳素水平增高.齐拉西酮影响相对较小,对女性患者催乳素水平影响更小.利培酮、齐拉西酮对患者认知功能改善显著优于氟哌啶醇.     

精神分裂症神经内分泌激发试验研究

目的：通过内分泌激发实验,探讨慢性精神分裂症中枢５－ＨＴ功能状态。方法：对７８例精神分裂症、１８例正常对照进行帕罗西汀激发实验研究,以皮质醇和催乳素作为激发实验的应答指标。同时,对病人进行阳性和阴性症状评定量表（ＰＡＮＳＳ）测查。结果：治疗前精神分裂症组催乳素基础值明显低于对照组,帕罗西汀激发实验后催乳素释放增高,曲线下面积（ＡＵＣ）与对照组无显著关异。病人治疗前皮质醇基础值明显高于对照组,帕罗西     

利培酮与舒必利对精神分裂症男性老年患者血清催乳素水平影响的对照研究

目的 探讨利培酮和舒必利对精神分裂症男性老年患者血清催乳素（PRL）水平的影响。方法 将51例精神分裂症男性老年患者随机分为利培酮组[（3．7±0、9）mg／d，24例]和舒必利组[（800±156）mg／d，27例]，采用酶联免疫方法测定两组治疗前后的PRL水平，并与25名正常男性老年人（对照组）进行对照。结果 （1）治疗前，患者组PRL水平[（26±11）彬L]与对照组[（24±14）μg／L]的差异无统计学意义，利培酮组[（26±11）μg/L]与舒必利组[（28±12）μg/L]的差异亦无统计学意义（均P〉0．05）。（2）治疗后，患者组PRL水平[（149±59）μg/L]高于治疗前（t=14．53，P〈0．01）；利培酮组[（118±47）μg/L]和舒必利组[（196±73）μg/L]亦均高于治疗前，其中舒必利组高于利培酮组（均P〈0．01）。结论 利培酮和舒必利均能升高精神分裂症男性老年患者的PRL水平，其中以舒必利更为显著。     

奥氮平与利培酮口服液治疗精神分裂症兴奋激越的临床观察

目的观察奥氮平与利培酮口服液治疗精神分裂症急性期兴奋激越的临床疗效及不良反应。方法将170例精神分裂症急性中度兴奋患者,随机分入奥氮平组56例,利培酮口服液组54例,氟哌啶醇组60例,共治疗7天;治疗前及治疗1周末评估阳性与阴性症状量表兴奋因子（PANSS-EC）,采用TESS评定不良反应。结果奥氮平组、利培酮口服液组与氟哌啶醇组比较,均获得明显改善,差异均无显著性（P均〉0.05）,氟哌啶醇组锥体外系反应发生率高于奥氮平组与利培酮口服液组（P〈0.01）,且奥氮平组几乎无锥体外系反应发生。结论奥氮平与利培酮口服液治疗精神分裂症急性中度兴奋患者与氟哌啶醇的疗效相当,且不良反应较小,安全性良好。     

精神分裂症患者神经内分泌激发试验对照研究

目的：以帕罗西汀为探针探讨首发精神分裂症的中枢5-羟色胺(5-HT)系统的功能。方法：患者组为首发精神分裂症患者24例；另选择年龄、性别相匹配的15名正常人为对照组。口服40mg帕罗西汀作为激发剂，每隔1．5h连续抽取静脉血，共5次。使用酶联免疫吸附法测定血浆皮质醇及催乳素浓度。结果：试验前患者组血浆基础催乳素及皮质醇浓度显著高于对照组，激发试验后患者组2种激素浓度显著高于基础值及对照组；而帕罗西汀对正常人催乳素、皮质醇的释放增加不明显。结论：首发精神分裂症患者中枢5-HT功能可能亢进。     

阿立哌唑治疗利培酮所致精神分裂症女性患者高催乳素血症的研究

目的 探讨阿立哌唑治疗利培酮所致女性患者高催乳素血症的疗效及安全性.方法 117例利培酮所致高催乳素血症的女性患者,随机分为治疗组(60例)和对照组(57例).维持原有利培酮治疗不变,治疗组加用阿立哌唑5 mg,对照组加用安慰剂治疗,疗程均为6周.于治疗第0,6周末检测催乳素,评定简明精神病量表(BPRS)、治疗中需处理的不良反应症状量表(TESS).结果 (1)治疗第6周末,治疗组催乳素[(26±6)μg/L]较基线[(112±40)μg/L]下降,差异有统计学意义(P=0.000);对照组催乳素[(99±44)μg/L]与基线[(104±34)μg/L]比较,差异无统计学意义(P=0.180).(2)治疗第6周末,治疗组催乳素下降率[(75±8)%]、正常率(82%),均高于对照组[分别为(5+30)%,4%];P均=0.000.(3)治疗第6周末,治疗组[(20.4±2.1)分]、对照组[(20.8±1.9)分]BPRS评分均较基线[分别为(21.1±1.8)分,(21.4±1.9)分]下降,P均=0.045;两组不良反应发生率相近(P=0.553).结论 阿立哌唑治疗利培酮所致精神分裂症女性患者的血高催乳症有效、安全.     

氯氮平,氟哌啶醇对精神分裂症患者血清催乳素的影响

本文对１６例服用氯氮平、氟哌啶醇的精神分裂症患者血清催乳素（ＰＲＬ）浓度进行测定分析。结果：氟哌啶醇组的血清ＰＲＬ浓度（Ｘ↑－＝３２．９μｇ／Ｌ）与治疗前相比有明显增高；氯氮平组的ＰＲＬ浓度（Ｘ↑－＝７．０１μｇ／Ｌ）与治疗前无显著差异。提示氯氮平与氟哌啶醇对多巴胺的影响不同。     

氯氮平对首发精神分裂症帕罗西汀激发试验的影响

目的　探讨首发精神分裂症的中枢 5 羟色胺 (5 HT)系统的功能 ,以及氯氮平对神经内分泌激发试验的影响。方法　无重大躯体疾病、既往未服过药物治疗的首发分裂症患者 2 4例 (患者组 ) ,另选择与患者组年龄、性别相匹配的 15名正常人为对照组。口服 4 0mg帕罗西汀作为激发剂 ,每隔 1 5h共 5次 (包括试验前 )连续抽取静脉血 ,使用酶联免疫吸附法测定血浆皮质醇 (COR)及催乳素 (PRL)浓度。患者组分别在氯氮平治疗前后各做 1次激发试验 ,对照组仅做 1次激发试验。氯氮平的平均日剂量为 (2 6 8± 75 )mg ,疗程为 12周。结果　治疗前患者组血浆基础PRL及COR浓度明显高于对照组 (P <0 0 5 ) ,PRL、COR对帕罗西汀的反应明显高于对照组 (P <0 0 5～ 0 0 1)。氯氮平治疗后 ,患者组PRL、COR对帕罗西汀反应明显迟缓 ,与对照组的反应的显差异无显著性 (P >0 0 5 ) ,氯氮平显著提高了外周血COR浓度 (P <0 0 5～ 0 0 1)。结论　首发精神分裂症患者中枢 5 HT功能可能存在亢进。     

利培酮与氟哌啶醇治疗精神分裂症阴性症状临床对照研究

目的 探索利培酮对精神分裂症阴性症状的疗效与副反应。方法 对40例精神分裂症（阴性症状为主）的病人通过随机数字表进行随机,奇数入实验组,偶数入对照组并随访半年,使用利培酮与氟哌啶醇进行对照研究;采用BPRS、SANS和TESS及临床疗效总评进行评定。结果 利培酮的疗效优于氟哌啶醇,而且副反应也低。结论 利培酮是治疗以阴性症状为主的精神分裂症较理想的药物。     

Neuroendocrine responsivities of the pituitary dopamine system in male schizophrenic patients during treatment with clozapine, olanzapine, risperidone, sulpiride, or haloperidol

Background Atypical antipsychotic drugs, in clinical doses, occupy 5-HT2 receptors near saturation, while D2 dopamine receptors, assessed usually in striatum by SPECT or PET methods, are occupied to different degrees. We hypothesized that these differences in D2 receptor occupancies may also be evaluated by a neuroendocrine approach, namely by measuring the plasma prolactin responses to i. m. administered haloperidol, since the expected elevations depend mainly on the free remaining D2 receptors in the tuberoinfundibular tract. Methods We measured the plasma prolactin levels at 0, 30, 60, 90, and 120 minutes after administration of 5 mg haloperidol i. m. in six groups of male patients with schizophrenia: a) 33 patients in a drug-free state, b) 15 patients on treatment with clozapine (range 200–600 mg/day), c) 15 patients on olanzapine (10–30 mg/day), d) 14 patients on risperidone (8–16 mg/day), e) 23 patients on haloperidol (10–40 mg/day), f) 14 patients on sulpiride (600–1600 mg/day). Data were also obtained from a group of 14 healthy male control subjects. The differences in baseline prolactin levels and in the responses to acute haloperidol of the seven groups were compared. Results The baseline prolactin levels did not differ significantly in the groups of controls (8.3±3.8 ng/ml), drug-free patients (8.0±3.6) and patients treated with clozapine (7.7±3.8), they were moderately elevated in patients treated with olanzapine (16.8±8.9), elevated in patients on haloperidol (34.4±17.3), and they were even higher in the groups of patients treated with risperidone (54.9±22.4) or sulpiride (58.8±27.0). All groups of patients gave attenuated prolactin responses to i. m. haloperidol compared to healthy controls. During treatment with haloperidol, risperidone, or sulpiride, no significant prolactin increases after i. m. haloperidol were observed. The group treated with olanzapine gave significant prolactin increases, which were lower than those obtained in the group of patients treated with clozapine, who gave responses similar to that of the drug-free patients. Conclusions Plasma prolactin levels and responses to i. m. haloperidol of patients on treatment with antipsychotic drugs, reflect the prolactin release potencies of the drugs, which are related, but not restricted, to their affinities to D2 dopamine receptors. According to the prolactin baseline levels and responses to i. m. haloperidol, the drugs of this study can be categorized for their potency to the pituitary dopamine system that controls prolactin release, as follows: sulpiride > risperidone > haloperidol > olanzapine > clozapine. This categorization is similar to that obtained by binding studies in striatal D2 dopamine receptors using brain imaging techniques. Received: 26 March 2001 / Accepted: 21 June 2001     

精神分裂症d－芬氟拉明激发的神经内分泌反应与临床症状的关系

目的探讨ｄ－芬氟拉明（ｄ－ＦＦ）激发的神经内分泌反应与精神分裂症临床症状的关系。方法把１５例精神分裂症患者在氯氮平治疗前、后行ｄ－ＦＦ激发试验，同时以简明精神病评定量表（ＢＰＲＳ）、阳性症状量表（ＳＡＰＳ）、阴性症状量表（ＳＡＮＳ）评定精神症状。结果混合型患者治疗前基础皮质醇（ＣＯＲ）值、治疗后ｄ－ＦＦ激发的ＣＯＲ值及治疗前、后ｄ－ＦＦ激发的催乳素（ＰＲＬ）值均显著高于阳性型。症状评分与激素反应有一定的相关关系。结论提示精神分裂症的发生可能与中枢５－羟色胺／多巴胺（５－ＨＴ／ＤＡ）功能失平衡有关。     

The effects of paroxetine and tianeptine on peripheral biochemical markers in major depression

Depression is related to the alterations of the central serotonergic system and some antidepressants achieve their therapeutic effects through alteration of serotonin (5-HT) (re)uptake. Peripheral biochemical markers, platelet and serum 5-HT concentrations, platelet monoamine oxidase (MAO) activity, plasma levels of cortisol and prolactin (PRL), were investigated in patients with major depression before and after 4 weeks of treatment with paroxetine (an inhibitor of 5-HT uptake) or tianeptine (a stimulator of 5-HT uptake). Study was open, single center and included female depressed patients, 21 treated with tianeptine (37.5 mg/day) and 15 treated with paroxetine (20 mg/day), and 11 drug-free healthy women (controls). Before treatment, depressed patients as a group had significantly higher serum 5-HT and cortisol concentrations than healthy controls. There were no differences in the other biochemical markers. Response to antidepressant treatment was estimated according to the 50% fall in the initial scores of Hamilton Depression Rating Scale (HAMD) after 4 weeks of treatment. Good therapeutic response was observed in 47% and 45% patients treated with paroxetine and tianeptine, respectively. Paroxetine treatment induced significant decrease in platelet 5-HT concentrations in both responders and nonresponders, while no alterations in platelet 5-HT values were found in tianeptine-treated patients. There was a subgroup of depressed patients in paroxetine-treated group with high pretreatment platelet 5-HT concentration and later poor therapeutic response to paroxetine treatment. Serum 5-HT values, platelet MAO activity or plasma cortisol or PRL levels were unchanged after both treatments. The results suggest that pretreatment platelet 5-HT levels, but not other peripheral biochemical markers, might predict therapeutic outcome at least in paroxetine-treated patients.     

Growth hormone, cortisol and prolactin responses to physical exercise: higher prolactin response in depressed patients

This study was designed to compare growth hormone, cortisol and prolactin responses to physical exercise in depressed patients and healthy comparison subjects. Patients fulfilled the DSM-IV diagnostic criteria for current major depressive disorder; subjective depressive symptoms were rated with Montgomery-Asberg Depression Rating Scale (MADRS) immediately before the experiment. Growth hormone, cortisol and prolactin were measured before and immediately after physiologically stressful bicycle cardiopulmonary exercise test. After exercise, there were three additional hormone measurements, with 30-min intervals. No significant difference was found in baseline growth hormone, cortisol or prolactin levels between patients and the control group. Plasma growth hormone and cortisol levels increased significantly during physical exercise in both patients and controls and returned to baseline in 90 min. There was no significant difference in growth hormone or cortisol responses to physical exercise between the two groups. However, prolactin levels increased only in the depressed patients group during the exercise. We hypothesize that acute exercise may have a stronger effect on serotonin (5-HT) release in depressed patients, which is reflected in increased plasma prolactin concentration.     

Effects of short-term administration of valproate on serotonin-1A and dopamine receptor function in healthy human subjects

OBJECTIVE: To examine the effects of short-term valproate treatment on human brain serotonin and dopamine function by means of challenge tests with ipsapirone, a partial agonist at 5-HT1A receptors, and apomorphine, a dopamine receptor agonist. DESIGN: Experimental challenge-rechallenge, within-subjects repeated measures, before and at the end of 14 days of treatment with valproate at a dosage of 625 mg/d (reached gradually over the first 5 days). PARTICIPANTS: Eight healthy male volunteers (mean age 38 years) selected for good physical and mental health who were nonsmokers. OUTCOME MEASURES: Pharmacological probes were used to evaluate the effects of valproate. In the ipsapirone challenge, changes in adrenocorticotropic hormone (ACTH), cortisol and body temperature were measured, and in the apomorphine challenge, growth hormone (GH) and prolactin were the dependent variables. RESULTS: Valproate treatment did not significantly alter the ACTH, cortisol or body temperature responses to ipsapirone (20 mg by mouth), which reached equivalent plasma levels at each challenge. Similarly, valproate treatment did not alter the GH or prolactin responses to apomorphine (5 micrograms/kg subcutaneously). CONCLUSIONS: These results suggest that short-term treatment with valproate at a dose of 625 mg/d does not alter hypothalamic or pituitary 5-HT1A or dopamine receptor responses to challenges with ipsapirone and apomorphine, respectively.     

抗精神病药对老年精神分裂症患者血清催乳素的影响

目的：探讨几种抗精神病药对老年精神分裂症患者血清催乳素（PRL）的影响。方法：随机选取抗精神病药治疗老年精神分裂症患者121例,分别在治疗前后测定血清PRL水平。结果：患者经舒必利、奋乃静、氟哌啶醇和利培酮治疗后血清PRL明显升高,各药物之间以及治疗前后比较差异均有显著性（F=15．95,P〈0．01）。PRL水平的升高与药物剂量呈正相关。氯氮平对PRL水平影响不明显。结论：典型和非典型抗精神病药对老年精神分裂症患者血清PRL水平的影响同样明显,强弱的顺序依次是舒必利、奋乃静、氟哌啶醇和利培酮。     

An evaluation of the role of 5-HT(2) receptor antagonism during subchronic antipsychotic drug administration in rats

A widely postulated mechanism of action for the atypical profile of many novel antipsychotic drugs (APDs) is their relatively high affinity for 5-HT(2) receptors. The present study investigated motor function and striatal dopamine (DA) efflux and metabolism in rats given 21 daily injections of drugs that differed in 5-HT(2) affinity. These drugs included: risperidone (high 5-HT(2A/2C)/high D(2)), clozapine (high 5-HT(2A/2C)/low D(2)), haloperidol (low 5-HT(2A/2C)/high D(2)), haloperidol+ritanserin (selective 5-HT(2A/2C)), or vehicle. Rats injected with haloperidol (0.5 mg/kg) or haloperidol+ritanserin (0.5 mg/kg and 1.0 mg/kg, respectively) showed extreme catalepsy on day 1, but significantly decreased catalepsy when tested again on days 7 and 21. Acute or subchronic risperidone (0.05 or 0.5 mg/kg), clozapine (20 mg/kg), or vehicle did not induce significant catalepsy. Microdialysis performed 24 h after the last injection demonstrated that rats treated with risperidone, clozapine, or vehicle showed similar increases in DA efflux and metabolism following an acute injection of a selective DA D(2/3) antagonist (raclopride, 0.5 mg/kg). DA efflux showed an attenuated response to raclopride in the haloperidol alone group; this effect was less apparent in the haloperidol+ritanserin group. However, both of these groups showed a similar tolerance effect to the raclopride-induced increase in DA metabolites. These results suggest that the profile seen after subchronic risperidone more closely resembles clozapine than haloperidol. While ritanserin reduced the tolerance-like effects of haloperidol on striatal DA efflux, the overall results demonstrate that potent 5-HT(2) blockade alone may not entirely account for the distinctive profile of novel APDs.     

Pindolol does not augment cortisol and prolactin responses to paroxetine in healthy subjects

OBJECTIVE: Animal studies have shown that pindolol augmentation of selective serotonin re-uptake inhibitors (SSRIs) may act through inhibition of 5-HT(1A) autoreceptors in the raphe. The combination of pindolol plus a SSRI produces increased synaptic 5-HT levels that are greater than those achieved with a SSRI alone. However, it is unclear whether this actually occurs in humans, and clinical studies of pindolol augmentation have produced inconsistent results. Since the release of cortisol and prolactin is under serotonergic control, we hypothesized that pindolol augmentation of synaptic 5-HT concentrations produced by an SSRI in humans should lead to enhanced SSRI-induced cortisol and prolactin responses. METHODS: Cortisol and prolactin responses were measured after challenge tests with paroxetine (20-40 mg) plus pindolol (5 mg) and after paroxetine plus placebo in six non-depressed, healthy control subjects. RESULTS: No differences were observed in the cortisol or prolactin responses between either neuroendocrine challenge test. CONCLUSIONS: These results suggest that SSRI augmentation with usual clinical doses of pindolol does not increase central synaptic 5-HT neurotransmission sufficient to induce an enhanced neuroendocrine response.