Prolactin fluctuation over the course of a day during treatments with three atypical antipsychotics in schizophrenic patients

Hyperprolactinemia is a frequent consequence of treatment with some antipsychotic agents. Although prolactin secretion varies over the course of a day and during psychological circumstances, there is little information in the literature regarding the time dependence of the prolactin response to antipsychotics. We evaluated prolactin levels in schizophrenic patients receiving risperidone (3 mg twice daily), olanzapine (10 mg twice daily), or perospirone (16 mg twice daily) for at least 4 weeks. The subjects were compared to matched healthy controls. Plasma sample collection for quantification of drug and prolactin levels was conducted before and 2, 4, 6, 8, and 12 h after the morning dosing. Prolactin concentrations before dosing during risperidone treatment were significantly higher than during treatment with olanzapine and perospirone in females. The daily fluctuation of prolactin concentration after perospirone treatment was larger than that observed after risperidone and olanzapine treatments. Areas under the plasma concentration‐time curves was greatest in subjects treated with risperidone, followed by perospirone and finally by olanzapine. These findings suggest that daily fluctuations in prolactin concentration after perospirone treatment are larger than following treatment with risperidone and olanzapine. The plasma concentration of prolactin during perospirone treatment therefore depends on the time of sampling. Copyright © 2010 John Wiley & Sons, Ltd.     

Model-based analysis of therapeutic efficacy of blonanserin and risperidone in schizophrenia patients and effects on prolactin: A randomized double-blind study

This study examined randomized controlled trial data for blonanserin and risperidone in Chinese schizophrenia patients (N = 264). Data related to historical changes in the Positive and Negative Syndrome Scale (PANSS) were used to successfully construct a longitudinal E_max model. Results: (a) The efficacy of the two drugs was similar after week 8, showing a small difference in PANSS reduction. (b) Using the model, we predicted that each 5-point increase in the baseline FPOS (positive score in PANSS five-factor subscales) leads to a decrease in the PANSS total scores at week 8 for 2 points in patients administered blonanserin. (c) The effect of blonanserin on prolactin (PRL) elevation was less. The model was used to predict that prolactin elevations in patients administered risperidone were 2.41-fold of those in patients administered blonanserin. (d) Model quantitation showed that gender is a risk factor for prolactin elevation. Prolactin elevations in female patients were 2.95-fold of the value in male patients administered the same drug. The model demonstrated Blonanserin has similar antischizophrenic efficacy and less serum prolactin rising compared to risperidone in Chinese patients.     

抗精神病药物对男性精神分裂症患者性激素水平的影响

目的探讨男性精神分裂症患者血清雌二醇、催乳素、睾酮和孕酮的水平及抗精神病药物对其影响。方法60例男性精神分裂症患者随机分为氯氮平组(30例)和利培酮组(30例),分别给予氯氮平和利培酮治疗4周,应用电化学发光免疫分析(ECLIA)技术分别于治疗前后测定血清雌二醇、催乳素、睾酮和孕酮水平,并与60名健康对照进行比较。结果治疗前患者组血清催乳素、孕酮高于对照组(P<0.05);治疗后患者组血清雌二醇、催乳素和孕酮高于对照组(P<0.05);与治疗前相比,治疗后氯氮平组血清催乳素显著升高(P<0.01),利培酮组血清雌二醇、催乳素、睾酮显著升高(P<0.01)。治疗后氯氮平组血清催乳素低于利培酮组(P<0.01),雌二醇、睾酮及孕酮的差异无统计学意义(P>0.05)。结论男性精神分裂症患者治疗前后均存在高催乳素状态,可能是精神分裂症的一种属性标志。氯氮平和利培酮均对男性精神分裂症患者性激素水平产生不同程度的影响。     

奥兰扎平利培酮及氯丙嗪对男性精神分裂症患者催乳素及勃起功能的影响

目的:探讨奥兰扎平、利培酮及氯丙嗪对男性精神分裂症患者催乳素(PRL)水平及勃起功能的影响。方法:60例首发男性精神分裂症患者随机分为奥兰扎平组、利培酮组及氯丙嗪组,检测治疗前、入组4周末及8周末PRL水平,利用男性勃起功能量表评估入组12周末勃起功能状况。结果:入组4周末利培酮组血清PRL水平显著高于氯丙嗪组及奥兰扎平组,氯丙嗪组勃起功能量表分显著低于奥兰扎平组。结论:奥兰扎平对催乳素水平及男性勃起功能的影响相对较小。     

Risperidone-induced symptomatic hyperprolactinaemia in adolescents

Studies performed in adult patients unambiguously demonstrate a marked effect of risperidone on prolactin blood levels, with possible clinical effects related to hyperprolactinemia, such as gynecomastia and galactorrhea. However, the largest study performed in children and adolescents showed a weak effect of risperidone on prolactin concentrations during short-term treatment and a negligible effect during long-term treatment, which was probably because of the relatively low dosages of risperidone used [approximately 0.04 mg/(kg x d)]. Among the 10 psychotic adolescents treated with risperidone in our unit, we had 3 cases of gynecomastia in 3 male patients and 2 cases of galactorrhea in 2 female patients. The prolactin blood levels in these cases and in 3 other patients without apparent prolactin-related side effects were all above the normal range (median, 59 ng/mL; range, 30-123 ng/mL). Thus, risperidone administered to adolescents at doses commonly used for the treatment of psychotic symptoms can strongly increase prolactin levels, with clinical consequences such as gynecomastia and/or galactorrhea. Given that the long-term effects of antipsychotic drug-induced hyperprolactinemia are not well documented, especially regarding osteopenia, infertility, growth, and pubertal delay, risperidone should be administered with caution to children and adolescents.     

Prolactin elevation of the antipsychotic risperidone is predominantly related to its 9-hydroxy metabolite

OBJECTIVE: Treatment with the antipsychotic risperidone is frequently associated with hyperprolactinemia. The aim of this study was to evaluate the role of the main compound risperidone and its active 9-hydroxy metabolite on elevating prolactin levels. METHODS: Twenty patients with psychotic disorders, on therapy with risperidone, were studied. All patients had been receiving risperidone for at least 2.5 months, and the median daily dose of risperidone was 3 mg (range 1-10). Morning serum samples for prolactin were analyzed and investigated in relation to the serum concentrations of risperidone and 9-hydroxyrisperidone. RESULTS: Elevated prolactin levels were found in 17 (85%) of the patients. Levels of prolactin were positively correlated to the 9-hydroxyrisperidone serum concentration (r(s) = 0.48, p = 0.03) and to the daily dose of risperidone (r(s) = 0.51, p = 0.03), but did not correlate to the risperidone serum concentration. CONCLUSION: The present results suggest that 9-hydroxyrisperidone and not risperidone is the main contributor to the increased serum levels of prolactin observed in many risperidone-treated patients.     

阿立哌唑对女性精神分裂症患者催乳素和血脂的影响

目的探讨阿立哌唑对女性精神分裂症患者催乳素及血脂的影响。方法将87例女性首发精神分裂症患者随机分为研究组(43例,阿立哌唑治疗)和对照组(44例,利培酮治疗),共治疗12周,基线时、治疗后第4周末、治疗后第8周末及治疗后第12周末应用阳性与阴性症状量表(PANSS)评定疗效,并进行催乳素和血脂的测定。结果研究组和对照组在治疗各阶段的PANSS各因子分及总分均低于基线时,差异具有统计学意义(P<0.05)。在治疗各阶段,研究组的催乳素和血脂水平较基线时均无显著性改变(P>0.05),而对照组在治疗后各阶段的催乳素、血脂水平较基线时均有不同程度的增加,且差异均具有统计学意义(P<0.05)。结论阿立哌唑可有效改善女性首发精神分裂症患者的精神症状,且对催乳素及血脂无明显影响。     

Steady-state pharmacokinetics of a new antipsychotic agent perospirone and its active metabolite, and its relationship with prolactin response

The authors investigated steady-state pharmacokinetics of perospirone and its active metabolite hydroxyperospirone (ID-15036) and its prolactin response in 10 schizophrenic patients receiving 16 mg twice daily. Plasma concentrations of perospirone, hydroxyperospirone, and prolactin were monitored just before and up to 12 hours after the dosing. Thereafter, the dose was decreased to 8 mg twice daily in 8 patients, and drug concentrations were determined. The geometric means of peak concentration (Css(max)), time to Css(max) (tmax), area under the plasma concentration-time curve from 0 to 12 hours [AUC (0-12)], and elimination half-life at steady state were 8.8 ng/mL, 0.8 hours, 22.0 ng x h/mL, and 1.9 hours, respectively, for perospirone, and those of Css(max), tmax, and AUC (0-12) for hydroxyperospirone were 29.4 ng/mL, 1.1 hours, and 133.7 ng x h/mL, respectively. There were no differences in dose-normalized Css(max) or AUC (0-12) perospirone and hydroxyperospirone between 16 mg/day and 32 mg/day of perospirone. Changes in prolactin concentration from 1 to 2 hours after the dosing were parallel with drug concentrations, and almost normal ranges of prolactin concentration were observed before the morning dose despite steady state. The current study indicated that perospirone is rapidly absorbed and rapidly eliminated, which influences the prolactin response. The active metabolite hydroxyperospirone may play an important role in the antipsychotic effect because the plasma concentration of this metabolite is higher than that of the parent compound.     

阿立哌唑与利培酮治疗精神分裂症的临床疗效及对血清催乳素的影响

目的：比较阿立哌唑与利培酮治疗精神分裂症的临床疗效及对血清催乳素的影响。方法：2005年5月至2006年5月在我院治疗的80例精神分裂症患者，随机分为两组：阿立哌唑组（40例）和利培酮组（40例），阿立哌唑组给予阿立哌唑初始剂量10mg／d，2周末增至20～30mg／d，利培酮组给予利培酮初始剂量1mg,／d，2周末增至4—6mg／d。总疗程为8周。采用阳性和阴性症状量表（PANSS）、副反应量表（TESS）评定临床疗效及不良反应；采用化学发光法测定血清催乳素（PRL）水平。结果：经8周治疗，阿立哌唑组显效率72．5％；利培酮组显效率77、5％，两者差异无显著性（P〉0．05）。阿立哌唑组主要不良反应为：嗜睡，头痛，胃肠道反应，也可产生静坐不能，但未发现泌乳或闭经现象；利培酮组主要不良反应为：急性肌张力障碍、震颤、静坐不能、泌乳或闭经、体重增加等。利培酮组治疗8周后，血清PRL水平较治疗前明显升高，差异非常显著（P〈0．01），其中男性PRL升高3．5倍，女性PRL升高8倍；而阿立哌唑组血清PRL水平无变化。结论：阿立哌唑是一种较为安全、有效的抗精神病药物。     

国产利培酮对男性精神分裂症患者催乳素影响的临床研究

目的探讨国产利培酮（索乐）对精神分裂症男性患者血清催乳素（PRL）水平影响。方法将60例符合中国精神疾病障碍分类第3版（CCMD-3）精神分裂症诊断标准的男性患者随机分为利培酮（索乐）组（30例）和氟哌啶醇组（30例）,采用酶联免疫法测定两组治疗前后的PRL水平;采用PANSS量表评定两组临床疗效。结果①两组治疗8周末的PANSS量表评分均显著低于治疗前（P〈0．01）;②治疗前利培酮（索乐）组与氟哌啶醇组的PRL水平差异无统计学意义;治疗后利培酮（索乐）组与氟哌啶醇组的PRL水平均比治疗前升高,但两组间无显著性差异（P〉0．05）。结论国产利培酮（索乐）和氟哌啶醇均能升高患者的PRL水平,但两者差异无显著性。     

Prolactin release in children treated with risperidone: impact and role of CYP2D6 metabolism

OBJECTIVE: Little is known about the role of CYP2D6 polymorphism in risperidone-induced prolactin release in children. METHOD: Twenty-five children (aged 5-15 years) with pervasive developmental disorders were genotyped for CYP2D6 polymorphisms. Serum prolactin, risperidone, and 9-hydroxyrisperidone were assessed at baseline and after 8 weeks of risperidone treatment (mean dosage, 0.06 +/- 0.03 mg/kg/d). After 24 weeks of treatment, prolactin was measured in a subsample of 15 children. Adverse effects were evaluated using a clinician-rated survey. RESULTS: Mean +/- SD prolactin levels increased from 7.8 +/- 8.0 ng/mL at baseline to 33.2 +/- 12.8 ng/mL at week 8 (P < 0.001), with a slight decrease to 28.8 +/- 13.6 ng/mL at week 24. At week 8, serum prolactin level was positively correlated with dose per kilogram (r = 0.648, P < 0.001), number of functional CYP2D6 genes (J = 2.117, P = 0.034), and serum 9-hydroxyrisperidone concentration (r = 0.664, P = 0.001) and was negatively correlated with the risperidone/9-hydroxyrisperidone ratio (r = -0.571, P = 0.004) but not with risperidone concentration (r = -0.243, P = 0.264) nor age (r = 0.072, P = 0.733). Prolactin elevation was not associated with adverse effects. CONCLUSIONS: Low-to-intermediate doses of risperidone induced a 4-fold prolactin increase in children without a clear development of tolerance up to 6 months. CYP2D6 ultrarapid metabolism may be a risk factor for more pronounced prolactin elevation.     

Multiple dose pharmacokinetics of risperidone and 9-hydroxyrisperidone in Chinese female patients with schizophrenia

AIM: To study the multiple dose clinical pharmacokinetics of risperidone and its main active metabolite, 9-hydroxyrisperidone, in Chinese female patients with schizophrenia. METHODS: The subjects were 23 Chinese female inpatients aged 18-65 years who met the CCMD-III (third revision of the Chinese Criteria of Mental Disorders) criteria for schizophrenia. Subjects were tested after 17 d of treatment with 2 mg risperidone twice daily. Plasma concentrations of risperidone and 9-hydroxy-risperidone were assayed by using validated high performance liquid chromatography-mass spectrometry (HPLC-MS) methods. RESULTS: Risperidone was rapidly absorbed (Tmax was 1.6 h) and its T1/2 in plasma was short (3.2 h). 9-hydroxy-risperidone was quickly metabolized from the parent drug with a mean Tmax of 2.5 h. It had a long half-life of 24.7 h. The C(ss)(av) of risperidone and 9-hydroxy-risperidone were 36.9+/-33.1 and 110.6+/-30.5 microg x h x L(-1), respectively, and the AUC(ss)0-12 were 443.2+/- 397.4 and 1327.2+/- 402.3 microg x h x L(-1), respectively. CL/F and V/F of risperidone were 8.7+/- 6.2 L/h and 34.1+/- 24.3 L, respectively. Interindividual variations for pharmacokinetic parameters were quite large for risperidone. All 23 subjects experienced high prolactin levels when treated with risperidone. However there was no correlation between prolactin level and the concentration of risperidone, 9-hydroxy-risperidone, or the active moiety. CONCLUSION: Risperidone showed large interindividual variations in pharmacokinetics. Administration of risperidone resulted in high serum prolactin levels. The results indicate that systemic exposure to risperidone and 9-hydroxy-risperidone in female Chinese schizophrenic patients is higher relative to published data for white Caucasian patients. Larger studies regarding the PK/PD relationship may be required to develop a reasonable clinical dosage regimen for Chinese female patients.     

Elevated serum triglycerides with clozapine resolved with risperidone in four patients

Serum triglyceride levels of four patients with psychotic disorders were decreased after switching therapy from clozapine to risperidone. In two patients clozapine was reinstated after risperidone was discontinued; serum triglyceride levels increased. This increase when clozapine was switched to risperidone and vice versa is consistent with our previous report of elevated serum triglyceride levels in clozapine-treated patients. Other reports show increases with the atypical antipsychotics, olanzapine and quetiapine. We believe serum triglyceride levels should be monitored in patients who have other cardiac risk factors and are receiving clozapine.     

盐酸哌罗匹隆片治疗精神分裂症的Ⅱ期临床研究

目的评价国产盐酸哌罗匹隆片治疗精神分裂症的疗效和安全性。方法对符合《CCMD-Ⅲ》精神分裂症和分裂样精神障碍诊断标准的48例精神分裂症和分裂样精神障碍患者进行哌罗匹隆,利培酮的对照研究。其中哌罗匹隆组24例,利培酮24例,共治疗6周,采用PANSS和CGI评定临床疗效,TESS评定不良反应。结果通过对PANSS量表总分和因子分进行疗效分析,两组疗效相当;两组副反应的发生率无显著差异,常见副反应为失眠,震颤,肌强直,静坐不能。结论哌罗匹隆与利培酮治疗精神分裂症安全有效,不良反应轻,适合临床应用。     

Chronic sustained stress increases levels of anterior pituitary prolactin mRNA

Our laboratory is investigating the effects of chronic stress on physiological, endocrine and behavioral measures, in order to elucidate the neuronal substrates for the pathophysiological consequences of stress in humans. In these studies, we have employed a rodent model of sustained stress in which rats are exposed to around-the-clock intermittent footshock that can be avoided or escaped by rats in the controllable stress group, but not by rats in the uncontrollable stress group. Each rat in the uncontrollable stress group is paired (yoked) to a rat in the controllable stress group such that the controllable stress group rat avoids or escapes shock for both rats. A third group of rats receives no shock (controls). We have previously reported that in male rats, plasma prolactin levels were elevated after 3 days of stress in both stress groups. In the present experiments we determined whether the increases in plasma prolactin were correlated with increases in anterior pituitary prolactin mRNA. In addition, we measured hormones and mRNA at three time points and we examined these responses in female as well as male rats. Adult male and female Sprague-Dawley rats were exposed to chronic stress for 1, 3 or 14 days. In unstressed control rats, levels of anterior pituitary prolactin mRNA were fivefold higher in female as compared to male rats. However, stress increased levels of anterior pituitary prolactin mRNA over baseline in both genders. After 1 day of stress, anterior pituitary prolactin mRNA levels increased in male and female rats belonging to both stress groups, with no significant difference seen between the uncontrollable vs. controllable stress groups. After 3 days of stress, anterior pituitary prolactin mRNA levels were even more elevated, and rats in the uncontrollable stress group had higher anterior pituitary prolactin mRNA levels than those in the controllable stress group. After 14 days of stress, there were no significant differences in control and stressed groups with respect to anterior pituitary prolactin mRNA. These data suggest that chronic sustained stress increases the synthesis of anterior pituitary prolactin mRNA during the first days of stress, and that levels return to prestress values sometime between 3 and 14 days of stress.     

Prolactin serum levels in paranoid versus nonparanoid male schizophrenia patients treated with risperidone

The frequently seen side effect of hyperprolactinemia thought to be the 'price' paid for the antipsychotic treatment of schizophrenia. Various reports have linked the use of risperidone, an atypical antipsychotic drug, with the significant rise of prolactin levels. Thus, we set to assess possible difference between prolactin levels among schizophrenia subtypes in 45 male patients treated with stable doses (2-6 mg/day) of risperidone as antipsychotic monotherapy. All patients showed increased prolactin levels beyond the normal range, with a significant difference between the paranoid and all other groups (P<0.0001). Specifically, the paranoid patients' prolactin levels were higher than those of the schizoaffective and the disorganized ones. These results suggest that the blockade of higher dopamine activity in the paranoid schizophrenia corresponds to the prolactin increase, more than in the schizoaffective and disorganized subtypes. These findings are opposite of what was observed in the previous study of unmedicated patients.     

Serum prolactin levels, plasma risperidone levels, polymorphism of cytochrome P450 2D6 and clinical response in patients with schizophrenia

The object of this study is to assess 1) the relationship between plasma antipsychotic drug concentration, serum prolactin levels and the clinical efficacy of risperidone, 2) the relationship between the CYP2D6 polymorphisms and metabolizing of risperidone and 3) the role of 9-hydroxyrisperidone in elevating prolactin levels. One-hundred and eighteen Chinese schizophrenia patients (40 males, 78 females, age 15-60 years) were given risperidone at dosages ranging from 2-8 mg/day for 8 weeks. Clinical efficacy was determined using the Brief Psychiatric Rating Scores (BPRS). Serum prolactin levels were assayed before and after the 8 week treatment and plasma risperidone and 9-hydroxyrisperidone levels were also measured at the end of the 8-week treatment. The results showed there was no significant correlation between the concentration of active moiety and clinical response. Risperidone treatment significantly increased serum prolactin levels. Furthermore, changes of prolactin levels were not correlated with the clinical response. For the risperidone/ 9-hydroxyrisperidone ratio, there was a statistically significant difference among the CYP2D6*1/*1, *1/*10, *10/*10 genotypes (Kruskal-Wallis test, p = 0.012). No significant differences were found in the concentration of 9-hydroxyrisperidone and active moiety among the genotypes. In addition, the concentration of 9-hydroxyrisperidone was not significantly correlated with the increase of serum prolactin. In conclusion, our study has, for the first time, produced evidence that in Chinese schizophrenic patients, the metabolism of risperidone is dependent on CYP2D6. Neither changes in serum prolactin levels nor plasma concentration of active moiety were significantly correlated with clinical efficacy of risperidone. 9-hydroxyrisperidone may not play a predominant role in elevating serum prolactin level.     

Effects of the atypical antipsychotics olanzapine and risperidone on plasma prolactin levels in male rats: a comparison with clinical data

Rationale Hyperprolactinaemia is a common side effect of antipsychotic treatment and the clinical consequences associated with this, e.g. sexual dysfunction, can have a negative impact on patient compliance. Objectives The aim of this study was to investigate the effect of the atypical antipsychotics olanzapine and risperidone on prolactin levels in rats using different treatment regimes and to compare these data with those reported clinically. Methods: All experiments were carried out in male CD rats. In separate studies, the effects of acute, sub-chronic (7 days) and chronic (28 days) olanzapine and risperidone administration on prolactin levels were determined. Further studies investigated the time course of the prolactin response following olanzapine and risperidone treatment over 24 h. Results Both drugs significantly increased prolactin levels in a similar manner following acute administration, in keeping with clinically reported data. However, this elevation was still present following sub-chronic and chronic treatment, contrasting with clinical data with respect to olanzapine but not risperidone. Over 24 h, olanzapine demonstrated a more transient elevation of prolactin levels, whereas risperidone caused a robust and persistent increase in prolactin up to 24 h post-dose, closely mimicking clinical results. Conclusions The present study has demonstrated that olanzapine and risperidone display similar effects on prolactin levels in the rat following acute and chronic administration but differ in their prolactin response over a 24-h period. In conclusion, prolactin levels in rats following atypical antipsychotic treatment may not be fully predictive of the clinical situation.     

奎硫平与利培酮对女性分裂症患者的血清催乳素影响的对照研究

目的：探讨女性精神分裂症患者采用奎硫平与利培酮治疗过程中,血清催乳素（PRL）的变化。方法：选择符合诊断标准的女性精神分裂症患者64例,随机分为奎硫平组与利培酮组,治疗8周,采用阳性和阴性症状量表（PANSS）在治疗前、治疗第4周和第8周分别评定;在治疗前和治疗第4、8周测定血清PRL浓度。结果：治疗前后两组在PANSS总分上无显著差异（P〉0．05）,治疗前两组血清PRL水平无显著差异（P〉0．05）,奎硫平组治疗后PRL水平变化不明显（P均〉0．05）,利培酮组治疗后PRL水平显著升高（P均〈0．01）。结论：奎硫平不引起明显的PRL升高,而利培酮有较强的致PRL升高的作用。     

不同配比的芍药甘草方对利培酮所致女性精神分裂症高催乳素血症的影响

目的：观察不同配比的芍药甘草方治疗抗精神病药利培酮所致女性精神分裂症患者高催乳素血症的临床疗效。方法收集2013年7月－2014年1月河北省第六人民医院门诊及住院的患者120例,按随机数字表法将患者随机分为对照组、芍甘组A、芍甘组B,每组均为40例,观察治疗前、治疗12周后3组患者血清催乳素、雌激素（雌二醇、睾酮、促卵泡刺激素、促黄体生成素、孕酮）表达水平,采用阳性及阴性症状量表（ PANSS）评价精神分裂症患者精神症状,药物副作用量表（TESS）评价药物不良反应。结果治疗前3组患者血清催乳素、雌激素水平及 PANSS 评分比较差异无统计学意义（ P＞0．05）。治疗12周后,3组患者血清雌激素水平比较差异无统计学意义（ P＞0．05）;A组、B组与对照组比较,血清催乳素水平均明显下降（P＜0．05）,B组与A组比较,血清催乳素水平明显下降（P＜0．05）。疗效方面：治疗12周后,3组患者PANSS评分比较差异无统计学意义（P＞0．05）,3组患者分别与同组治疗前比较,PANSS评分均明显下降（P＜0．05）。安全性方面：3组患者治疗前后TESS 评分比较差异无统计学意义（ P＞0．05）。结论不同配比的芍药甘草方能明显降低利培酮所致女性精神分裂症患者血清催乳素水平,尤以2∶1的芍药甘草方能降低催乳素水平,并且不影响抗精神病药利培酮的临床疗效。