Elevated prolactin levels in male youths treated with risperidone and quetiapine

The aim of this study was to report on the serum prolactin levels in 70 male youths at a residential treatment center who were treated with either risperidone or quetiapine. This is a cross-sectional retrospective medical chart review of 50 males (mean age, 13.5+/-2.8 years) treated with risperidone (mean dose, 2.4+/-1.6 mg/day) and 20 males (mean age, 13.5+/-2.4 years) treated with quetiapine (mean dose, 317.5+/-238 mg/day). Serum prolactin levels were drawn according to a protocol, after at least 6 weeks of treatment. Prolactin was above the upper limit of normal for 68% of the patients on risperidone and 20% of the patients on quetiapine (chi2 analysis: R>Q; p<0.001). Both risperidone and quetiapine produced dose-related increases in serum prolactin levels (R, r=0.34, p=0.017; Q, r=0.45, p=0.05). No correlation was found between duration of treatment and prolactin levels. Given that hyperprolactinemia secondary to antipsychotic treatment may result in reproductive and growth irregularities, periodic long-term monitoring during treatment with these two atypical antipsychotics (and perhaps others as well) may be warranted.     

氯氮平和利培酮对血清催乳素及体重的影响

目的：比较氯氮平、利培酮对男性精神分裂症患者血清催乳素(PRL)及体重的影响。方法：将80例符合中国精神疾病分类方案与诊断标准第2版修订本诊断标准的男性精神分裂症患者，随机分为氯氮平组和利培酮组，治疗6周。在治疗前后分别测定血清PRL水平及体重。结果：氯氮平组和利培酮组治疗后血清PRL、体重均显著增高，尤以利培酮组增加率显著较多。体重与血清PRL水平变化呈正相关。结论：氯氮平组及利培酮组血清PRL水平及体重均明显增加，利培酮组增加幅度更大。血清PRL水平的增加可能是引起体重增加的重要因素。     

氯氮平与利培酮对血清催乳素水平的影响

目的：了解氯氮平或利培酮对首发女性精神分裂症患者血清催乳素水平的变化,方法：采用ELISA方法制定血清催乳素水平,结果：治疗后氯氮平组血清催乳素水平没有显著变化。而利培酮组血清催乳素水平显著升高。结论催乳素水平不能说明精神分裂症发病及严重程度,也不能作为非典型抗精神病药疗效的指标。     

Gender differences in the relationship between the risperidone metabolism and the plasma prolactin levels in psychiatric patients

Background

Risperidone (RIS) has the highest propensity to elevate plasma prolactin (PRL) levels. While the active metabolite 9-hydroxy-risperidone (9-OH-RIS) plays a predominant role in the efficacy and side effects of RIS, the mechanistic details are still poorly understood. The present study evaluated the gender differences in the relationship between plasma levels of RIS or 9-OH-RIS and PRL.

Methods

Twenty-one male and 19 female subjects treated with RIS were enrolled in the present series. All patients had been receiving RIS for at least 4 weeks at an average dosage of 4.7 mg/day. Plasma RIS, 9-OH-RIS and PRL levels were measured.

Results

In the male patients, there was no correlation between the RIS dosage and plasma PRL levels, between plasma RIS levels and PRL levels, or between the plasma 9-OH-RIS levels and PRL levels. In the female patients, there was a significant positive correlation between the plasma 9-OH-RIS levels and PRL levels (rs = 0.456, p = 0.049). There was a trend toward a significant positive correlation between the RIS dosage and plasma PRL levels. There was no correlation between the plasma RIS levels and PRL levels.

Conclusion

9-OH-RIS is considered to play a more important role in PRL elevation than RIS, and a gender difference exists in the effect of 9-OH-RIS on PRL level.     

Effects of short- and long-term risperidone treatment on prolactin levels in children with autism.

BACKGROUND: The effects of short- and long-term risperidone treatment on serum prolactin were assessed in children and adolescents with autism. METHODS: Patients with autism (N = 101, 5-17 years of age) were randomized to an 8-week trial of risperidone or placebo and 63 then took part in a 4-month open-label follow-up phase. Serum samples were obtained at Baseline and Week-8 (N = 78), and at 6-month (N = 43) and 22-month (N = 30) follow-up. Serum prolactin was determined by immunoradiometric assay; dopamine type-2 receptor (DRD2) polymorphisms were genotyped. RESULTS: Baseline prolactin levels were similar in the risperidone (N = 42) and placebo (N = 36) groups (9.3 +/- 7.5 and 9.3 +/- 7.6 ng/ml, respectively). After 8 weeks of risperidone, prolactin increased to 39.0 +/- 19.2 ng/ml, compared with 10.1 +/- 8.8 ng/ml for placebo (p < .0001). Prolactin levels were also significantly increased at 6 months (32.4 +/- 17.8 ng/ml; N = 43, p < .0001) and at 22 months (N = 30, 25.3 +/- 15.6 ng/ml, p < .0001). Prolactin levels were not associated with adverse effects and DRD2 alleles (Taq1A, -141C Ins/Del, C957T) did not significantly influence baseline levels or risperidone-induced increases in prolactin. CONCLUSIONS: Risperidone treatment was associated with two- to four-fold mean increases in serum prolactin in children with autism. Although risperidone-induced increases tended to diminish with time, further research on the consequences of long-term prolactin elevations in children and adolescents is needed.     

Effects of olanzapine on prolactin levels of female patients with schizophrenia treated with risperidone

BACKGROUND: This study was conducted to prospectively examine the effect of switching from risperidone to olanzapine on female schizophrenia patients who experienced menstrual disturbances, galactorrhea, and/or sexual dysfunction. METHOD: Twenty female patients with DSM-IV schizophrenia who were taking risperidone and were suffering from menstrual disturbances, galactorrhea, and/or sexual dysfunction were enrolled. Patients were switched from risperidone to olanzapine over a 2-week period, then treated with olanzapine for 8 additional weeks. The serum prolactin concentrations were examined every 2 weeks. The Positive and Negative Syndrome Scale (PANSS), Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale for Extrapyramidal Symptoms (SAS), and questions from the Dickson-Glazer Sexual Functioning Scale were administered to evaluate efficacy, extrapyramidal side effects, and sexual and reproductive functioning at baseline and the endpoint of 10 weeks. RESULTS: Serum prolactin levels decreased significantly (p < .01) following the switch from risperidone to olanzapine. Scores of PANSS, AIMS, and SAS at the endpoint were also significantly decreased (p < .01) compared to those of baseline. Patients experienced improvements in menstrual functioning and perceptions of sexual side effects. CONCLUSION: Olanzapine reversed hyperprolactinemia in risperidone-treated female schizophrenic patients. This was associated with a decrease in amenorrhea, improved cycle regularity, and a decrease in sexual side effects that the women attributed to antipsychotic medication. This study suggests that switching to olanzapine is a safe and effective alternative method for patients with antipsychotic-induced hyperprolactinemia associated sexual and/or reproductive dysfunction. Long-term follow-up studies are warranted, with particular attention to the course of sexual and reproductive dysfunction.     

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。     

Differential effects of delta-9-tetrahydrocannabinol and its 11-hydroxy metabolite on sodium current in neuroblastoma cells

Whole-cell voltage-clamp techniques were used to study the comparative effects of delta-9-tetrahydrocannabinol (THC) and its principal metabolite, 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC), on the voltage-gated sodium current in neuroblastoma cells. The parent compound markedly depressed the inward sodium current with minimal reduction of the outward current, demonstrating that the effects of the drug were related to the membrane potential. In addition, THC reduced the reversal potential, indicating that the drug modified the ion selectivity of the channel. 11-OH-THC similarly depressed inward sodium current; however, in marked contrast to the effects of the parent compound, the drug equally depressed the outward voltage-gated sodium current, indicating that its effects were not related to the membrane potential. Furthermore, 11-OH-THC differed from THC in that it did not alter the reversal potential. The results demonstrate that THC and its 11-OH metabolite both reduce inward sodium current, but their effects on the outward current and ion selectivity are distinctly different. The sum of the actions of these two cannabinoids on the voltage-gated sodium channel provides a plausible cellular basis for THC's depression of action potentials in vivo and for some of its central depressant effects.     

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。     

Relationship between prolactin secretion, and plasma risperidone and 9-hydroxyrisperidone concentrations in adolescents with schizophreniform disorder

BACKGROUND: Treatment with the atypical antipsychotic risperidone can result in elevated prolactin levels. To date, the relationships between plasma concentrations of prolactin, risperidone and its active 9-hydroxy-metabolite have been little investigated in adolescents with psychosis. METHODS: Prolactin levels were determined at baseline in 16 hospitalized drug-na?ve adolescents meeting DSM-IV criteria for schizophreniform disorder. Prolactin, risperidone, 9-hydroxyrisperidone levels were subsequently determined after 3 weeks of oral risperidone treatment. RESULTS: Compared with pretreatment values, prolactin levels at endpoint were significantly increased (p<0.00001) and correlated with risperidone doses (r=0.58, N=16, p<0.02), and plasma levels of risperidone (r=0.60, N=16, p<0.02) and 9-hydroxyrisperidone (r=0.54, N=16, p=0.03). CONCLUSIONS: These data suggest that risperidone's effect on prolactin release is dose-dependent in adolescents and is linked to both plasma risperidone and 9-hydroxyrisperidone concentrations.     

利培酮对慢性精神分裂症泌乳素的影响

目的探讨非典型抗精神病药利培酮对泌乳素的影响及其与临床疗效的关系。方法采用固定剂量利培酮（６ｍｇ／ｄ）治疗慢性、男性精神分裂症３０例,疗程１２周;在治疗前后评定ＰＡＮＳＳ量表,并用放射免疫法测查血浆中泌乳素（ＰＲＬ）浓度。以１６例健康人为对照。结果治疗后,患者ＰＡＮＳＳ总分及其分量表均显著降低;治疗前患者ＰＲＬ较对照组显著降低,治疗后显著性增高。治疗前后泌乳素差值与ＰＡＮＳＳ阳性症状分量表减分值、减分率显著相关。结论利培酮对精神分裂症血泌乳素水平有明显影响,而且泌乳素水平与临床疗效相关。     

齐拉西酮与利培酮对精神分裂症患者泌乳素及体质量、血糖、血脂的影响

目的探讨齐拉西酮与利培酮对精神分裂症患者血清泌乳素水平、体质量、血糖、血脂的影响。方法将100例精神分裂症患者随机分为研究组（齐拉西酮系统治疗）与对照组（利培酮系统治疗）,共治疗8周,于基线、治疗第4周末和弟8周末分别对患者的泌乳素、体质量、血糖、血脂进行测定、结果在治疗4周末和8周末研究组患者的泌乳素、体质量、血糖、血脂与基线相比,均无统计学差异（P〉0．05）,对照组患者在第4周末和8周末的泌乳素、体质量较基线明显升高,差异有统计学意义（P〈0．05）。两组患者的泌乳素在第4周末和8周末相比,均具有非常显著的统计学差异（P〈0．01）。结论齐拉西酮对精神分裂症患者的泌乳素、体质量无明显影响,而利培酮对泌乳素、体质量有明显影响,两者对血糖、血脂均无明显影响。     

Serum concentrations of risperidone and 9-OH risperidone following intramuscular injection of long-acting risperidone compared with oral risperidone medication

OBJECTIVE: To compare serum concentrations of risperidone, 9-hydroxy (OH) risperidone and risperidone plus 9-OH risperidone, as well as the 9-OH risperidone/risperidone ratio in patients receiving depot and oral risperidone. METHOD: Serum concentrations from 78 patients receiving three different doses of risperidone depot were measured and compared with serum concentrations from 82 patients taking three different doses of oral risperidone. RESULTS: Patients receiving risperidone depot had significantly lower serum concentrations of risperidone plus 9-OH risperidone than patients taking oral risperidone. More interestingly, the 9-OH risperidone/risperidone ratio was also significantly lower in patients receiving risperidone depot than in patients taking oral risperidone. CONCLUSION: Serum concentrations of risperidone plus 9-OH risperidone may be a rather poor indication of the antipsychotic efficacy of risperidone unless their ratio is also considered.     

阿立哌唑与利培酮对血清催乳素及体质量的影响

目的:比较阿立哌唑与利培酮治疗女性首发精神分裂症的疗效及对血清催乳素(PRL)水平及体质量的影响. 方法:70例女性首发精神分裂症患者分为阿立哌唑组和利培酮组,每组35例.分别给予阿立哌唑和利培酮治疗8周.以阳性与阴性症状量表(PANSS)及治疗中出现的症状量表(TESS)评估疗效和不良反应,同时检测两组的血清PRL水平. 结果:两组间PANSS各项评分及临床有效率差异无显著性(P>0.05);阿立哌唑组在PRL水平改变及体质量增加方面优于利培酮组(P<0.05或P<0.01),泌乳、月经紊乱明显少于利培酮组. 结论:两药治疗女性精神分裂症均有较好疗效,以阿立哌唑对内分泌影响较小,更适合于女性患者.     

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。     

利培酮与喹硫平对老年期痴呆患者体重及糖脂代谢的影响

目的探讨利培酮与喹硫平对伴精神行为症状的老年期痴呆患者（BPSD）的体重、血糖及血脂的影响。方法将60例伴精神行为症状的老年期痴呆患者分为喹硫平组及利培酮组进行治疗,于治疗前及治疗后（第4、8周末）分别测体重、空腹血糖及血脂包括胆固醇（TC）、甘油三脂（TG）、低密度脂蛋白（LDL）及高密度脂蛋白（HDL）。结果喹硫平组的体重及LDL在治疗第8周末较治疗前升高,HDL较治疗前下降,差异具有显著性（P〈0.05）。利培酮组治疗前后各数值的变化无显著差异（P〉0.05）。两组患者体重的第8周末与治疗前差值,LDL的第8周末与第4周末的差值比较有统计学意义（P〈0.05）。结论喹硫平对伴精神行为症状的痴呆患者体重、血脂的影响较利培酮明显,两者对糖代谢影响不大。