Improvement in hyperprolactinemia and reproductive comorbidities in patients with schizophrenia switched from conventional antipsychotics or risperidone to olanzapine

This open-label, prospective, 4-month study in hyperprolactinemic patients with schizophrenia explored whether prolactin levels decrease after switching antipsychotic therapy to olanzapine. A secondary objective was to determine if reproductive morbidities and sexual dysfunction occurring with hyperprolactinemia improved with prolactin normalization. Clinically stable patients with schizophrenia, who had hyperprolactinemia defined as >18.8 ng/ml for males and >24.2 ng/ml for females, were randomized to: remain on current therapy (n=27) or switch to olanzapine, 5-20 mg/day, (n=27). Baseline prolactin levels in female patients randomized to receive olanzapine (n=14) were 66.3+/-38.7 ng/ml and were 82.0+/-37.6 (p=.32) in those remaining on their pre-study antipsychotic medication (n=14). In male patients, baseline prolactin levels were 33.7+/-12.1 and 33.5+/-13.8 ng/ml (p=.97), respectively, for those randomized to olanzapine (n=13) or remaining on pre-study treatment (n=13). At study end, patients switched to olanzapine experienced significant reductions in mean serum prolactin levels of 19.8+/-18.1 ng/ml in males (p=.02), and 32.3+/-47.5 ng/ml in females (p=.01), but prolactin continued to be elevated in patients who remained on pre-study antipsychotic treatment. After switching to olanzapine treatment, male patients experienced significantly (p=.03) increased free testosterone levels but there were no significant improvements in total testosterone levels; some female patients experienced improved menstrual cycling, as well as resolution of galactorrhea and gynecomastia, and sexual functioning was significantly improved in both genders. Patients switched to olanzapine, as well as those remaining on their pre-study medication, maintained clinical stability, their symptoms continued to improve, although there were no significant between-treatment differences in improvement. Treatment-emergent adverse events did occur in both treatment groups; however, they were not significantly different between groups. Olanzapine-treated patients experienced significantly lower eosinophil counts and higher elevations in low-density lipoproteins and standing blood pressure than non-switched patients. Olanzapine treatment may offer sustained reduction in serum prolactin and improvement in sexual and reproductive comorbid symptoms in patients with schizophrenia who have treatment-emergent hyperprolactinemia.     

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.     

奥氮平和利培酮治疗精神分裂症临床对照研究

目的比较奥氮平和利培酮对精神分裂症的治疗效果和安全性。方法以奥氮平与利培酮对120例精神分裂症患者进行为期6周的对照治疗,采用阳性和阴性症状量表（PANSS）评定疗效,用副反应量表（TESS）评定副反应。结果奥氮平组显效率76．7％,有效率95％;利培酮组显效率76．7％。有效率93％。奥氮平的主要副反应为嗜睡,利培酮的主要副反应为锥体外系反应。结论两药治疗精神分裂痘均有良好疗效．且安全性较高。     

奥氮平与利培酮治疗难治性精神分裂症的对照研究

目的 比较奥氮平与利培酮对难治性精神分裂症的疗效及安全性.方法 68例难治性精神分裂症患者按照排列表法随机分为奥氮平组[34例,(24.1±5.4)mg/d]和利培酮组[34例,(7.9±1.8)mg/d],疗程均为12周.采用阳性和阴性症状量表(PANSS)、临床总体印象量表(CGI)及治疗中需处理的不良反应症状量表(TESS),在治疗前及治疗第1,2,4,8,12周末分别评定疗效和不良反应.结果 (1)奥氮平组PANSS总分、阳性症状分、阴性症状分及一般病理分均从治疗第2周末起较治疗前下降(P<0.05～0.01);利培酮组PANSS总分、阳性症状分、一般病理分从治疗第2周末起,阴性症状分从第4周末起,较治疗前下降(P<0.05～0.01);奥氮平组从治疗第2周末起各时点PANSS总分、阴性症状分均低于利培酮组(P<0.05～0.01).(2)治疗第2周末起,2组临床总体印象量表-严重程度和改善程度(CGI-SI)总分均较治疗前下降(P<0.05～0.01);2组间各时点CGI-SI分的差异无统计学意义(P>0.05).(3)治疗第12周末,奥氮平组、利培酮组临床总有效率分别为65%、41%,差异有统计学意义(P<0.05).(4)奥氮平组、利培酮组不良反应发生率分别为53%(18/34)和59%(20/34),差异无统计学意义(P>0.05);奥氮平组体质量增加发生率高于利培酮组(P<0.05);利培酮组静坐不能、异常泌乳和(或)闭经、肌张力增高的发生率高于奥氮平组(P<0.05).结论 奥氮平对难治性精神分裂症有良好疗效,不良反应轻微.     

International multisite double-blind trial of the atypical antipsychotics risperidone and olanzapine in 175 elderly patients with chronic schizophrenia.

OBJECTIVE: The authors compared the effects of the two most commonly used atypical antipsychotics, risperidone and olanzapine, in elderly patients with schizophrenia. METHODS: In an 8-week, international, double-blind study, patients (outpatients, hospital inpatients, and residents of nursing or boarding homes) were randomly assigned to receive risperidone (1 mg to 3 mg/day) or olanzapine (5 mg to 20 mg/day). The main outcome measures were changes in Positive and Negative Syndrome Scale (PANSS) total scores and rates of extrapyramidal symptoms (EPS). RESULTS: Subjects were 175 patients age 60 years or over with schizophrenia or schizoaffective disorder. The mean duration of illness was 36.5 years. Median doses were 2 mg/day of risperidone and 10 mg/day of olanzapine. PANSS total scores and four of the five PANSS factor scores (positive symptoms, negative symptoms, disorganized thoughts, and anxiety/depression) improved significantly at all time-points and at endpoint in both groups; between-treatment differences were not significant. EPS-related adverse events were reported by 9.2% of patients in the risperidone group and 15.9% in the olanzapine group; the between-treatment difference was not significant. Total scores on the Extrapyramidal Symptom Rating Scale were reduced in both groups at endpoint; between-treatment differences were not significant. Clinically relevant weight gain was seen in both groups, but was significantly less frequent in risperidone patients than in olanzapine patients. CONCLUSIONS: Stable elderly patients with chronic schizophrenia receiving appropriate doses of risperidone or olanzapine over an 8-week period experienced significant reductions in the severity of psychotic and extrapyramidal symptoms, with a relatively low risk of side effects.     

Antipsychotic medication,prolactin elevation,and ovarian function in women with schizophrenia and schizoaffective disorder

Some, but not all, antipsychotics elevate serum prolactin. Antipsychotic-induced hyperprolactinemia is thought to account for high rates of menstrual dysfunction and diminished estrogen levels in women with schizophrenia. However, few studies have directly assessed the relationships between prolactin, menstrual function, and ovarian hormone levels in this population. Sixteen premenopausal women with schizophrenia and schizoaffective disorder, eight treated with an antipsychotic with prolactin-elevating potential (five with typical antipsychotics and three with risperidone) and eight treated with an antipsychotic with prolactin-sparing potential (seven with olanzapine and one with clozapine), were studied for eight weeks. Data were collected on menstrual functioning and on serum prolactin, estradiol, and progesterone levels, and were compared between subjects who received an antipsychotic with prolactin-elevating potential and an antipsychotic with prolactin-sparing potential, and between subjects with hyperprolactinemia (N=6) and normoprolactinemia (N=10). Additionally, peak ovarian hormone levels were compared to normal values. While mean prolactin levels of subjects who received an antipsychotic with prolactin-elevating potential were significantly greater than those of subjects who received an antipsychotic with prolactin-sparing potential, there were no differences in rates of menstrual dysfunction or in ovarian hormone values between the two groups. Additionally, similar rates of menstrual dysfunction and ovarian hormone values were observed between the hyperprolactinemic and normoprolactinemic subjects. Moreover, irrespective of medication type or prolactin status, most subjects had peak estradiol levels below normal reference values for the periovulatory phase of the menstrual cycle. While our sample size is small, warranting the need for further investigation, the findings of this preliminary study suggest that antipsychotic-induced hyperprolactinemia, alone, may not adequately explain the observed ovarian dysfunction in women with schizophrenia.     

阿立哌唑预防女性分裂症患者抗精神病药所致高泌乳素血症的研究

目的探讨阿立哌唑预防女性分裂症患者抗精神病药所致高泌乳素血症的作用。方法对100例女性精神分裂症患者随机分为两组,各50例,研究组给予利培酮及小剂量的阿立哌唑联合治疗,对照组单用利培酮治疗,观察6月,治疗前和治疗后第1、3、6月末分别予以阳性和阴性综合症状量表（PANSS）、临床疗效总评量表（CGI）和治疗中出现的症状量表（TESS）评定病情的严重程度、疗效和不良反应,并完善实验室检查。结果①两组患者治疗后的总有效率类似（92％与90％）,差异无统计学意义;PANSS及CGI总分均低于治疗前,差异有统计学意义,但两组间差异无统计学意义;②研究第1月末,两组药物副反应主要表现为锥体外系症状,TESS评分两组之间差异无统计学意义;研究结束时对照组TESS的严重程度及痛苦感觉的评分均要高于研究组,差异有显著统计学意义。药物副作用主要表现为月经紊乱、闭经、溢乳等高泌乳素血症综合征症状;③研究结束时,两组患者血清泌乳素水平差异有显著统计学意义,对照组明显高于研究组。结论小剂量的阿立哌唑可以减少发生女性分裂症患者抗精神病药所致的高泌乳素血症。     

Switch to quetiapine in antipsychotic agent-related hyperprolactinemia

Novel antipsychotics (clozapine, risperidone, olanzapine, quetiapine) are effective in treating psychotic symptoms, also in neurological disease. Hyperprolactinemia is a side effect related to antipsychotics that can cause galactorrhea, gynecomastia, amenorrhea, anovulation, impaired spermatogenesis, decreased libido and sexual arousal, impotence, and anorgasmia, consequent to removal of tonic dopaminergic inhibition of prolactin secretion via hypothalamic dopaminergic receptor blockade in the tuberoinfundibolar tract. Hyperprolactinemia occurs more frequently during treatment with risperidone and olanzapine compared with clozapine and quetiapine. The therapeutic algorithm to antipsychotic-relatedhyperprolactinemia is the following: reduction in antipsychotic dose, addition of cabergoline, bromocriptine, amantadine, and/or switch to another antipsychotic. We propose switching to quetiapine in symptomatic hyperprolactinemia related to antipsychotics and describe five cases. Received: 27 April 2002 / Accepted in revised form: 16 July 2002     

An open-label randomized comparison of olanzapine versus risperidone in the treatment of childhood-onset schizophrenia

BACKGROUND AND PURPOSE: Childhood-onset schizophrenia (COS) is a clinically severe form of schizophrenia, which causes severe impairment to cognitive, linguistic, and social development. There are few prospective and retrospective open clinical trials of risperidone and olanzapine in COS. In this open-label, randomized, prospective study, we compared the tolerability and effectiveness of risperidone versus olanzapine in the treatment of COS patients. METHODS: The study population consisted of 25 children with COS (mean age 11.09 +/- 1.55 years). After an evaluation, patients received risperidone (0.25-4.5 mg/day, mean dose 1.62 +/- 1.02 mg/day) or olanzapine (2.5-20 mg/day, mean dose 8.18 +/- 4.41 mg/day) for 12 weeks, with weekly evaluations. RESULTS: Both groups showed comparable significant (p < 0.001) within-group improvement from baseline to endpoint (LOCF) in Positive and Negative Symptoms Scale (PANSS) total and subscale scores. Of the olanzapine-treated children, 11 (91.7%) completed the 12 weeks of the study, whereas in the risperidone-treated children only 9 (69.2%) did. No significant differences between risperidone-treated children and olanzapine-treated children were observed on Barnes Akathisia Rating Scale (BAS) and Simpson-Angus Scale (SAS) rating scales. Both treatment groups showed significant (p < 0.001) increase in weight from baseline to endpoint. CONCLUSION: Our open-label, small-scale comparative study suggests that both risperidone and olanzapine appear to be efficacious antipsychotic medications in COS, with a slight nonsignificant advantage of olanzapine in the dropout rate.     

Olanzapine vs risperidone in the management of schizophrenia: a randomized double-blind trial in Australia and New Zealand

Improved drug therapy for schizophrenia may represent the best strategy for reducing the costs of schizophrenia and the recurrent chronic course of the disease. Olanzapine and risperidone are atypical antipsychotic agents developed to meet this need. We report a multicenter, double-blind, parallel, 30-week study designed to compare the efficacy, safety, and associated resource use for olanzapine and risperidone in Australia and New Zealand. The study sample consisted of 65 patients who met DSM-IV criteria for schizophrenia, schizoaffective disorder, or schizophreniform disorder. Olanzapine-treated patients showed a significantly greater reduction in Positive and Negative Syndrome Scale (PANSS) total, Brief Psychiatric Rating Scale (BPRS) total, and PANSS General Psychopathology scores at endpoint compared to the risperidone-treated patients. Response rates through 30 weeks showed a significantly greater proportion of olanzapine-treated patients had achieved a 20% or greater improvement in their PANSS total score compared to risperidone-treated patients. Olanzapine and risperidone were equivalent in their improvement of PANSS positive and negative scores and Clinical Global Impression-Severity of Illness scale (CGI-S) at endpoint. Using generic and disease-specific measures of quality of life, olanzapine-treated patients showed significant within-group improvement in most measures, and significant differences were observed in favor of olanzapine over risperidone in Quality of Life Scale (QLS) Intrapsychic Foundation and Medical Outcomes Study Short Form 36-item instrument (SF-36) Role Functioning Limitations-Emotional subscale scores. Despite the relatively small sample size, our study suggests that olanzapine has a superior risk:benefit profile compared to risperidone.     

奥氮平与利培酮治疗首发精神分裂症对照研究

目的 比较奥氮平与利培酮治疗首发精神分裂症的疗效及不良反应。方法 随机将符合CCMD-2R精神分裂症的诊断标准70例患者进入奥氮平或利培酮组接受治疗,分别在治疗0、1、2、4、6、8周评定PANSS和TESS量表,在0、4、8周检查心脑电图和肝肾功能,在0、8周检查血催乳素和空腹血糖。结果 奥氮平与利培酮疗效相当,奥氮平能迅速减轻精神症状,其产生的不良反应少、严重程度轻,很少引起血催乳素变化;利培酮会显著提高血催乳素水平。结论 奥氮平对首发精神分裂症治疗安全有效。     

Switching from depot antipsychotic drugs to olanzapine in patients with chronic schizophrenia

BACKGROUND: Patients with chronic schizophrenia (DSM-IV criteria) often receive depot antipsychotic medications to assure longer administration and better compliance with their treatment regimen. This study evaluated whether patients stabilized on depot antipsychotic medication could be successfully transitioned to oral olanzapine. METHOD: In a 3-month open-label study, 26 clinically stable patients with schizophrenia taking depot antipsychotics for over 3 years were randomly assigned to continue on their current depot dose or to switch to oral olanzapine. Clinical ratings (Positive and Negative Syndrome Scale [PANSS], Global Assessment of Functioning [GAF] scale, and Clinical Global Impressions [CGI] scale) and side effect parameters (Abnormal Involuntary Movement Scale [AIMS], Barnes Akathisia Scale, AMDP-5 scale, vital signs, and weight) were obtained monthly. RESULTS: Oral olanzapine patients (N = 13) demonstrated significant clinical improvement over the depot control group (N = 13) from baseline to 3-month endpoint (PANSS total, p =.012; PANSS general, p =.068; PANSS negative, p =.098; CGI-Improvement, p =.007; CGI-Severity, p =.026; GAF, p =.015). Side effect rating scales showed no statistical differences between the 2 groups (AIMS, Barnes Akathisia Scale, AMDP-5, vital signs). The depot control group showed no statistical superiority in any measure except weight change (p =.0005). After 3 months, all olanzapine patients preferred olanzapine to their previous depot medications and chose to continue on olanzapine treatment. CONCLUSION: Clinicians may expect clinical improvement when switching chronically psychotic patients from traditional depot antipsychotic drugs to oral olanzapine. Switching may be completed within a 4-week period with relative compliance being maintained and patients preferring oral olanzapine to their previous depot medications.     

Hyperprolactinemia and schizophrenia: mechanisms and clinical aspects

The association between elevated prolactin levels and conventional antipsychotics is well-established. The novel antipsychotic, risperidone, has also been shown to elevate prolactin levels. Patients undergoing treatment with these medications are at high risk for developing hyperprolactinemia, which is associated with decreased bone mineral density, osteoporosis, menstrual disruptions and infertility, galactorrhea, breast cancer, cardiovascular disorders, and sexual impairment. Patients treated with conventional antipsychotics and risperidone should be routinely screened for hyperprolactinemia, and monitored for known sequelae. Optimally, patients with hyperprolactinemia secondary to antipsychotic drug treatment should be switched to a prolactin-sparing antipsychotic. This review will briefly highlight the regulation and function of prolactin secretion, discuss clinical effects of antipsychotic-induced hyperprolactinemia, and suggest a course of treatment.     

奥氮平与利培酮对精神分裂症认知功能影响的对照研究

目的 比较两种非经典抗精神病药奥氮平、利培酮对精神分裂症病人认知功能的影响.方法 62例急性发病期的精神分裂症患者(包括首发与复发)为研究对象,随机分为两组,分别予以奥氮平、利培酮治疗12周,在基线和12周末分别用阳性与阴性症状量表(PANSS)及副反应量表(TESS)、韦氏智能测验的数字广度和数字符号测验、连线测验A、连线测验B、MMSE依次评价疗效、安全性、认知功能.结果 12周末时两组的PANSS量表总分和各因子分较基线时有显著差异,治疗后两组之间无统计学差异.12周末与基线时比较奥氮平在数字广度顺背数、数字符号、TMT-A连线时间、TMT-A正确数、TMT-B连线时间、MMSE比较差异有统计学意义(P＜0.05).利培酮组在数字广度、数字符号、TMT-A连线时间、TMT-B连线时间、MMSE上有统计学的差异(P＜0.05).12周末时,两组之间相比较,显示利培酮在数字广度顺背数、TMT-B连线时间比较差异有统计学意义(P＜0.05).两组之间不良反应比较,利培酮组肌强直高于奥氮平组,差异有统计学意义(P＜0.05).结论 奥氮平组和利培酮组治疗精神分裂症疗效相当,改善认知功能疗效相当,利培酮可能在改善注意方面优于奥氮平.     

Efficacy of risperidone versus olanzapine in patients with schizophrenia previously on chronic conventional antipsychotic therapy: a switch study

The objective of the study was to examine whether patients with schizophrenia who were judged to be stable on long-term treatment with conventional antipsychotic medications would further benefit from a switch to an atypical antipsychotic drug. Thirty-six subjects with schizophrenia spectrum disorder, on conventional antipsychotic medication therapy for at least 2 years, were randomized in double-blind fashion to risperidone versus olanzapine. Patients were titrated up to 6 mg risperidone or 15 mg olanzapine as tolerated, followed by tapering and discontinuation of conventional antipsychotic medication. Atypical antipsychotic agents were then administered alone (monotherapy) for 12 weeks. Efficacy and tolerability were assessed using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale, and Simpson Angus Scale. Body weight was measured at each visit. Both treatment groups exhibited marked and similar improvement in the total PANSS score from baseline to study endpoint (22 weeks) [risperidone: baseline=59.3 (SE 3.1), 22 weeks=44.3 (SE 2.3) (p<0.001); olanzapine: baseline=55.9 (SE 3.3), 22 weeks=46.9 (SE 3.2) (p<0.001). Both groups also exhibited significant reductions in PANSS factor scores for positive and negative symptoms and disorganized thoughts. Only risperidone-treated patients exhibited significant decreases in uncontrolled hostility/excitement and anxiety and depression. Of note, while positive factor scores exhibited the majority of change within the first 10 weeks, negative factor scores continued to decline significantly in both treatment groups throughout the study. Tolerability assessments did not differ between groups. The results indicate that both atypical antipsychotic medications provided significant additional improvement in symptom severity in patients with schizophrenia previously on conventional antipsychotic agents.     

A randomized double-blind 12-week study of quetiapine, risperidone or fluphenazine on sexual functioning in people with schizophrenia

Sexual dysfunction is common in people suffering from schizophrenia and is reported by patients to be a significant reason for medication nonadherence. This report contains data for 27 people with schizophrenia who participated in a randomized double-blind 12-week trial of risperidone (4 mg/day), quetiapine (400 mg/day) or fluphenazine (12.5 mg/day). At baseline and endpoint, subjects were rated on the Changes in Sexual Function Questionnaire (CSFQ), the Prolactin-Related Adverse Event Questionnaire (PRAEQ) and had prolactin levels drawn. Endpoint prolactin levels were 50.6 +/- 40.4, 24.4 +/- 18.5, and 8.2 +/- 4.4 mg/dl for risperidone (N = 12), fluphenazine (N = 9) and quetiapine (N=6), respectively (F = 7.5,df = 2, p = 0.005, controlling for sex). Orgasm quality/ability improved significantly for quetiapine as compared to fluphenazine and risperidone (F = 4.41, df = 2, p = 0.033). Seventy-eight percent of patients on fluphenazine reported sexual dysfunction whereas did only 42 and 50% of those on risperidone and quetiapine. Forty percent of quetiapine patients reported they felt better about their sexuality as compared to previous treatment, as did 55% on risperidone. Conversely, only 13% of fluphenazine subjects reported any improvement. Hormonal problems (menstrual problems, gynecomastia, galactorrhea) were predominately observed in risperidone-treated subjects. Overall, quetiapine was associated with a normalization of prolactin levels and had the greatest benefits among these drugs regarding sexual functioning.     

Effect of risperidone on prolactinoma--a case report

Risperidone induced galactorrhea and hyperprolactinemia have been reported but its role in the growth of prolactinoma is not yet conclusive, due to extreme rarity of such cases. We describe a woman, suffering from Bipolar Disorder-manic episode, who exhibited prolactinoma while on risperidone therapy. The withdrawal of risperidone resulted in disappearance of prolactinoma though her prolactin level remained elevated along with persistent galactorrhea. The change to olanzapine therapy did not show much change in serum prolactin level and galactorrhea. Ultimately, only adding of bromocriptine resulted in disappearance of symptoms of prolactinemia and normal serum prolactin level was achieved and galactorrhea stopped. Further study is recommended to find out relationship between the growth of prolactinoma and risperidone.     

奥氮平与利培酮治疗青少年首发精神分裂症对照研究

目的比较奥氮平与利培酮治疗青少年首发精神分裂症的疗效和安全性。方法对60例青少年期首发精神分裂症患者随机分为两组,分别给予奥氮平与利培酮治疗8周。于治疗前及治疗后1、2、6、8周末进行阳性和阴性症状量表(PANSS)及副反应量表(TESS)评定。结果奥氮平与利培酮总的疗效无显著性差异,均能快速起效,PANSS总分比较治疗第1周与第2周末奥氮平组显著低于利培酮组,利培酮组锥体外系反应显著多于奥氮平组。结论奥氮平与利培酮均是治疗首发青少年精神分裂症安全有效的非典型抗精神病药物,可根据患者的不同情况分别选择。     

Adjunctive treatment with a dopamine partial agonist, aripiprazole, for antipsychotic-induced hyperprolactinemia: a placebo-controlled trial

OBJECTIVE: Hyperprolactinemia and associated side effects often occur with antipsychotics. The authors investigated the effect of adjunctive treatment with aripiprazole on hyperprolactinemia and psychopathology in patients with schizophrenia maintained with haloperidol. METHOD: Fifty-six patients with hyperprolactinemia taking haloperidol were enrolled. Haloperidol dose was fixed; aripiprazole was dosed at 15 mg/day for the first 4 weeks, then 30 mg/day for the following 4 weeks. Serum prolactin, haloperidol, and aripiprazole levels were measured. Symptoms and side effects were assessed with the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms, Clinical Global Impression symptom scale, Simpson-Angus Rating Scale, and Barnes Akathisia Rating Scale at weeks 1, 2, 4, 6, and 8. RESULTS: Prolactin levels of patients receiving aripiprazole significantly decreased over time, demonstrating a significant time effect and a time-by-group interaction. In the aripiprazole group, 88.5% of patients at week 8 had prolactin levels normalize compared to 3.6% of patients receiving placebo. Among 11 female patients with menstrual disturbances randomly assigned to aripiprazole, seven patients regained menstruation during the study, whereas none receiving placebo did. Plasma levels of haloperidol were not significantly altered. No significant time effect and time-by-group interactions on BPRS, Scale for the Assessment of Negative Symptoms, and Simpson-Angus Rating Scale scores were noted. CONCLUSIONS: Adjunctive aripiprazole treatment reversed hyperprolactinemia in both sexes, resulting in reinstatement of menstruation in female patients, with no significant effects on psychopathology and extrapyramidal symptoms. Aripiprazole has higher affinity to dopamine D(2) receptors than haloperidol, which is the likely cause of this observation.     

Gender-specific prolactin response to antipsychotic treatments with risperidone and olanzapine and its relationship to drug concentrations in patients with acutely exacerbated schizophrenia

Hyperprolactinemia is a frequent consequence of treatment with antipsychotic agents, partially because the prolactin response to antipsychotics is related to dopamine blockade. Recent studies have suggested that the prolactin response to olanzapine is weaker than that to risperidone. Thus, we studied the effects of various factors on the elevated plasma prolactin levels caused by these medications. The subjects were 94 patients with acutely exacerbated schizophrenia (46 males, 48 females). For four weeks, they received 6 mg of risperidone and 20 mg of olanzapine daily. Plasma samples were collected before the medications were given and 12 h after the bedtime dosing each week. Treatment with either risperidone or olanzapine boosted plasma prolactin levels above baseline in both males and females. Prolactin levels were significantly higher in females than in males at all sampling points in both treatments. Risperidone increased prolactin significantly more than did olanzapine in both males and females. Delta prolactin (prolactin level at four weeks minus the baseline prolactin level) during olanzapine treatment significantly correlated with olanzapine concentration at 4th week (r = − 0.518, p < 0.01) only in males. Multiple regression analyses showed that delta prolactin during risperidone was significantly correlated with gender (p < 0.001) and age (p < 0.05) and that delta prolactin during olanzapine significantly correlated with gender (p < 0.001) and drug concentration (p < 0.01). The present study suggests that the predominant factors influencing hyperprolactinemia are young female for risperidone treatment, and being female and lower drug concentration as a predictor for hyperprolactinemia under olanzapine.