Using aripiprazole to resolve antipsychotic-induced symptomatic hyperprolactinemia: a pilot study

OBJECTIVE: To assess the effectiveness of substituting aripiprazole for other antipsychotic drugs taken by stable schizophrenic patients suffering from antipsychotic agent-induced symptomatic hyperprolactinemia. METHODS: Seven female schizophrenic patients with symptomatic hyperprolactinemia (167.6+/-58.0 microg/L) were recruited to take part in an 8-week open label trial of aripiprazole (10-20 mg/day) as a replacement for amisulpride or risperidone. Efficacy was assessed via PANSS and CGI-I scores. Serum prolactin levels were measured at baseline, week 4, and week 8. Data were collected from November, 2004 to May, 2005. RESULTS: At the end of weeks 4, serum prolactin levels were normalized (8.8+/-5.5 microg/L) and hyperprolactinemic symptoms were resolved in all patients. However, aripiprazole treatment was discontinued within 6 weeks for 2 of the 7 subjects due to aggravated auditory hallucinations. CONCLUSION: Results from this admittedly small-scale open-label study indicate that switching to aripiprazole may be useful for resolving antipsychotic-induced hyperprolactinemia and associated symptoms.     

阿立哌唑对利培酮所致高催乳素血症的疗效

目的:探讨阿立哌唑治疗利培酮所致高催乳素血症的有效性和安全性。方法:对19例利培酮所致高催乳素血症的男性精神分裂症患者,合并阿立哌唑10 mg/d。分别于治疗前、治疗2、4、8周检测血清催乳素水平;在治疗前、治疗8周评定阳性与阴性症状量表(PANSS)、临床总体印象量表-疾病严重度(CGI-S)、Barnes锥体外系不良反应量表(SAS)、Barnes静坐不能量表(BAS)和UKU不良反应量表(UKU)。结果:治疗4周催乳素水平显著下降(P<0.001),而治疗4周与治疗8周催乳素水平差异无显著性(P>0.05);研究结束时,所有患者催乳素水平下降超过50%,其中6例降至正常,5例患者催乳素相关症状均有改善;治疗前后PANSS、CGI-S、BAS和SAS评分差异无显著性(P>0.05)。结论:阿立哌唑可有效治疗利培酮所致的高催乳素血症,不良反应少。     

Improvement of serum prolactin and sexual function after switching to aripiprazole from risperidone in schizophrenia: a case series

This study examined prolactin levels, sexual function and clinical improvement after switching to aripiprazole from risperidone. Nine schizophrenic male Chinese patients who reported risperidone-induced sexual dysfunction were studied. Clinical Global Impression Scale Scores for Severity (CGI-S), Clinical Global Impression Scale Scores for Improvement (CGI-I), Arizona Sexual Experience Scale results and serum prolactin concentrations were determined over 16 weeks. After treatment with aripiprazole, all patients showed reduced serum prolactin (26.54 ± 17.03 ng/mL to 3.71 ± 1.87 ng/mL, P=0.008) and five reported improved sexual function. Mean baseline CGI-S (5.11 ± 0.93) decreased to 3.78 ± 1.39 (P=0.010) by week 16. Compared to baseline (4.0), the mean CGI-I significantly declined by the end of the study (3.44 ± 0.53, P=0.025).     

Switching female schizophrenic patients to quetiapine from conventional antipsychotic drugs: effects on hyperprolactinemia

INTRODUCTION: Conventional antipsychotic medications are associated with elevated prolactin levels, resulting in hyperprolactinemia and a number of unwanted side effects. Several atypical antipsychotics, on the other hand, are less likely to evoke hyperprolactinemia. The aim of this study was to investigate the prevalence of hyperprolactinemia induced by conventional antipsychotic drugs, examine changes in serum prolactin levels and psychiatric symptoms after switching to quetiapine, and identify the relevant characteristics of patients who may be suitable to switch to quetiapine. METHOD: Sixty-nine of 74 consecutive female patients who had received conventional antipsychotic drugs were initially included in the study. Of these, 49 (71 %) patients suffered from hyperprolactinemia, of which a further 25 were subsequently switched to quetiapine. Psychiatric symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS), and serum prolactin levels were measured just before and at 4 and 8 weeks after switching. RESULTS: Eight of the 25 (32 %) "switch" patients dropped out due to psychotic exacerbation during the 8 weeks. In the remaining 17 (68 %) patients, serum prolactin levels were significantly decreased without any significant change in PANSS scores after switching. The 17 patients who completed the switch had previously demonstrated significantly lower positive symptom scores compared to the 8 dropout patients. CONCLUSION: The present findings suggest that 71 % of female patients receiving conventional antipsychotic drugs may suffer from hyperprolactinemia and that approximately two-thirds of patients can be switched to quetiapine, resulting in an improvement in hyperprolactinemia. The main characteristic of the switched patients may be fewer positive symptoms.     

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.     

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。     

Prolactin levels in young children with pervasive developmental disorders during risperidone treatment

Although hyperprolactinemia is a common side effect during risperidone treatment in adult patients, no information is available on young children. The aim of this study is to report on serum prolactin levels in 25 young autistic children (22 males and 3 females, age range 3.9-7 years, mean age 4.10 years) during treatment with risperidone (dosage range 0.25-0.90 mg/day, mean dosage 0.52 mg/day). Prolactin levels were measured at baseline and after 10 weeks of treatment. The clinical outcome measure used was the Clinical Global Impression-Improvement. Serum prolactin was 9.77 +/- 3.94 ng/mL at baseline and 25.92 +/- 13.9 ng/mL during the 10th week of treatment (p < 0.001). Six children (24%) showed prolactin levels lower than 15 ng/mL, which is the upper normal level; eight children (28%) had prolactin levels higher than two times the upper limit (30 ng/mL). Hyperprolactinemia did not show significant correlations with age, weight, or risperidone dosage. There was no relation with clinical outcome. Dose reduction of risperidone resulted in a decrease of prolactin levels. None of the children showed clinical signs of hyperprolactinemia. Given the paucity of available data on potential effects of long-term hyperprolactinemia, a monitoring of prolactin during treatment with risperidone and other typical and atypical antipsychotics may be warranted.     

Association between dopamine-related polymorphisms and plasma concentrations of prolactin during risperidone treatment in schizophrenic patients

Hyperprolactinemia is an inevitable consequence of treatment with antipsychotic agents to some extent because prolactin response to antipsychotics is related to dopamine blockade. Recent studies have suggested that polymorphisms of the dopamine receptors are associated with therapeutic response to antipsychotics. Thus, we studied the effects of major polymorphisms of dopamine-related genes on plasma concentration of prolactin. Subjects were 174 schizophrenic patients (68 males, 106 females) receiving 3 mg twice daily of risperidone for at least 4 weeks. Sample collections were conducted 12 h after the bedtime dosing. Five dopamine-related polymorphisms (Taq1A, -141C ins/del for DRD2, Ser9Gly for DRD3, 48 bp VNTR for DRD4, Val158Met for COMT) were identified. The mean (+/-SD) plasma concentration of prolactin in females was significantly higher than males (54.3+/-27.2 ng/ml versus 126.8+/-70.2 ng/ml, p<0.001). No dopamine-related polymorphisms differed the plasma concentration of prolactin in males or females. Multiple regression analyses including plasma drug concentration and age revealed that plasma concentration of prolactin correlated with gender (standardized partial correlation coefficients (beta)=0.551, p<0.001) and negatively with age (standardized beta=-0.202, p<0.01). No correlations were found between prolactin concentration and dopamine-related polymorphisms. These findings suggest that plasma prolactin concentrations in females are much higher than in males but the dopamine-related variants are not predominantly associated with plasma concentration of prolactin.     

Risperidone-induced increase in serum prolactin is correlated with positive symptom improvement in chronic schizophrenia

The elevation in serum prolactin (PRL) concentration in schizophrenic patients treated with typical antipsychotic drugs is well documented. Recently, increased prolactin levels have been reported in patients taking risperidone. The purpose of this study was to explore the effect of the atypical antipsychotic drug risperidone on serum prolactin, and to investigate the relationship between the change in PRL and the therapeutic outcome. In this study, 30 male inpatients with a diagnosis of chronic schizophrenia (DSM-III-R) were assigned to 12 weeks of treatment with risperidone after a 2-week washout period. The risperidone dose was fixed at 6 mg/day. Clinical efficacy was determined using the Positive and Negative Syndrome Scale (PANSS). Serum PRL was assayed in serum by radioimmunometric assay in schizophrenic patients before and after 12-week treatment, as compared to 30 age-matched normal male subjects. The results showed that risperidone treatment significantly increased the serum PRL. A significant and positive relationship between the change in PRL at pre- and post-treatment and the reduction rate of PANSS positive subscore was observed. Risperidone treatment significantly increased the serum PRL levels of schizophrenic patients. There was a close relationship between the improvement in positive symptoms and the change of serum PRL level before and after risperidone treatment. The serum PRL levels at baseline could be used to predict the responses of schizophrenic patients to risperidone.     

Sexual dysfunction and hyperprolactinemia in Japanese schizophrenic patients taking antipsychotics

This study aimed to estimate the prevalence of sexual dysfunction, evaluated by the Nagoya Sexual Function Questionnaire (NSFQ), and hyperprolactinemia in patients with schizophrenia and examine a relationship between sexual dysfunction and serum prolactin levels. This cross-sectional, comparative study was performed using a sample comprising 195 Japanese schizophrenic in- and outpatients treated with antipsychotics (117 males and 78 females). Data were collected from October 2009 to January 2010 using single, cross-sectional ratings of sexual function assessed by the NSFQ and concurrent measurement of serum prolactin levels. The prevalence of sexual dysfunction in patients with schizophrenia was high (males 66.7%; females 79.5%). Hyperprolactinemia (>25ng/ml) was highly prevalent among schizophrenia patients, affecting 53.8% of females and 51.3% of males. Among female patients, 16.7% had prolactin levels>100ng/ml. There was no relationship between sexual dysfunction and serum prolactin levels. The present study demonstrated a higher prevalence of sexual dysfunction and hyperprolactinemia in Japanese schizophrenia patients. Clinicians should keep these problems in mind and discuss potential solutions with patients to improve patients' quality of life and adherence to therapy.     

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.     

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.     

阿立哌唑治疗抗精神病药所致闭经的精神分裂症对照研究

目的:探讨阿立哌唑对抗精神病药所致闭经的精神分裂症患者的影响.方法:69例抗精神病药引起闭经的女性精神分裂症患者,随机分为A组(单用阿立哌唑治疗)34例和B组(用其他抗精神病药联合中药血府逐瘀汤治疗)35例,观察疗程3个月.于治疗前、治疗后1、2、3个月测定血清催乳素浓度,并评定闭经的疗效.结果:治疗后两组血清催乳素浓...     

二甲双胍治疗抗精神病药所致高催乳素血症患者的初步观察

目的：探讨二甲双胍对抗精神病药所致高催乳素血症（HPRL）的治疗效果。方法：选择抗精神病药治疗过程中出现HPRL的住院精神疾病患者共24例,给予二甲双胍0．75g/d口服,观察12周。分别于治疗前和治疗4周、8周和12周后测定PRL水平。结果：24例患者二甲双胍治疗前PRL水平平均（80．62±56．26）ng/ml,治疗4周后PRL水平降至（62．94±43．49）ng／ml,平均降低（17．69±25．30）ng/ml,治疗前后比较,差异有统计学意义（t=3．424,P〈0．01）。结论：二甲双胍对于抗精神病药所致HPRL可能具有降低PRL的作用。     

Plasma concentrations of estradiol in women suffering from schizophrenia treated with conventional versus atypical antipsychotics

BACKGROUND: Low estrogen levels leading to an elevated rate of menstrual dysfunctions such as amenorrhea and irregular menstruation have been described in women with schizophrenia and have often been attributed to antipsychotic-induced hyperprolactinemia. However, there is some evidence that "hypoestrogenism" in schizophrenic women does not occur exclusively under medication with hyperprolactinemia-inducing antipsychotics. While the precise mechanism of low estrogen levels in schizophrenic women has not been elucidated yet, "hypoestrogenism" is of clinical relevance because estrogen seems to endow an antipsychotic-like effect in schizophrenia and thus positively affect the course of illness in schizophrenic women. In addition, low levels of estrogen might have a negative effect on bone mineral density and on the cardiovascular system. METHODS: To test the "hypoestrogenism hypothesis", hormone levels in 75 women with schizophrenia diagnosed according to DSM-IV and ICD-10 were determined in the follicular, periovulatory, and luteal phases of the menstrual cycle. Levels of estradiol, prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone, and testosterone were assessed. RESULTS: The serum levels of estradiol were generally reduced during the entire menstrual cycle compared to normal reference values. With low levels of LH over the entire cycle and of progesterone in the luteal phase, anovulatory cycles were assumed. Hypoestrogenism was found in about 60% of the patients in accordance with a strict definition (estradiol serum level below 30 pg/ml in the follicular phase and below 100 pg/ml in the periovulatory phase). To rule out a possible effect of hyperprolactinemia on the gonadal axis and a subsequent effect on estradiol levels from treatment with conventional ("typical") antipsychotics, serum estradiol levels of patients treated with certain atypical antipsychotics known to induce only a mild increase in prolactin, or no increase at all, were compared with those from patients treated with conventional antipsychotics. The data clearly indicate high prolactin levels in the latter, but low levels in the group treated with atypical antipsychotics. In both groups, however, low levels of estradiol compared to normal reference values were measured. CONCLUSIONS: The present findings provide evidence that hypoestrogenism in schizophrenia occurs in women with and without antipsychotic-induced hyperprolactinemia. Further research should be conducted to clarify the cause of hypoestrogenism in schizophrenic women and focus on possible clinical implications.     

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.     

Aripiprazole for the prevention of relapse in stabilized patients with chronic schizophrenia: a placebo-controlled 26-week study

BACKGROUND: Aripiprazole is a novel antipsychotic for the management of schizophrenia. This study investigated the efficacy, safety, and tolerability of aripiprazole in preventing relapse in adult chronic schizophrenia patients experiencing ongoing stable symptomatology. METHOD: In this 26-week, randomized, double-blind, placebo-controlled, parallel-group, multi-center study, 310 patients with DSM-IV schizophrenia (mean Positive and Negative Syndrome Scale [PANSS] total score = 82) were randomly assigned to receive a once-daily fixed dose of aripiprazole, 15 mg, or placebo. The primary outcome measure was time to relapse following randomization. Secondary objectives were to assess the efficacy, safety, and tolerability of aripiprazole, 15 mg, compared with placebo, in the study population. The study was conducted between Dec. 21, 2000, and Aug. 20, 2001. RESULTS: The time to relapse following randomization was significantly (p < .001) longer for aripiprazole compared with placebo. More patients relapsed with placebo (N = 85; 57%) than aripiprazole (N = 50; 34%); the relative risk of relapse for the aripiprazole group was 0.59 (p < .001). Aripiprazole was significantly superior to placebo from baseline to endpoint in PANSS total, PANSS positive, PANSS-derived Brief Psychiatric Rating Scale, and Clinical Global Impressions-Severity of Illness scale (CGI-S) scores and demonstrated significantly better mean Clinical Global Impressions-Global Improvement scale scores (p < or = .01 for all comparisons except CGI-S: .01 < p < or = .05). Aripiprazole was well tolerated, with no evidence of marked sedation and no evidence of hyperprolactinemia or prolonged heart rate-corrected QT interval (QTc). Extrapyramidal symptoms were comparable in the aripiprazole and placebo groups. Modest mean weight loss at endpoint was evident in both groups. CONCLUSION: Aripiprazole, 15 mg once daily, is an effective, well-tolerated treatment for prevention of relapse in patients with chronic, stable schizophrenia.     

Prolactin and antipsychotic medications: mechanism of action

Until the introduction of the first atypical antipsychotic, clozapine, in 1975, hyperprolactinemia was assumed to be an inevitable consequence of treatment with any antipsychotic agent. Now we know that atypical antipsychotics such as clozapine, olanzapine, quetiapine, sertindole, and ziprasidone are not associated with significant prolactin increase. These new antipsychotics appear to spare dopamine blockade within the brain's tubero-infundibular tract, a dopamine pathway that also controls prolactin secretion. Since the release of prolactin is tonically inhibited by the hypothalamus, with dopamine acting as the prolactin release-inhibiting factor, any disruption of the connection between the hypothalamus and the pituitary gland is associated with hyperprolactinemia. Other factors that can increase prolactin secretion are also reviewed (e.g. estrogens, thyroid-releasing factor, vasoactive intestinal peptides, opioids, surgery, illness such as epilepsy or herpes zoster infection, and psychic or physical stress). Prolactin levels are at their highest 1–2 hours before waking, and early waking interrupts its secretion. The major effects of hyperprolactinemia in women are amenorrhea, cessation of normal cyclic ovarian function, loss of libido, occasional hirsutism, and increased long-term risk of osteoporosis. The effects in men are impotence, loss of libido, and hypospermatogenesis. Current data indicate that conventional antipsychotics, as well as high doses of risperidone (>6 mg/day), increase prolactin levels to a range associated with sexual dysfunction in nonpsychiatric patients. The lack of prolactin elevation reported with the atypical antipsychotics is believed to be due to their much greater specificity, which results in less blockade of dopamine receptors in the tubero-infundibular pathway.     

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.     

加用阿立哌唑对利培酮所致精神分裂症男性患者高催乳素血症的影响

目的 探讨加用阿立哌唑对利培酮所致的首次发病的男性精神分裂症患者高催乳素血症的影响及安全性.方法 将80例男性精神分裂症首次发病住院患者随机分为研究组(40例)和对照组(40例).使用利培酮治疗4周后催乳素水平≥60 μg/L的患者,在维持原有治疗不变的基础上,研究组加用阿立哌唑5 mg/d,对照组加用安慰剂治疗,总疗程12周,研究周期8周(第4～12周末).于治疗第0,4,8,12周末检测血清催乳素含量,并用阳性和阴性症状评定量表(PANSS)、治疗中需要处理的不良反应量表(TESS)进行评定.结果 研究组治疗第12周末血清催乳素[(25±7)μg/L]较第4周末[(76±17)μg/L]下降,差异有统计学意义(t=15.87;P＜0.01).对照组治疗第12周末催乳素[(79±13)μg/L]与第4周末[(78±15)μg/L]比较,差异无统计学意义(t=0.72;P＞0.05);治疗第12周末催乳素下降率为(66 ±11)%、正常率为67.6%,均高于对照组[分别为(-1±18)%、6.5%](P均＜0.01).两组患者治疗前后比较,PANSS评分总分及分量表分均明显下降(P均＜0.01);在治疗第12周未两组之间各项评分比较,筹异均无统计学意义(t=0.40,0.76,0.22,0.88;P均＞0.05).治疗第12周未研究组TESS评分(4.8±4.3)与对照组(4.5±3.9)的差异无统计学意义(t=0.29;P＞0.05).结论阿立哌唑治疗利培酮所致精神分裂症男性患者高催乳素血症有效,安全.