Pituitary microadenoma treated with antipsychotic drug aripiprazole

Male patient 24 years old with a pituitary microadenoma and mental and behavioural disorders due to multiple drug use and use of other psychoactive substances (cocaine, cannabis and alcohol) were treated with haloperidol (dopamine receptor blocker) 10 mg daily. In the last control, the patient presented mammary hypertrophy; laboratory testing and brain magnetic resonance imaging (MRI) was performed, reporting the presence of a pituitary microadenoma syndrome with hormonal alteration (Prolactin levels 28.4 ng/ml). Haloperidol, carbamazepine and levomepromazine were then discontinued. He was started on aripiprazole 15 mg po daily for 4 days; the dosage was then increased to 30 mg po daily, with Valproic Acid 500 mg po tid. After 3 weeks on aripiprazole, the mammary hypertrophy that had increased in the patient had resolved. After 10 weeks follow up of prolactin revealed a normal level, at 4.33 ng/ml. Insomnia, aggressiveness, irritability, visual, tactile and auditory hallucinations remained absent after treatment with aripiprazole which is not a first line drug in multiple drug use patient with psychosis. We also consider the correlation of drug use in patient with psychosis, haloperidol treatment, pituitary microadenoma syndrome, hyperprolactinemia, and dopamine D2- receptor partial agonist aripiprazole treatment. This article also summarizes some relevant patents.     

Partial agonist properties of the antipsychotics SSR181507, aripiprazole and bifeprunox at dopamine D2 receptors: G protein activation and prolactin release

Dopamine D2 receptor antagonists induce hyperprolactinemia depending on the extent of D2 receptor blockade. We compared the effects of the new antipsychotic agents SSR181507 ((3-exo)-8-benzoyl-N-[[(2 s)7-chloro-2,3-dihydro-1,4-benzodioxin-1-yl]methyl]-8-azabicyclo[3.2.1]octane-3-methanamine monohydrochloride), bifeprunox (DU127090: 1-(2-Oxo-benzoxazolin-7-yl)-4-(3-biphenyl)methylpiperazinemesylate) and SLV313 (1-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-4-[5-(4-fluorophenyl)-pyridin-3-ylmethyl]-piperazine) with those of aripiprazole (7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]-butyloxy)-3,4-dihydro-2(1 H)-quinolinone), clozapine and haloperidol, on functional measures of dopamine D2 receptor activity in vitro and in vivo: [35S]-GTPgammaS binding to membranes from Sf9 insect cells expressing human dopamine D2 Long (hD2 L) receptors, and serum prolactin levels in the rat. All compounds antagonized apomorphine-induced G protein activation at dopamine hD2 L receptors. Antagonist potencies of aripiprazole, bifeprunox and SLV313 were similar to haloperidol (pK(b) = 9.12), whereas SSR181507 (8.16) and clozapine (7.35) were less potent. Haloperidol, SLV313 and clozapine were silent antagonists but SSR181507, bifeprunox and aripiprazole stimulated [35S]-GTPgammaS binding by 17.5%, 26.3% and 25.6%, respectively, relative to 100 microM apomorphine (Emax = 100%). pEC50s were: SSR181507, 8.08; bifeprunox, 8.97; aripiprazole, 8.56. These effects were antagonized by raclopride. Following oral administration in vivo, the drugs increased prolactin release to different extents. SLV313 and haloperidol potently (ED50 0.12 and 0.22 mg/kg p.o., respectively) stimulated prolactin release up to 86 and 83 ng/ml. Aripiprazole potently (ED50 0.66 mg/kg p.o.) but partially (32 ng/ml) induced prolactin release. SSR181507 (ED50 4.9 mg/kg p.o.) also partially (23 ng/ml) enhanced prolactin release. Bifeprunox only weakly increased prolactin at high doses (13 ng/ml at 40 mg/kg) and clozapine only affected prolactin at the highest dose tested (41 ng/ml at 40 mg/kg). Prolactin levels of the corresponding vehicle-treated animals were <4.3 ng/ml. These data show that (1) SSR181507, aripiprazole and bifeprunox, but not SLV313, are partial agonists at dopamine hD2 L receptors in vitro; (2) SSR181507, bifeprunox and aripiprazole exhibit reduced prolactin release in vivo compared with drugs that are neutral antagonists at dopamine D2 receptors.     

Modulation of stress-induced and stimulated hyperprolactinemia with the group II metabotropic glutamate receptor selective agonist,LY379268

It is well recognized that glutamate is an integral excitatory neurotransmitter in the neuroendocrine control of several hormonal factors. While the ability of pharmacological agents acting at ionotropic glutamate receptors to modulate the levels of serum prolactin levels has been investigated, there have been few reports of the effects mediated by the G-protein coupled, metabotropic glutamate (mGlu) receptors. The present work was undertaken to investigate the role of the Group II mGlu receptors, mGlu2 and mGlu3 in the regulation of serum polactin levels. LY379268, a Group II selective agonist, did not alter basal levels of circulating prolactin in young (36-40 day old) male rats. However, when an immobilization stress-induced hyperprolactinemia was examined, 10 mg/kg s.c. of LY379268 significantly lowered serum prolactin levels. Similarly, pretreatment with LY379268 was able to reverse the hyperprolactinemia induced with the catecholamine synthesis inhibitor, alpha-methyl-p-tyrosine (aMPT). This inhibition of hyperprolactinemia could be prevented by pretreatment with LY341495, a Group II mGlu receptor antagonist. The Group II antagonist alone had no effect on either basal nor stimulated prolactin levels. The agonist LY379268 was able to prevent the transient hyperprolactinemia associated with stimulation of serotonin 5-HT2A receptors by 2,5-dimethoxy-4-iodoamphetamine (DOI), but did not alter the high levels of circulating prolactin induced with the D2 antagonist, haloperidol. When treatment with LY379268 was delayed until 1 h after aMPT, a time demonstrated to show a full effect of aMPT on serum prolactin levels, the Group II agonist was similarly able to reverse hyperprolactinemia, suggesting LY379268 did not act by preventing the partial catecholamine depletion by aMPT. Similarly, high doses of amphetamine, a dopamine (DA) releaser, were able to reverse the aMPT-induced hyperprolactinemia, consistent with sufficient levels of dopamine remaining after aMPT treatment to modulate prolactin levels. LY379268 did not alter the hyperprolactinemia seen in estrogen-primed, ovariectomized female rats. Taken together the results indicate that stimulation of mGlu2/3 has an indirect inhibitory action on pituitary prolactin release. It is speculated that disinhibition of tubero-infundibular DA release by presynaptic Group II mGlu receptors located on inhibitory inputs to the arcuate hypothalamic nucleus is a possible explanation for the findings.     

阿立哌唑和氨磺必利对女性首发精神分裂症患者性激素的影响研究

目的研究阿立哌唑和氨磺必利对女性首发精神分裂症患者性激素的影响。方法 59例首次发作的绝经前女性精神分裂症患者,随机分为阿立哌唑组(30例)和氨磺必利组(29例)。阿立哌唑组采用阿立哌唑进行治疗,氨磺必利组采用氨磺必利进行治疗。比较两组不同时间(治疗前及治疗后第4、8、12周)的血清泌乳素(PRL)、孕酮(P)、卵泡刺激素(FSH)、黄体生成素(LH)水平及月经周期变化情况。结果治疗前,两组血清泌乳素水平比较差异无统计学意义(P>0.05);治疗第4、8、12周,阿立哌唑组血清泌乳素水平均低于治疗前,氨磺必利组血清泌乳素水平高于治疗前,差异有统计学意义(P<0.05);治疗第4、8、12周,阿立哌唑组血清泌乳素水平(10.545±5.675)、(9.358±7.807)、(6.366±3.587)ng/ml低于氨磺必利组的(153.405±56.225)、(170.204±65.227)、(226.702±80.431)ng/ml,差异有统计学意义(P<0.05)。治疗前及治疗第4、8、12周,两组孕酮水平比较,差异无统计学意义(P>0.05)。治疗前,两组卵泡刺激素水平比较,差异无统计学意义(P>0.05);治疗第12周,氨磺必利组卵泡刺激素水平低于治疗前及阿立哌唑组,差异有统计学意义(P<0.05)。治疗前,两组黄体生成素水平比较,差异无统计学意义(P>0.05);治疗第12周,氨磺必利组黄体生成素水平低于治疗前及阿立哌唑组,差异有统计学意义(P<0.05)。阿立哌唑组月经周期规律患者比例高于氨磺必利组,差异有统计学意义(P<0.05)。结论阿立哌唑对女性精神分裂症患者性激素水平及月经影响小。     

经颅磁刺激对精神分裂症患者催乳素水平的影响

目的探讨经颅磁刺激（rTMS）治疗抗精神病药所致高催乳素血症的疗效及安全性。方法将61例利培酮所致高催乳素血症的慢性精神分裂症随机分为两组,研究组（31例）予以低频rTMS刺激,对照组（30例）以假rTMS刺激治疗;并观察血清催乳素、PANSS表、17项汉密尔顿抑郁量表的情况。结果①研究组rTMS刺激后PRL水平[（27.9±7.1）μg/L]较治疗前[（101.5±41.2）μg/L]下降,差异有统计学意义（P〈0.01）;对照组差异无统计学意义（P〉0.05）;研究组治疗1个月后复测PRL[（96.7±38.3）μg/L],已恢复至治疗前水平（P〉0.05）。②治疗前后两组患者PANSS及HAMD17评分变化均无统计学意义（P均〉0.05）。结论低频rTMS治疗可使慢性精神分裂症患者血清高催乳素短期下降。     

Change in sexual dysfunction with aripiprazole: a switching or add-on study

Sexual dysfunction and raised prolactin are common adverse effects of many anti-psychotics. Aripiprazole is an atypical anti-psychotic associated with a reduction in prolactin level in anti-psychotic-induced hyperprolactinemia. Our hypothesis was that switching from another anti-psychotic to aripiprazole would be associated with a reduction in sexual dysfunction. An open label switch to aripiprazole was offered to 27 subjects with inadequate therapeutic response or intolerance to another anti-psychotic, who were followed up for 26 weeks. Serial clinical ratings included the Anti-psychotic Non-Neurological Side-Effects Rating Scale (ANNSERS), and the Sexual Functioning Questionnaire. Our primary analysis point was week 12. In both sexes, there was a significant reduction in prolactin by week 12 (P = 0.003), accompanied by a significant improvement in libido (P = 0.028). In males, both erectile and ejaculatory difficulties were also significantly reduced (P = 0.04 and P = 0.017, respectively). In females, menstrual dysfunction was also significantly reduced at week 12 (P = 0.04). By week 26, the changes in all of the above remained significant, and were accompanied by a significant increase in satisfaction in overall sexual functioning (P = 0.007), despite the fact that 54.5% of subjects at were also taking their original antipsychotic. There was also a significant decrease in the total ANNSERS score (P < 0.001) and a significant improvement in all other measures of psychopathology (PANSS, CGI-S/I, GAF-S/D, and QoL). We conclude that switching to aripiprazole or the addition of aripiprazole to another antipsychotic regime is associated with a reduction in sexual dysfunction.     

阿立哌唑与利培酮治疗痴呆精神行为症状的疗效及安全性比较

目的观察阿立哌唑和利培酮治疗老年痴呆精神行为症状的疗效及安全性。方法采用随机对照研究,将具有精神行为症状的痴呆患者68例完全随机分为阿立哌唑组及利培酮组,各34例。阿立哌唑组患者服用阿立哌唑,起始剂量2．5mg／d,最大剂量不超过15mg／d;利培酮组患者口服利培酮,起始剂量0．5mg／d,最大剂量不超过3mg／d。疗程均为8周。治疗前和治疗第2、4、8周末采用痴呆病理分析评定量表（BEHAVE—AD）评定疗效,用副反应量表（TESS）评定不良反应,并于入组时和治疗第8周末分别检测2组患者空腹血糖、餐后2h血糖、TC、TG、LDL—C、HDL—C及体重。结果阿立哌唑组和利培酮组患者治疗2、4、8周后BEHAVE—AD评分均明显低于治疗前[阿立哌唑组：（14．8±4．2）、（10．2±3．6）、（6．8±2．8）分比（16．4±4．6）分;利培酮组：（15．2±3．9）、（11．8±3．8）、（7．2±3．0）分比（17．2±5．O）分,P〈0．05或P〈0．01]。2组患者间治疗前及治疗后BEHAVE—AD评分比较,差异均无统计学意义（P〉0．05）。2组不良反应发生率均为8．8％（3／34）,差异无统计学意义（P〉0．05）。利培酮组治疗8周末体重较治疗前增加明显[（71±6）kg比（66±6）kg,P〈0．05],TG及LDL—C升高[分别为（1．62±0．46）mmol／L比（0．96±0．29）mmol／L．（3．82±0．86）mmol／L比（3．08±0．74）mmol／L,而阿立哌唑组则改变不明显（均P〉0．05）。结论阿立哌唑治疗老年痴呆精神行为症状总体疗效、安全性与利培酮相当,但阿立哌唑对患者血糖、血脂及体重影响小于利培酮。     

Effects of aripiprazole on circadian prolactin secretion related to pharmacogenetics in healthy volunteers

Aripiprazole treatment in schizophrenic patients was previously associated with lower or normalized prolactin levels. Genetic variants in cytochrome P450 (CYP) (CYP2D6), dopamine receptor (DRD2, DRD3) and serotonin receptor (HTR2A, HTR2C) genes were previously associated with antipsychotic‐induced hyperprolactinaemia. Our aim was to evaluate whether aripiprazole affects prolactin secretion and its relationship with pharmacogenetics. Thirty‐one healthy volunteers receiving a 10‐mg single oral dose of aripiprazole were genotyped for 12 polymorphisms in CYP2D6, DRD2, DRD3, HTR2A and HTR2C genes by qPCR. Aripiprazole and dehydro‐aripiprazole plasma concentrations were measured by HPLC‐MS/MS. Prolactin concentrations of the 31 volunteers taking aripiprazole and 12 volunteers receiving ibuprofen were determined by ELISA. Prolactin concentrations after ibuprofen intake were considered as control, since it is known to cause no effect. Prolactin concentrations were slightly higher in the aripiprazole group compared to the ibuprofen group. All prolactin pharmacokinetic parameters were higher in females than in males. CYP2D6 poor and intermediate metabolizers had notably higher prolactin C_max and AUC_0‐12 than normal and ultrarapid metabolizers. The DRD3 rs6280 polymorphism affected prolactin levels: volunteers carrying Ser/Ser genotype had significantly lower prolactin levels than volunteers carrying the Gly allele. Furthermore, HTR2C rs3813929 C/C homozygotes had significantly lower prolactin levels than T allele carriers. Nevertheless, aripiprazole did increase prolactin levels compared to ibuprofen.     

Aripiprazole

Aripiprazole is a quinolinone derivative and the first of a new class of atypical antipsychotics. The drug has partial agonist activity at dopamine D(2) and serotonin 5-HT(1A) receptors, and is also an antagonist at 5-HT(2A) receptors. In patients with acute relapse of schizophrenia or schizoaffective disorder, aripiprazole 15 to 30 mg/day was at least as effective as haloperidol 10 mg/day and had similar efficacy to risperidone 6 mg/day in well designed, 4-week, placebo-controlled trials. Negative symptoms improved earlier in the aripiprazole than the risperidone group. Efficacy of aripiprazole was observed at week 1 in several trials and was sustained throughout the study periods. Aripiprazole was superior to placebo in a 26-week trial in patients with stable, chronic schizophrenia. In a 52-week trial involving patients with acute relapsing disease, aripiprazole was similar to haloperidol as assessed by time to failure to maintain response and was superior in ameliorating negative and depressive symptoms. The incidence of extrapyramidal symptoms during aripiprazole therapy was similar to that with risperidone and placebo but lower than with haloperidol. Compared with placebo, the proportion of patients with increased plasma prolactin levels and QTc prolongation was similar in patients treated with aripiprazole 15 to 30 mg/day but was significantly increased with haloperidol and risperidone.     

三种抗精神病药治疗女性首发精神分裂症对糖脂代谢及催乳素的影响

目的评价奥氮平、利培酮及阿立哌唑对女性首发精神分裂症患者糖脂代谢及催乳素水平的影响。方法随机选择女性首发精神分裂症患者97例,分别使用奥氮平、利培酮及阿立哌唑治疗8周。治疗前及治疗期间每周记录体重变化,治疗前及治疗第2、4、8周末检验空腹血糖、甘油三脂、总胆固醇及高密度脂蛋白胆固醇、催乳素水平。结果在研究结束时,三组患者体重改变,血脂及催乳素水平变化均有显著性差异,空腹血糖变化无显著性差异。结论对于首发女性分裂症患者,奥氮平及利培酮对体重增加,脂代谢及催乳素水平有明显影响,而阿立哌唑则影响轻微。短期使用三种药物不影响患者空腹血糖水平。     

Efficacy and safety of aripiprazole vs. haloperidol for long-term maintenance treatment following acute relapse of schizophrenia

Aripiprazole is a novel atypical antipsychotic for the treatment of schizophrenia. It is a D2 receptor partial agonist with partial agonist activity at 5-HT1A receptors and antagonist activity at 5-HT2A receptors. The long-term efficacy and safety of aripiprazole (30 mg/d) relative to haloperidol (10 mg/d) were investigated in two 52-wk, randomized, double-blind, multicentre studies (using similar protocols which were prospectively identified to be pooled for analysis) in 1294 patients in acute relapse with a diagnosis of chronic schizophrenia and who had previously responded to antipsychotic medications. Aripiprazole demonstrated long-term efficacy that was comparable or superior to haloperidol across all symptoms measures, including significantly greater improvements for PANSS negative subscale scores and MADRS total score (p<0.05). The time to discontinuation for any reason was significantly greater with aripiprazole than with haloperidol (p=0.0001). Time to discontinuation due to adverse events or lack of efficacy was significantly greater with aripiprazole than with haloperidol (p=0.0001). Aripiprazole was associated with significantly lower scores on all extrapyramidal symptoms assessments than haloperidol (p<0.001). In summary, aripiprazole demonstrated efficacy equivalent or superior to haloperidol with associated benefits for safety and tolerability. Aripiprazole represents a promising new option for the long-term treatment of schizophrenia.     

Comparison of prolactin concentrations between haloperidol and risperidone treatments in the same female patients with schizophrenia

The present study aimed to investigate intraindividual changes in plasma prolactin concentrations by switching from haloperidol treatment to risperidone treatment. The subjects were 15 female schizophrenic inpatients who received firstly haloperidol 12 mg/day for at least 2 weeks and, thereafter, risperidone 6 mg/day. Prolactin concentration in plasma during risperidone treatment (median 87.5 ng/ml, range 5.3-298.1 ng/ml) was significantly ( P<0.01) higher than during haloperidol treatment (median 50.7 ng/ml, range 11.6-226.6 ng/ml). In contrast, the ratio of prolactin concentration to nmol/l unit drug concentration (the active moiety: the sum of risperidone and 9-hydroxyrisperidone) during risperidone treatment (median 1.10, range 0.02-3.73) was significantly lower ( P<0.001) than that of haloperidol (median 1.81, range 0.41-8.24). Prolactin concentrations during both treatment phases correlated well in individuals (r=0.619, P<0.05), whereas better correlation was found in the ratio of prolactin concentration to drug concentration (r=0.779, P<0.01). These findings suggest the higher risk of hyperprolactinemia during risperidone treatment than during haloperidol treatment at clinically used dosages. However, from a purely pharmacological point of view, prolactin response per drug concentration was more sensitive during haloperidol treatment than risperidone treatment, probably resulting from the potent and selective antagonistic effect of haloperidol on dopamine D(2) receptor, compared with the broader pharmacological spectrum of risperidone.     

Effect of d- and l-amphetamine on rat plasma prolactin levels

Although d- and l-amphetamine had no effect on plasma prolactin levels in untreated male rats, both d- and l-amphetamine reversed the increase in plasma prolactin levels produced by reserpine and 5-hydroxytryptophan (5-HTP). Only d-amphetamine significantly reversed the effect of alpha-methylparatyrosine (AMPT) on plasma prolactin levels. This reversal is probably due to a direct or indirect dopamine agonist effect of amphetamine, rather than to an effect on norepinephrine. This conclusion is based on the finding that apomorphine, a direct-acting dopamine agonist, reversed the reserpine-induced increase in prolactin secretion, while clonidine, a direct-acting alpha-adrenergic agonist, potentiated the reserpine-induced stimulation of prolactin secretion. The effect of d-amphetamine on the increase in plasma prolactin levels produced by reserpine, 5-HTP, or AMPT was always greater than that of the l-isomer, suggesting that the d-isomer has a more profound effect on dopaminerelease or neuronal reuptake, or both, than l-amphetamine. Chronic administration of d-amphetamine prior to reserpine did not inhibit the ability of d-amphetamine to reverse the reserpine-induced increase in plasma prolactin. Chronic administration of AMPT did not enhance the ability of d-amphetamine to reverse the AMPT-induced increase in plasma prolactin.     

Changes in sexual function and gonadal axis hormones after switching to aripiprazole in male schizophrenia patients: a prospective pilot study

Antipsychotic-induced sexual dysfunction is a common problem in patients with schizophrenia. The aim of the study was to investigate the effect of switching to aripiprazole on sexual dysfunction and the hypothalamic-pituitary-gonadal axis in male patients with schizophrenia. In this prospective, open-label study, the participants were 10 male schizophrenia patients treated with atypical antipsychotics, risperidone, amisulpride, and olanzapine. Before and after switching to aripiprazole, they were assessed on the Arizona Sexual Experience Scale, and hormonal levels were measured. Our results showed a significant improvement in the severity of sexual dysfunction, especially in 'ease of sexual arousal' and 'penile erection,' as measured by the Arizona Sexual Experience Scale total scores after switching to aripiprazole (χ(2) = 12.45 and P = 0.002). The serum prolactin level decreased significantly after switching to aripiprazole (χ(2) = 11.14 and P = 0.004), but the changes in the total testosterone level were not significant (χ(2) = 4.75 and P = 0.93). Our results suggest that sexual dysfunction in schizophrenia patients seems to improve after switching to aripiprazole from other atypical antipsychotics (risperiodone, amisulpride, or olanzapine). This may be associated with a change in dopamine and serotonin transmissions and a decrease in the serum prolactin concentration.     

阿立哌唑对舒必利所致高催乳素血症的影响

目的 探讨阿立哌唑对舒必利所致高催乳素血症的影响及安全性.方法 对61例服用舒必利6周后的精神分裂症患者,随机分为治疗组31例,对照组30例.治疗组在服用原药的基础上,每天加用阿立哌唑10 mg,对照组维持以前的药物治疗.服用舒必利治疗第6周及第9周末分别测定患者血清催乳素水平,并进行比较.同时用不良反应量表（TESS）评定不良反应.结果 经阿立哌唑治疗后,治疗组患者血清催乳素水平明显下降（P<0.01）,对照组血清催乳素水平无明显变化.两组TESS评分差异无显著性（P>0.05）.结论 阿立哌唑对舒必利所致高催乳素血症有一定的治疗作用,并且相对安全.     

阿立哌唑和利培酮治疗精神分裂症的有效性和安全性比较

目的 比较阿立哌唑和利培酮治疗精神分裂的有效性及安全性.方法 将102例患者采用随机数字表法分为2组：阿立哌唑组53例,应用阿立哌唑治疗,药物起始剂量为10 mg/d,在入组2周内根据病情变化情况逐渐将剂量增加至20 ～ 30 mg/d;利培酮组49例,应用利培酮治疗,药物初始剂量为1 nmg/d,在入组2周内根据病情变化情况逐渐将剂量增加至2 ～6 mg/d.于治疗前和治疗第4、8周评定并比较2组的阳性与阴性症状量表（PANNS量表）、副反应量表（TESS量表）评分和空腹血糖、血脂及体重指数值.结果 阿立哌唑组患者治疗前阳性症状、阴性症状、精神病理评分和PANSS总分分别为（25±7）、（21±5）、（38±10）、（85±15）分,治疗第4周分别为（15±6）、（15±5）、（29±7）、（59±13）分,治疗第8周分别为（11±5）、（11±5）、（21±6）、（44±11）分;利培酮组治疗前分别为（25±7）、（22±6）、（37±9）、（84±14）分,治疗第4周分别为（14±6）、（16±6）、（30 ±6）、（60±11）分,治疗第8周分别为（9±5）、（13 ±5）、（25 ±6）、（48 ±11）分;2组治疗后较治疗前均明显下降,差异有统计学意义（P＜0.05）,且治疗第8周与第4周相比,各项指标也明显下降,差异有统计学意义（P＜0.05）;但组间比较差异无统计学意义（P＞0.05）.阿立哌唑组治疗第4、8周TESS评分分别为（10 ±5）、（8±4）分;利培酮组分别为（10±5）、（9±4）分;阿立哌唑组明显低于利培酮组,差异有统计学意义（P＜0.05）.阿立哌唑组患者的空腹血糖、血脂和体重指数水平治疗后无明显改变（P＞0.05）;而利培酮组患者治疗后空腹血糖、高密度脂蛋白胆固醇、三酰甘油及体重指数均较基线明显升高[（5.4±0.6）mmol/L比（4.8±0.6）mmol/L,（2.1±0.4）μmol/L比（1.3±0.4）μmol/L,（2.0±0.8）mmol/L比（1.2±0.3）mmoL/L,（24.1±1.2） kg/m^2比（22.2 ±1.2）kg/m^2],差异有统计学意义（P＜0.05）.阿立哌唑组治疗后空腹血糖、高密度脂蛋白胆固醇、三酰甘油及体重指数[（4.8±0.6） mmol/L,（1.3±0.4）μmol/L,（1.4±0.4）mmol/L,（22.2±1.1） kg/m^2]均明显低于利培酮组治疗后,差异均有统计学意义（均P ＜0.05）.结论 立哌唑和利培酮在改善精神分裂症患者阳性、阴性及精神病理症状方面疗效相当,但阿立哌唑不良反应发生率低,对血糖血脂代谢影响更小,治疗安全性相对更高.     

Effects of haloperidol treatment on prolactin response to D-fenfluramine challenge in acute schizophrenia

We have previously described an association between higher serotonin (5-HT) responsivity, indexed by prolactin response to D-fenfluramine challenge, and poorer treatment response to haloperidol in non-medicated schizophrenics. The aim of the present study was to investigate the effects of antidopaminergic treatment on the prolactin response in the repeated challenge test. D-Fenfluramine was administered to 22 young, acutely ill schizophrenics (11 females and 11 males) after 4 weeks of haloperidol treatment. Whereas neuroleptic administration significantly raised basal prolactin levels (P <0.0001), subsequent D-fenfluramine challenge produced an additional significant increase (P <0.001). Moreover, the magnitude of this increase was not different from the pretreatment response. Our results demonstrate that prolactin response to the challenge is mediated through the 5-HT system. An observed negative association between posttreatment prolactin response and therapeutic response to haloperidol did not reach statistical significance. Received: 4 May 1998/Final version: 7 July 1998     

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.     

Further evidence for effects of ethanol on gonadotrophins and prolactin secretion in female rats

The effect of different doses of ethanol (0.5, 1.0, 2.0 and 4.0 g/kg) on LH, FSH and prolactin levels has been studied in female rats. Ethanol was administered in preovulatory periods (18 hr of diestrous or 9 hr of proestrous) and hormonal levels were measured at the 18 hr of proestrous. Ethanol administered at the 18 hr of diestrous produces a biphasic effect on serum LH levels. High doses of alcohol significantly decreased LH levels, whereas low doses (0.5 g/kg) increased the hormonal levels. When ethanol-treatment was at the 9 hr of proestrous, it only decreased LH levels with the dose of 4.0 g/kg. Serum FSH levels were unaffected by the preovulatory administration of ethanol. Serum prolactin concentrations were significantly elevated after i.p. administration of ethanol at the 18 hr of diestrous and the 9 hr of proestrous. The hyperprolactinemia is more pronounced in the rats treated at the 9 hr of proestrous. The results of these studies suggest that the ability of ethanol to modify LH and prolactin levels is due to a central depression caused for alcohol. These effects of ethanol could be mediated by the hypothalamic releasing factors and/or could be due to a direct action on the pituitary function. The sum of these effects produces important failures of the reproductive function in the female rat.     

白血病患者血清Ⅲ型前胶原、Ⅳ型胶原、层粘连蛋白、红细胞生成素及血小板生成素水平的变化

目的检测急慢性白血病患者血清Ⅲ型前胶原（PCⅢ）、Ⅳ型胶原（Ⅳ-C）、层粘连蛋白（LN）、红细胞生成素（EPO）及血小板生成素（TPO）的水平,探讨其改变的临床意义。方法选择26例急性白血病（AL）、16例慢性白血病（EL）和16例健康者,采用放射免疫分析法测定其PCⅢ、Ⅳ-C和LN水平,同时采用夹心酶联免疫法测定其血清TPO、EPO。结果急慢性自血病化疗前后PCⅢ[（164．02±118．53）μg/L,（176．30±75．66）μg/L]、Ⅳ-C[（66．54±19．48）μg/L,（73．12±24．88）μg/L]、LN[（122．85±25．10）μg/L,（121．56±24．62）μg/L]、EPO[（52.90±34.87）mU／ml,（72．21±52．15）mU／m1]、TPO[（443．68±208．53）ng／L,（642．54±318．49）ng／L]水平均高于健康对照组（均P〈0.05）。AL化疗后EPO[（72．21±52．15）mU／m1]、TPO[（642．54±318．49）ng／L]水平高于化疗前（均P〈0．05）,PCⅢ、Ⅳ-C、LN水平差异无统计学意义（均P〉0．05）;CL化疗前后PCⅢ、Ⅳ-C、LN、EPO、TPO水平均差异无统计学意义（均P〉0．05）。结论急慢性白血病患者存在PCⅢ、Ⅳ-C、LN、TPO及EPO的异常,动态监测EPO、TPO水平可一定程度上反映AL化疗疗效,但无助于病情严重程度和治疗效果的预测。