碳酸锂合并奋乃静治疗有精神病性症状躁狂发作的疗效

目的比较单一大剂量经典抗精神病药物奋乃静与稳定剂碳酸锂合并小剂量奋乃静治疗有精神病性症状的躁狂发作的疗效和安全性。方法将79洌有精神病性症状的躁狂发作患者随机分成两组分别接受为期6周的单一大剂量奋乃静（标准剂量为40mg/日）治疗和碳酸锂（标准血锂浓度为0．9—1．2mmol／L）合并小剂量奋乃静（标准剂量为16mg／日）治疗。以Beth—Rafaelsen躁狂量表（BRMS）和临床总体印象量表（CGI）评定患者的疗效,以治疗中需处理的不良反应症状量表（TESS）评定患者的副反应。结果在治疗第6周末,单用奋乃静治疗组患者的临床治愈率37．5％（12／32）,有效率96．9％（31／32）;碳酸锂合并小剂量奋乃静组的临床治愈率63．9％（23／36）,有效率100％（36／36）,两组患者在临床疗效（X^2=8．072,P=0．045）和副反应（X^2=15．576,P=0．000）方面的差异达到统计学显著程度。碳酸锂合并小剂量奋乃静治疗组的副作用发生率（30．6％,11／36）显著低于单一大剂量奋乃静治疗组（81．3％,26／32）,两组之间的差异达到统计学显著程度（X^2=16．82,P=0．000）。结论碳酸锂合并小剂量奋乃静治疗有精神病性症状的躁狂发作临床疗效优于单一大剂量奋乃静治疗且副反应相对少见。     

Serum prolactin response to chlorpromazine and psychopathology in schizophrenics: implications for the dopamine hypothesis

The prolactin (PRL) response to 12.5 and 25 mg of chlorpromazine (CPZ) was studied in unmedicated schizophrenic patients and normal control subjects. Both doses produced significant increases in serum PRL levels compared to saline, but the response to 25 mg CPZ was significantly greater than that to 12.5 mg. The PRL response to the 12.5 mg dose only was significantly correlated with baseline PRL levels for both males and females, suggesting that endogenous dopamine release from tuberoinfundibular neurons has a much greater effect upon the PRL response to the 12.5 mg dose of CPZ than to the 25 mg dose. Both doses of CPZ tended to show lower PRL responses in the schizophrenic females. The PRL response to the 25 mg dose was negatively correlated with ratings of severity of delusions at the time of study. The PRL response to 25 mg correlated highly with the morning serum PRL levels following treatment with CPZ 100 mg and 200 mg orally b.i.d. for 1 week at each dose. The PRL response to both doses did not predict clinical response at the end of 2 weeks of treatment with fixed dosages of CPZ. Serum PRL levels during treatment with CPZ 200 mg b.i.d. were significantly negatively correlated with ratings of hallucinations. The negative correlations between severity of delusions and hallucinations and various PRL measures suggest that increased dopaminergic activity in the tuberoinfundibular hypothalamic-pituitary axis may be associated with increased activity of subcortical and cortical dopaminergic systems.     

Double-blind trial of thiothixene and chlorpromazine in acute schizophrenia.

In a double-blind trial of chlorpromazine and thiothixene conducted with 79 acutely ill, newly hospitalized schizophrenic patients, chlorpromazine and thiothixene were shown to be equally effective in producing meaningful symptomatic improvment over an average period of approximately 3 weeks, as measured by Global Assessments (CGI), BPRS, and NOSIE.     

喹硫平、氯氮平合并碳酸锂治疗女性躁狂发作的随机对照研究

背景越来越多的第二代抗精神病药被用于躁狂症的治疗,但相比较而言,不同药物治疗对患者,特别是女性躁狂患者的益处仍存在争议。目的以碳酸锂治疗女性躁狂发作患者,比较喹硫平和氯氮平辅助治疗的疗效和安全性。方法将符合疾病及有关健康问题的国际分类第10版目前为躁狂发作诊断标准的64例女性患者随机分为碳酸锂合并喹硫平组（n=32）与碳酸锂合并氯氮平组（n=32）,开放性治疗6周。在基线及治疗1、2、4、6周后采Bech．Rafaelson躁狂量表（BeckRafaelson’sManiaRatingScale,BRMS）及治疗时出现的症状量表评定临床疗效及不良反应。结果氯氮平组有2例因白细胞降低退出研究。在完成6周研究的所有患者中,研究各时点2组的BRMS均分无统计学差异。研究结束时,喹硫平组的治疗有效率（也就是BMRS评分自基线下降50％）为87．5％（28／32）,氯氮平组为90．0％（27／30）（x^2=0．76,P=0．385）。治疗期间氯氮平组头晕、体重增加、嗜睡、便秘、流流涎、血糖与心电图异常的发生率显著高于喹硫平组。治疗2周后氯氮平组总的不良反应严重程度明显高于喹硫平组,其余治疗时段内2组间不良反应的严重程度无统计学差异。尽管喹硫平的治疗费用是氯氮平的23倍,但因为氯氮平组的附加治疗中使用了较多的价高药物,因此两药的总成本-效益接近。结论喹硫平和氯氮平辅助碳酸锂治疗女性躁狂患者的临床疗效相似,但有着不同的药物不良反应。采用普通的氯氮平治疗患者,对其所致不良反应的治疗费用可能掩盖了它的成本-效益。     

Effects of naloxone and pimozide on initiation and maintenance measures of free feeding

Latency to initiate and duration of eating of 18 daily 5-pellet meal segments was measured in 22-h food-deprived rats under conditions of pimozide (1 mg/kg, i.p.) and naloxone (2.5, 5.0 and 10.0 mg/kg, i.p.) pretreatment. Neither drug increased latency on the first or second day of testing; pimozide increased mean latency slightly on the third test. Both drugs slowed duration scores dramatically; the slowing was progressive both within and across test sessions in the case of pimozide; it was dose-dependent and progressive within (but not across) sessions in the case of naloxone. In each case, shifts in mean duration scores. In each case, shifts in mean duration score reflected an increase in score variance caused by an increase in the number and extremity of long duration scores. In each case best scores under the drug condition were equal to best scores under control conditions; indeed, very fast latency scores were slightly more frequent under each drug on the first day of testing. Thus each drug decreased the probability of moderate scores but neither drug caused a simple change in the ability to make occasional fast responses. While the effects of the two drugs were similar in some ways, naloxone, unlike pimozide, did not completely suppress feeding.     

抗抑郁药治疗强迫症引起躁狂发作

目的：探讨抗抑郁药在强迫症治疗中引起躁狂发作的情况。方法：回顾性分析近10年中83例强迫症住院患者的临床资料。结果：治疗强迫症引起躁狂的发生率为19．28％，各种抗抑郁药均可引起。联合小剂量抗精神药可降低其发生率。结论：抗抑郁药物治疗强迫症可引起躁狂发作，其机制尚不清楚。     

Effect of sodium valproate on mania

Summary A possible antimanic property of the GABA-ergic anticonvulsant valproate was examined by use of a double-blind placebo-controlled ABA design in 5 acutely ill manic patients. In 4 cases a marked improvement was observed after valproate medication whereas one patient showed no response. Seven further patients with frequently recurrent episodes of a manic or maniform schizoaffective psychosis, irresponsive to lithium prophylaxis, were chronically treated with valproate in combination with low doses of lithium (one case only with valproate). Over an observation period of 1 1/2–3 years none of the patients exhibited a relapse. It is proposed that, in general, GABA-ergic anticonvulsants possess antimanic properties and that the specific antimanic effect of lithium is due to a GABA-ergic mode of action. The possible role of GABA-systems in affective disorders and in organic types of psychoses (e.g., porphyria-psychosis, delirium tremens) is discussed on the basis of pharmacopsychiatric considerations.Supported by the Heisenberg-grant of the Deutsche Forschungsgemeinschaft     

Effects of pimozide and naloxone on latency for hypothalamically induced eating

Latency to feed in response to lateral hypothalamic electrical stimulation was assessed at a variety of stimulation frequencies using moderate stimulation intensity; shorter latencies accompanied higher stimulation frequencies. Pimozide (0.0625, 0.125, 0.25 and 0.5 mg/kg, i.p.) and naloxone (0.5, 1.0, 2.0 and 4.0 mg/kg, i.p.) increased latencies in a dose-dependent manner. At 0.5 mg/kg (4 X the lowest effective dose), pimozide blocked eating completely for most trials and in all animals. Naloxone attenuated eating at 1.0 mg/kg, but 4.0 mg/kg was not more effective than 2.0 mg/kg and did not block the behavior completely in any animal. With each drug, latencies were normal or near-normal at the beginning of each session and anorexic effects developed with repeated testing. Thus neither drug caused a simple overall impairment in performance capability. In both cases it is inferred that the proximal food cues lost the ability to maintain eating well before the distal food cues lost the ability to elicit eating. The similarity between the effects of pimozide and naloxone raises the possibility that opioid-containing and dopamine-containing neurons interact to influence feeding through common brain circuitry.     

Predictors of switch from depression to mania in bipolar disorder

Manic switch is a relevant issue when treating bipolar depression. Some risk factors have been suggested, but unequivocal findings are lacking. We therefore investigated predictors of switch from depression to mania in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) sample. Manic switch was defined as a depressive episode followed by a (hypo)manic or mixed episode within the following 12 weeks. We assessed possible predictors of switch using generalized linear mixed models (GLMM).8403 episodes without switch and 512 episodes with switch (1720 subjects) were included in the analysis. Several baseline variables were associated with a higher risk of switch. They were younger age, previous history of: rapid cycling, severe manic symptoms, suicide attempts, amphetamine use and some pharmacological and psychotherapeutic treatments. During the current depressive episode, the identified risk factors were: any possible mood elevation, multiple mania-associated symptoms with at least moderate severity, and comorbid panic attacks.In conclusion, our study suggests that both characteristics of the disease history and clinical features of the current depressive episode may be risk factors for manic switch.     

Lithium and chlorpromazine in psychotic inpatients

A sample of recently hospitalized psychotic patients was assigned to treatment with lithium or chlorpromazine in a double-blind drug trial. Several diagnostic systems were used to characterize the patients. No relationship was found, regardless of criterion system used, between dignosis and differences in drug effectiveness; specifically, the presence of “schizophrenic” symptoms did not predict a poor response to lithium. Among patients with physical overactivity, those treated with lithium terminated earlier and had poorer outcome than those treated with chlorpromazine. In patients who were not overactive, the two drugs were equally effective, and chronically psychotic patients had poorer outcomes regardless of drug. Lithium may be an effective treatment for acutely psychotic patients who are not overactive. The use of a lithium trial as a diagnostic tool may be unwarranted.     

奎硫平与氯丙嗪治疗精神分裂症对照研究

目的:比较奎硫平与氯丙嗪对精神分裂症的疗效及不良反应。方法:来自4个精神卫生中心的住院患者191例,采用随机对照、多中心、开放研究。以阳性与阴性症状量表(PANSS)评估疗效,副反应量表(TESS)评定不良反应。同时检测血糖,催乳素等生化指标。结果:奎硫平与氯丙嗪的总体疗效相当(P>0.05)。氯丙嗪较易引起锥体外系反应(EPS),及胆碱能系统不良反应。结论:奎硫平对精神分裂症疗效与氯丙嗪无显著差异,前者不良反应较小,是治疗精神分裂症的较好选择。     

奎硫平与氯丙嗪对血清催乳素的影响

目的:探讨奎硫平与氯丙嗪对精神分裂症患者血清催乳素(PRL)的影响及血清PRL水平与药物疗效的相互关系。方法:对191例精神分裂症患者分别以奎硫平或氯丙嗪治疗。以阳性与阴性症状量表(PANSS)进行评估,同时测血清PRL浓度,于治疗前及治疗8周时各测1次。结果:经8周治疗,氯丙嗪组血清PRL(680.23±90.26)μg/L,显著高于奎硫平组(124.24±13.56)μg/L(P<0.001)。奎硫平组男女患者血清PRL水平差异无显著性(P>0.05);氯丙嗪组女性血清PRL(785.72±15.81)μg/L,显著高于男性的(557.75±99.23)μg/L(P<0.05),两组患者血清PRL浓度与PANSS减分率均无显著相关。结论:奎硫平对精神分裂症患者血清PRL水平基本无影响,氯丙嗪可明显升高患者血清PRL水平。血清PRL水平与药物疗效无显著相关。     

A controlled clinical trial of L-tryptophan in acute mania

In a 2-week study, 24 newly admitted manic patients were treated for 1 week with L-tryptophan (12 g/day); during the second week, half the patients, chosen at random, continued to receive tryptophan, while placebo was substituted in the other half under double-blind conditions. In the open phase of the study, there was a clinically and statistically (p less than 0.001) significant reduction in manic symptom scores, with little need for haloperidol prn. Patients who continued to be treated with tryptophan showed no significant change in mean scores during the second week, but those who were switched to placebo tended (p less than 0.10) to show an increase in the mean scores for manic symptoms. There was a significant (p less than 0.05) increase in the geometric mean of morning fasting total and free plasma tryptophan concentrations in men, but not in women. These results suggest that increasing the synthesis of 5-hydroxytryptamine has some therapeutic effect in mania.     

Electroencephalographic studies of chlorpromazine methiodide and somatostatin-induced barrel rotation in rats

It has been reported that intraventricular injection of chlorpromazine methiodide (CPZMI), a quaternary ammonium derivative of chlorpromazine, in rats induces abnormal, twisting postures which may serve as an experimental model of the human movement disorder dystonia. We have shown elsewhere that the behavior induced by intraventricular CPMZI is identical to what has been called "barrel rotation," first observed to follow intraventricular injection of somatostatin (SRIF), which consists of twisting about the long axis, with repetitive lateral rolling. The suitability of barrel rotation, induced by CPZMI or SRIF, as an experimental model for dystonia depends on its physiologic basis. Human dystonia is clinically not a convulsive phenomenon. SRIF-induced barrel rotation has been reported to be associated with epileptiform activity recorded by the electroencephalogram (EEG). The purpose of this study was to investigate EEG activity during CPZMI- and SRIF-induced rotation. We found that CPZMI barrel rotation was not associated with epileptiform activity in cortex, amygdala, or hippocampus, and contrary to prior reports, neither was SRIF rotation. Both CPZMI and SRIF injected in high doses could induce epileptiform activity, but this was associated with clonic motor phenomena and not barrel rotation. We conclude that electroencephalographic criteria do not exclude either CPZMI- or SRIF-induced rotation as models for movement disorders, but their validity as such requires further study.     

Conditioned Drug Effects of Pimozide, Haloperidol and Chlorpromazine on Methamphetamine-Induced Behavior

Abstract: The separate effects of pimozide, haloperidol and chlorpromazine on conditioned behavioral responses and whether there is a difference when the drug is administered accompanied by a sound stimulus were examined in rats. The results showed a similar degree of inhibition could be obtained by saline plus sound as that by pimozide alone. The pimozide with sound group showed a higher inhibition rate than that of the other two groups of rats. In the haloperidol with sound group, a stronger inhibition appeared and furthermore when the injection was discontinued, conditioned abnormal behavior that had been inhibited began to recover. The chlorpromazine group was similar to the haloperidol group. This means that repeated saline injections accompanied by sound and each drug individually inhibits conditioned abnormal behavior and that each drug combined with sound causes the strongest inhibition. The findings obtained suggested that the antipsychotics examined could have conditioned drug effects.     

Effects of pimozide on cognition in children with Tourette syndrome: interaction with comorbid attention deficit hyperactivity disorder

Pimozide, a dopamine receptor antagonist, dopamine uptake inhibitor and L-type calcium channel blocker, is used in children suffering from Tourette syndrome (TS), but its effect on frequently comorbid attention deficit hyperactivity disorder (ADHD) is unknown. We have characterized the cognitive effects of pimozide and haloperidol in TS in relation to comorbid ADHD. Sixty-six consecutive outpatients with TS (DSM-III-R), ages 7–16, were randomly assigned to pimozide, haloperidol or medication-free clinical treatment and evaluated cognitively after 6 weeks. Continuous performance task (CPT) and memory search efficiency were compared across treatments. Treatment, comorbid ADHD and their interaction were significant on the CPT task. Pimozide treatment was superior to haloperidol and improved memory search efficiently over the no-drug condition.