Prediction of response to risperidone treatment with respect to plasma concencentrations of risperidone, catecholamine metabolites, and polymorphism of cytochrome P450 2D6

In the present study, we examined the relationships between plasma concentrations of risperidone and clinical responses, extrapyramidal symptoms, plasma levels of cotinine and caffeine, or cytochrome (cyp)2D6 genotypes. In addition, we also investigated the relationships between plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) or homovanillic (HVA) acid and clinical responses to risperidone. One hundred and 36 patients (male/female: 58/78, age 37+/-13 years) who met DSM-IV criteria for schizophrenia, schizoaffective disorder, delusional disorder and brief psychotic disorder, and who were being treated with risperidone alone, were evaluated regarding their clinical improvement and extrapyramidal symptoms using the Positive and Negative Syndrome Scale (PANSS) and Simpson and Angus (SAS), respectively, and plasma levels of cotinine, caffeine, MHPG and HVA were analysed by high-performance liquid chromatography. The cyp2D6*5 and *10 alleles were identified using the polymerase chain reaction. There was a positive correlation between plasma levels of risperidone plus 9-hydroxyrisperidone (active moiety) and SAS scores, but not the PANSS. Pretreatment HVA levels in responders were higher than those in nonresponders. In addition, there was a negative correlation between changes in HVA levels and improvement in PANSS scores. There was no association between plasma levels of risperidone and plasma levels of cotinine or caffeine. Furthermore, there were no differences in the risperidone/9-hydroxyrisperidone ratio, clinical improvements and extrapyramidal symptoms among cyp2D6 genotypes. These results indicate that pretreatment HVA levels and plasma concentrations of active moiety might play a part in predicting the clinical response and occurrence of extrapyramidal symptoms, respectively, when treating patients with risperidone.     

Plasma levels of homovanillic acid and the response to risperidone in first episode untreated acute schizophrenia

We have previously reported that risperidone might improve negative symptoms in schizophrenia by influencing noradrenergic neurons. In the present study, we focused on the clinical efficacy and mechanisms of risperidone towards positive symptoms in the acute phase of schizophrenia. Thirty-four patients meeting DSM-IV criteria for schizophrenia and treated with risperidone alone were evaluated regarding their clinical improvement using the Positive and Negative Syndrome Scale (PANSS) before and 2 weeks after risperidone administration, and blood samples were also drawn at the same times. Plasma concentrations of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol were analysed by high-performance liquid chromatography with electrochemical detection. Plasma HVA levels in the responders to the risperidone treatment (more than 50% improvement in scores of positive symptoms in PANSS) were higher than those of non-responders before risperidone administration. Furthermore, there was a negative trend between changes in plasma HVA levels and improvement of total scores for positive symptoms in PANSS. These results suggest that higher levels of plasma HVA before risperidone administration might be a predictor of a good response to risperidone treatment, and the influence of risperidone on dopaminergic activity might be associated with its efficacy in treating symptoms of schizophrenia in the acute phase.     

Effect of risperidone on plasma catecholamine metabolites and brain-derived neurotrophic factor in patients with bipolar disorders

A combination treatment with a mood stabilizer and an antipsychotic drug is often used in as many as 90% of subjects with acute mania. Recently, augmentation therapy with atypical antipsychotics has been investigated in both the acute and long-term treatment of bipolar disorder with or without psychosis. In the present study, the authors investigated the efficacy of risperidone treatment for both acute manic and depressive episodes in bipolar disorder. Eighteen patients (M/F: 8/10, age: 34 +/- 15 yr) who met the DSM-IV criteria for bipolar I disorder (12 cases of manic episodes, 6 cases of depressive episodes) with risperidone treatment were evaluated regarding their clinical improvement using the Young Mania rating Scale (YMRS) and the Hamilton rating Scale for Depression (Ham-D). Plasma concentrations of HVA and MHPG were analyzed by HPLC-ECD and plasma brain-derived neurotrophic factor (BDNF) levels were detected by sandwich ELISA. The mean scores of the YMRS were 22, 18, 12, 8, and 5 at time points before and 1, 2, 3, and 4 weeks after the risperidone administration, respectively. The mean scores of the Ham-D were 24, 25, 21, 21, and 19 at time points before and 1, 2, 3, and 4 weeks after the risperidone administration, respectively. The plasma levels of HVA and 3-methoxy-4-hydroxyphenylglycol (MHPG) were observed to have decreased 4 weeks after risperidone administration in manic patients. The levels did not change in depressive patients. The plasma levels of BDNF were decreased in depressive patients compared with manic patients or healthy controls. However, the administration of risperidone did not alter plasma BDNF levels.     

Investigation of target plasma concentration-effect relationships for olanzapine in schizophrenia

Olanzapine is an atypical antipsychotic effective in the treatment of schizophrenia. The present study has examined the potential use of target concentration monitoring of olanzapine in plasma as a marker of clinical response and an aid in patient management. Fifty-three patients (mean age 32 years; 40 M, 13 F) with a DSM-IVR diagnosis of schizophrenia completed a 6-week trial of oral olanzapine. Participants received once-daily olanzapine, and their psychotic symptoms were measured with the PANSS (Positive and Negative Symptom Scale) on admission and again after 6 weeks. Responders were classified as having a >/=20% decrease in PANSS scores. Plasma olanzapine was quantified by high-performance liquid chromatography. Receiver operator characteristic (ROC) curve analysis was used to identify a break point in plasma olanzapine that might serve as a surrogate for PANSS classification, and the two methods were compared using the McNemar chi2 test. After 6 weeks the median olanzapine dose was 15 mg/d (range 5-30 mg/d), and the mean plasma olanzapine was 32 micrograms/L at a mean of 13.5 hours after dose. With the PANSS (total), there were 42 responders and 11 nonresponders. ROC curve analysis for total PANSS identified a break point at 23 micrograms/L plasma olanzapine, with the proportions of responders and nonresponders identified by PANSS and the plasma break point being similar. Similar break points were found for the positive, negative, and global PANSS subscores. Nevertheless, these relationships were very modest, and at best the target plasma olanzapine concentration identified only 20% more responders than nonresponders. We suggest that plasma olanzapine monitoring can be used for dose-response optimization, but only to complement the normal clinical evaluation process.     

Effects of acute paroxetine treatment on the consumption of cigarette smoking and caffeine in depressed patients

In the present study, we examined the effects of acute treatment with paroxetine on the consumption of cigarette smoking and caffeine in 65 patients who met the DSM-IV criteria for major depressive disorder (M/F: 28/37, age: 48 +/- 15 years). Plasma levels of cotinine or caffeine were analysed using high-performance liquid chromatography (HPLC). The amount of cigarette smoking and plasma levels of cotinine, but not caffeine, decreased 4 weeks after paroxetine treatment. There was no difference between smokers and nonsmokers with respect to their response to paroxetine treatment. In addition, plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in responders to paroxetine treatment was higher than those in nonresponders, and there was a negative correlation between the changes in plasma MHPG levels and the changes in Hamilton rating scale for depression (Ham-D) scores before and 4 weeks after paroxetine administration. These results suggest that paroxetine has the potential to reduce the amount of cigarette smoking in depressed smokers, and we reconfirmed our previous results that depressed patients with higher plasma MHPG levels had better response to paroxetine treatment than those with lower plasma MHPG levels using larger depressed samples.     

Aripiprazole and dehydroaripiprazole plasma concentrations and clinical responses in patients with schizophrenia

Aripiprazole is widely used to treat schizophrenia. Plasma levels of aripiprazole and its active metabolite dehydroaripiprazole and their clinical responses in patients were explored. Forty-five (male/female: 19/26) patients with schizophrenia were treated with aripiprazole after a washout period of at least 3 days. There was no concomitant psychotropic except benzodiazepines for insomnia. The Positive and Negative Syndrome Scale (PANSS) was used to measure the clinical response at baseline and at weeks 2, 4, and 6. Blood was drawn at week 6 to measure the plasma concentrations of aripiprazole and dehydroaripiprazole. Patients with a PANSS score that decreased by more than 20% were defined as responders after 6 weeks of treatment. There was no difference in baseline PANSS scores or the daily dosage used between responders (n = 28) and nonresponders (n = 17) (15.0 ± 5.9 vs 12.9 ± 6.9 mg, respectively; P = 0.203). The responders showed a trend toward a higher plasma concentration of aripiprazole than nonresponders (234.4 ± 156.7 vs 163.5 ± 77.2 ng/mL, respectively; P = 0.117) and a significantly higher plasma concentration of dehydroaripiprazole (101.6 ± 58.0 vs 66.0 ± 48.4, respectively; P = 0.023). Higher plasma concentrations of aripiprazole and its active metabolite dehydroaripiprazole were noted in responders than nonresponders. Compared with Western patients, Oriental patients had higher plasma concentrations of aripiprazole and dehydroaripiprazole at the same dose. We suggest that therapeutic drug monitoring of aripiprazole will help improve the response in clinical practice.     

Effects of mianserin on negative symptoms in schizophrenia.

The efficacy of mianserin as a supplement in treating chronic schizophrenia was tested in 20 inpatients with schizophrenia who were receiving fixed doses of neuroleptics. Mianserin was given for six weeks with a starting dose of 60 mg/day. A brief psychiatric rating scale (BPRS) was completed before starting mianserin and thereafter BPRS scoring was carried out once weekly. The total BPRS score and the score for negative symptoms were decreased by mianserin treatment as compared to the pre-treatment values. Plasma 5-HIAA concentrations were increased after medication in both responding patients and nonresponding patients. However, the 5-HIAA values of responders were lower than those of nonresponders. Plasma HVA levels were slightly increased by mianserin in the responders. There were no significant changes in MHPG levels. These results suggest that the negative symptoms of schizophrenia may be improved by mianserin treatment.     

Addition of risperidone to sertraline improves sertraline-resistant refractory depression without influencing plasma concentrations of sertraline and desmethylsertraline

In the present study, we examined the efficacy of risperidone addition on sertraline-resistant depressed patients and the effects of risperidone on the metabolism of sertraline. Ten patients (M/F: 4/6, age: 54 +/- 10 years) met the DSM-IV criteria for major depressive disorder enrolled the study. Hamilton Dating Scale for Depression (HAM-D) scores (mean +/- SD) in all 10 patients significantly decreased from 19 +/- 4 (before risperidone addition) to 11 +/- 3 (4 weeks after risperidone addition). Plasma levels of sertraline and desmethylsertraline did not change after risperidone addition. Serum BDNF levels in responders to risperidone addition were changed from 8.1 +/- 2.7 ng/ml (before risperidone addition) to 11.5 +/- 0.9 ng/ml (4 weeks after risperidone addition); in contrast, those in nonresponders changed from 7.8 +/- 2.2 ng/ml (before risperidone addition) to 7.9 +/- 2.4 ng/ml (4 weeks after risperidone addition). These results suggest that the addition of risperidone to sertraline is effective and well tolerated for sertraline-resistant depressive patients, which is accompanied with the increase in serum BDNF levels in responders to the risperidone addition, and the addition of risperidone to sertraline does not seem to influence sertraline metabolism.     

利培酮联合艾司西酞普兰治疗慢性精神分裂症阴性症状的对照研究

目的：探讨利培酮联合艾司西酞普兰治疗慢性精神分裂症阴性症状的临床疗效以及安全性。方法将80例以阴性症状为主的慢性精神分裂症患者随机分为合用组和单用组,疗程12周,采用阳性和阴性症状量表（PANSS）和治疗中出现的症状量表（TESS）评定疗效和安全性。结果合用组显效率77.5%,单用组显效率55%。治疗后两组PASS评分均较治疗前有显著性下降,差异有统计学意义（P〈0.01）。治疗后2、4、8、12周末,合用组阴性因子分较单用组明显下降,差异有统计学意义（P〈0.05）。两组不良反应差异无统计学意义（P〉0.05）。结论利培酮联合艾司西酞普兰治疗慢性精神分裂症阴性症状起效快、疗效好,不良反应少。     

Effect of risperidone on plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels in schizophrenic patients: relationship among plasma concentrations of risperidone and 9-hydroxyrisperidone, pMHPG levels, and clinical improvement

We examined the relationships among the clinical efficacies of risperidone, plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, and changes in plasma free MHPG (pMHPG) in 14 schizophrenic patients. Clinical improvement in negative symptoms of schizophrenia treated with risperidone has been associated with increased pMHPG and, in the present study, there were positive correlations between plasma 9-hydroxyrisperidone concentrations and increased pMHPG levels. These results suggest that risperidone might improve negative symptoms in schizophrenia by influencing noradrenergic neurons.     

Urinary 3-methoxy-4-hydroxyphenylglycol and the depression-type score as predictors of differential responses to antidepressants.

Pretreatment 24 hr urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and the Depression-type (D-type) scores (derived from a multivariate discriminant function equation based on levels of urinary catecholamines and metabolites) were examined as possible predictors of antidepressant responses to either imipramine or alprazolam. In the case of imipramine, the responders had significantly lower pretreatment urinary MHPG levels (p = 0.002) and D-type scores (p less than 0.001) than did nonresponders. In contrast, responders to the antidepressant effects of alprazolam had significantly higher pretreatment urinary MHPG levels (p less than 0.05) and D-type scores (p = 0.02) than did nonresponders. For each antidepressant treatment, D-type scores appeared to provide a better separation of responders from nonresponders than did urinary MHPG levels. For each drug, the effect size for the difference in mean log-transformed D-type scores between responders and nonresponders was greater than the effect size for the difference in mean log-transformed MHPG levels. The difference between the effect sizes was statistically significant for imipramine (p = 0.02) and tended toward significance for alprazolam using two-tailed tests. These results suggest that the D-type equation, which was initially derived to separate bipolar manic-depressive depressions from other subgroups of depressive disorders, can also be used to predict differential responses to certain antidepressant drugs in patients with unipolar depressions.     

帕利哌酮缓释片门诊治疗精神分裂症疗效及社会功能的临床研究

目的:探讨帕利哌酮缓释片对精神分裂症的疗效及安全性。方法:门诊确认的精神分裂症患者分为帕利哌酮缓释片治疗组(n=76)和利培酮对照组(n=79),共治疗4周,治疗前及治疗4周后分别应用阳性与阴性症状量表(PANSS)、个人和社会功能量表(PSP)和副反应量表(TESS)评定疗效及安全性。结果:帕利哌酮组治疗4周后PANSS总分及各因子评分低于基线,差异均具有统计学意义(P<0.05);帕利哌酮组PANSS总分及阴性症状评分均低于对照组,差异具有统计学意义(P<0.05)。治疗4周后,帕利哌酮组PSP评分较利培酮组有不同程度提高,差异具有统计学意义(P<0.05)。帕利哌酮组不良反应与利培酮组相当,均未见严重不良反应。结论:帕利哌酮缓释片可有效改善精神分裂症患者的阳性症状、阴性症状以及社会功能,安全性较高。     

氨磺必利与利培酮治疗首发精神分裂症的随机双盲双模拟平行对照试验

目的：探讨氨磺必利与利培酮治疗精神分裂症的疗效及安全性。方法：采用随机、双盲、双模拟、平行对照试验方法,将34例符合诊断标准的首发精神分裂症患者随机分为氨磺必利组和利培酮组,每组17例。氨磺必利和利培酮的治疗剂量分别为800～1 200 mg·d~（-1）和2～6 mg·d~（-1）。疗程均为8周。于治疗前及治疗第1,2,4,8周末采用阳性和阴性症状评定量表（PANSS）评定疗效,采用治疗中出现的症状量表（TESS）及实验室检查来评价安全性。结果：治疗后第2,4,8周末,两组PANSS总分较治疗前均显著降低（P〈0.05）;氨磺必利组和利培酮组总有效率分别为88.2%和82.4%,差异无统计学意义（P〉0.05）。两组不良反应发生率比较差异亦无统计学意义（P〉0.05）。结论：氨磺必利和利培酮对治疗精神分裂症的疗效相当,不良反应轻,值得临床应用。     

帕利哌酮与利司哌酮治疗精神分裂症近期疗效与安全性比较

目的比较帕利哌酮与利司哌酮治疗精神分裂症的近期疗效及安全性。方法 94例精神分裂症患者分为帕利哌酮组与利司哌酮组,每组47例。帕利哌酮组起始剂量3mg·d~(-1),每隔1～2wk增加剂量1次,增幅为每次3mg,剂量稳定在3～12mg·d~(-1);利司哌酮组起始剂量2m·d~(-1),每隔1～3d增加剂量1次,增幅为每次2mg,2wk内加至4～6mg·d~(-1),观察6wk。于基线及wk 2、4、6末,采用阳性和阴性症状量表(PANSS)评定疗效,采用副反应量表(TESS)评定不良反应。结果最终纳入分析的有91例,其中帕利哌酮组47例,利司哌酮组44例。治疗4、6 wk末2组PANSS总分、阳性症状分、阴性症状分和精神病理症状分均显著降低(P<0.05或P<0.01)。wk 6末帕利哌酮组治疗有效率为70%,利司哌酮组为66%,疗效无显著差异(P>0.05)。wk 2末2组间PANSS总分、阳性症状分和精神病理症状分有非常显著差异(P<0.01),阴性症状分无显著差异(P>0.05);wk 4、wk 6末2组间PANSS总分及各分项分均无显著差异(P>0.05)。帕利哌酮组和利司哌酮组不良发应发生率无显著差异(72%vs.80%,P>0.05),帕利哌酮组锥体外系反应发生显著少于利司哌酮组(P<0.01)。结论帕利哌酮治疗精神分裂症的疗效与利司哌酮相当,且起效较快,锥体外系反应发生较少,安全性较好。     

Clinical improvement in 336 stable chronically psychotic patients changed from oral to long-acting risperidone: a 12-month open trial

Modern atypical antipsychotics have advantages over older neuroleptics. We hypothesize that their utility may be further enhanced by sustained drug delivery without daily oral self-dosing. This report examines the effects of a year of treatment with long-acting risperidone for chronically psychotic patients previously stabilized with oral risperidone. This open trial of long-acting risperidone involved 336 patients diagnosed with DSM-IV schizophrenia or schizoaffective disorder judged clinically stable on a consistent daily oral dose of risperidone for > or =4 wk. Based on oral doses, subjects were assigned clinically to bi-weekly intramuscular injections of 25-75 mg of long-acting risperidone for up to 50 wk. Clinical assessments at regular intervals included the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions (CGI) scale, adverse event reports, and the Extrapyramidal Symptom Rating Scale (ESRS). PANSS total scores improved overall from a moderate baseline score of 64.5+/-17.7 to 58.8+/-19.9 at end-point (p<0.001), by> or =20% in 50% of patients, with greatest improvement in negative symptoms. Prevalence of favourable CGI - Severity ratings increased by 2.4-fold (p<0.0001). Ratings of extrapyramidal symptoms also improved [e.g. physician-rated parkinsonism scores decreased by 20% (p<0.0001)]. Tissue reactions and other adverse effects of repeated intramuscular injections were rare and mild. Psychotic patients considered stable but symptomatic with oral risperidone treatment showed further improvements in symptom ratings and extrapyramidal dysfunction during a year of bi-weekly injections of long-acting risperidone.     

Milnacipran plasma levels and antidepressant response in Japanese major depressive patients

The relationship between antidepressant effects and plasma levels of milnacipran was studied in 49 cases of major depression without psychotic features during 6 weeks of milnacipran treatment. The daily dose of milnacipran was 50 mg/day for the first week, and up to 100 mg/day thereafter. Depressive symptoms were evaluated by the Montgomery and Asberg depression rating scale (MADRS) before treatment and at 1, 2, 4 and 6 weeks after the beginning of this study. Thirty-four patients (69.4%) were responders (defined as a 50% or greater decrease in the baseline MADRS score). Significant differences of MADRS scores were seen from 1 week after the beginning of this study (p=0.004, unpaired t-test) between responders and nonresponders. The mean plasma milnacipran level of responders, 82.0 +/- 29.4 ng/ml, was similar to that of non-responders, 78.6+/-23.1 ng/ml; there was no significant difference between responders and nonresponders. Neither a significant linear nor a curvilinear relationship was obtained between the final MADRS score and the plasma levels of milnacipran. Although there was no significant relationship between the plasma levels of milnacipran and the antidepressant response, milnacipran should be considered an efficacious agent in the treatment of major depressive patients.     

帕潘立酮与利培酮用于精神分裂症的对比分析

目的探讨帕潘立酮与利培酮片治疗精神分裂症的效果和不良反应。方法60例精神分裂症患者随机分为观察组和对照组各30例,分别给予帕潘立酮与利培酮治疗,疗程8周。分别于治疗前和治疗1、2、4和8周采用阳性与阴性症状量表（PANSS）评定疗效;以治疗中出现的症状量表评定不良反应。结果治疗后两组PANSS计分均比治疗前显著下降（均P〈0．01）;观察组阴性症状计分在治疗4周与8周时明显比对照组更低（均P〈0．05）。观察组显效率（70％）明显高于对照组（47％）,两组有效率（90％与80％）差异无统计学意义（P〉0．05）。结论帕潘立酮是安全有效的抗精神病药物,对阴性症状的改善尤为显著。     

Differential efficacy of risperidone versus haloperidol in psychopathological subtypes of subchronic schizophrenia

The aim of this study was to evaluate the efficacy and tolerability of risperidone versus haloperidol in subchronic schizophrenia, using psychopathological subgroups of patients with negative or positive and mixed symptoms to analyse the possible differential efficacy of the drugs. A total of 33 patients diagnosed using DSM-IV criteria entered the 6 week double-blind study with either risperidone or haloperidol 5 mg/day. Twenty-nine patients completed at least 2 weeks of treatment and entered the last observation carried-forward analysis. Both treatments were effective in reducing total scores and positive and negative subscale scores on the Positive and Negative Scale for Schizophrenia (PANSS), with a significantly better extrapyramidal profile in the risperidone-treated group. When analysis was repeated in each treatment group by psychopathological subtype (negative vs positive-mixed subgroups based on the PANSS composite index), risperidone was significantly superior to haloperidol in the intention to treat analysis in the negative subgroup. Repeated measures multivariate analysis of variance showed a significantly greater improvement in the PANSS negative subscale scores of risperidone-treated patients in the negative subgroup and a significant improvement in the PANSS positive subscale scores in both psychopathological subtypes. Haloperidol was significantly effective only in reducing positive symptoms in the positive subtype. Our results indicate that risperidone may be proposed for first-line treatment of subchronic schizophrenia, in particular the negative subtype. Copyright 2001 John Wiley & Sons, Ltd.     

帕利哌酮与利培酮治疗首发精神分裂症的临床疗效与安全性Δ

目的:比较帕利哌酮与利培酮治疗首发精神分裂症的临床疗效及安全性。方法:92例首发精神分裂症患者分为帕利哌酮(3～12 mg.d-1)组和利培酮(4～6 mg.d-1)组各46例,疗程为8周。于基线及服药2、4、6、8周末,采用阳性和阴性症状量表(PANSS)评定疗效、副反应量表(TESS)评定不良反应。结果:最终入组的患者为89例,其中帕利哌酮组45例,利培酮组44例,治疗4、6、8周末2组的PANSS总分、阳性症状评分、阴性症状评分和精神病理评分均显著降低(P<0.01)。治疗2周末,2组间PANSS总分、阳性症状评分和一般病理症状评分比较,有显著差异(P<0.01),阴性症状评分比较无显著差异(P>0.05)。治疗8周末帕利哌酮组PANSS总分减分率为(68.3±11.7)%,利培酮组为(67.8±12.1)%;帕利哌酮组有效率为71.1%,利培酮组为68.2%,2组疗效比较无显著差异(P>0.05)。帕利哌酮组锥体外系反应发生少于利培酮组(P<0.05)。结论:帕利哌酮治疗首发精神分裂症疗效与利培酮相当,且起效快、锥体外系反应少、安全性较好。     

Catatonia: short-term response to lorazepam and dopaminergic metabolism

Therapeutic response to lorazepam and dopaminergic metabolism were investigated in 18 neuroleptically naive acute catatonic patients. They were diagnosed as catatonic according to criteria by Lohr and Rosebush and treated exclusively with lorazepam (2–4 mg) during the first 24 h. Dopaminergic metabolism (plasma HVA, plasma MHPG), anxiety (HAM-A) and parkinsonic/dyskinetic movements (SEPS, AIMS) were measured under standard conditions before initial treatment with lorazepam (day 0) and 24 h after initial treatment (day 1). On day 0 responders to lorazepam treatment (complete remission of catatonic syndrome after 24 h according to Rosebush and Lohr) showed significantly higher (P=0.004) plasma HVA (130.4±51.2 pmol/ml; means ± SD) than non-responders (no remission of catatonic syndrome after 24 h; 73.2±40.5 pmol/ml; means ± SD). On day 1 plasma HVA did not differ any more significantly between both groups Clinically, responders showed significantly higher HAM-A (P=0.025) and AIMS (P=0.022) scores as well as significantly lower SEPS (P=0.049) scores than non-responders on day 0. Hence catatonic short-term responders and non-responders to lorazepam can be distinguished with regard to plasma HVA, anxiety and dyskinetic/parkinsonic movements.