Amisulpride improves depressive symptoms in acute exacerbations of schizophrenia: comparison with haloperidol and risperidone.

The Brief Psychiatric Rating Scale (BPRS) anxiety/depression subscore has been used to assess affective symptoms in three studies (n = 612) comparing amisulpride (400-800 mg/day, n = 339) with haloperidol (15-20 mg/day, n = 160) and risperidone (8 mg/day, n = 113) in the treatment of acute exacerbations of schizophrenia. At endpoint, the mean improvement in the anxiety/depression subscore showed a significant (P = 0.011) difference in favour of amisulpride (5.6+/-6.1) compared with haloperidol (4.4+/-5.5) and risperidone (3.7+/-4.7). Amisulpride provided a significantly greater improvement compared both to haloperidol and risperidone in more severely depressed patients (BPRS anxiety/depression subscore > or = 16 at baseline, P = 0.001). This significant advantage in favour of amisulpride is seen from the 2nd week of treatment.     

Amisulpride: progress and outcomes

Amisulpride is a unique atypical antipsychotic that selectively blocks D2 and D3 receptors presynaptically in the frontal cortex, possibly enhancing dopaminergic transmission, and postsynaptically in the limbic areas, possibly reducing it. Thus dopaminergic over-activity in the frontal cortex, and under-activity in the limbic areas, can be treated simultaneously, alleviating both positive and negative symptoms of schizophrenia, respectively. In acute schizophrenia, amisulpride is at least as effective as haloperidol, with a greater number of patients responding to treatment as determined by Clinical Global Impression (CGI scores (p = 0.014). In addition, amisulpride is associated with a lower incidence of extrapyramidal symptoms (EPS) as determined by Simpson-Angus scores (SAS) when compared with haloperidol (p = 0.0053). Amisulpride showed similar efficacy to risperidone as determined by the Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Symptom Score (PANSS) positive subscale; a trend towards greater improvement of negative symptoms as determined by PANSS negative subscale compared with risperidone; and similar levels of EPS. Amisulpride uniquely benefits patients with negative symptoms and is the only antipsychotic to demonstrate efficacy in patients with predominantly negative symptoms. Amisulpride maintains its efficacy when used for medium/long-term treatment as demonstrated in studies of up to 12 months. Amisulpride demonstrates greater improvement in controlling symptoms compared to haloperidol. In terms of the relevance of the effects, a superiority is observed for quality of life, social adaptation and functioning as measured by the Quality of Life Scale (QLS), Clinical Glocal Impression scale (CGI) and Functional Status Questionnaire (FSQ) scales. Amisulpride also has one of the lowest potentials of all the antipsychotic agents for weight gain. The clinical evidence for amisulpride supports its earlier pre-clinical potential, showing it to be an atypical antipsychotic agent with specific clinical advantages.     

Practical issues with amisulpride in the management of patients with schizophrenia

Amisulpride is an atypical antipsychotic with a significantly greater effect size than first-generation, typical antipsychotics, and efficacy at least similar to that of olanzapine and risperidone in large-scale clinical trials in schizophrenia. Amisulpride provides greater improvement in positive and negative symptoms of schizophrenia, a better long-term outcome than typical antipsychotics, and distinct tolerability advantages over typical antipsychotics, which are reported to cause extrapyramidal symptoms (EPS) in 20-50% of patients. In addition, amisulpride is associated with significantly less weight gain than olanzapine and risperidone, does not increase body mass index, and favourably influences lipid profiles. In many patients with schizophrenia, adverse events impair adherence to treatment, and switching from typical or atypical antipsychotic therapy to amisulpride may be clinically appropriate. Observational drug-utilization studies suggest that many physicians switch to amisulpride because of fewer EPS and/or less weight gain and improved patient adherence. Cross-tapering (over 4 weeks), rather than abrupt cessation of pre-switch treatment, is preferred. Amisulpride has a low risk of drug-drug interactions, and, during cross-tapering, patients can remain on concurrent treatments (e.g. anticholinergics and antiparkinsonian agents) until the effective dosage has been reached. An appropriate amisulpride starting dose is 800 mg/day for patients with acute psychotic exacerbations, 400-800 mg/day for patients with predominantly positive symptoms, and 100-300 mg/day for predominantly negative symptoms. Amisulpride may be particularly suitable for clozapine-augmentation therapy in patients with refractory schizophrenia. Indeed, amisulpride is more effective than quetiapine as augmentation therapy in patients partially responsive to clozapine, and several prospective open-label studies and case series have reported promising results for amisulpride/clozapine combination therapy. In three prospective studies, addition of amisulpride 200-800 mg/day to clozapine significantly reduced mean scores on the Brief Psychiatric Rating Scale (BPRS) total (-33% to -35%), Clinical Global Impression (CGI)-Severity scale (-31%), Positive and Negative Syndrome Scale total (-22%), and Scale for the Assessment of Negative Symptoms (-34%). The proportion of responders (CGI score > or =3 or BPRS improvement >20%) was 71-86%. Retrospective case-series analyses have also reported improved psychopathological state, reduced adverse events, and lower clozapine dosage requirement with use of this combination. The pharmacological and clinical profiles of amisulpride suggest that this agent is a viable clinical option when a change of antipsychotic therapy is required in patients with schizophrenia because of lack of efficacy, adverse events and poor adherence to treatment, or for augmentation of clozapine in treatment-resistant illness.     

Long-term safety and efficacy of amisulpride in subchronic or chronic schizophrenia. Amisulpride Study Group

Amisulpride is an atypical antipsychotic with selective affinity for dopamine D2/3 receptors. In this long-term, open, randomised, multicentre trial, patients with chronic or subchronic schizophrenia received amisulpride (n =370) or haloperidol (n = 118) for 12 months. Dosage regimens were flexible (amisulpride 200-800 mg/day, haloperidol 5-20 mg/day). Improvement in mean Brief Psychiatric Rating Scale total score was significantly greater for amisulpride than haloperidol (17.0 versus 12.8, P = 0.01). Positive symptoms (Positive and Negative Syndrome Scale [PANSS] positive) improved in a similar way in each group but amisulpride caused a significantly better improvement in negative symptoms (PANSS negative) (7.1 versus 3.7, P < 0.0001). Improvements in Global Assessment of Functioning (GAF) and Quality of Life Scale (QLS) scores were also significantly greater in the amisulpride group (GAF -20.1 versus -13.6, P = 0.001; QLS -0.64 versus -0.30, P = 0.02). Adverse events were mainly psychiatric in nature, and occurred with similar frequency in each group (amisulpride 254/370, 69%; haloperidol 82/118, 70%). Extrapyramidal symptoms were more frequent for haloperidol (48/118, 41% versus 96/370, 26% for amisulpride), leading to a greater requirement for antiparkinsonian medication (haloperidol 66/118, 56% versus amisulpride 118/370, 32%). Haloperidol significantly aggravated parkinsonism, akathisia and involuntary movement compared to amisulpride. The overall incidence of endocrine events was comparable between groups (4% for amisulpride, 3% for haloperidol). Maintenance of efficacy was comparable in both treatment groups; 59% of amisulpride patients and 55% of haloperidol patients improved after 1 month of therapy remained improved throughout the study period. Amisulpride is effective following flexible long-term administration and significantly improves social functioning and quality of life.     

Amisulpride: a review of its use in the management of schizophrenia.

Amisulpride, a substituted benzamide derivative, is a second-generation (atypical) antipsychotic. At low doses, it enhances dopaminergic neurotransmission by preferentially blocking presynaptic dopamine D2/D3 autoreceptors. At higher doses, amisupride antagonises postsynaptic dopamine D2 and D3 receptors, preferentially in the limbic system rather than the striatum, thereby reducing dopaminergic transmission. In patients with acute exacerbations of schizophrenia, the recommended dosage of amisulpride is 400 to 800 mg/day, although dosages < or =1200 mg/day may be administered. In comparative trials, amisulpride administered within this range (400 to 1200 mg/day) was as effective as haloperidol 5 to 40 mg/day, flupenthixol 25 mg/day and risperidone 8 mg/day in patients with acute exacerbations of schizophrenia with predominantly positive symptoms. Amisulpride was more effective than haloperidol but equally effective as risperidone in controlling negative symptoms. Amisulpride 400 to 800 mg/day was more effective than haloperidol, risperidone and flupenthixol in controlling affective symptoms in these patients. In randomised, double-blind trials involving patients with predominantly negative symptoms of schizophrenia, amisulpride 50 to 300 mg/day was more effective than placebo. Amisulpride is effective as maintenance therapy in patients with chronic schizophrenia. Long-term treatment with amisulpride was associated with improvements in quality of life and social functioning. Amisulpride is generally well tolerated. In well-controlled trials, the neurological tolerability profile (including ratings on extrapyramidal symptom scales) of amisulpride 400 to 1200 mg/day was superior to that of the conventional antipsychotics (haloperidol or flupenthixol), but was similar to that of the atypical antipsychotic risperidone. At low dosages of amisulpride (< or =300 mg/day), the incidence of adverse events (including extrapyramidal symptoms) reported with amisulpride was similar to that with placebo. CONCLUSION: In comparative trials, amisulpride 400 to 1200 mg/day showed efficacy in reducing overall symptomatology and positive symptoms similar to that of conventional antipsychotics and newer atypical antipsychotics in patients with acute exacerbations of schizophrenia. Moreover, its effective alleviation of negative and affective symptoms, its lower association with extrapyramidal symptoms and loss of cognitive function than conventional antipsychotics and its long-term efficacy justifies consideration of the use of higher dosages of amisulpride in this group of patients. Consequently, the dosage of amisulpride that is recommended in patients with acute exacerbations of schizophrenia is 400 to 800 mg/day, although dosages < or =1200 mg/day may be administered. Lower dosages of amisulpride (50 to 300 mg/day) should be considered for the management of patients with negative symptoms of schizophrenia. Amisulpride is a first-line treatment option in the management of schizophrenia in the acute phase and for the maintenance of treatment response.     

Amisulpride: a review of its use in the management of schizophrenia

Amisulpride (Solian), a substituted benzamide derivative, is a second-generation antipsychotic that preferentially binds to dopamine D2/D3 receptors in limbic rather than striatal structures. High dosages preferentially antagonise postsynaptic D2/D3 receptors, resulting in reduced dopamine transmission, and low dosages preferentially block presynaptic D2/D3 receptors, resulting in enhanced dopamine transmission. Amisulpride (200-1200 mg/day) was at least as effective as haloperidol and as effective as risperidone or olanzapine, in studies of up to 1 year in patients with schizophrenia manifesting predominantly positive symptoms. Amisulpride (50-300 mg/day) was significantly more effective than placebo in studies of up to 6 months in patients manifesting predominantly negative symptoms. Quality of life was also improved significantly more in patients receiving amisulpride than in those receiving haloperidol in 4- and 12-month studies in patients with predominantly mixed symptoms. Amisulpride was generally well tolerated in clinical trials. In patients with predominantly positive symptoms, amisulpride appeared to be better tolerated than haloperidol and was tolerated as well as risperidone and olanzapine. The incidence of extrapyramidal adverse effects with amisulpride was lower than with haloperidol but was generally similar to risperidone or olanzapine. Weight gain with amisulpride was less than that with risperidone or olanzapine and, unlike these agents, amisulpride does not seem to be associated with diabetogenic effects. Plasma prolactin levels are increased during amisulpride therapy and amenorrhoea occurs in about 4% of women. The incidence of adverse events with low dosages of amisulpride (< or = 300 mg/day) in patients with predominantly negative symptoms was similar to that observed with placebo. In conclusion, oral amisulpride (200-1200 mg/day) is at least as effective as haloperidol, and as effective as risperidone or olanzapine, in the treatment of patients with schizophrenia manifesting predominantly positive symptoms. In the treatment of patients manifesting predominantly negative symptoms, low dosages of amisulpride (50-300 mg/day) are significantly more effective than placebo. Amisulpride appears to be better tolerated than haloperidol, causing a lower incidence of extrapyramidal adverse effects and an improved quality of life. Compared with risperidone or olanzapine, amisulpride is more likely to cause hyperprolactinaemia, but has a lower propensity to cause weight gain and does not seem to be associated with diabetogenic effects. Thus, amisulpride is an effective and well tolerated option for the first-line treatment of patients with acute schizophrenia as well as for those requiring long-term maintenance therapy.     

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。     

Spotlight on amisulpride in schizophrenia

Amisulpride, a substituted benzamide derivative, is a second-generation (atypical) antipsychotic. At low doses, it enhances dopaminergic neurotransmission by preferentially blocking presynaptic dopamine D(2)/D(3) autoreceptors. At higher doses, amisulpride antagonises postsynaptic D(2) and D(3) receptors, preferentially in the limbic system rather than the striatum, thereby reducing dopaminergic transmission. In patients with acute exacerbations of schizophrenia, the recommended dosage of amisulpride is 400 to 800 mg/day, although dosages < or = 1200 mg/day may be administered. In comparative trials, amisulpride administered within this range (400 to 1200 mg/day) was as effective as haloperidol 5 to 40 mg/day, flupenthixol 25 mg/day and risperidone 8 mg/day in patients with acute exacerbations of schizophrenia with predominantly positive symptoms. Amisulpride was more effective than haloperidol but equally effective as risperidone in controlling negative symptoms. Amisulpride 400 to 800 mg/day was more effective than haloperidol, risperidone and flupenthixol in controlling affective symptoms in these patients. In randomised, double-blind trials involving patients with predominantly negative symptoms of schizophrenia, amisulpride 50 to 300 mg/day was more effective than placebo. Amisulpride is effective as maintenance therapy in patients with chronic schizophrenia. Long-term treatment with amisulpride was associated with improvements in quality of life and social functioning. Amisulpride is generally well tolerated. In well-controlled trials, the neurological tolerability profile (including ratings on extrapyramidal symptom scales) of amisulpride 400 to 1200 mg/day was superior to that of the conventional antipsychotics (haloperidol or flupenthixol), but was similar to that of the atypical antipsychotic risperidone. At low dosages of amisulpride (< or = 300 mg/day), the incidence of adverse events (including extrapyramidal symptoms) reported with amisulpride was similar to that with placebo. Conclusion: In comparative trials, amisulpride 400 to 1200 mg/day showed efficacy in reducing overall symptomatology and positive symptoms similar to that of conventional antipsychotics and newer atypical antipsychotics in patients with acute exacerbations of schizophrenia. Moreover, its effective alleviation of negative and affective symptoms, its lower association with extrapyramidal symptoms and loss of cognitive function than conventional antipsychotics and its long-term efficacy justifies consideration of the use of higher dosages of amisulpride in this group of patients. Consequently, the dosage of amisulpride that is recommended in patients with acute exacerbations of schizophrenia is 400 to 800 mg/day, although dosages < or = 1200 mg/day may be administered. Lower dosages of amisulpride (50 to 300 mg/day) should be considered for the management of patients with negative symptoms of schizophrenia. Amisulpride is a first-line treatment option in the management of schizophrenia in the acute phase and for the maintenance of treatment response.     

Amisulpride treatment of clozapine-induced hypersalivation in schizophrenia patients: a randomized, double-blind, placebo-controlled cross-over study

The beneficial effect of sulpiride augmentation of clozapine therapy for treatment-resistant schizophrenia patients is enhanced by its antisalivatory effect on clozapine-induced hypersalivation (CIH). Amisulpride, similar to sulpiride, is a substitute benzamide derivative with higher selective binding to the D2/D3 dopamine receptor. We hypothesized that add-on amisulpride would also be beneficial in controlling CIH. In a randomized, double-blind, placebo-controlled cross-over study, 20 clozapine-treated schizophrenia (DSM-IV criteria) inpatients with CIH were randomly initially assigned to add-on amisulpride (nine patients; 400 mg/day up-titrated from 100 mg/day over 1 week) or placebo (11 patients). Primary outcome was change in the five-point Nocturnal Hypersalivation Rating Scale (NHRS). Other measures included the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression scale (CGI) and Simpson-Angus Scale (SAS). Mean NHRS indices were considerably lower with amisulpride (1.79 +/- 1.25) than with placebo (2.63 +/- 1.33) [F(1,38) = 5.36, P < 0.05]. With amisulpride treatment, there was a significant improvement on the negative symptoms subscale of the PANSS [F(3,57) = 3.76, P < 0.05], but not on the SAS, CGI or other subscales of the PANSS (all F < 1). Short-term amisulpride augmentation has a strong ameliorating effect on CIH. A long-term, large-scale study with a broader dose range is warranted to evaluate the stability of this effect across time.     

A double-blind,randomised comparative trial of amisulpride versus olanzapine in the treatment of schizophrenia: short-term results at two months

OBJECTIVE: To compare the efficacy and safety of the atypical antipsychotics amisulpride and olanzapine in the treatment of acute psychotic exacerbations of schizophrenia. DESIGN AND SETTING: A multinational, double-blind randomised clinical trial. PATIENTS AND TREATMENT: Three hundred and seventy-seven patients with predominantly positive symptomatology were treated for six months with either amisulpride (200-800 mg/d) or olanzapine (5-20 mg/d). MAIN OUTCOME MEASURES: Short-term results were analysed after two months of treatment. The primary efficacy measure was the change of score on the Brief Psychiatric Rating Scale (BPRS). Other measures of efficacy and safety were also evaluated. RESULTS: Psychotic symptoms, as measured on the BPRS score, improved with both treatments, amisulpride being equivalent to olanzapine. All BPRS factor scores, as well as depressive symptoms, improved to a similar extent with both treatments. Less than five per cent of patients withdrew for adverse events, and there was no evidence for the emergence of extrapyramidal symptoms with either treatment. Statistically significant greater weight gain (2.7 +/- 3.9 kg) was observed during the study in the olanzapine group, compared with the amisulpride group (0.9 +/- 3.2 kg, p < 0.0001). CONCLUSIONS: Amisulpride and olanzapine show equivalent efficacy at 2 months in the treatment of acute psychotic exacerbations of schizophrenia. Amisulpride offers a significant advantage in preserving body weight.     

Amisulpride a selective dopamine antagonist and atypical antipsychotic: results of a meta-analysis of randomized controlled trials

The pharmacological profiles of the atypical antipsychotics, clozapine, olanzapine, quetiapine and risperidone, all show a combined serotonin (5-HT2) and dopamine type-2 (D2) receptor antagonism. Amisulpride, a highly selective dopamine D2/D3 receptor antagonist that binds preferentially to receptors in the mesolimbic system, is also an 'atypical' antipsychotic despite having a different receptor-affinity profile. A meta-analysis of 18 clinical trials was undertaken to compare the efficacy and safety of amisulpride with conventional antipsychotics. The improvement in mental state was assessed using the Brief Psychiatric Rating Scale (BPRS) or the Scale for the Assessment of Negative Symptoms (SANS). In a pooled analysis of 10 studies of acutely ill patients, amisulpride was significantly more effective than conventional neuroleptics with regard to improvement of global symptoms. Amisulpride is, to date, the only atypical antipsychotic for which several studies on patients suffering predominantly from negative symptoms have been published. In four such studies, amisulpride was significantly superior to placebo. Three small studies with conventional neuroleptics as a comparator showed only a trend in favour of amisulpride in this regard. Amisulpride was associated with fewer extrapyramidal side-effects and fewer drop-outs due to adverse events than conventional neuroleptics. These results clearly show that amisulpride is an 'atypical' antipsychotic, and they cast some doubt on the notion that combined 5-HT2-D2 antagonism is the only reason for the high efficacy against negative symptoms and fewer extrapyramidal side-effects.     

Improvement of acute exacerbations of schizophrenia with amisulpride: a comparison with haloperidol

Amisulpride is a substituted benzamide with high selectivity for dopaminergic D₂ and D₃ receptors. This study compared 800 mg/day amisulpride and 20 mg/day haloperidol in patients with acute exacerbations of schizophrenia. This multicenter, double-blind trial involved 191 patients allocated, after a 1 to 7-day wash-out period, to amisulpride (n = 95) or haloperidol (n = 96) for 6 weeks. Improvement of mean BPRS total score was 48% for amisulpride and 38% for haloperidol (NS), whereas improvement in the Negative PANSS subscale was greater in the amisulpride group (37%) compared to haloperidol (24%) (P = 0.038). CGI scores showed a higher number of responders in the amisulpride (62%) than in the haloperidol group (44%) (P = 0.014). More extrapyramidal symptoms measured with the Simpson-Angus scale were provoked in the haloperidol group (P = 0.0009). Amisulpride is at least as effective as haloperidol in the treatment of acute exacerbations of schizophrenia, and is more effective in the treatment of negative symptoms whilst causing less parkinsonism. Received: 13 December 1996/Final version: 12 March 1997     

No negative symptoms in healthy volunteers after single doses of amisulpride, aripiprazole, and haloperidol: a double-blind placebo-controlled trial

Noncompliance and poor outcome in patients with schizophrenia are closely related to the negative symptoms secondary to antipsychotics. No controlled study has evaluated whether amisulpride and aripiprazole induce negative symptoms. The aim of this study was to assess the effects of single doses of amisulpride, aripiprazole, haloperidol, and risperidone in healthy volunteers. Seventy-eight young volunteers took part in this double-blind, randomized, placebo-controlled, parallel study of four antipsychotics: 400 mg amisulpride, 10 mg aripiprazole, 3 mg haloperidol, and 2 mg risperidone. Assessments of negative symptoms were done 4 h after administration using both subjective rating scales (Neuroleptic Induced Deficit Syndrome Scale and Subjective Deficit Syndrome Scale) and an objective rating scale (Scale for the Assessment of Negative Symptoms). Risperidone only produced significant increases on the avolition score of the Neuroleptic Induced Deficit Syndrome Scale and blunted affect and alogia scores of the Scale for the Assessment of Negative Symptoms compared with placebo. The effect on blunted affect persisted after controlling for mental sedation. Amisulpride, aripiprazole, and haloperidol did not induce negative symptoms. Aripiprazole and risperidone induced mild extrapyramidal symptoms. The most common adverse events were somnolence and cognitive slowing. These data indicate that a single risperidone dose induces negative symptoms in normal volunteers, whereas amisulpride, aripiprazole, and haloperidol do not. These characteristics of antipsychotics should be considered when choosing optimal drugs for patients with psychosis.     

氨磺必利与利培酮治疗精神分裂症患者疗效及安全性对照研究

目的探讨氨磺必利与利培酮对精神分裂症患者的疗效及安全性的差异。方法选择北京回龙观医院住院患者60例,分别予氨磺必利（32例）及利培酮（28例）治疗,于治疗前及治疗后分别进行临床疗效与安全性等方面的观察。结果①两组患者治疗前后PANSS总分均差异显著（P〈0.05）;与利培酮组相比,氨磺必利组患者的阴性症状、抑郁症状及认知功能均明显改善（P〈0.05）。②治疗8周末,两组不良反应发生率及心电图QT间期均无显著性差异。结论氨磺必利和利培酮治疗精神分裂症安全有效,在改善阴性症状、抑郁症状、认知功能方面,氨磺必利优于利培酮。     

A Double-blind,Randomised Comparative Trial of Amisulpride Versus Olanzapine in the Treatment of Schizophrenia: Short-term Results at Two Months

Summary

Objective: To compare the efficacy and safety of the atypical antipsychotics amisulpride and olanzapine in the treatment of acute psychotic exacerbations of schizophrenia.

Design and setting: A multinational, double-blind randomised clinical trial.

Patients and treatment:Three hundred and seventy-seven patients with predominantly positive symptomatology were treated for six months with either amisulpride (200-800?mg/d) or olanzapine (5-20?mg/d).

Main outcome measures: Short-term results were analysed after two months of treatment. The primary efficacy measure was the change of score on the Brief Psychiatric Rating Scale (BPRS). Other measures of efficacy and safety were also evaluated.

Results: Psychotic symptoms, as measured on the BPRS score, improved with both treatments, amisulpride being equivalent to olanzapine. All BPRS factor scores, as well as depressive symptoms, improved to a similar extent with both treatments. Less than five per cent of patients withdrew for adverse events, and there was no evidence for the emergence of extrapyramidal symptoms with either treatment. Statistically significant greater weight gain (2.7?±?3.9?kg) was observed during the study in the olanzapine group, compared with the amisulpride group (0.9?±?3.2?kg, p?<?0.0001).

Conclusions: Amisulpride and olanzapine show equivalent efficacy at 2 months in the treatment of acute psychotic exacerbations of schizophrenia. Amisulpride offers a significant advantage in preserving body weight.     

氨磺必利与利培酮治疗精神分裂症对照研究

目的：观察氨磺必利治疗精神分裂症的临床疗效与安全性。方法将60例首发精神分裂症患者,随机分为氨磺必利组30例,利培酮组30例,疗程8周。采用阳性与阴性症状量表（ PANSS ）评定疗效,采用副反应量表（ TESS ）评定治疗中出现的不良反应。结果氨磺必利组的治疗总有效率为83.33%,利培酮组为80.00%,两组疗效差异无统计学意义（ P＞0.05）;氨磺必利组的体重增加明显少于利培酮组（ P〈0.05）。结论氨磺必利与利培酮治疗精神分裂症疗效相当,且氨磺必利引起体重增加数例明显较少,值得临床推广。     

Risperidone versus haloperidol in the treatment of acute exacerbations of chronic inpatients with schizophrenia: a randomized double-blind study.

The purpose of this study was to compare the efficacy and safety of risperidone and haloperidol in treatment-resistant chronic schizophrenic patients. Subjects (n = 78) who met DSM-III criteria for schizophrenia were randomly assigned to receive 6 mg/day of risperidone or 20 mg/day of haloperidol for 12 weeks. Clinical efficacy was determined using the Positive and Negative Syndrome Scale (PANSS), and side-effects with the Treatment Emergent Symptom Scale (TESS). Risperidone produced a mean 39.8 +/- 24.1% reduction in total PANSS score compared to a mean 28.3 + 19.4% reduction in the haloperidol group (P < 0.05). Analysis of changes for the three subscores of the PANSS revealed that the general psychopathology and negative subscores were significantly improved in the risperidone group compared to the haloperidol group. As for the side-effects, the risperidone group showed a significantly lower TESS total score, as well as nervous system symptoms subscore and cardiovascular symptoms subscore, compared to the haloperidol group. Risperidone appears to be a more effective and better tolerated antipsychotic drug in treatment-refractory Chinese schizophrenia than haloperidol.     

Faster response on amisulpride 50 mg versus sertraline 50-100 mg in patients with dysthymia or double depression: a randomized, double-blind, parallel group study.

Amisulpride (50 mg o.d.) was compared with sertraline (50-100 mg o.d.) for 12 weeks in a double-blind, parallel-group study in 313 outpatients with dysthymia (DSM-IV +/- episode of major depression). Full response rate [> or = 50% decrease in Hamilton Depression Rating Scale (HAMD) total score] was higher with amisulpride after 4 weeks (63% versus 50%, P < 0.02) and 8 weeks (82% versus 69%, P < 0.009). Time to initial improvement (> or = 25% decrease in HAMD total score) and to > or = 50% HAMD decrease were significantly shorter with amisulpride (P < 0.0033 and P < 0.0080, respectively). A faster response was also present in the subgroup of patients with pure dysthymia. The improvement in HAMD, Montgomery and Asberg Depression Rating Scale and Social and Occupational Assessment Scale total scores, as well as Clinical Global Impression improvement, was significantly greater with amisulpride after 4 weeks. Both drugs were equally effective at week 12. The tolerability of both drugs was satisfactory. Amisulpride is significantly more effective than sertraline during the first weeks of treatment in dysthymia.     

A double-blind, randomized comparative trial of amisulpride versus olanzapine for 6 months in the treatment of schizophrenia

Atypical antipsychotics offer advantages over earlier drugs for the treatment of schizophrenia, although few data exist on the relative merits of different atypical antipsychotics. A multicentre, double-blind, randomized trial was performed to compare amisulpride and olanzapine in the treatment of acute schizophrenia. Adult schizophrenic patients with dominant positive symptomatology received amisulpride (200-800 mg/day) or olanzapine (5-20 mg/day) for 6 months. The primary efficacy variable was change from baseline of the Brief Psychiatric Rating Scale (BPRS) score, assessed with a non-inferiority analysis. The evolution of positive and negative symptomatology, depression, social functioning and quality of life were assessed. Safety evaluation included adverse event reporting, neurological status and body weight. The improvement of BPRS score was 32.7% in the amisulpride group and 33.0% in the olanzapine group; thus, the efficacy of amisulpride was not inferior to that of olanzapine. All other secondary efficacy outcome variables evolved to a similar extent in both groups. Adverse event frequency was similar in both groups. Amenorrhoea was encountered only in the amisulpride group (6.2% of patients), whereas elevations of liver transaminases were more frequent in the olanzapine group (17% versus 3.7% of patients). The incidence and mean extent of clinically relevant weight gain were higher in the olanzapine group (35.1% and 3.9 kg) than in the amisulpride group (20.6% and 1.6 kg). The efficacy of amisulpride is not inferior to that of olanzapine in the treatment of acute schizophrenia. The side-effect profile of the two drugs differed.     

Ziprasidone and amisulpride effectively treat negative symptoms of schizophrenia: results of a 12-week, double-blind study

We compared the efficacy of ziprasidone and amisulpride in the treatment of negative symptoms and overall psychopathology in subjects who had chronic schizophrenia with predominantly negative symptoms. This multicentre, 12-week, double-blind study randomly assigned subjects with predominantly negative-symptom schizophrenia [i.e. Positive and Negative Syndrome Scale (PANSS) Negative Subscale score >or=6 points greater than Positive Subscale score] to ziprasidone (40-80 mg b.i.d.; n=60) or amisulpride (50-100 mg b.i.d.; n=63). The primary efficacy variable was the change from baseline in PANSS Negative Subscale score. Secondary efficacy variables included change in scores for PANSS Total, Global Assessment of Functioning, Brief Psychiatric Rating Scale derived from PANSS Total and Core, Clinical Global Impression (CGI)-Severity and CGI-Improvement. For the change in PANSS Negative Subscale score, a ratio to assess the equivalence of the treatment groups was calculated from the least squares mean changes from baseline, with equivalence claimed if the lower limit of the 95% confidence interval of the ratio exceeded 0.60. Mean daily dose, adjusted for differential numbers of subjects and differential days between visits, was 118.0 mg for ziprasidone and 144.7 mg for amisulpride. Mean PANSS Negative Subscale scores improved over the 12-week treatment period for intent-to-treat subjects, evaluable subjects (subjects with >or=4 weeks of double-blind treatment and no protocol deviations) and completers in both treatment groups. Ziprasidone demonstrated efficacy comparable to amisulpride in improving negative symptoms and global psychopathology. The groups demonstrated comparable improvements in secondary efficacy variables. Both agents were generally well tolerated, with comparably low incidences of movement disorders. In subjects with negative symptom-prominent schizophrenia, ziprasidone in mean daily doses of 118 mg was equivalent to amisulpride in mean daily doses of 148 mg in ameliorating negative symptoms and comparable in improving overall psychopathology and global illness severity.