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PubMed2000

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.

Adolescent↗
PubMed1999

Amisulpride vs. risperidone in the treatment of acute exacerbations of schizophrenia. Amisulpride study group.

Amisulpride, a substituted benzamide with high selectivity for dopamine D3 and D2 receptors, was compared with the antipsychotic risperidone in patients with acute exacerbations of schizophrenia. The study was double-blind and involved 228 patients allocated, after a 3-6-day wash-out period, to amisulpride 800 mg (n = 115) or risperidone 8 mg (n = 113) for 8 weeks. Both treatments produced a marked improvement in schizophrenic symptomatology. Decreases in mean BPRS total score were 17.7 +/- 14.9 for amisulpride and 15.2 +/- 13.9 for risperidone, and all of the individual factors on the BPRS showed a numerically greater improvement in the amisulpride than in the risperidone patients. Both treatments were equally effective against positive symptoms on the PANSS positive syndrome subscale; however, there was a trend in favor of greater improvement in negative symptoms assessed on the PANSS negative subscale in patients receiving amisulpride with a decrease of 6.9 +/- 7.5 vs. 5.3 +/- 6.6 for risperidone (P = 0.09). Both drugs demonstrated good safety profiles, and scores on neurological scales (SAS, AIMS, and BAS) did not increase during treatment. A comparable proportion of patients received antiparkinsonian medication, 30 and 23% in the amisulpride and risperidone groups, respectively (P = 0.21). Patients receiving risperidone experienced an increase in body weight, which was significantly greater than for amisulpride (P = 0.026).

Acute Disease↗
PubMed2000

Amisulpride has a superior benefit/risk profile to haloperidol in schizophrenia: results of a multicentre, double-blind study (the Amisulpride Study Group).

In a multicentre, double-blind, flexible-dose study, 199 patients with paranoid schizophrenia or schizophreniform disorders received haloperidol (10-30 mg/d) or amisulpride (400-1200 mg/d) for four months. More patients in the haloperidol group withdrew prematurely (44% vs 26%; P = 0.0077) due to a higher incidence of adverse events. Amisulpride was at least as effective as haloperidol in reducing the Brief Psychiatric Rating Scale (BPRS) total score (-27.3 vs -21.9) (non-inferiority test; P < 0.001). The PANSS positive score improved to a similar extent in both groups whilst improvement in the PANSS negative score was significantly greater with amisulpride (-10.5 vs -7.2; P = 0.01). The percentage of responders on the Clinical Global Impression scale was also significantly greater with amisulpride (71% vs 47%; P < 0.001). Both the Quality of Life Scale (QLS) and the Functional Status Questionnaire (FSQ) improved to a significantly greater extent under amisulpride. Haloperidol was associated with a greater incidence in extrapyramidal symptoms and with a greater increase in the Simpson-Angus score than was seen with amisulpride (0.32 vs 0.02; P < 0.001). In conclusion, amisulpride is globally superior to haloperidol in the treatment of acute exacerbations of schizophrenia and significantly improves patients' quality of life and social adjustment.

Adolescent↗
PubMed1998

Amisulpride, and atypical antipsychotic, in the treatment of acute episodes of schizophrenia: a dose-ranging study vs. haloperidol. The Amisulpride Study Group.

This 4-week, double-blind, randomized study was undertaken to determine the dose-response relationship of amisulpride in 319 patients with acute exacerbation of schizophrenia. Fixed doses of amisulpride (400, 800 and 1200 mg/day) and haloperidol (16 mg/day) were compared to amisulpride, 100 mg/day, as a potentially subtherapeutic dose. Efficacy data (BPRS total score and PANSS positive subscale) in the amisulpride groups generated a bell-shaped dose-response curve, with 400 mg/day and 800 mg/day being the most effective treatments for positive symptoms. Parkinsonism did not increase significantly between baseline and endpoint with amisulpride 400, 800 and 1200 mg/day compared to the amisulpride 100 mg/day group, whereas the difference was significant for haloperidol (P<0.05). It is concluded that amisulpride 400 mg and 800 mg/day is highly effective in treating the positive symptoms of schizophrenia, with less extrapyramidal side-effects than haloperidol 16 mg/day.

Acute Disease↗
PubMed1999

Improvement of schizophrenic patients with primary negative symptoms treated with amisulpride. Amisulpride Study Group.

OBJECTIVE: The goal of this placebo-controlled study was to evaluate the efficacy and safety of low doses of amisulpride, an atypical antipsychotic of the benzamide class with high affinity for D2 and D3 dopamine receptors, in the treatment of schizophrenic patients with predominantly primary negative symptoms. METHOD: After completion of a 4-week washout period, schizophrenic patients with primary negative symptoms participated in a 12-week, multicenter double-blind trial of placebo (N = 83), amisulpride, 50 mg/day (N = 84), or amisulpride, 100 mg/day (N = 75). They were evaluated with the Scale for the Assessment of Negative Symptoms, the Scale for the Assessment of Positive Symptoms, the Brief Psychiatric Rating Scale, and the Montgomery-Asberg Depression Rating Scale. RESULTS: Both amisulpride treatment groups showed significantly greater improvement in negative symptoms than the placebo group. Positive symptom scores were low at baseline and changed minimally during the study, suggesting that the improvement in negative symptoms was independent of improvement in positive symptoms. The safety of amisulpride was comparable to that of placebo, and extrapyramidal symptoms were infrequent. Comparable efficacy and safety results were observed with either dose of amisulpride. CONCLUSIONS: These findings confirm and extend those of earlier placebo-controlled studies of low-dose amisulpride in the treatment of patients with predominantly negative symptoms of schizophrenia.

Adolescent↗
PubMed1997

Amisulpride versus imipramine and placebo in dysthymia and major depression. Amisulpride Study Group.

Amisulpride, a selective antagonist of D2 and D3 dopamine receptors, acts preferentially on presynaptic receptors increasing dopaminergic transmission at low doses. In a multicentre, 6 months, placebo-controlled trial, amisulpride (50 mg/daily) was compared to imipramine (100 mg/daily) in the treatment of patients with DSM-III-R criteria for primary dysthymia, dysthymia with major depression or major depression in partial remission. A total of 219 patients were included. Both analyses (intention-to-treat and "per protocol' analysis) detected significant differences between groups (active treatment vs. placebo) on all main rating scales (CGI, MADRS, ERD, and SANS). The number of patients reporting at least one adverse event was higher in the imipramine group than in the two other, mainly due to anticholinergic effects. Endocrine symptoms were more frequent in female patients treated with amisulpride. These results confirm the interest of a drug acting on dopaminergic transmission such as amisulpride in the treatment of depressed patients.

Adult↗
PubMed1998

Amisulpride versus flupentixol in schizophrenia with predominantly positive symptomatology -- a double-blind controlled study comparing a selective D2-like antagonist to a mixed D1-/D2-like antagonist. The Amisulpride Study Group.

The benzamide amisulpride (ASP) is a selective D2-like dopamine antagonist, while flupentixol (FPX), a thioxanthene, blocks D2-like, D1-like and 5-HT2 receptors. To evaluate efficacy and safety of ASP and to investigate the importance of an additional D1-like antagonism for antipsychotic effects and extrapyramidal tolerability, a randomized double-blind multi- center study versus FPX as reference drug was performed for 6 weeks in 132 patients suffering from acute schizophrenia (DSM-III-R) with predominant positive symptomatology. Doses were initially fixed (ASP: 1000 mg/day; FPX: 25 mg/day) but could be reduced by 40% in case of side effects (mean daily doses: ASP: 956 mg; FPX: 22.6 mg). Intention-to-treat evaluation demonstrated significant improvement under both medications. The difference between the mean BPRS decreases of both treatment groups was 5.6 points (95% CI: 0.55; 10.65) in favour of ASP. According to CGI, 62% of patients in either drug group were treatment responders. ANCOVA analysis showed that reductions of BPRS (ASP: -42%; FPX: -32%) and SAPS (ASP: -78%; FPX: -65%) were more pronounced under ASP. Due to adverse events, significantly fewer ASP patients (6%) were withdrawn from the study (FPX: 18%). Extrapyramidal tolerability was better in the ASP group, as demonstrated by smaller increases in the Simpson-Angus Scale, the AIMS, and the Barnes Akathisia Scale in ANCOVA analyses with dosage as covariate. ASP appears to be as effective as FPX with regard to antipsychotic effects on positive schizophrenic symptomatology, while extrapyramidal tolerability is better. These conclusions have to be drawn cautiously, as dosage effects on outcome parameters cannot be entirely ruled out. The present results question the notion that additional blockade of D1-like receptors may be necessary to achieve sufficient antipsychotic effects or to improve extrapyramidal tolerability.

Adult↗
PubMed2003

How does the benzamide antipsychotic amisulpride get into the brain?--An in vitro approach comparing amisulpride with clozapine.

This study evaluated the disposition of the two atypical antipsychotics, amisulpride (AMS) and clozapine (CLZ), and its main metabolite N-desmethylclozapine (DCLZ), to their target structures in the central nervous system by applying an in vitro blood-brain barrier and blood-cerebrospinal fluid (CSF) barrier based on monolayers of porcine brain microvessel endothelial cells (PMEC) or porcine choroid plexus epithelial cells (PCEC). Permeation studies through PMEC- and PCEC-monolayers were conducted for 60 min at drug concentrations of 1, 5, 10, and 30 muM applied to the donor compartment. PMEC were almost impermeable for AMS (permeation coefficient, P<1 x 10(-7) cm/s) in the resorptive direction, whereas transport in the secretory direction was observed with a P (+/-SD) of 5.2+/-3.6 x 10(-6) cm/s. The resorptive P of CLZ and DCLZ were 2.3+/-1.2 x 10(-4) and 9.6+/-5.0 x 10(-5) cm/s, respectively. For the permeation across PCEC in the resorptive direction, a P of 1.7+/-2.5 x 10(-6) cm/s was found for AMS and a P of 1.6+/-0.9 x 10(-4) and 2.3+/-1.3 x 10(-5) cm/s was calculated for CLZ and DCLZ, respectively. Both, CLZ and DCLZ, could easily pass both barriers with about a five-fold higher permeation rate of CLZ at the PCEC. The permeation of AMS across the BBB was restricted partly due to an efflux transport. It is thus suggested that AMS reaches its target structures via transport across the blood-CSF barrier.

Amisulpride↗
PubMed2002

Spotlight on amisulpride in schizophrenia.

UNLABELLED: 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↗
PubMed2001

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

UNLABELLED: 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.

Acute Disease↗
PubMed2004

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.

Amisulpride↗
PubMed2002

Amisulpride for schizophrenia.

BACKGROUND: The treatment of schizophrenia with old, 'typical' antipsychotic drugs such as haloperidol can be problematic, because many people treated with these drugs will suffer from movement disorders. Amisulpride is said to be an "atypical" antipsychotic which induces less movement disorder and which is effective for the negative symptoms of schizophrenia. OBJECTIVES: To evaluate the effects of amisulpride as compared with placebo, typical and atypical antipsychotic drugs for schizophrenia. SEARCH STRATEGY: The authors carried out electronic searches of Biological Abstracts (1982-1999), CINAHL (1982-1999), Cochrane Library (Issue 4, 1999), Cochrane Schizophrenia Group's Register (November 2000), EMBASE (1980-1999), LILACS(1982-1999), MEDLINE (1966-1999) and PsycLIT (1974-1999). They checked all identified studies for further trial citations, and sought these studies in the Science Citation Index. They also contacted authors of trials and the manufacturer of amisulpride. SELECTION CRITERIA: All randomised controlled trials comparing amisulpride to placebo, typical or atypical antipsychotic drugs for schizophrenia or other non-affective serious mental illnesses. DATA COLLECTION AND ANALYSIS: Data were independently extracted and analysed on an intention-to-treat basis. The relative risk (RR) and 95% confidence intervals (CI) of dichotomous data were calculated using a random effects model, and, where possible, the number needed to treat was calculated. Weighted mean differences (WMD) were calculated for continuous data. MAIN RESULTS: This review currently includes 19 randomised studies with a total of 2443 participants. Most trials were of short duration. Data from 4 trials with 514 participants with predominantly negative symptoms suggest that low-dose (up to 300mg/day) amisulpride was a more acceptable treatment than placebo (n=514, RR 0.6 CI 0.5 to 0.8, NNT 3 CI 3 to 7), the improvement of the participants' global state (n=242, RR 0.6 CI 0.5 to 0.8, NNT 3 CI 2 to 6) and the treatment of negative symptoms (n=177, WMD -10.1 CI -16.6 to -3.5). Amisulpride was shown to be more likely to cause extrapyramidal symptoms than placebo in two studies (n=269, RR 2.2 CI 1.2 to 4.2), but this result did not hold calculating the risk reduction so that an NNT-statistic could not be indicated. Compared to typical antipsychotics, the pooled results of a total of fourteen trials suggest that amisulpride was more effective in improving global state (n=651, RR 0.7 CI 0.5 to 0.9, NNT 6 CI 4 to 11), the general mental state (n=695, WMD -4.2 CI -6.5 to -1.9) and the negative symptoms of schizophrenia (n=506, WMD -2.8 CI -4.3 to -1.3). Regarding positive symptoms, amisulpride was as effective as typical antipsychotics. Amisulpride was less prone to cause at least one general adverse event (n=751, RR 0.9 CI 0.8 to 0.97, NNH 9 CI 6 to 18), one extrapyramidal symptom (n=771, RR 0.7 CI 0.6 to 0.9, NNH 5 CI 4 to 9) or to require the use of antiparkinson medication (n=851, RR 0.6 CI 0.5 to 0.8, NNH 4 CI 3 to 6). No clear differences in other adverse events compared to typical drugs were found. Amisulpride also seemed to be more acceptable than conventional drugs as measured by the outcome 'leaving the studies early' (n=1512, RR 0.8 CI 0.7 to 0.9, NNT 16 CI 9 to 69) than conventional drugs, but this result might have been overestimated due to a publication bias which could not be excluded with certainty. A single trial compared amisulpride to another 'atypical' antipsychotic, risperidone. With the exception of agitation, which was more frequent in the amisulpride group (n=228, RR 3.4 CI 1.2 to 10.1, NNH 11 CI 6 to 50) no significant differences were recorded on efficacy or acceptability. REVIEWER'S CONCLUSIONS: This systematic review confirms that amisulpride is an effective 'atypical' antipsychotic drug for those with schizophrenia. Amisulpride may offer a good general profile, at least compared to high-potency 'typical' antipsychotics. It may also yield better results in some specific outcomes related to efficacy, such as improvement of global state and general negative symptoms. It might be more acceptable and more tolerable than high-potency conventional antipsychotics, especially regarding extrapyramidal side-effects. Longer term randomised trials are needed to evaluate the comparative value of amisulpride, particularly compared to other expensive atypical antipsychotics. These should focus on important outcomes which have not been sufficiently monitored such as service use, family burden and quality of life.

Amisulpride↗
PubMed1997

Amisulpride compared with standard neuroleptics in acute exacerbations of schizophrenia: three efficacy studies.

Three double-blind studies that included acutely ill schizophrenic patients were undertaken to assess the efficacy of amisulpride, an atypical antipsychotic with a selective affinity for dopamine D2, and D3, receptors. In the first study fixed doses of amisulpride (400, 800 and 1200 mg/day) and 16 mg/day of haloperidol were compared with 100 mg/day of amisulpride for a 4-week period. Efficacy was assessed using the Brief Psychiatric Rating Scale (BPRS), subscales of the Positive and Negative Symptom Scales (PANSS) and the Clinical Global Evaluation (CGI). Data were obtained on 319 subjects with the revised third-edition Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) criteria for schizophrenia. The highest improvement, in terms of BPRS total scores, occurred in the two groups taking 400 mg or 800 mg amisulpride. These doses also induced less extrapyramidal disturbance compared with haloperidol. The second study compared amisulpride with haloperidol: 95 patients were treated for 6 weeks with 800 mg/day of amisulpride and 96 patients with 20 mg/day of haloperidol. Efficacy criteria were the same as in the first study. Amisulpride at 800 mg/day was at least as efficacious as 20 mg haloperidol for the positive symptoms of schizophrenia, but was significantly more effective against negative symptoms (PANSS negative subscale, P = 0.038). There was also a significantly lower incidence of parkisonism in the amisulpride group. The third study compared amisulpride with flupenthixol: 70 patients were treated with 1000 mg/day of amisulpride and 62 patients with 25 mg/day of flupenthixol for a 6-week period. The mean improvement in the BPRS total score was greater in the amisulpride group, although this difference just failed to reach statistical significance (P = 0.059). Both drugs improved negative symptoms (Scale for the Assessment of Negative Symptoms), but the effect was more marked with amisulpride. Differences were statistically different in favour of amisulpride for positive symptoms. These studies show that amisulpride has optimal efficacy at doses of between 400 and 800 mg/day. It was at least as effective as reference drugs in the treatment of positive symptoms, and also reduced negative symptoms. Furthermore, amisulpride provoked fewer extrapyramidal side effects than standard reference drugs.

Adult↗
PubMed2004

Plasma amisulpride levels in schizophrenia or schizoaffective disorder.

The atypical antipsychotic drug amisulpride is a benzamide with specific antagonistic properties, which target dopamine D(2) and D(3) receptors, preferentially in the limbic system. Amisulpride is readily absorbed from the gastrointestinal tract, distributed to all body systems with little binding to plasma proteins. Elimination occurs mainly through the kidneys as unchanged drug. In contrast, hepatic metabolism is of minor significance and primarily yields two inactive metabolites. Very little is known about the plasma concentrations of amisulpride in patients at varying oral doses or about clinically relevant interactions with co-medication. The aim of the present investigation was to elucidate the factors, which affect amisulpride levels in schizophrenic patients. The plasma amisulpride levels of 85 patients with schizophrenia or schizoaffective disorder (mean age: 34.0+/-11.4 years; 40 women, 45 men) were assessed by high-performance liquid chromatography (HPLC) with fluorometric detection. The average daily dose of amisulpride was 772.3 mg (S.D. 346.7 mg) and the mean amisulpride plasma concentration was 424.4 ng/ml (S.D. 292.8 ng/ml). The interindividual variance of the amisulpride plasma concentration was high; furthermore, the plasma concentration increased linearly with the daily oral dose (r=0.50, p<0.001). Age and gender showed a significant effect on the dose-corrected amisulpride plasma concentrations-older patients and women had higher dose-corrected amisulpride plasma concentrations than younger patients and men. However, cigarette consumption had no effect on the amisulpride plasma concentrations. Regarding co-medication with lithium and/or clozapine, significantly higher amisulpride plasma concentrations were found as compared to monotherapy, whereas other co-medications such as benzodiazepines and various conventional antipsychotics had no effect on the amisulpride plasma concentrations. The results, the possible pathomechanisms and the clinical relevance are discussed. The findings need to be confirmed in larger patient samples and with a wider range of co-medications.

Adolescent↗
PubMed2003

Amisulpride versus risperidone in the treatment of schizophrenic patients: a double-blind pilot study in Taiwan.

BACKGROUND AND PURPOSE: The atypical antipsychotics, amisulpride and risperidone, have different receptor affinity characteristics. Although the relative efficacy of both drugs compared to conventional antipsychotics is well established, it remains unclear how the efficacy of amisulpride compares with risperidone. There have been no controlled studies comparing amisulpride to risperidone in Asian patients. The purpose of this study was to compare the efficacy and safety of amisulpride with that of risperidone in Taiwanese schizophrenic patients. METHODS: Patients with productive positive symptoms (n = 48) were enrolled into this double-blind, randomized pilot study for 6 weeks. Patients received either amisulpride (400-800 mg/day) or risperidone (4-8 mg/day). Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI), Social and Occupational Functioning Assessment Scale (SOFAS), and patients' subjective responses to treatment were assessed during the trial period. Adverse events were recorded at each follow-up visit. RESULTS: At the end of the trial, the mean dosage was 630 +/- 134 mg/day and 6.88 +/- 1.54 mg/day for amisulpride and risperidone, respectively. There was no significant difference in the reduction of the PANSS total score (amisulpride -24.1 versus risperidone -28.4, p = 0.999), the PANSS positive subscale score (amisulpride -6.8 versus risperidone -8.3, p = 0.467), the PANSS negative subscale score (amisulpride -5.6 versus risperidone -6.4, p = 0.999), or the CGI score between the two groups. The extrapyramidal symptom ratings, the improvement in the SOFAS (amisulpride 11.1 versus risperidone 10.0) and the subjective response (amisulpride 82% versus risperidone 83%) were comparable. No serious adverse events were recorded in either treatment group. There was a statistically significant body weight gain in the risperidone group. In contrast, there was a statistically, though not clinically, significant reduction of blood pressure and heart rate in the amisulpride group. CONCLUSIONS: This study suggests that amisulpride is as effective as risperidone in the treatment of patients with schizophrenia. Both drugs were well tolerated, but had different side effect profiles.

Amisulpride↗
PubMed2005

Therapeutic drug monitoring for optimizing amisulpride therapy in patients with schizophrenia.

Amisulpride is a clinically effective antipsychotic drug in a broad dose range with low propensity for extrapyramidal symptoms (EPS). Daily doses and plasma levels of amisulpride were analyzed within a large-scale therapeutic drug monitoring (TDM) survey to find plasma level ranges for optimized treatment under naturalistic conditions. Data of 378 schizophrenic patients treated with amisulpride (100-1550 mg) were included (40% female). Amisulpride plasma levels were analyzed at steady state; assessment comprised improvement (CGI-I) and side-effects, particularly EPS. For detection of cut-off values regarding non-response or EPS, receiver operating characteristics (ROC) curves were applied and the area under the ROC curve (AUC) was calculated. Amisulpride daily doses (594+/-262 mg) and plasma levels (315+/-277 ng/ml) were significantly correlated (r=0.53; P<0.0001). Patients with non-response to amisulpride (8.9%) had significantly (P<0.05) lower plasma levels (248+/-291 ng/ml) than patients with at least moderate improvement (316+/-253 ng/ml) despite comparable amisulpride doses (628+/-253 vs. 590+/-263 mg). Patients with EPS (14.6%) had significantly (P<0.05) higher amisulpride plasma levels (377+/-290 ng/ml) than patients without EPS (305+/-274 ng/ml) despite similar doses in both groups (595+/-266 vs. 594+/-246 mg). ROC analyses revealed significant predictive properties of amisulpride plasma levels (P<0.05) for non-response (AUC=0.65+/-0.05) and EPS (AUC=0.62+/-0.05), respectively. Daily amisulpride doses did not significantly predict non-response or EPS. Optimal amisulpride plasma level values to avoid non-response and EPS were 100 or 320 ng/ml, respectively. Analysis of clinical utility revealed that blood levels must be analyzed in 7 patients until one patient benefits from the TDM procedure by avoiding non-response or EPS. Although our results were mainly explorative, TDM of amisulpride seems very useful for clinical decision making.

Adolescent↗
PubMed2002

Effect of the amisulpride isomers on rat catalepsy.

The substituted benzamide amisulpride is currently administered in its racemic form. In the present study, the biochemical and cataleptogenic profiles of the two enantiomers (R+ and S-) were compared with those of the racemic mixture. Displacement binding studies showed that the (S-)-isomer possesses an higher affinity for dopamine D2-like receptor (K(i) 5.2+/-0.4 nM) compared to (R+)-amisulpride (K(i) 244+/-12 nM) and to (RS)-amisulpride (K(i) 9.8+/-0.8 nM). In contrast, (S-)-amisulpride binds the alpha(2)-receptor with an affinity (K(i) 1528+/-45 nM) lower than that of the (R+)-isomer (K(i) 375+/-34 nM) and of (RS)-amisulpride (K(i) 783+/-27 nM). The bar test was used to evaluate the catalepsy induced by each drug. (RS)-amisulpride induced catalepsy only at very high doses (>100 mg/kg, s.c.) whereas, (S-)-amisulpride produced a catalepsy at a lower dose (30 mg/kg, s.c.) and (R+)-amisulpride did not produce any catalepsy up to the dose of 75 mg/kg. Interestingly, (R+)-amisulpride reduced the catalepsy induced by (S-)-amisulpride (50 mg/kg, s.c.) or haloperidol (0.3 mg/kg, s.c.), at the doses of 50 or 30 mg/kg, respectively. These results indicate that the weak cataleptic properties of (RS)-amisulpride might partially rely on its (R+)-isomer and provide a further explanation for the atypical properties of amisulpride as an antipsychotic.

Amisulpride↗
PubMed1998

Effects of acute and repeated administration of amisulpride, a dopamine D2/D3 receptor antagonist, on the electrical activity of midbrain dopaminergic neurons.

Electrophysiological techniques were used to study the effects of amisulpride, a D2/D3 dopamine receptor blocker, on the activity of dopaminergic neurons in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA). Administration of single bolus doses of amisulpride (8-32 mg/kg i.v.) induced a dose-dependent increase in the basal activity of dopaminergic neurons, in both the SNc and the VTA. The effect of amisulpride was more evident in the VTA, where it elicited a maximal excitation of 38.5 +/- 12%, whereas in the SNc it caused a peak excitation of only 22.1 +/- 9.8%. Amisulpride also increased the bursting activity of dopaminergic neurons in the VTA but not in the SNc. Microiontophoretic application of amisulpride (10-40 nA) into the SNc and the VTA caused an increase in the basal firing rate of the majority of dopaminergic neurons sampled. The excitation induced by 40 nA amisulpride was more marked in the VTA (36.1 +/- 21%) than in the SNc (25.0 +/- 18%). Moreover, microiontophoretic amisulpride (40 nA) increased the bursting activity of dopaminergic neurons in the VTA only. Repeated administration of amisulpride (20 and 50 mg/kg i.p.) for 21 consecutive days produced a significant decrease in the number of spontaneously active dopaminergic neurons in the VTA but not in the SNc. Repeated admistration of haloperidol (0.5 mg/kg i.p. ) decreased the number of dopaminergic cells both in the SNc and the VTA. The effect of repeated admistration of amisulpride on the activity of VTA dopaminergic neurons was reversed by apomorphine, suggesting that these neurons were probably under a state of depolarization block. Taken together, these data confirm previous findings indicating that low doses of amisulpride preferentially increase dopaminergic transmission in the mesolimbic system. Moreover, results obtained from long-term experiments are consistent with clinical data indicating that amisulpride given at high doses is an effective antipsychotic agent, associated with a low incidence of extrapyramidal side effects.

Amisulpride↗