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PubMed2002

Comparative efficacy of SSRIs and amisulpride in burning mouth syndrome: a single-blind study.

INTRODUCTION: Although a significant amount of evidence indicates the efficacy of some antidepressants in treating psychogenic pain and somatoform disorder, very few studies have investigated their possible therapeutic action in burning mouth syndrome (BMS). The purpose of this 8-week, single-blind study was to provide preliminary data on the efficacy and tolerability of amisulpride and the selective serotonin reuptake inhibitors (SSRIs) paroxetine and sertraline for patients with BMS. METHOD: Seventy-six patients with BMS (diagnosed according to the criteria in the literature and integrating the Diagnostic Interview Schedule-Revised for a complete psychiatric assessment), with no possible local or systemic causes and without concurrent major depression, were randomly assigned to receive amisulpride (50 mg/day), paroxetine (20 mg/day), or sertraline (50 mg/day). Efficacy assessments included a visual analogue scale (VAS) for pain intensity, the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), and the Clinical Global Impressions scale (CGI). RESULTS: All 3 treatment regimens resulted in a significant improvement from baseline in burning mouth symptoms at week 8 as demonstrated by the quantitative (mean reduction in VAS, HAM-D, and HAM-A scores) and qualitative (percentage of responders) analyses. Amisulpride showed a shorter response latency than the SSRIs. No serious adverse events were reported, and the incidence of side effects did not differ among the 3 groups. None of the patients who received amisulpride withdrew from the trial, whereas withdrawal from the trial occurred within the first week of treatment in 11.5% of patients (N = 3) treated with paroxetine and in 21.7% of patients (N = 5) treated with sertraline. CONCLUSION: The data suggest that amisulpride and SSRIs may be effective treatments for BMS; they are equally effective and equally well tolerated in the short-term treatment of BMS. Amisulpride is associated with better compliance within the first week of treatment and with a shorter response latency in comparison with SSRIs. This finding may indicate that amisulpride is especially useful at the beginning of drug therapy of BMS. Double-blind, placebo-controlled trials are needed to further document the efficacy of amisulpride and SSRIs in the treatment of BMS.

Amisulpride↗
PubMed2000

Which role for amisulpride in rehabilitation of schizophrenic patients with acute exacerbation?

Amisulpride is a substituted benzamide derivative with selective binding to the D2/D3 dopamine receptor. In patients, a beneficial effect on negative signs has been demonstrated for doses up to 300 mg daily. On the other hand, amisulpride demonstrate efficacy in the treatment of classical form of schizophrenia at higher doses (400 to 800 mg/day up to 1,200 mg/day at the maximum). Five studies that included acutely ill schizophrenic patients are reviewed. All were double blind, randomized parallel group studies and the primary efficacy criterion was the BPRS total score. In these study amisulpride was at least as efficacious as haloperidol (10-30 mg), risperidone (8 mg daily), or flupentixol (25 mg daily) in controlling positive symptoms, but was significantly more effective than haloperidol on secondary negative symptoms. When quality of life (QLS) was assessed, amisulpride led to a better improvement than haloperidol. In the long term treatment of schizophrenia, amisulpride maintained antipsychotic efficacy over a 12-month period in an open randomized study. In this study, amisulpride led to a better improvement on Global Assessment of Functioning than haloperidol, the standard reference drug. Furthermore, amisulpride has a favorable benefit/risk profile and induces fewer extrapyramidal side effects than haloperidol the standard reference drug. Therefore, amisulpride is proposed for first-line treatment of schizophrenia in acute exacerbations. It contributes to favor a better social rehabilitation of schizophrenic patients.

Acute Disease↗
PubMedDate not supplied

[Treatment of negative symptoms in schizophrenia by amisulpride. Review of the literature].

The deficit forms of schizophrenia have given rise to important research and controversy for the last 15 years. It is now recognized that some negative symptoms in schizophrenia are part of a pure and primary deficit syndrome which could be related to decreased dopaminergic function and which is not well improved by standard antipsychotic drugs. Amisulpride is a substituted benzamide neuroleptic with an original pharmacologic profile. Prescription of high doses (600-1 200 mg/day) yields to an usual antipsychotic activity on positive symptoms, through the blockage of post-synaptic dopamine receptors. At low doses, amisulpride preferentially blocks presynaptic dopamine autoreceptors, with a poor affinity for striatal sites. Three recent double-blind placebo controlled studies have suggested an efficacy of low doses (50-300 mg/day) of amisulpride in deficit forms of schizophrenia. The first study was carried out in young never-treated schizophrenic patients, and showed a significant improvement of negative symptoms with a 6-week amisulpride treatment. In the second study, subjects with a long-course deficit schizophrenia were included after a 6-week wash-out period. Reduction of scores of negative symptoms (Andreasen's scale) was about twice as important in the amisulpride group compared to the placebo group, whereas positive symptoms, modest at inclusion, remained unchanged. Finally, the efficacy of amisulpride was shown in another double-blind long-term study over 6 months in patients with predominantly negative symptoms. The overall safety profile of amisulpride in these studies was good, in particular with a low incidence of extrapyramidal symptoms. Thus, amisulpride at low doses appeared to be a well tolerated treatment for various deficit forms of schizophrenia, with a short-term and long-term efficacy.

Amisulpride↗
PubMed2002

A review of the pharmacokinetics, tolerability and pharmacodynamics of amisulpride in healthy volunteers.

Amisulpride binds selectively to dopamine D(2) and D(3) receptors in the limbic system. Low doses of amisulpride preferentially block presynaptic D(2)/D(3)-dopamine autoreceptors, thereby enhancing dopaminergic transmission, whereas higher doses block postsynaptic receptors, thus inhibiting dopaminergic hyperactivity. Amisulpride is clinically effective on the negative symptoms of acute schizophrenia exacerbations at low dosages (50-300 mg/day), and also on the positive symptoms of the disease at high dosages (400-800 mg/day). Nineteen clinical studies involving 358 volunteers have investigated the pharmacokinetics, pharmacodynamics and tolerability of amisulpride. Amisulpride shows linear pharmacokinetics, a bioavailability of 48%, low protein binding (17%) and an elimination half-life of approximately 12 h. It is predominantly eliminated in the urine as the parent compound. It exhibits no significant detrimental effects in psychometric or memory tests up to the dose of 400 mg/day, inducing only mild impairment at high doses, whereas EEG data suggest an alertness-enhancing effect at low doses (<or= 50 mg). Moreover, amisulpride does not potentiate the depressant effects on the central nervous system of alcohol and lorazepam. This tolerability profile is clearly better than that of haloperidol 4 mg/day and is consistent with a weak blocking effect on striatal D(2) receptors. In summary, studies in humans have shown that amisulpride is free of behavioural toxicity at doses exerting clear antipsychotic efficacy and confirm that its CNS effects may vary with the dose administered.

Amisulpride↗
PubMed1997

Improvement of acute exacerbations of schizophrenia with amisulpride: a comparison with haloperidol. PROD-ASLP Study Group.

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.

Adult↗
PubMed2003

The antinociceptive effect of amisulpride in mice is mediated through opioid mechanisms.

Antinociceptive effects of various neuroleptics in animal acute pain-models have been described, mediated trough different pathways including the opioid system. In this study, we assessed the antinociceptive effects of the atypical neuroleptic drug amisulpride, which acts as a selective blocker of dopamine D2 and D3 receptors. Furthermore, at low doses amisulpride has a selective preference for presynaptic dopamine autoreceptors, while at high doses it manifests a preferential action at post-synaptic dopamine receptors. We found amisulpride to be a potent antinociceptor agent in the mouse tail-flick assay, with an ED50 of 36.6 mg/kg. This effect was antagonized by naloxone (P<0.05), indicating an involvement of opioid mechanisms as mediators of the antinociceptive effect of amisulpride. Beta-funaltrexamine (mu1- and mu2-opioid receptor antagonist), naloxonazine (selective mu1-opioid receptor antagonist), naltrindole (selective delta-opioid receptor antagonist), Nor-binaltorphamine (kappa1-opioid receptor antagonist) reversed amisulpride antinociception at the same dose that they antagonized morphine's antinociceptive effect (all P<0.005). We found that the sensitivity of amisulpride-induced antinociception is mediated through selective involvement of all three opioid receptor subtypes. Based on previous studies with risperidone, clozapine and olanzapine we tend to attribute this global interaction with the opioid system to amisulpride's action at the dopamine D2 receptor sites.

Amisulpride↗
PubMed2004

High striatal occupancy of D2-like dopamine receptors by amisulpride in the brain of patients with schizophrenia.

The 'atypicality' of the antipsychotic drug, amisulpride, has been attributed to preferential extrastriatal binding. Previous investigations of striatal D2 receptor occupancy by amisulpride revealed conflicting results. The aim of this PET study was to measure the striatal occupancy by amisulpride and to correlate it with the corresponding drug plasma concentrations. Nine amisulpride-treated patients and 12 healthy volunteers serving as controls were studied with PET and [18F]desmethoxyfallypride. Occupancy values and plasma concentrations were nonlinearly fitted to an E max model. Results showed 43-85% (putamen) and 67-90% (caudate) D2-like receptor occupancy. Plasma amisulpride concentrations at the time of tracer injection, but not administered doses, were significantly nonlinearly correlated to occupancy levels (putamen: rS=0.88, p=0.0017; caudate: r S=0.78, p=0.0127). Calculated Emax was similar in both caudate and putamen, but occupancy levels were lower in caudate at lower amisulpride plasma concentrations. Calculated plasma levels to attain 60-80% receptor occupancy ranged from 119 to 474 ng/ml (caudate) and from 241 to 732 ng/ml (putamen). This reveals a broad range of plasma concentrations producing less than 80% striatal receptor occupancy. However, our data show high striatal D2-like receptor occupancies under rising plasma concentrations. Using the full range of recommended amisulpride dosage, striatal occupancies up to 90% can be measured.

Adult↗
PubMed1999

Safety of amisulpride (Solian): a review of 11 clinical studies.

We assessed the overall safety profile of amisulpride based on the results from 11 clinical studies performed in patients suffering from schizophrenia with predominance of positive or negative symptoms. A total of 1933 patients were randomly assigned to treatment with amisulpride (n = 1247) or haloperidol (n = 309), risperidone (n = 113), flupentixol (n = 62) and placebo (n = 202). Safety data collection was performed using open reporting, UKU scales or specific extrapyramidal side-effect scales; electrocardiogram recording and vital signs examination; laboratory data collection. Amisulpride demonstrated a satisfactory global safety profile in the range of doses usually prescribed. The number of patients having at least one extrapyramidal side-effect was higher in haloperidol patients compared with both amisulpride and risperidone patients (50% versus 30% in the two latter groups). For endocrine events, a similar rate was observed between amisulpride and risperidone groups (4% versus 6%, respectively) versus 1% in the haloperidol group. Electrocardiogram results were satisfactory, confirmed by the absence of cardiovascular events. The overall laboratory safety profile of amisulpride did not show clinically relevant abnormalities in liver function tests nor haematological abnormalities. Our extensive clinical data confirm the satisfactory safety profile of amisulpride which is superior to standard reference compounds.

Adolescent↗
PubMed2004

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.

Acute Disease↗
PubMed2002

Amisulpride does not prevent relapse in primary alcohol dependence: results of a pilot randomized, placebo-controlled trial.

BACKGROUND: Few medications have been proved to be effective in preventing relapse in alcoholism. The mesolimbic dopamine system is known to play an important role in alcohol dependence. Amisulpride, a substituted benzamide, seems to facilitate dopaminergic neurotransmission at low doses. METHODS: After short-term, inpatient detoxification, 71 patients participated in a randomized, double-blind, placebo-controlled study to evaluate the efficacy of amisulpride in relapse prevention. Patients received amisulpride 50 mg/day or placebo for 6 months. RESULTS: There were no differences between the two groups of treatment for time to first drink, length of time before dropout, number of drinking days, and number of heavy drinking days. However, significantly more patients who were treated with amisulpride than those who were treated with placebo were nonabstinent and had relapsed at each visit. Craving for alcohol was significantly higher in the amisulpride than in the placebo group. Transaminases, gamma-glutamyl-transferase, and mean erythrocyte corpuscular volume were regularly higher in the amisulpride group than in the placebo group. CONCLUSIONS: The results indicate that treatment with amisulpride was not effective in preventing relapse to drinking in detoxified, alcohol-dependent patients. The significance of this finding is discussed, particularly in terms of the effects of neuroleptics on alcohol consumption.

Adult↗
PubMedDate not supplied

Augmentation with amisulpride for schizophrenic patients nonresponsive to antipsychotic monotherapy.

Despite the effectiveness of antipsychotic medications in treatment of schizophrenia, about 30% of patients who receive an adequate treatment have significant persisting symptoms. The problem of treatment-resistant psychosis is an important and difficult one. The aim of this study was to retrospectively evaluate the efficacy and safety of amisulpride augmentation in treatment-resistant schizophrenic patients. To the best of our knowledge, this is the first report about resistant schizophrenic and schizoaffective patients treated with the combinations of risperidone and amisulpride and ziprasidone and amisulpride. Data were collected from patient records. A total of 15 resistant schizophrenic patients (7 men, 8 women, 54.0 +/- 16.9 years old) were included in the study. Before addition of amisulpride, the patients were treated with monotherapy by atypical neuroleptics (clozapine, olanzapine, risperidone, or ziprasidone). The mean amisulpride dose was 693.3 +/- 279.6 mg/d. The mental state of 12 (80%) patients treated with combination was improved. Three (20%) patients showed no change in their mental state. Only 2 patients treated with a combination of risperidone and amisulpride had mild side effects. The results are preliminary and require confirmation in a randomized controlled trial. The authors suggest that amisulpride may be a promising option as an augmentation strategy in treatment-resistant schizophrenic patients.

Adult↗
PubMed2000

Safety profile of amisulpride in short- and long-term use.

OBJECTIVE: To assess the safety of the new atypical antipsychotic drug, amisulpride, in short- and long-term use. METHOD: Studies comparing the safety of amisulpride with that of haloperidol and risperidone, respectively, are reviewed. Safety was monitored by open adverse event reporting, the Simpson-Angus Scale, the Barnes Akathisia Scale and the Abnormal Involuntary Movement scale. RESULTS: In short- and long-term studies, amisulpride induced significantly less EPS and akathisia than haloperidol. Safety ratings were similar to risperidone in short-term studies. In studies of chronic schizophrenia with predominant negative symptoms, amisulpride was similar to placebo. Endocrine effects were similar in amisulpride-, haloperidol- and risperidone-treated patients. Weight gain with amisulpride was significantly less than risperidone in a short-term study. No clinically important effects on haematological, hepatic or cardiac function were recorded. Data obtained in short- and long-term studies have been confirmed in extensive post-marketing surveillance data. CONCLUSION: Amisulpride has a broad spectrum of efficacy in schizophrenia without introducing the iatrogenic consequences associated with older therapies.

Amisulpride↗
PubMed2006

Blockade of cue-induced brain activation of abstinent alcoholics by a single administration of amisulpride as measured with fMRI.

BACKGROUND: Once alcohol dependence is established, alcohol-associated cues may induce dopamine release in the reward system, which is accompanied by alcohol craving and may lead to relapse. In cocaine addicts, dopamine release in the thalamus was positively correlated with cocaine craving. We tested the effects of the atypical dopamine D(2/3) blocker amisulpride on cue-induced brain activation in a functional magnetic resonance imaging (fMRI) paradigm. METHODS: Alcohol-associated and neutral pictures were presented in a block design to 10 male abstinent alcoholics (1-3 weeks after detoxification) and 10 healthy men during fMRI. The fMRI scans were acquired before and 2 hours after the oral application of 400 mg amisulpride. Before and after each scan, alcohol craving was measured with visual analogue scales. RESULTS: Before the application of amisulpride, alcohol versus control cues elicited a higher blood oxygen level-dependent (BOLD) signal in the left frontal and orbitofrontal lobe, left cingulate gyrus, bilateral parietal lobe, and bilateral hippocampus in alcoholics compared with healthy controls. After amisulpride, alcoholics showed a reduced activation in the right thalamus compared with the first scan. Alcoholics no longer showed significant differences in their cue-elicited BOLD response after amisulpride medication compared with medication-free controls. Self-reported craving was not affected by amisulpride medication. CONCLUSIONS: Amisulpride medication was associated with reduced cue-induced activation of the thalamus, a brain region closely connected with frontostriatal circuits that regulate behavior and may influence relapse risk.

Adult↗
PubMed2004

Hyperprolactinemia after low dose of amisulpride.

OBJECTIVES: Amisulpride in antipsychotic doses can induce hyperprolactinemia. The aim of this study was to prove whether the same is true for low doses of amisulpride. METHODOLOGY: Plasma prolactin levels were measured in 5 males and 5 females with depressive symptoms who were treated with 50 mg of amisulpride per day as an augmentation to antidepressants (n=5), benzodiazepine anxiolytics (n=8) or in monotherapy (n=1). Six of these patients were assessed prior to onset of amisulpride treatment and after 10 days of amisulpride use. Four patients had been using amisulpride for more than a month. RESULTS: There was a significant increase of prolactin levels from mean 16+/-6 ng/ml to 113+/-65 ng/ml (median 14.5 ng/ml to median 92 ng/ml; Wilcoxon matched pair test, p=0.027). All patients had hyperprolactinemia (30-200 ng/ml). The prolactinemia was significantly higher in females (mean 160+/-50 ng/ml; median 198 ng/ml) than in males (mean 48+/-12 ng/ml; median 48 ng/ml; Mann-Whitney U test, p=0.041). CONCLUSION: Even low doses of amisulpride used as an augmentation to antidepressant treatment, benzodiazepines or in monotherapy seem to be associated with hyperprolactinemia. The co-medication of antidepressants and benzodiazepines can potentially increase intensity of prolactinemia.

Adult↗
PubMedDate not supplied

[Amisulpride, neuroleptic and antinegative action].

Amisulpride (Solian), a substituted benzamide derivative, is distinguished pharmacologically by its marked affinity for dopamine D2 receptors and its higher affinity for limbic and hippocampic as compared with striatal dopamine receptors. The originality of this molecule lies in its observed 2 opposed actions at 2 distinct dose levels. High amisulpride doses, antidopaminergic, inhibit, in animals, the hyperdopaminergic symptomatology considered equivalent to positive schizophrenia, whereas low doses, dopamine-releasing and activating, improve hypodopaminergic symptomatology of negative schizophrenia. The ratio of about 300 between activating and inhibiting doses demonstrates the clear dose-related dissociation of effects, this ratio being, furthermore, much higher than that of other neuroleptics possessing bipolar activity. In contrast to conventional neuroleptics, amisulpride possesses only weak sedative activity and practically lacks cataleptigenic effects. This twofold action has been confirmed in clinical practice by open and double-blind studies, demonstrating in each case the rapidity of action (by the end of the 1st week) and very good tolerance, notably neurological, of amisulpride. Clinical studies (5 open and 4 double-blind) in patients with psychosis and positive symptomatology, have demonstrated that high doses of amisulpride (Solian 200) are effective against overall positive symptomatology at doses of 600 to 1,200 mg/day, doses of less than 300 mg/day being ineffective or aggravating. Improvement is obtained without "damping effect", amisulpride being as effective as haloperidol in this indication with a significantly better tolerance. In patients with negative schizophrenia (4 open and 3 double-blind studies) the effective dosage of amisulpride (Solian 50) is about 150 mg/day, doses above 300 mg being ineffective or aggravating. Improvement is marked and occurs in all negative symptomatology.(ABSTRACT TRUNCATED AT 250 WORDS)

Amisulpride↗
PubMed1996

[The place of amisulpride in the atypical neuroleptic class].

Amisulpride is a benzamide derivative which displays a pharmacological profile distinct from that of classical neuroleptics such as haloperidol. In vitro, amisulpride selectively binds to dopamine (DA) receptors and is devoid of any affinity for serotonergic, alpha-adrenergic, histaminergic or muscarinic receptors. It has high and equal affinities for human D2 and D3 receptors, without affinity for D1 and D4 receptors. In vivo, in rats, amisulpride preferentially blocked D2 and D3 receptors localized in limbic structures in comparison with receptors found in the striatum. In addition, amisulpride selectively blocked presynaptic DA receptors. Thus, amisulpride antagonized apomorphine-induced effects (yawning, hypomotility) related to presynaptic DA receptor stimulation at very low doses (ED50 = 0.3-1 mg/kg, ip) compared to those needed to inhibit hypermotility and gnawing (60-80 mg/kg, ip) which involve post-synaptic DA receptor stimulation. The high affinity of amisulpride for D2 and D3 receptors, and its high degree of limbic selectivity may explain the lack of catalepsy in rats and the low incidence of neurological side effects in clinical studies. The enhancement of DA function produced by its selective presynaptic receptor DA blockade may account for the clinical efficacy of amisulpride against negative symptoms of schizophrenia.

Amisulpride↗
PubMed1997

Neurochemical characteristics of amisulpride, an atypical dopamine D2/D3 receptor antagonist with both presynaptic and limbic selectivity.

The benzamide derivative amisulpride shows a unique therapeutic profile being antipsychotic, at high doses, and disinhibitory, at low doses, while giving rise to only a low incidence of extrapyramidal side effects. In vitro, amisulpride has high affinity and selectivity for the human dopamine D2 (Ki = 2.8 nM) and D3 (Ki = 3.2 nM) receptors. Amisulpride shows antagonist properties toward D3 and both pre- and postsynaptic D2-like dopamine receptors of the rat striatum or nucleus accumbens in vitro. At low doses (< or = 10 mg/kg) amisulpride preferentially blocks presynaptic dopamine autoreceptors that control dopamine synthesis and release in the rat, whereas at higher doses (40-80 mg/kg) postsynaptic dopamine D2 receptor occupancy and antagonism is apparent. In contrast, haloperidol is active in all of these paradigms within the same dose range. Amisulpride preferentially inhibits in vivo binding of the D2/D3 antagonist [3H]raclopride to the limbic system (ID50 = 17 mg/kg) in comparison to the striatum (ID50 = 44 mg/kg) of the rat, increases striatal and limbic tissue 3,4-dihydroxyphenylacetic acid levels with similar potency and efficacy, and preferentially increases extracellular 3,4-dihydroxyphenylacetic acid levels in the nucleus accumbens when compared to the striatum. Haloperidol shows similar potency for the displacement of in vivo [3H]raclopride binding in striatal and limbic regions and preferentially increases striatal tissue 3,4-dihydroxyphenylacetic acid levels. The present data characterize amisulpride as a specific dopamine receptor antagonist with high and similar affinity for the dopamine D2 and D3 receptor. In vivo, it displays a degree of limbic selectivity and a preferential effect, at low doses, on dopamine D2/D3 autoreceptors. This atypical profile may explain the therapeutic efficacy of amisulpride in the treatment of both positive and negative symptoms of schizophrenia.

Acetylcholine↗
PubMedDate not supplied

[Use of atypical antipsychotics in Charles Perrens psychiatric hospital (Bordeaux) analysis of prescribing practices for Amisulpride, Clozapine, Olanzapine and Risperidone].

UNLABELLED: The commercial introduction of atypical antipsychotics (AAP) constitutes a considerable step forward in the sense that it has led to a world-wide reappraisal of the established treatment strategies for people with psychoses (including schizophrenia and affective psychoses). They have allowed refinements in the pharmacologic management of psychoses but they have a higher acquisition cost than conventional neuroleptics. The cost of the newer AAP had a substantial effect on medical resources: the AAP account for only 43.2% of neuroleptic prescriptions, but 76.1% of medical costs associated with neuroleptic drugs, and in terms of treatment costs, a reduction (50%) was found with risperidone compared with olanzapine for a same number of treated patients. The aim of this paper was to examine the use of these drugs, to compare them and to assess their impact within the context of psychiatric hospital practice, by means of analysis of prescribing practices for amisulpride, clozapine, olanzapine and risperidone for all treated patients. We conducted an observational, naturalistic study at Charles Perrens psychiatric Hospital in Bordeaux (France) that reproduced the clinical conditions in which these new drugs are used. Four photographies of all the medical prescriptions concerning atypical antipsychotic drugs were done between October 1999 (four months after the introduction in France of the olanzapine, the last of the new antipsychotics) and June 2001 (n=682 prescriptions). The total amount of these prescriptions corresponded to 527 patients. Treatment groups were compared - first overall and after by considering 2 groups: psychotic and non-psychotic patients - through descriptive analyses of sociodemographic characteristics of patients, diagnosis, percentages of patients receiving concomitant psychotropic medication and/or receiving treatment-emergent side effects and mean dosages of AAP therapy according to concomitant medication. In the same way, we compared the four AAP through their prescribing practices'evolution during the four survey. RESULTS: AAP drugs account for 43.2% of prescriptions (and conventional neuroleptics 56.8% of them). We recorded a significant increase between the four surveys (p<0.02): 36.6% at the beginning to 47.8% at the end of the study. From the 682 collected prescriptions, 72 (10.6%) included clozapine, 130 (19.1%) amisulpride, 229 (33.6%) olanzapine and 251 (36.8%) risperidone. Sixty five percent of AAP prescriptions involved psychotic patients. A relative stability in characteristics of AAP prescriptions during the four surveys was found. So, no significant differences were observed between amisulpride, olanzapine, risperidone, in terms of age, sex, sociodemographic characteristics, unlike clozapine. However, there were statistical differences between all the AAP in the concurrent use of other neuroleptic agents (p<0.02), hypnotic drugs (p<0.006), mood stabilizer drugs (p<0.03), and anticholinergic drugs (p<0.007). Statistically, the mean dosage of amisulpride increased when a mood stabilizer drug was coprescribed (p<0.0007), but it decreased with an antidepressant drug (p<0.004) or an hypnotic drug (p<0.02); clozapine 's one decreased every time an antidepressant drug was coprescribed (p<0.02); with olanzapine, there was a significant increase every time an other neuroleptic agent (p<0.03) or an anticholinergic drug (p<0.006) was associated; then for risperidone, the mean dosage increased with the coprescription of an other neuroleptic agent (p<0.00002), an anticholinergic (p<0.00003) or an adrenolytic drug (p<0.04). The pattern of prescribing practices that emerges from our four surveys suggests that these new AAP are significantly more and more often associated with a stabilizer mood drug (p<0.009) (particularly the olanzapine) or/and an anxiolytic drug (p<0.05) (like the amisulpride in particular). Considering the four AAP globally, but more with the risperidone, the association with a neurovegetative corrector agent decreased (p<0.004) during the four surveys. Then, concerning the psychoticng the four surveys. Then, concerning the psychotic patients, the AAP were significantly more often associated with other neuroleptic agents (p<0.03), the amisulpride in particular, with anticholinergic drugs (p<0.00005), but significantly less with mood stabilizer drugs (p<0.00003) principally the amisulpride and the risperidone, with antidepressant drugs (p<0.02) particularly the risperidone. This kind of survey, however it is too much rare, is very important because it shows the clinical conditions in which these new drugs are really used. The results show that AAP appear to be the replacements of the older neuroleptics used in the treatment of psychoses, including particularly schizophrenia, but also in the treatment of mood disorders, and they reflect actual clinical practices. Other surveys must be achieved to see if our study confirms the general trend concerning the use of these drugs and so as to reassess these prescribing practices.

Adolescent↗