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PubMed2004

Prolactinemia is uncoupled from central D2/D3 dopamine receptor occupancy in amisulpride treated patients.

RATIONALE: Atypical antipsychotic drugs are classically associated with lower propensity to extrapyramidal symptoms (EPS) and hyperprolactinemia than typical antipsychotic drugs. It has not been clarified why some atypical antipsychotic drugs, such as amisulpride, induce prolactin plasma concentration (PRL) elevation, but little EPS. Previous studies have found an association between striatal D2/D3 receptor occupancy and PRL in typical antipsychotic treated patients suggesting that PRL is a marker of central D2/D3 receptors blockade. OBJECTIVE: We have evaluated the relationship between PRL and central (striatum, temporal cortex and thalamus) D2/D3 receptor occupancy in amisulpride treated schizophrenic patients. METHODS: Single photon emission tomography (SPET) and [123I]-epidepride were used to determine D2/D3 receptor occupancy in eight amisulpride treated patients. PRL was measured concurrently with the scans. RESULTS: The mean PRL was 1166 (range 499-1892 mIU/l) for a mean amisulpride dose of 406 mg/day (range 150-600 mg/day). Amisulpride plasma concentration and central D2/D3 receptor occupancy were positively correlated (r=0.83-0.89, df=4, P<0.05). No significant correlations were observed between PRL and amisulpride (daily dose or plasma concentration, P>0.05), or between PRL and central D2/D3 receptor occupancy (P>0.05). CONCLUSIONS: Our findings show that amisulpride-induced hyperprolactinemia is uncoupled from central D2/D3 receptor occupancy. Amisulpride has poor blood-brain barrier penetration and reaches much higher concentration at the pituitary, which is outside the blood-brain barrier. Higher D2/D3 receptor occupancy at the pituitary gland than at central regions is a possible explanation for amisulpride PRL elevation with low EPS. Further studies evaluating pituitary D2/D3 receptor occupancy in vivo are necessary to confirm this hypothesis.

Adult↗
PubMed1996

Single oral doses of amisulpride do not enhance the effects of alcohol on the performance and memory of healthy subjects.

OBJECTIVES: Amisulpride is a benzamide antipsychotic that binds selectively to dopamine D2- and D3-receptors, preferentially in limbic and hippocampal structures. Since other substituted benzamides have a limited or negligible interaction with alcohol on human performance, amisulpride was studied for this potential. METHODS: In a randomised double-blind crossover study, 18 young, non-smoking men took single oral doses of placebo and amisulpride 50 mg and 200 mg, without and with ethanol (0.8 g. kg-1) taken 30 min later. Objective performance tests and self-ratings were done at baseline and 1.5, 3.5 and 6.5 h after drug intake. Memory (immediate and delayed recall) was tested 2 h after dosing. Breath ethanol and the plasma concentrations of amisulpride and prolactin were measured. Three-way ANOVA + Newman-Keul tests were used for statistical analyses; interactions were confirmed by factorial contrast ANOVA. RESULTS: Mean blood ethanol was 0.94, 0.62 and 0.26 g.1(-1) at the three test times. It produced significant impairment in all performance tests (symbol digit substitution, simulated driving, body sway, flicker fusion, tapping, nystagmus), reduced both immediate and delayed recall in memory tests, and caused subjective clumsiness, muzziness and mental slowness, mainly between 1.5 to 4.5 h after dosing. Amisulpride, 50 and 200 mg elevated plasma prolactin but had minimal or no effect on performance, attention and memory. The decreases in immediate free recall after the 50 mg dose and in delayed free recall after the 200 mg dose were slight. Amisulpride neither modified blood ethanol concentrations nor enhanced the detrimental effect of ethanol on skilled and cognitive performance; it slightly antagonised ethanol in the digit copying test. Ethanol did not modify the effect of amisulpride on plasma prolactin, and the plasma concentrations of amisulpride were little changed by ethanol. CONCLUSIONS: Amisulpride in single oral doses of 50 and 200 mg did not interact significantly with the effects of high, moderate or low concentrations of ethanol on human skilled and cognitive performance. The drugs did interact pharmacokinetically.

Adult↗
PubMed2006

Amisulpride-induced hyperprolactinemia is reversible following discontinuation.

BACKGROUND: Although amisulpride is considered to be a prolactin-raising atypical antipsychotic drug, a limited number of studies have documented the extent of its prolactin-elevating properties. In the present study the effect of amisulpride on plasma levels of prolactin and the reversibility of this untoward side effect were investigated. METHODS: 17 patients with various diagnoses received amisulpride (50-800 mg/day) or a combination of amisulpride plus other medication as needed. Plasma prolactin was determined 26.7+/-9.4 days (range: 13-50 days) after initiation of treatment and in 3 cases after a much longer period, and 14-51 days following its withdrawal. RESULTS: All patients on amisulpride had hyperprolactinemia (mean+/-S.D. prolactin levels: 62.5+/-33.0 ng/ml) with females exhibiting considerably higher prolactin levels than males. Following amisulpride discontinuation prolactin levels were significantly (p<000) reduced (mean+/-S.D. prolactin levels: 12.3+/-6.7 ng/ml). No significant correlation was detected between prolactin levels and either amisulpride dosage or duration of administration. CONCLUSION: Amisulpride has a pronounced prolactin-elevating effect which appears to be independent of dosage and duration of administration. Hyperprolactinemia rapidly reverses following amisulpride discontinuation.

Adult↗
PubMed1999

Psychomotor, Cognitive, extrapyramidal, and affective functions of healthy volunteers during treatment with an atypical (amisulpride) and a classic (haloperidol) antipsychotic.

The primary objective of this study was to compare the objective and subjective effects of amisulpride with those of a classic antipsychotic, haloperidol, when both were given to healthy volunteers in representative therapeutic doses over 5 days. The secondary objective was to compare the effects of relatively low and high doses of amisulpride to confirm the suspected duality of its pharmacologic activity. Twenty-one subjects participated in the four-way, randomized, double-blind, crossover study with repeated daily doses of amisulpride 50 mg, amisulpride 400 mg, haloperidol 4 mg, and placebo. Subjects were institutionalized during treatment periods and were under 24-hour medical supervision. They underwent a series of psychomotor and cognitive tests 1 hour before and 3 and 6 hours after dosing on days 1 and 5. Their extrapyramidal disturbances and drug-related feelings were assessed at the end of each replication. Psychiatric interviews and ratings of depression, subjective well-being, and negative symptoms occurred on day 4. Amisulpride 50 mg had no significant effect on any parameter. Amisulpride 400 mg had several adverse effects on psychomotor and, although less severe, on cognitive performance on the fifth day only. Amisulpride 400 mg produced no significant extrapyramidal disturbances in the group as a whole, although it may have in some individual subjects. Also, it produced no signs of mental disturbances on clinical rating scales or during a structured psychiatric interview. Haloperidol ubiquitously impaired psychomotor and cognitive performance in a similar fashion after the first and the final doses. It produced extrapyramidal disturbances in nearly every subject, the most common being akathisia and the most severe, in the case of one individual, being acute dystonia. Unlike amisulpride, haloperidol produced a number of mental disturbances, the most noteworthy being negative symptoms. Amisulpride seems to be a well-tolerated drug. Its side effects should be much less troublesome to patients using the drug on a long-term basis than those of classic antipsychotics, like haloperidol.

Adult↗
PubMed1999

Effects of 50mg amisulpride on EEG, psychomotor and cognitive functions in healthy sleep-deprived subjects.

Amisulpride, a substituted benzamide, binds selectively to the dopamine D2- and D3-receptors. It has higher affinity for limbic compared to striatal dopamine receptors in vivo. At low doses, amisulpride facilitates dopamine transmission via a selective blockade of presynaptic D2- and D3-receptors. Amisulpride is an active antipsychotic compound effective at low doses for negative symptoms and at high doses for positive symptoms of schizophrenia. The CNS profile of multiple doses of a low dosage regimen of amisulpride (50 mg once daily for 4 days) was assessed in a randomised, double-blind, 3-way crossover, placebo-controlled study carried out in 12 young sleep-deprived (for 36 h) subjects, using EEG and various measures of psychomotor and cognitive functions. Caffeine slow release (600 mg) was used as a positive reference. Multiple doses of 50 mg amisulpride once daily were devoid of any detrimental effects on EEG and psychomotor performance and cognitive function after total sleep deprivation. In addition, 50mg amisulpride partially antagonized the deleterious effects of sleep deprivation on EEG and subjective sedation as shown by trends, and a significant increase in EEG relative beta power and a decrease in subjective sedation. These effects were more pronounced at the end of sleep deprivation, suggesting possible alerting effects of amisulpride at this dose level. Caffeine significantly antagonized the detrimental effects of sleep deprivation on vigilance (increase in EEG beta waves, speed of reaction, sustained attention and reduction in subjective sedation). In conclusion, the present results demonstrate that 50 mg amisulpride is devoid of detrimental effects on EEG, psychomotor and cognitive performance after sleep deprivation, a situation well-known to amplify such effects if they exist. Moreover, some data suggest possible alerting effects of this low dosage regimen of amisulpride.

Adult↗
PubMed2002

Amisulpride, an unusual "atypical" antipsychotic: a meta-analysis of randomized controlled trials.

OBJECTIVE: The "atypical" profile of the new antipsychotics clozapine, olanzapine, quetiapine, and risperidone has been linked to combined antagonism of serotonin 2 (5-HT(2)) and dopamine 2 (D(2)) receptors. Although amisulpride is a highly selective D(3)/D(2) receptor antagonist, it is assumed to have atypical properties as well. The purpose of this article was to compare the atypical profile of amisulpride with that of the 5-HT(2)/D(2) antagonists. METHOD: Randomized controlled trials that compared amisulpride with conventional antipsychotics or placebo for patients with schizophrenia were identified and included in a meta-analysis. The mean effect sizes found for amisulpride were compared with those of an updated meta-analysis of the 5-HT(2)/D(2) antagonists. RESULTS: Eighteen randomized controlled trials of amisulpride (N=2,214) were found. In 11 studies of acutely ill patients it proved to be consistently more effective than conventional antipsychotics for global schizophrenic symptoms (measured with the Brief Psychiatric Rating Scale) and negative symptoms. Amisulpride is to date the only atypical antipsychotic for which several studies of patients suffering predominantly from negative symptoms have been published. In four such studies amisulpride was significantly more effective than placebo. Three small studies with conventional antipsychotics as comparators showed only a trend in favor of amisulpride in this regard. Amisulpride was associated with clearly lower use of antiparkinsonian medication and with fewer dropouts due to adverse events than conventional antipsychotics. CONCLUSIONS: These results cast some doubt on the notion that combined 5-HT(2)/D(2) antagonism is the reason that the newer antipsychotic medications are effective for negative symptoms and have fewer extrapyramidal side effects.

Amisulpride↗
PubMed2000

Antidepressant-like activity of amisulpride in two animal models of depression.

Clinical reports suggest that amisulpride, in addition to its antipsychotic efficacy, may also have antidepressant properties. The present study was designed to evaluate potential antidepressant-like activity of amisulpride in two behavioural procedures: the forced swim test (FST) and the chronic mild stress (CMS) model. The duration of immobility time in FST was reduced by subchronic (three injections over a 24 h period) administration of imipramine (10 mg/kg) and amisulpride (1 and 3 mg/kg), although the effect of imipramine was more potent. The 5 mg/kg dose of amisulpride was marginally effective and higher doses of 10 and 30 mg/kg were inactive. In CMS, the stress-induced decrease in the consumption of 1% sucrose solution was gradually reversed by chronic treatment with imipramine (10 mg/kg) and amisulpride (5 and 10 mg/kg). Lower (1 or 3 mg/kg) or higher (30 mg/kg) doses of amisulpride were inactive. The magnitude of the effect of active doses of amisulpride in the CMS model was comparable to that of imipramine but its onset of action was faster; at the most active dose of 10 mg/kg, amisulpride significantly increased the sucrose intake in stressed animals within 2 weeks of treatment while imipramine required 4 weeks before first effects on the stress-induced deficit in sucrose consumption could be observed. These results provide further support for clinical observations that amisulpride may possess potent and rapid antidepressant activity.

Amisulpride↗
PubMed2002

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.

Amisulpride↗
PubMed1997

Amisulpride versus placebo in the medium-term treatment of the negative symptoms of schizophrenia.

BACKGROUND: Amisulpride is a substituted benzamide with high selectivity for dopamine D2 and D3 receptors. The purpose of the study was to evaluate the effect of 100 mg amisulpride in patients with predominantly negative symptoms of schizophrenia. METHOD: This was a multi-centre, randomised, parallel-group, double-blind study. Patients received either amisulpride (100 mg/day) or placebo over a six-month treatment period. RESULTS: A total of 141 patients were included, 69 received amisulpride, 72 placebo. Fifty-eight patients (41%) had received neuroleptic treatment prior to inclusion. The percentage of amisulpride patients completing the study (55%) was significantly higher than that with placebo (32%), and drop-out rates due to lack of efficacy were 27% with amisulpride and 47% with placebo. All efficacy assessments were statistically in favour of amisulpride compared with placebo. The overall incidence of extrapyramidal symptoms was comparable in both groups; only five patients started anti-Parkinsonian treatment during the study (one in the placebo and four in the amisulpride group). CONCLUSION: Amisulpride is effective in the medium-term treatment schizophrenic patients with predominantly negative symptoms.

Adult↗
PubMed2005

D2 receptor occupancy during high- and low-dose therapy with the atypical antipsychotic amisulpride: a 123I-iodobenzamide SPECT study.

UNLABELLED: Amisulpride appears to be an effective agent for treating positive or negative symptoms of schizophrenia, depending on dose. The aim of this study was to assess striatal dopamine D(2) receptor availability by means of (123)I-iodobenzamide (IBZM) SPECT in patients treated with high and low doses of this atypical antipsychotic drug. METHODS: Twenty-nine patients (19 men and 10 women, age range, 19-68 y) with schizophrenia treated with high doses (15 patients; 400-1,200 mg/d; mean dose, 666.7 +/- 219.3 mg/d) or low doses (14 patients; 50-300 mg/d; mean dose, 228.6 +/- 93.5 mg/d) of amisulpride were examined. For assessment of plasma amisulpride concentration, blood samples were taken. Brain SPECT was performed 2 h after intravenous injection of 185 MBq of (123)I-IBZM. For semiquantitative evaluation, transverse slices corrected for attenuation (Chang's first-order method) were used to calculate specific binding in the striatum, with the frontal cortex used as background. RESULTS: In all patients treated with amisulpride, specific binding of (123)I-IBZM to D(2) receptors was significantly lower (P < 0.001) than in healthy controls (0.95). Both groups treated with amisulpride differed significantly in specific binding of (123)I-IBZM to dopamine D(2) receptors (0.20 vs. 0.31, P < 0.05). D(2) receptor blockade correlated well with the administered dose of amisulpride and with amisulpride plasma concentration. CONCLUSION: Our findings suggest that amisulpride treatment leads to a significant occupancy of postsynaptic dopamine D(2) receptors. The blockade of D(2) receptors tends to be significantly lower in patients receiving low-dose amisulpride therapy than in patients receiving high-dose therapy.

Adult↗
PubMed1997

Psychopharmacological profile of amisulpride: an antipsychotic drug with presynaptic D2/D3 dopamine receptor antagonist activity and limbic selectivity.

Amisulpride, a benzamide derivative, is an antipsychotic drug with a pharmacological profile distinct from that of classical neuroleptics such as haloperidol and from that of another benzamide, remoxipride. In mice, amisulpride antagonized hypothermia induced by apomorphine, quinpirole or (+/-) 7-hydroxy-2-(di-n-propylamino)-tetralin, an effect involving D2/D3 receptors, at similar doses (ED50 approximately 2 mg/kg i.p.), which were much lower than doses that blocked apomorphine-induced climbing, an effect involving postsynaptic D2 and D1 receptor activation (ED50 = 21 mg/kg i.p.). Much higher doses (ED50 = 54 mg/kg i.p.) of amisulpride were needed to block grooming behavior observed after a short period in water, a D1 receptor-mediated behavior. In rats, amisulpride preferentially inhibited effects produced by low doses of apomorphine (hypomotility and yawning), related to stimulation of presynaptic D2/D3 dopamine autoreceptors (ED50 = 0.3 and 0.19 mg/kg i.p.). By contrast, amisulpride antagonized apomorphine-induced hypermotility, a postsynaptic dopamine receptor-mediated effect, at a much higher dose (ED50 = 30 mg/kg i.p.). Amisulpride (100 mg/kg i.p.) only partially inhibited apomorphine-induced stereotypies (gnawing) and had no effect on stereotypies induced by d-amphetamine. However, d-amphetamine-induced hyperactivity was antagonized by doses of amisulpride as low as 3 mg/kg i.p., which may indicate selectivity of this drug for limbic dopaminergic mechanisms. In addition, in contrast to haloperidol or remoxipride, which produced catalepsy at doses 2 or 3 times higher than those that antagonized stereotypies induced by apomorphine, amisulpride did not induce catalepsy up to a dose of 100 mg/kg i.p., which occupies 80% of striatal D2 receptors. This pharmacological profile of amisulpride, characterized by a preferential blockade of effects involving presynaptic mechanisms and limbic structures, may explain the clinical efficacy of this drug against both negative and positive symptoms of schizophrenia and its low propensity to produce extrapyramidal side effects.

Amisulpride↗
PubMed2006

An open label follow-up study on amisulpride in the add-on treatment of bipolar I patients.

BACKGROUND: Atypical antipsychotics are widely used in the treatment of bipolar disorders. Amisulpride is an atypical antipsychotic that has been proven to be effective in treatment of schizophrenia, major depressive disorder and, more recently, acute mania. At the moment, however, no study has assessed the effectiveness of this compound in maintenance therapy of bipolar disorders. The purpose of this study was to assess the long-term effectiveness of amisulpride in combination with standard treatments in patients with bipolar I disorder who have shown inadequate responses to ongoing standard therapies. METHODS: The study enrolled fourteen bipolar I outpatients, not responding to ongoing standard therapy. Three patients discontinued treatment but 11 were followed-up for 11.7 +/- 8.2 months before (range 3-24 months) and 5.2 +/- 2.7 months after the introduction of amisulpride (range 3-9 months). Relapse rates before and during treatment with amisulpride were calculated in accordance to an increase of 1 or more in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) score that was accompanied by a change in therapy or to an exacerbation of the symptoms that required hospitalization. RESULTS: A statistically significant decrease in overall relapse rate was observed during the period of amisulpride therapy compared with months previous to the introduction of amisulpride. The relative risk of relapse in the absence of amisulpride therapy was 3.1 (chi2 = 4.2, P < 0.05). Similarly, the rates of manic/mixed and depressive relapse were decreased but only manic episodes reached statistical significance (RR = 5.3, chi2 = 5.2, P < 0.02). DISCUSSION AND CONCLUSION: This open-label study suggests that long-term therapy with amisulpride may benefit patients by improving global symptoms of bipolar disorder and reducing the rate of manic/mixed relapses. Large, randomized, double-blind, placebo-controlled studies are needed to explore the benefits of adding long-term amisulpride to standard therapies for bipolar disorder.

Journal Article↗
PubMed2003

Amisulpride: limbic specificity and the mechanism of antipsychotic atypicality.

Amisulpride clearly has the clinical profile of an atypical antipsychotic, characterised in particular by its lower propensity to induce extrapyramidal side effects as well as its greater efficacy in treating negative symptoms compared with classical neuroleptics. In addition to the clinical advantages over classical neuroleptics, it has also been demonstrated that the clinical profile of amisulpride is comparable to that of other modern atypical neuroleptics. Animal data also allow the conclusion to be drawn that amisulpride has an atypical profile. For example, amisulpride does not provoke catalepsy which is characteristic of postsynaptic D2 blockade in the rat. The induction of catalepsy in animal models is usually seen as an indicator of the propensity to induce extrapyramidal side effects in patients. In relation to the widely accepted hypothesis that the inclusion of 5-HT2A antagonism in addition to D2 antagonism is of great relevance for the atypicality of an antipsychotic, and given the fact that amisulpride lacks 5-HT2A antagonism, the pharmacological explanation of the clinically well-proven atypicality of amisulpride is of great interest. Based on basic research and in vivo imaging studies, two mechanisms in particular seem to explain the atypicality of amisulpride: preferential action on limbic D2/D3 receptors and preferential blockade of presynaptic D2/D3 receptors. In addition, the fast dissociation hypothesis can contribute to the explanation of the atypical clinical profile of amisulpride. The relevance of the D3 blockade in the context of atypicality is not yet completely clear.

Amisulpride↗
PubMed2005

Cost analysis of treating schizophrenia with amisulpride: naturalistic mirror image study.

The aim of the study was to examine the costs of schizophrenia treatment using the atypical antipsychotic amisulpride relative to treatment with other antipsychotics. Service use data were collected for one year of amisulpride treatment. The patients were also assessed with the Global Assessment of Functioning (GAF) scale and scales of Quality of Life. These were compared with retrospectively collected data for the 1-year period prior to the patients commencing amisulpride. The findings indicate that, compared with the year before, the clinical and quality of life scores improved during the year of treatment with amisulpride. There was a numerical reduction of total costs, as well as costs of in- and out-patient service use per patient per year during the year on amisulpride compared with the year before the patients started amisulpride. Patients on amisulpride spent fewer days as acute in-patients, but stayed longer in rehabilitation wards. Amisulpride treatment may lead to a reduction in the cost of treating schizophrenia in comparison with treatment with other antipsychotic medications.

Adult↗
PubMed2004

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.

Amisulpride↗
PubMed1997

Clinical update on amisulpride in deficit schizophrenia.

Amisulpride is an atypical antipsychotic drug. Low doses increase dopaminergic transmission via presynaptic blockade and are effective in patients with predominantly negative (deficit) symptoms of schizophrenia. In three double-blind studies, two short-term and one medium/long-term, comparing amisulpride with placebo, 272 patients with schizophrenia were carefully selected for a predominance of negative symptoms (low severity of positive symptoms, depression and extrapyramidal side effects). Fixed daily doses of amisulpride (100 and 300 mg) were used in a 6-week dose-range finding study (104 patients). Daily doses of between 50 and 100 mg amisulpride were used in a second 6-week study (27 patients), and in a third study, 100 mg amisulpride was administered for 6 months (141 patients) with an extension of up to 1 year. Mean total scores for the Scale for the Assessment of Negative Symptoms (SANS) at baseline in the different treatment groups varied from 98 to 74, and improved significantly in the amisulpride groups (mean change from 24 to 40 points) compared with the placebo groups. Positive symptoms measured by the Scale for the Assessment of Positive Symptoms (SAPS) were low at baseline, and the change at the end of the studies was minimal. Extrapyramidal side effects were of low severity in these studies and parkinsonism scores for amisulpride were not different from placebo. Overall, these findings indicate that the improvement in negative symptoms was not linked to a concomitant improvement in positive symptoms, parkinsonism or depressive symptoms as would be expected in the case of secondary negative symptoms. The results of these studies thus confirm the efficacy of amisulpride in schizophrenic patients with primary negative or deficit symptoms at a dose of 100 mg/day.

Adult↗
PubMed2002

Long-term effects of the substituted benzamide derivative amisulpride on baseline and stimulated prolactin levels.

In the present study, we investigated the long-term effects of treatment with amisulpride, a substituted benzamide derivative, as compared with the effects of treatment with flupenthixol, a thioxanthene, on the prolactin levels in schizophrenic patients. After completing 6 weeks of medication with either amisulpride or flupenthixol, the patients entered a long-term maintenance treatment with amisulpride 200-600 mg/day or flupenthixol 5-15 mg/day for a maximum of 12 months with a subsequent drug-free follow-up until month 15. Eighteen initially included patients were still participating in the study at month 6. In the flupenthixol group, only 1 patient treated reached month 12, and none of the patients reached month 15. For the amisulpride treatment group, months 12 and 15 were completed by 9 and 6 patients, respectively. After 1, 3, 6, and 12 months of treatment, and finally 3 months after cessation of treatment, the basal and thyrotropin-releasing hormone-stimulated secretions of prolactin were investigated. The prolactin plasma levels were elevated in both treatment groups during the course of maintenance treatment with a maximum effect at month 1. Flupenthixol treatment initially raised the prolactin levels about two- or threefold, and a subsequent decline during months 3 and 6 occurred. However, only the changes for month 1 reached the level of a statistical trend. The prolactin secretion was initially increased over tenfold by amisulpride. The prolactin levels at months 1, 3, 6, and 12 were significantly elevated as compared with the baseline values. A continuous decline of prolactin levels in both treatment groups occurred over the course of the next months. The prolactin response after the thyrotropin-releasing hormone challenge was not significantly changed over the long-term course. Notably, in the amisulpride group, 3 months after cessation of treatment at month 12, the elevated levels of prolactin returned to baseline at month 15. In summary, amisulpride demonstrated more pronounced effects than flupenthixol on the prolactin levels. However, the findings indicate also that treatment with amisulpride at clinically effective doses can be achieved at significantly lower prolactin levels during the long-term maintenance phase than during the prior acute phase.

Adult↗
PubMed1999

Amisulpride in medium-term treatment of dysthymia: a six-month, double-blind safety study versus amitriptyline. AMILONG investigators.

Two hundred and fifty patients participated in a 6-month, double-blind study to evaluate safety and efficacy of a medium-term treatment with amisulpride 50 mg/day versus amitriptyline 25-75 mg/day in dysthymia. Patients in treatment groups (165 amisulpride; 85 amitriptyline) were well balanced for demographic and baseline characteristics. A total of 139 patients (93 amisulpride, 46 amitriptyline) completed the study with no statistically significant differences in reasons for premature termination between the two groups. A tendency towards a higher incidence of treatment-emergent adverse events with amitriptyline was observed (73% versus 64% amisulpride). In the amitriptyline group, a statistically significantly higher incidence of central nervous system (41% versus 24%, p=0.004) and autonomic nervous system disorders (45% versus 16%, p < 0.0001) was reported. Conversely, endocrine disorders were more frequent with amisulpride (18% versus 7%, p=0.023). Efficacy was a secondary end-point. Results of the symptom rating scales indicate that both drugs were equally effective: 60% and 62% of patients under amisulpride and amitriptyline, respectively, achieved a reduction > or = 50% of the Montgomery and Asberg Rating Scale total score at end-point. On the item 'global improvement' of the Clinical Global Impression, 67% of amisulpride and 68% of amitriptyline patients were rated as 'very much' or 'much' improved. Results of the present study in a large patient population further confirm the safe use of amisulpride in dysthymia and support its administration upon a medium-term treatment period.

Adult↗