In order to assess the therapeutic efficacy of amisulpride in dysthymic disorder, two randomised double-blind trials were conducted in France. Both studies included outpatients meeting DSM-III-R criteria for primary dysthymia. Cases of double depressed patients with a mild or moderate major depressive episode superimposed to dysthymia were also eligible. The first study of a three-month duration compared amineptine (200 mg/day) to amisulpride (50 mg/day) and placebo. The second study of a six-month duration compared the therapeutic effects of imipramine (100 mg/day) to amisulpride (50 mg/day) and placebo. Results of the intention to treat analysis and of the end-point analysis were compelling and very similar: significant differences were demonstrated for all primary criteria between amisulpride and placebo and between imipramine and placebo but not between amisulpride and imipramine. For both primary criteria and the responder rate (CGI), statistically significant differences were evidenced between amisulpride and placebo and amineptine and placebo. The same differences were evidenced for SANS subscores. Beneficial effects of low doses of amisulpride in chronic depressive condition can therefore be discussed.

A naturalistic study was conducted in general practice in Portugal on the efficacy and tolerance of low doses of amisulpride in the treatment of dysthymia. A total of 109 patients received low doses (50 – 100 mg) of amisulpride for four weeks. A global evaluation showed good or very good efficacy and tolerance in more than 80% of the patients. The social disability observed at baseline was significantly improved after the four-week treatment period. Few adverse events were observed and only four patients dropped out due to side effects. Our results suggest that low doses of amisulpride might be a safe and effective treatment for dysthymia in clinical practice.

It is not clear whether patient's psycho-education enhances compliance to antipsychotic treatments and reduces the number of relapses. Here we investigated the impact of a new psycho-educational program (SOLEDUC®) on the one- and two-years rate of relapse (primary outcome measure) and a number of clinical assessments (secondary outcome measures). This was a multicentric French clinical trial (51 centers) of Phase IV, open, controlled, randomized, consisting in two parallel groups: the Soleduc group (N = 111) and the control group (N = 109). All subjects received a variable dose over the 2-year period of the same antipsychotic drug (amisulpride). Soleduc consisted of a 7-session program (1 h per session), presented three times (at baseline, 6-months and 12-months). Patients in the control group received a non-specific psychosocial training for an equivalent period of time. The models of Andersen-Gill (AG) and Prentice, Williams and Peterson (PWP) were used to analyze relapses. Patients in the Soleduc group attended 14.8 ± 6.1 sessions (mean ± SD), including 17 patients who never attended a session. Intent to treat analysis showed less patients relapsing in the Soleduc group as compared to the control group (21.6% versus 28.4% after 1 year and 84.4% versus 90.8% after 2 years), but the differences were not statistically significant. Relapse risk was significantly reduced for patients who followed at least 7 modules (p = 0.015 AG-test; p < 0.001 PWP-test). In conclusion, no significant differences in relapse rates were found between patients attending the Soleduc program and the control group. Attendance of at least 7 out of 21 program sessions was required to see a modest, but significant two-year relapse prevention in schizophrenia. Other well designed studies are required to evaluate the medical impact of patient's education programs.

The objective of this study was to assess switching to amisulpride (AMS) in treatment-resistant schizophrenia. Seven male subjects were switched to AMS and followed for 8 weeks. PANSS scores improved from 123 to 66 over this period. We conclude that AMS is of interest in the treatment of refractory schizophrenia.

More than half of all patients consulting at public health facilities in Cali, Colombia have been shown to present mental disorders, the majority of which were non-psychotic; there is a high female preponderance amongst the affective disorders. As in other developing countries, in Colombia depressive disorders tend to present as somatic complaints, rather than as mood disturbances. The nomenclature used to describe these disorders is poorly codified, with most patients classed as “neurotic” or “depressed”; the diagnosis of “dysthymia” is very seldom encountered. Mental disorders are frequently misdiagnosed in primary care settings; when identified, treatment of depression by GPs generally involves TCAs or MAOIs, sometimes in conjunction with anxiolytics or neuroleptics. Only very severe cases are referred to psychiatrists, and many patients purchase drugs upon the recommendation of a pharmacist. Diagnostic trends and treatment results of a comparative study of amisulpride and viloxazine carried out in 80 patients assessed by DSM III-R criteria are reported.

The results of early therapeutic trials (1960s and 70s) in mild chronic depression (neurotic patients) are difficult to extrapolate to dysthymia. Most studies conducted in the early 1980s showed reference drugs (TCAs and MAOIs) to be poorly effective in chronic mild depression usually defined with RDC. The most recent trials using DSM-III-R criteria for dysthymic recruitment showed TCAs, new MAOIs (RIMA) and SSRI to be effective. AU these compounds have a rather similar pharmacological mechanism of action. It is therefore of both practical and theoretical interest that amisulpride, a benzamide derivative blocking D2 and D3 pre-synaptic receptors, has been found effective in the treatment of dysthymia in different placebo and reference controlled trials. This result is in line with the pharmacological data on animal ‘anhedonic models’.

The efficacy and safety of low doses of amisulpride (50 mg/day) and of fluoxetine (20 mg/day) were compared respectively in 139 and 129 outpatients with dysthymia during three months in a multi-centre double-blind trial. No statistically significant difference between the two groups was found in the number of responders at study-end with the Montgomery and Asberg Depressive Rating Scale, which was the main criterion for efficacy. In addition, amisulpride was well tolerated. These preliminary results suggest that low doses of amisulpride may be effective in the treatment of dysthymic patients.

Treatment-resistant schizophrenia often leads to combined application of antipsychotic drugs. We report first experience with the combination of olanzapine and amisulpride. Improvement of psychopathological state and side effects could be achieved, and drug doses were lower than under monotherapy. We thus conclude that this approach represents a useful therapeutic option.

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.

In terms of the phenomenology of schizophrenia, there are four targets for drug treatments: positive symptoms, negative symptoms, affective dysfunction, and cognitive dysfunction. Because of the side-effects of both conventional antipsychotics and the new atypicals, there still is a need to search for better-tolerated antipsychotics. Conventional antipsychotics have two principal limitations: 30–40% of patients have an insufficient response to them, and they have a large variety of adverse effects. Side-effects will reduce patients’ compliance with treatment, as well as their immediate quality of life, and may therefore unfavorably affect rehabilitation. Four principal features differentiate atypical from conventional antipsychotics, yet have not been established for all atypicals: fewer extrapyramidal side-effects, greater efficacy in the treatment of negative symptoms, specific pharmacological receptor binding profiles, and greater selective effect on the mesolimbic dopamine neurons than on nigrostriatal neurons. The pharmacological profile of amisulpride is completely different to that of other atypical antipsychotics. It has a high selectivity for D2 and D3 dopamine receptors, and thus would be expected to be devoid of unwanted side-effects associated with action on other neurotransmitter systems. It acts preferentially on the mesocortical and mesolimbic systems. It has an earlier onset of action than haloperidol. Amisulpride is a compound with a dual mode of action. At low doses it blocks presynaptic dopamine autoreceptors, inducing an increased dopaminergic neurotransmission, and at high doses it blocks postsynaptic dopaminergic activity. It is at least as effective as haloperidol, flupenthixol, and risperidone in controlling positive symptoms, as well as having efficacy for negative symptoms. It has less propensity to induce weight gain than do other atypical antipsychotics. For the 60–80% of patients with schizophrenia who require long-term treatment, drug tolerability is crucially important, as it will improve compliance, and therefore reduce relapse rate.

Currently, tardive dyskinesia (TD) remains an important clinical problem. The average prevalence is estimated at 30%. The appearance of antipsychotics has opened new paths. The extrapyramidal profile of these molecules is more favorable than that of conventional neuroleptics. In order to assess their prophylactic as well as curative potential, we reviewed the literature concerning four of these atypical antipsychotics: clozapine, risperidone olanzapine and amisulpride. Clozapine seems to induce fewer cases of TD than the conventional neuroleptics, and has a specific therapeutic effect. However, the risk of agranulocytosis reduces the possibility of utilisation. Risperidone appears to be an effective therapy, but several authors report cases of TD during treatment. Furthermore, larger studies and longer follow-ups are necessary to confirm the efficiency of olanzapine and amisulpride. Further studies and observations are still necessary before drawing any conclusion for these new atypical antipsychotic actions. They are doubtlessly promising, but we cannot ignore the notion of risk–benefit; regular monitoring and listening to the subjective experience of the patients must remain uppermost in the choice of therapy.

Therapeutic effects of neuroleptics (NLP) in schizophrenia are well established in numerous international studies. Varying modalities of evolution under NLP treatment are described and require a clinical analysis. Neuroleptics are a necessary but insufficient condition for the therapy of schizophrenia. Via NLP treatment, other therapeutic approaches, such as psychotherapy, or sociotherapy become more effective. Consecutively, we present the effects of two compounds with dopaminergic selective activity (amisulpride, remoxipride) and of two other compounds with non-selective activity (risperidone, clozapine) regarding rehabilitation in schizophrenic patients. Data were collected from international studies with a medico-economic perspective and from French experience of clozapine in refractory schizophrenic patients. All these data stress the importance of several areas of study: clinical features, everyday life consequences and therapeutical effects observed with the atypical neuroleptics.

Antipsychotic drugs are effective in psychoses, whatever the etiology of the disorder. The positive symptoms tend to respond more readily. The need for developing new drugs arises from the refractoriness of the negative symptoms, the 10-25% of the patients that are treatment-resistant and the problems of short-, and long-term extrapyramidal side-effects. Thus far, six drugs, differing from the classical antipsychotics, have been licensedfor use: olanzepine, risperidone and quetiapine; the longest registration exists for sulpiride and clozapine while the most recent one is for amisulpride. This review starts with a brief introduction to symptomatology, and takes differences with the classical drugs in pharmacology, pharmacokinetics, clinical aspects and side-effects into consideration. Clozapine, risperidone and sulpiride may be considered for clinical use in refractory patients; these three, olanzapine and amisulpride when extrapyramidal side-effects cause a clinical problem. Amisulpride and sulpiride have a dual therapeutic acion: On negative symptoms at low dose, on positive symptomen at high doses.