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Switching to amisulpride.

Abstract

The introduction of atypical antipsychotics represents an important advance in the treatment of schizophrenia. As their therapeutic efficacy, tolerability and safety profiles are clearly superior to classical neuroleptics, atypical antipsychotic agents are considered to be the treatment of choice in first episode patients. In addition, an increasing number of patients are being switched from classical to atypical antipsychotic agents. Switching is especially relevant in patients with a poor therapeutic response to classical neuroleptics and persistent symptoms (positive symptoms, negative symptoms, depressive syndromes, cognitive deficit); in patients with a psychotic relapse despite compliance; in patients with important side-effects (not only acute and tardive extrapyramidal symptoms [EPS] and general side-effects, but also dysphoria or neuroleptic-induced deficit syndrome [NIDS]); and in patients who are non-compliant due to side-effects. Switching to atypical antipsychotics should be performed with extreme care in stabilised patients; or in patients who present a danger to themselves or others at relapse; or in patients who are on depot neuroleptics who were non-compliant to previous oral treatment. Switching requires careful planning to reduce the risk of withdrawal effects (neuroleptic withdrawal syndrome, cholinergic rebound, exacerbation of symptoms or relapse, rebound of parkinsonism, dystonia, akathisia, dyskinesia), which may mask the beneficial effects and lead to early discontinuation of the new treatment. Patients, family and carers should be actively involved at all stages, and educated about the possible benefits and problems associated with switching therapy. Cross-tapering old and new treatment is the preferred method for switching and this involves tapering off the previous antipsychotic agent and any adjunctive treatment (sedatives, anticholinergic medication), while gradually titrating the new atypical antipsychotic agent to the established therapeutic dose. Switching patients to amisulpride treatment offers effective antipsychotic therapy, with a positive effect on negative and depressive symptoms. Amisulpride treatment also results in improved quality of life and social functioning in addition to fewer relapses and days of hospitalisation during long-term follow-up.

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BibTeXRIS

J Peuskens. 2002. Switching to amisulpride.. https://doi.org/10.1185/030079902125001092

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The treatment of Tourette's syndrome is a challenge. Dopamine receptor antagonists are the drugs of first choice for the treatment of tics. Because large controlled trials are lacking, there is no consensus about which of the different neuroleptic drugs should be preferred. In Germany, tiapride seems to be used most often for the treatment of tics in children - although only one small controlled trial has been performed on it till now. In adults, other dopamine receptor antagonists such as risperidone, pimozide, and sulpiride seem to be more effective than tiapride. Today it is unknown whether new atypical neuroleptic drugs including the benzamide amisulpride are more effective than the older benzamides tiapride and sulpiride.

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Is the superior efficacy of new generation antipsychotics an artifact of LOCF?

It has been argued that the efficacy superiority found in meta-analyses for some of the atypical antipsychotics is an artifact of higher dropout rates due to side effects in the haloperidol group combined with last-observation-carried-forward (LOCF) analyses. We therefore reanalyzed a number of pivotal studies comparing new generation antipsychotics (NGAs) and conventional antipsychotics (CAs). A total of 5 studies (n = 1271) comparing amisulpride and 3 studies (n = 2454) comparing olanzapine with CAs were reanalyzed using original patient data. We applied 4 different models: LOCF, completer analysis, LOCF but excluding dropouts due to adverse events, and LOCF but excluding all dropouts with the exception of dropouts related to efficacy. Effect sizes expressed as standardized mean differences between NGAs and CAs based on the 4 different analysis models were compared. The overall results were not different irrespective of the model used. Single studies, however, showed higher effect sizes when LOCF instead of other models was used. Overall, it does not seem that higher dropout rates due to side effects in the haloperidol groups together with LOCF analyses consistently biased the results in favor of amisulpride and olanzapine. Because the results of the single studies, however, showed that this may occasionally be the case, future studies should look at the data from different angles applying sensitivity analyses, and they may use alternative statistics such as mixed models, which need to be developed further. Ultimately, strategies to reduce dropout rates are needed.

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