The use of amisulpride in the treatment of acute psychosis

Abstract

The management of acute episodes in schizophrenia is frequently initiated in the psychiatric emergency department and requires rapid intervention to relieve distress and psychiatric symptoms. Both non-pharmacological and pharmacological interventions are needed to calm the patient and prevent potential harm to the patient or others. Treatment is a step-by-step process including management of behavioral symptomatology, diagnosis of potential organic causes, and evaluation of potential substance abuse. Better care is delivered if predefined standard operating procedures are adopted systematically. The ultimate goal of treatment is to establish a therapeutic alliance with the patient. Atypical antipsychotics given orally are recommended as a first-line treatment. As the treatment endpoint is calmness rather than sleep, a non-sedative antipsychotic agent is usually preferred. Drug tolerance is a major issue for the patient. Amisulpride is an effective atypical antipsychotic agent in this context. The optimal dose is 800 mg/day, which is effective on positive and negative symptoms and can be given from the first day with a low risk of extrapyramidal symptoms. Since drug-drug interactions are limited, agitation and anxiety may be controlled by short-term adjunctive therapy with benzodiazepines. In conclusion, amisulpride is an appropriate first-line treatment for the management of acute psychosis.

Figure 1

Meta-analysis of effect sizes in clinical studies of amisulpride compared with first-generation drugs with respect to primary efficacy outcome (change in score on the Brief Psychiatric Rating Scale). 95% confidence intervals were generated using a randomized effects model. Reprinted with permission from the American Journal of Psychiatry, Copyright © 2002, American Psychiatric Association. Leucht S, Pitschel-Walz G, Engel RR, et al. 2002. Amisulpride, an unusual “atypical” antipsychotic: a meta-analysis of randomized controlled trials. Am J Psychiatry, 159:180-90.

Figure 2

Meta-analysis of effect sizes of second-generation antipsychotic drugs compared to first-generation drugs with respect to primary efficacy outcome. Data for amisulpride are combined from twelve individual studies. Copyright © 2005. Reprinted with permission from Davis JM, Chen N. 2005. Old versus new: weighing the evidence between the first- and second-generation antipsychotics. Eur Psychiatry, 20:7-14.

Figure 3

Meta-analysis of effect sizes in clinical studies of amisulpride compared with first-generation drugs with respect to recourse to anticholinergic medication. 95% confidence intervals were generated using a randomized effects model. Reproduced with permission from the American Journal of Psychiatry, Copyright © 2002, American Psychiatric Association. Leucht S, Pitschel-Walz G, Engel RR, et al. 2002. Amisulpride, an unusual “atypical” antipsychotic: a meta-analysis of randomized controlled trials. Am J Psychiatry, 159:180-90.

Figure 4

Antipsychotic effect of amisulpride as a function of dose. The data represent the mean (SD) scores on the Brief Psychiatric Rating Scale (BPRS) at inclusion (filled symbols) and after treatment (open symbols) for four weeks with the indicated doses of amisulpride or haloperidol. Data are taken from Puech et al 1998.

Figure 5

Extrapyramidal impact of amisulpride as a function of dose. The data represent the mean changes from baseline on the Simpson-Angus Scale (SAS) after initiation of treatment with the indicated doses of amisulpride or haloperidol. The open columns represent the maximal change from baseline observed over the course of the study and the filled columns the residual change at study end. Data are taken from Puesch et al 1998.

Figure 6

Occupation of striatal D₂ dopamine receptors measured using positron emission tomography with [⁷⁶Br]-bromolisuride as a function of amisulpride dose. The points represent individual patient data and the shaded bar the zone of receptor occupation believed to be optimal for antipsychotic activity. Data are taken from Martinot et al 1996.

Figure 7

Evolution of Brief Psychiatric Rating Scale (BPRS) total scores after administration of amisulpride 800 mg in patients with acute psychosis. Data are taken from Möller et al 1997.

Figure 8

Evolution of Brief Psychiatric Rating Scale (BPRS) dimension scores in a comparative randomised clinical trial of amisulpride versus olanzapine in the treatment of acute psychosis. Data are presented as mean (± SD) change from baseline at two months in patients with acute schizophrenia treated with amisulpride (filled columns) or olanzapine (open columns). Adapted from Martin et al 2002.