What is Amisulpride (AMIS)

From the Guidelines

Amisulpride is a viable treatment option for schizophrenia, with a unique dose-dependent effect that allows it to address both positive and negative symptoms of the disorder. The medication works by blocking dopamine D2 and D3 receptors in the brain, with lower doses (50-300 mg daily) preferentially blocking presynaptic dopamine receptors and increasing dopamine transmission to help with negative symptoms, while higher doses (400-800 mg daily) block postsynaptic receptors to reduce dopamine activity and address positive symptoms like hallucinations and delusions 1.

Some key points to consider when using amisulpride include:

• Common side effects such as weight gain, sedation, and extrapyramidal symptoms, though it generally causes fewer metabolic issues than some other antipsychotics
• Potential increase in prolactin levels, which can cause sexual dysfunction, menstrual irregularities, or breast enlargement
• Need for regular monitoring of metabolic parameters, prolactin levels, and electrocardiograms during treatment
• Cautious use in elderly patients and those with kidney problems, and contraindication in patients with prolactin-dependent tumors or pheochromocytoma

In terms of treatment strategies, combining amisulpride with other medications may be a cost-effective approach, as demonstrated by a study that found similar efficacy and side effects between 800 mg/day of amisulpride and 400 mg/day of amisulpride combined with 800 mg/day of sulpiride, with the combination strategy being cheaper 1. However, the evidence for amisulpride in other contexts, such as alcohol dependence, is limited and of low quality, with a network meta-analysis finding a low quality of evidence for amisulpride as a treatment for maintaining abstinence from alcohol 1.

From the FDA Drug Label

The pharmacological action of amisulpride, a dopamine-2 (D2) receptor antagonist, may result in an increase in serum prolactin levels, which may lead to a reversible increase in maternal milk production [see Adverse Reactions (6. 1)]. There are no reports of adverse effects on the breastfed child and no information on the effects of amisulpride on milk production A lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk for 48 hours after BARHEMSYS administration to minimize drug exposure to a breastfed infant.

Amisulpride and Breastfeeding: The FDA drug label does not provide enough information to fully answer the question about amisulpride. However, it does mention that:

• Amisulpride may increase serum prolactin levels, potentially leading to a reversible increase in maternal milk production.
• There are no reports of adverse effects on the breastfed child.
• A lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk for 48 hours after BARHEMSYS administration to minimize drug exposure to a breastfed infant. It is recommended to consult a healthcare professional for personalized advice on amisulpride and breastfeeding 2.

From the Research

Amisulpride Overview

• Amisulpride is a second-generation antipsychotic that preferentially binds to dopamine D2/D3 receptors in limbic rather than striatal structures 3
• It is used in the management of schizophrenia, with high dosages (200-1200 mg/day) effective in treating patients with predominantly positive symptoms, and low dosages (50-300 mg/day) effective in treating patients with predominantly negative symptoms 3

Efficacy and Safety

• Amisulpride has been shown to be at least as effective as haloperidol, and as effective as risperidone or olanzapine, in the treatment of patients with schizophrenia manifesting predominantly positive symptoms 3
• It has also been shown to be significantly more effective than placebo in treating patients with predominantly negative symptoms 3
• Amisulpride is generally well tolerated, with a lower incidence of extrapyramidal adverse effects compared to haloperidol, and a lower propensity for weight gain and diabetogenic effects compared to risperidone or olanzapine 3, 4

Dosage and Plasma Concentration

• The optimal clinical response to amisulpride has been found to be at doses of 400-800 mg/day, corresponding to plasma levels of approximately 200-500 ng/ml 5
• Plasma amisulpride levels have been shown to increase linearly with the daily oral dose, with older patients and women having higher dose-corrected amisulpride plasma concentrations than younger patients and men 6

Clinical Trials

• A double-blind, randomised comparative trial of amisulpride versus olanzapine in the treatment of schizophrenia found that amisulpride was equivalent to olanzapine in terms of efficacy, but offered a significant advantage in preserving body weight 4
• A three-arm, parallel-group, placebo-controlled, double-blind, randomised controlled trial of amisulpride in the treatment of very late-onset schizophrenia-like psychosis found that low-dose amisulpride was effective and well tolerated, with benefits maintained by prolonging treatment 7