What is the mechanism of action, efficacy, and side effects of amisulpride (Antipsychotic medication) in the treatment of schizophrenia?

From the Guidelines

Amisulpride is a highly effective treatment for schizophrenia, helping to alleviate both positive and negative symptoms by blocking dopamine D2 and D3 receptors in the brain, with a recommended starting dose of 400-800 mg/day for acute psychotic episodes, and maintenance doses ranging from 200-400 mg/day 1.

Mechanism of Action

Amisulpride's unique dose-dependent action allows it to preferentially block presynaptic dopamine receptors at lower doses (50-300 mg/day), increasing dopamine release and helping with negative symptoms like social withdrawal and emotional flatness. At higher doses (400-800 mg/day), it blocks postsynaptic receptors, reducing excessive dopamine activity that causes positive symptoms like hallucinations and delusions 1.

Side Effects and Dosage

Common side effects of amisulpride include:

• Extrapyramidal symptoms (muscle stiffness, tremors)
• Hyperprolactinemia (causing menstrual irregularities, sexual dysfunction, or breast enlargement)
• Weight gain
• QT interval prolongation Elderly patients and those with renal impairment require lower doses, and blood tests for prolactin levels and ECG monitoring may be necessary during treatment 1.

Treatment Considerations

Amisulpride should be taken consistently, and patients should not stop taking it suddenly without medical supervision as this could cause symptom relapse. The American Psychiatric Association recommends that patients with schizophrenia be treated with an antipsychotic medication, such as amisulpride, and monitored for effectiveness and side effects 1.

Key Recommendations

• Start amisulpride at 400-800 mg/day for acute psychotic episodes, and maintain at 200-400 mg/day 1
• Monitor for side effects, including extrapyramidal symptoms, hyperprolactinemia, weight gain, and QT interval prolongation 1
• Adjust doses for elderly patients and those with renal impairment 1
• Consider anticholinergic medication for acute dystonia, and options like lowering the dosage, switching to another antipsychotic, or treating with an anticholinergic medication for parkinsonism and akathisia 1

From the FDA Drug Label

Amisulpride is a selective dopamine-2 (D2) and dopamine-3 (D3) receptor antagonist. D2 receptors are located in the chemoreceptor trigger zone (CTZ) and respond to the dopamine released from the nerve endings.

The mechanism of action of amisulpride in schizophrenia is as a dopamine-2 (D2) and dopamine-3 (D3) receptor antagonist. However, the provided drug label does not directly support the use of amisulpride for schizophrenia, but rather discusses its use in the context of emesis and postoperative nausea and vomiting (PONV). The side effects and dosage information provided in the label are also in the context of PONV, with a recommended infusion rate of 1 to 2 minutes for 5 mg or 10 mg of amisulpride 2. Key points about amisulpride include:

• Mechanism of action: selective dopamine-2 (D2) and dopamine-3 (D3) receptor antagonist
• Pharmacokinetics: peak plasma concentration achieved at the end of the infusion period, with a half-life of approximately 4 to 5 hours
• Dosage: 5 mg or 10 mg infusion, with a recommended infusion rate of 1 to 2 minutes 2

From the Research

Mechanism of Action

• Amisulpride is a second-generation (atypical) antipsychotic that preferentially binds to dopamine D2/D3 receptors in limbic rather than striatal structures 3, 4, 5.
• At low doses, it enhances dopaminergic neurotransmission by preferentially blocking presynaptic dopamine D2/D3 autoreceptors 3, 4, 5.
• At higher doses, amisulpride antagonises postsynaptic dopamine D2 and D3 receptors, preferentially in the limbic system rather than the striatum, thereby reducing dopaminergic transmission 3, 4, 5.

Dosage

• The recommended dosage of amisulpride is 400 to 800 mg/day for patients with acute exacerbations of schizophrenia, although dosages ≤ 1200 mg/day may be administered 3, 4.
• Lower dosages of amisulpride (50 to 300 mg/day) should be considered for the management of patients with negative symptoms of schizophrenia 3, 4, 6.

Efficacy

• Amisulpride is effective in reducing overall symptomatology and positive symptoms in patients with acute exacerbations of schizophrenia 3, 4, 5.
• It is also effective in alleviating negative and affective symptoms in patients with schizophrenia 3, 4, 5.
• Amisulpride is effective as maintenance therapy in patients with chronic schizophrenia, with improvements in quality of life and social functioning 3, 4, 5.

Side Effects

• Amisulpride is generally well tolerated, with a lower incidence of extrapyramidal symptoms compared to conventional antipsychotics 3, 4, 5.
• The incidence of adverse events, including extrapyramidal symptoms, is similar to that of placebo at low dosages of amisulpride (< 300 mg/day) 3, 4.
• Amisulpride may cause hyperprolactinemia, but has a lower propensity to cause weight gain and does not seem to be associated with diabetogenic effects compared to other atypical antipsychotics 5.
• Amisulpride may be more likely to cause extrapyramidal symptoms than placebo, but this result did not hold when calculating the risk reduction 7.