What is the starting dose of amisulpiride?

Starting Dose of Amisulpiride

For acute exacerbations of schizophrenia with predominantly positive symptoms, start amisulpiride at 400-800 mg/day, with evidence supporting initiation at 800 mg/day for maximal efficacy without significant additional side effects. 1, 2, 3

Dosing by Clinical Presentation

Acute Psychotic Exacerbations (Positive Symptoms)

• Start at 800 mg/day as a single dose or divided into two doses 2, 3
• The 2025 INTEGRATE guidelines from The Lancet Psychiatry recommend amisulpride as a second-line treatment option at standard antipsychotic doses 1
• A randomized controlled trial demonstrated that starting at 800 mg/day achieved significantly higher response rates (68.4% vs 40.0% at week 4) compared to titrating from 400 mg/day, without increased side effects 3
• Maximum recommended dose is 1200 mg/day 2

Predominantly Negative Symptoms

• Start at 50-100 mg/day for patients with primary negative symptoms 1, 2, 4
• The 2025 INTEGRATE guidelines specifically recommend "low-dose amisulpride (eg, 50 mg twice daily)" for predominant negative symptoms where positive symptoms are not a concern 1
• Doses of 50-300 mg/day have demonstrated efficacy superior to placebo for negative symptoms 2, 4
• At these low doses, extrapyramidal symptoms occur at rates similar to placebo 2, 4

Mixed Symptomatology

• Start at 400-800 mg/day for patients with both positive and negative symptoms 2, 5
• This dose range provides efficacy for both symptom domains 2

Practical Initiation Considerations

No Titration Required for Standard Doses

• Unlike many antipsychotics, amisulpride can be initiated at the target therapeutic dose without gradual titration 2, 3
• The 800 mg/day starting dose can be given from day one with low risk of extrapyramidal symptoms 3

Administration Schedule

• Can be given as a single daily dose or divided into two doses 2
• For negative symptoms, twice-daily dosing (e.g., 50 mg BID) is commonly used 1

When Switching from Other Antipsychotics

• Cross-tapering over 4 weeks is preferred rather than abrupt cessation 5
• Patients can remain on concurrent anticholinergics and antiparkinsonian agents during cross-tapering until effective amisulpride dose is reached 5
• Start amisulpride at 800 mg/day for acute symptoms or 400-800 mg/day for predominantly positive symptoms during the switch 5

Important Caveats

Dose-Response Relationship

• Low doses (50-300 mg/day) preferentially block presynaptic D2/D3 autoreceptors, enhancing dopaminergic transmission 2
• Higher doses (400-1200 mg/day) antagonize postsynaptic D2/D3 receptors, reducing dopaminergic transmission 2
• This bimodal mechanism explains why low doses treat negative symptoms while higher doses treat positive symptoms 2

Tolerability Profile

• Extrapyramidal symptoms occur less frequently than with typical antipsychotics at standard doses 2, 6
• Hyperprolactinemia is common (86% in one study) regardless of dose 3
• Weight gain is significantly less than with olanzapine and risperidone 5
• Low risk of drug-drug interactions 5

Special Populations

• For clozapine augmentation in treatment-resistant schizophrenia, add amisulpride 200-800 mg/day to existing clozapine regimen 5
• Renal impairment requires dose adjustment (amisulpride is renally excreted) 2