Amisulpride Dosing: 400mg BD vs 800mg Nocte
For acute exacerbations of schizophrenia with predominantly positive symptoms, prescribe amisulpride 800mg once daily (nocte) rather than 400mg twice daily (BD), as both regimens deliver the same total daily dose with equivalent efficacy, but once-daily dosing may improve adherence. 1, 2
Dosing Strategy by Clinical Presentation
Acute Psychotic Exacerbations (Predominantly Positive Symptoms)
- Start with 800mg/day as a single dose 1, 3
- The 800mg/day dose can be given from day one without titration, with low risk of extrapyramidal symptoms 3
- A study comparing 400mg/day titrated up versus 800mg/day from initiation found that starting at 800mg/day resulted in significantly more responders by week 4 (68.4% vs 40.0%) and maintained this advantage through week 6 (71.1% vs 43.3%) 3
- Maximum dose may reach 1200mg/day if needed 2, 4
Predominantly Negative Symptoms
- Use low-dose amisulpride: 50-300mg/day 5, 1, 2
- The Lancet Psychiatry guidelines specifically recommend 50mg twice daily for predominant negative symptoms where positive symptoms are not a concern 5
Dosing Frequency Considerations
- Amisulpride has an elimination half-life of approximately 12 hours, supporting once-daily dosing 6
- The pharmacokinetics are linear with 48% bioavailability and low protein binding (17%) 6
- Once-daily dosing (nocte) may enhance medication adherence compared to twice-daily regimens, which is critical given that adherence issues are a major reason physicians switch to amisulpride 1
Clinical Evidence Supporting 800mg Daily Dosing
The recommended dosage range of 400-800mg/day has been validated in multiple comparative trials 2, 4:
- Amisulpride 400-1200mg/day was equally effective as haloperidol 5-40mg/day, flupenthixol 25mg/day, and risperidone 8mg/day for acute exacerbations 2
- A Cochrane review of 19 trials (2443 participants) confirmed amisulpride's superiority over typical antipsychotics for global state improvement and negative symptoms 4
- Amisulpride showed better tolerability than high-potency typical antipsychotics, with lower rates of extrapyramidal symptoms (NNH 5) 4
Important Caveats
Hyperprolactinemia is common (86% of patients) regardless of dosing schedule, as amisulpride selectively blocks dopamine D2/D3 receptors 3. Monitor prolactin levels and watch for associated symptoms.
Extrapyramidal symptoms occur in approximately 35% of patients at therapeutic doses, though this is still lower than with typical antipsychotics 3, 4. The risk increases at doses above 300mg/day but remains acceptable at 800mg/day 1, 3.
Practical Recommendation
Prescribe amisulpride 800mg once daily at night for acute schizophrenia with positive symptoms. This approach:
- Delivers the full therapeutic dose immediately without titration 3
- Achieves faster response rates (by week 4) 3
- Simplifies the regimen to once-daily dosing, potentially improving adherence 1
- Maintains the same safety profile as divided dosing 3
The 400mg BD regimen is not inferior in terms of final efficacy, but the 800mg nocte approach offers practical advantages in real-world clinical practice where medication adherence is paramount 1, 3.