Amisulpride 100 mg for Negative Symptoms: Dosing Frequency
For amisulpride 100 mg daily targeting negative symptoms in schizophrenia, the dose should be given as 50 mg twice daily rather than 100 mg once in the morning. 1
Recommended Dosing Schedule
The most recent international guidelines from The Lancet Psychiatry (2025) specifically recommend 50 mg twice daily for low-dose amisulpride when targeting predominant negative symptoms where positive symptoms are not a concern. 1
The European College of Neuropsychopharmacology supports this twice-daily dosing at 50 mg per dose (100 mg total daily) because it selectively blocks presynaptic D2/D3 autoreceptors, enhancing dopamine release in a manner that optimally addresses negative symptoms. 2
Evidence Supporting Twice-Daily Dosing
Multiple controlled trials in patients with predominantly negative symptoms used divided dosing regimens, with the most effective dose identified as 100 mg/day administered in split doses, demonstrating significant improvement on the Scale for the Assessment of Negative Symptoms (SANS) compared to placebo. 3
The pharmacological rationale for divided dosing at low doses (50-100 mg/day total) relates to amisulpride's unique mechanism: at these low concentrations, it preferentially blocks presynaptic dopamine D2/D3 autoreceptors, enhancing dopaminergic neurotransmission, and maintaining consistent presynaptic blockade throughout the day requires twice-daily administration. 4, 5
Dosing Range for Negative Symptoms
The therapeutic range for negative symptoms is 50-300 mg/day, with 100 mg/day (given as 50 mg twice daily) representing the most commonly studied and effective dose in clinical trials. 6, 4
Starting at 50 mg twice daily allows for dose optimization: if inadequate response occurs after 4 weeks, the dose can be increased to 150 mg twice daily (300 mg/day total) while still maintaining the presynaptic mechanism of action. 5
Critical Distinction from Higher Doses
This twice-daily low-dose regimen (50 mg BID) is fundamentally different from dosing for positive symptoms, where amisulpride 400-800 mg/day is given once or twice daily to achieve postsynaptic D2/D3 receptor blockade in the limbic system. 6, 4
At doses above 300 mg/day, amisulpride's mechanism shifts from presynaptic enhancement to postsynaptic blockade, making the low-dose twice-daily strategy specifically suited for negative symptom management. 4, 5
Common Pitfall to Avoid
Do not use once-daily morning dosing for the 100 mg total daily dose targeting negative symptoms - this fails to maintain the consistent presynaptic receptor occupancy needed throughout the day and may result in suboptimal efficacy for negative symptoms. 2, 3
Ensure that positive symptoms are adequately controlled before using this low-dose strategy, as 100 mg/day is insufficient for managing active positive symptoms, which require 400-800 mg/day. 1, 4
Monitoring and Expected Response
Assess negative symptom improvement using standardized scales (such as SANS) at 4-6 weeks, as this is the timeframe in which significant improvement should become evident with appropriate dosing. 3
The extrapyramidal symptom profile at 100 mg/day (50 mg BID) is similar to placebo, making this a well-tolerated regimen for long-term management of negative symptoms. 3, 5