Amisulpride is an atypical antipsychotic belonging to the benzamide class. It is a selective dopamine D2 and D3 receptor antagonist with high affinity and low nanomolar potency. At low doses (50-300 mg/day), it preferentially blocks presynaptic dopamine autoreceptors, increasing dopaminergic neurotransmission, making it effective for negative symptoms and dysthymia. At higher doses (>400 mg/day), it blocks postsynaptic receptors, treating positive psychotic symptoms. It has minimal affinity for serotonin, histamine, adrenergic, and cholinergic receptors, contributing to a favorable side effect profile regarding sedation, weight gain, and anticholinergic effects.
Adult: Schizophrenia (Negative Symptoms): 50-300 mg/day, usually 50-100 mg once daily. Schizophrenia (Positive Symptoms): 400-800 mg/day in 2 divided doses, max 1200 mg/day. Dysthymia: 50 mg once daily.
Note: Oral administration. Can be taken with or without food. Tablet should be swallowed whole with a glass of water. For doses above 300 mg/day, it is recommended to divide the dose into two (morning and evening). Consistent timing is advised.
Amisulpride exhibits a unique dose-dependent dual action on dopaminergic pathways. At low doses, it selectively blocks presynaptic dopamine D2/D3 autoreceptors in the mesocortical and mesolimbic pathways. This blockade disinhibits dopamine release, increasing dopaminergic tone, which is theorized to improve negative symptoms (avolition, anhedonia, blunted affect) and mood. At high doses, it antagonizes postsynaptic D2/D3 receptors in the mesolimbic pathway, reducing dopaminergic hyperactivity associated with positive symptoms (hallucinations, delusions). Its high selectivity for D2/D3 receptors with negligible affinity for other neurotransmitter receptors underlies its atypical profile.
Pregnancy: Category not assigned by Indian FDA. International data (US FDA Category not established, AU TGA Category C) suggest potential risk. Use only if potential benefit justifies potential fetal risk. Neonates exposed in 3rd trimester are at risk for EPS and withdrawal symptoms. Register with a pregnancy registry if used.
Driving: May impair alertness, reaction time, and motor coordination, especially during initial treatment and dose escalation. Patients should be cautioned against driving or operating machinery until their individual response is known.
| Levodopa, Dopamine Agonists (e.g., Pramipexole) | Antagonistic effect; reduces efficacy of dopaminergic drugs. | Major |
| QT-prolonging drugs (e.g., Amiodarone, Sotalol, Quinidine, Erythromycin, Clarithromycin, Fluoroquinolones, Tricyclic Antidepressants) | Additive risk of QTc prolongation and cardiac arrhythmias like Torsades de Pointes. | Contraindicated/Major |
| CNS Depressants (Alcohol, Benzodiazepines, Opioids, Sedative Antihistamines) | Additive sedative effects, impaired alertness, and respiratory depression. | Moderate |
| Antihypertensives | Potentiation of hypotensive effects, especially orthostatic hypotension. | Moderate |
| Other Antipsychotics (typical and atypical) | Increased risk of EPS, sedation, and metabolic side effects. | Moderate |