Sulpride

Approved Indications:

• Schizophrenia (Acute and Chronic):
  Indicated for the treatment of schizophrenia, including both positive symptoms (e.g., delusions, hallucinations) and negative symptoms (e.g., social withdrawal, emotional blunting).
• Persistent Depressive Disorder (Dysthymia):
  In some countries, low-dose amisulpride is approved for the short-term treatment of dysthymia in adults.

Clinically Accepted Off-Label Uses:

• Bipolar Disorder:
  Used as an adjunct in the treatment of manic episodes or psychotic features in bipolar disorder.
• Delusional Disorders:
  Employed off-label for managing persistent delusional states.
• Treatment-Resistant Depression (Adjunctive):
  Low-dose amisulpride is occasionally used alongside antidepressants for augmentation.
• Psychotic Depression (with careful monitoring):
  Occasionally used in conjunction with antidepressants.

Adults:

• Positive Symptoms of Schizophrenia:
  400–800 mg/day in two divided doses; maximum daily dose: 1200 mg.
• Predominant Negative Symptoms:
  50–300 mg/day as a single oral dose.
• Dysthymia (Low-Dose Use):
  50–100 mg/day, administered once daily.

Elderly:

• Start with the lowest effective dose (e.g., 50 mg/day).
• Monitor for sedation, hypotension, and QT prolongation. Dose adjustments should be made cautiously.

Pediatrics:

• Not recommended for use in children and adolescents under 18 years due to insufficient safety and efficacy data.

Renal Impairment:

• Mild impairment (CrCl 30–60 mL/min): Reduce dose by 50%.
• Severe impairment (CrCl <30 mL/min): Reduce dose by 75%.
• End-stage renal disease (CrCl <10 mL/min): Avoid use.

Hepatic Impairment:

• No dosage adjustment typically necessary, as amisulpride undergoes minimal hepatic metabolism. However, use with caution.

Administration Route:

• Oral: Tablets should be swallowed whole, with or without food.
• Injectable (for acute agitation): Intramuscular injection of 50 mg up to three times per day for short-term use only.

Amisulpride is a selective dopamine D2 and D3 receptor antagonist that acts differently at low and high doses. At low doses, it primarily blocks presynaptic D2/D3 autoreceptors, enhancing dopaminergic transmission—this helps alleviate negative symptoms of schizophrenia and dysthymia. At higher doses, amisulpride blocks postsynaptic D2/D3 receptors, inhibiting dopamine overactivity responsible for positive symptoms like hallucinations and delusions. This dual-action mechanism contributes to its antipsychotic effects with a relatively lower risk of extrapyramidal side effects compared to typical antipsychotics.

• Absorption: Rapid oral absorption; peak plasma levels reached within 1–2 hours.
• Bioavailability: Approximately 48%.
• Distribution: Low plasma protein binding (~17%); wide distribution (volume of distribution ~5.8 L/kg).
• Metabolism: Minimal hepatic metabolism; does not extensively involve cytochrome P450 enzymes.
• Elimination Half-Life: Approximately 12 hours.
• Excretion: Primarily excreted unchanged in urine (~75%); minor fecal elimination.
• Onset of Action: Therapeutic effects are usually observed within 1–2 weeks.

• Pregnancy:
  Classified as Pregnancy Category C. Animal studies have shown adverse effects on fetal development. Use only if potential benefits justify the risks. Neonates exposed during the third trimester may develop extrapyramidal or withdrawal symptoms.
• Lactation:
  Amisulpride is excreted in human breast milk. Due to potential serious adverse effects (e.g., sedation, hypotonia) in nursing infants, breastfeeding is not recommended during therapy.

• Primary Class: Atypical Antipsychotic
• Subgroup: Benzamide Derivative
• Generation: Second-Generation Antipsychotic (SGA)

• Known hypersensitivity to amisulpride or its excipients
• Pheochromocytoma
• Prolactin-dependent tumors (e.g., breast cancer, pituitary prolactinoma)
• Children and adolescents under 18 years
• Severe renal impairment (CrCl <10 mL/min)
• Lactation

• QT Interval Prolongation: Risk of serious arrhythmias; ECG monitoring is advised in high-risk patients.
• Neuroleptic Malignant Syndrome (NMS): Discontinue immediately if hyperthermia, rigidity, or autonomic instability occurs.
• Hyperprolactinemia: May cause galactorrhea, amenorrhea, gynecomastia, infertility.
• Diabetes Mellitus: Monitor for hyperglycemia or worsening glycemic control.
• Seizures: Use cautiously in patients with a history of seizures or epilepsy.
• Elderly with Dementia-Related Psychosis: Increased risk of cerebrovascular events and mortality—use not recommended.

Common Side Effects:

• Neurological: Extrapyramidal symptoms (dose-dependent), insomnia, anxiety, agitation, dizziness
• Endocrine/Metabolic: Hyperprolactinemia, weight gain
• Cardiovascular: QT prolongation, hypotension
• Gastrointestinal: Nausea, constipation
• Sexual/Reproductive: Amenorrhea, decreased libido, erectile dysfunction

Serious or Rare Adverse Effects:

• Neuroleptic Malignant Syndrome (NMS)
• Torsades de pointes
• Seizures
• Hepatic dysfunction
• Blood dyscrasias (very rare)
• Allergic reactions (rash, angioedema)

• Levodopa: Antagonistic effects; concurrent use contraindicated.
• QT-Prolonging Agents: Additive risk of arrhythmias with drugs such as sotalol, amiodarone, macrolides.
• CNS Depressants (e.g., alcohol, benzodiazepines): Enhanced sedative effect.
• Antihypertensives: Risk of additive hypotensive effects.
• Minimal CYP450 Interaction: Safe in patients on polytherapy involving CYP-metabolized drugs.

• Regulatory Updates (2023–2024):
• Reinforced recommendations for ECG monitoring before and during treatment in high-risk populations.
• Emphasis on using the lowest effective dose, especially in elderly patients.
• No recent changes to approved indications or black box warnings by major agencies (FDA, EMA, NICE, WHO).

• Tablets: Store below 25°C in a dry place.
• Liquid Form (if available): Refrigerate at 2°C to 8°C.
• Protection: Protect from light and moisture.
• Handling: Keep in original packaging. Do not use past expiry. Do not freeze oral solution.