Sulpiride

Usage

Sulpiride is prescribed for the treatment of acute and chronic schizophrenia, and short-term symptomatic treatment of anxiety in adults when other therapeutic measures have failed. Its pharmacological classification is as a typical (first-generation) antipsychotic. It primarily acts as a dopamine D2 and D3 receptor antagonist, increasing blood flow in the gastric mucosa and promoting gastrointestinal motility. It also promotes the repair of gastric/duodenal mucosal tissue, making it useful in treating gastric/duodenal ulcers.

Alternate Names

While “Sulpiride” is the generic name, brand names may vary depending on the region and manufacturer. Some examples include Sulpiride 200mg Tablets, Sulpiride 200mg Film-Coated Tablets, Sulpiride Grindeks, Sulpiride STELLA 50 mg, and SULPIRIDE 50 OETHMAAN Capsules. The specific brand names available in India should be confirmed.

How It Works

Pharmacodynamics: Sulpiride primarily acts as a dopamine D2 and D3 receptor antagonist, particularly in the limbic system and hypothalamus. At lower doses, it preferentially blocks presynaptic dopamine receptors, leading to increased dopamine turnover and potential antidepressant and activating effects. At higher doses, postsynaptic dopamine receptor blockade predominates, producing antipsychotic effects. Sulpiride also increases prolactin secretion due to its dopamine receptor blockade in the pituitary gland.

Pharmacokinetics:

• Absorption: Sulpiride is well absorbed orally, with peak plasma concentrations reached within 2-6 hours. Food may slightly reduce its bioavailability.
• Distribution: It distributes widely throughout the body, including the brain, and crosses the placenta.
• Metabolism: Sulpiride undergoes limited hepatic metabolism.
• Elimination: It is primarily excreted unchanged in the urine, with a half-life of around 7-9 hours. Renal impairment necessitates dose adjustments.

Mode of Action/Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Sulpiride acts mainly as an antagonist at dopamine D2 and D3 receptors. At low doses, it preferentially binds to presynaptic D2 autoreceptors, which normally inhibit dopamine release. This can lead to an increase in dopamine synthesis and release, potentially explaining its mood-elevating and activating effects. At higher doses, sulpiride also blocks postsynaptic D2 receptors, resulting in antipsychotic activity by reducing dopaminergic neurotransmission in the mesolimbic pathway.

Elimination pathways: Primarily renal excretion.

Dosage

Standard Dosage

Adults:

For schizophrenia: 400-800 mg daily, divided into two doses, morning and early evening. Doses can be adjusted based on individual patient response and predominant symptoms. Maximum dose is 1200 mg twice daily. For predominantly negative symptoms, lower doses (200-400 mg twice daily) may be sufficient. For anxiety: 50-150 mg daily for a maximum of 4 weeks.

Children:

Not recommended for children under 14 years of age due to insufficient clinical experience. For children over 14 years: 3-5 mg/kg daily.

Special Cases:

• Elderly Patients Start with lower doses (50-100 mg twice daily) and adjust as needed. Reduce the dose in cases of renal impairment.
• Patients with Renal Impairment Reduce the dose based on creatinine clearance.
• Patients with Hepatic Dysfunction Use with caution as sulpiride is primarily eliminated renally, but it may be contraindicated in severe impairment.
• Patients with Comorbid Conditions Use cautiously in patients with cardiovascular disease, diabetes, epilepsy, glaucoma, prostatic hyperplasia, and other conditions.

Clinical Use Cases

Sulpiride’s use in intubation, surgical procedures, mechanical ventilation, ICU, and emergency situations is not routinely indicated. It is primarily an antipsychotic medication.

Dosage Adjustments

Adjustments are necessary for renal impairment based on creatinine clearance:

• CrCl 30-60 mL/min: Two-thirds of the normal dose, or prolong the dosage interval by a factor of 1.5.
• CrCl 10-30 mL/min: Half the normal dose, or prolong the dosage interval by a factor of 2.
• CrCl < 10 mL/min: One-third of the normal dose, or prolong the dosage interval by a factor of 3.

Side Effects

Common Side Effects

Hyperprolactinemia, insomnia, sedation, drowsiness, extrapyramidal symptoms (tremor, akathisia, dystonia), constipation, increased liver enzymes, maculopapular rash, breast pain, weight gain.

Rare but Serious Side Effects

Neuroleptic malignant syndrome (NMS), QT prolongation, ventricular arrhythmias (torsades de pointes), tardive dyskinesia, hypertensive crisis, blood dyscrasias (leukopenia, neutropenia, agranulocytosis).

Long-Term Effects

Tardive dyskinesia, weight gain, metabolic changes (dyslipidemia, hyperglycemia).

Adverse Drug Reactions (ADR)

NMS, QT prolongation, torsades de pointes, agranulocytosis.

Contraindications

Phaeochromocytoma, acute porphyria, hypersensitivity to sulpiride, concomitant prolactin-dependent tumors (e.g., pituitary prolactinomas, breast cancer), severe renal or hepatic impairment, CNS depression, coma, alcohol intoxication, concomitant use of levodopa or antiparkinsonian drugs, bone marrow suppression.

Drug Interactions

Drugs that prolong the QT interval (e.g., some antiarrhythmics, antidepressants), antihypertensives, CNS depressants (alcohol, sedatives), antacids, sucralfate, lithium, dopaminergic agents (levodopa, ropinirole), sympathomimetics.

Pregnancy and Breastfeeding

Sulpiride crosses the placenta and is excreted in breast milk. Its use during pregnancy is not recommended unless the benefits clearly outweigh the potential risks. Neonates exposed to sulpiride during the third trimester are at risk of extrapyramidal and/or withdrawal symptoms. A decision should be made whether to discontinue breastfeeding or discontinue sulpiride therapy, taking into account the benefits and risks for both the mother and the child.

Drug Profile Summary

• Mechanism of Action: Dopamine D2 and D3 receptor antagonist.
• Side Effects: Sedation, extrapyramidal symptoms, hyperprolactinemia, constipation, weight gain. Serious side effects include NMS, QT prolongation.
• Contraindications: Phaeochromocytoma, prolactin-dependent tumors, concomitant use of levodopa.
• Drug Interactions: QT prolonging drugs, antihypertensives, CNS depressants.
• Pregnancy & Breastfeeding: Not recommended unless benefits outweigh risks.
• Dosage: Adults: 400-800mg daily divided twice daily; Children (over 14): 3-5mg/kg daily.
• Monitoring Parameters: Mental status, vital signs, blood pressure, weight, CBC, liver function tests, electrolytes, glucose, lipids, prolactin levels, ECG (for QT interval).

Popular Combinations

Data on popular combinations specifically within the Indian medical context is limited in the provided sources. However, clinicians might combine sulpiride with other psychotropics depending on individual patient needs and the presence of comorbid psychiatric conditions.

Precautions

• General Precautions: Monitor for NMS, QT prolongation, blood dyscrasias, and extrapyramidal symptoms. Screen for pre-existing conditions like cardiovascular disease, diabetes, epilepsy, glaucoma.
• Specific Populations: Pregnant women, breastfeeding mothers: weigh benefits against risks. Children and Elderly: Adjust dose and monitor carefully.
• Lifestyle Considerations: Avoid alcohol; Caution with driving and operating machinery.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Sulpiride?

A: Adults: Initially 400-800 mg daily, divided into two doses. Dose can be adjusted based on response and predominant symptoms, up to a maximum of 1200 mg twice daily. Children (over 14): 3-5mg/kg daily. Elderly: Start with lower doses and adjust carefully.

Q2: What are the common side effects of Sulpiride?

A: Common side effects include sedation, drowsiness, extrapyramidal symptoms (tremor, restlessness, muscle stiffness), hyperprolactinemia, constipation, and weight gain.

Q3: What are the serious side effects of Sulpiride?

A: Serious side effects include Neuroleptic Malignant Syndrome (NMS), QT interval prolongation, ventricular arrhythmias (torsades de pointes), tardive dyskinesia, and blood dyscrasias.

Q4: Can Sulpiride be used during pregnancy?

A: Sulpiride is generally not recommended during pregnancy unless the benefits clearly outweigh the risks. It crosses the placenta and may cause extrapyramidal and/or withdrawal symptoms in newborns.

Q5: Is Sulpiride safe during breastfeeding?

A: Sulpiride is excreted in breast milk. The decision to breastfeed while taking sulpiride should be made in consultation with a physician, weighing the benefits and risks for both mother and child.

Q6: How does Sulpiride work in the body?

A: Sulpiride primarily acts as a dopamine D2 and D3 receptor antagonist, primarily in the limbic system and hypothalamus. At lower doses, its preferential blockade of presynaptic dopamine receptors can increase dopamine turnover. At higher doses, postsynaptic blockade leads to antipsychotic effects.

Q7: What are the contraindications for Sulpiride use?

A: Contraindications include phaeochromocytoma, acute porphyria, hypersensitivity to sulpiride, prolactin-dependent tumors, severe renal or hepatic impairment, concomitant use of levodopa, bone marrow suppression.

Q8: Does Sulpiride interact with other medications?

A: Yes, Sulpiride can interact with several medications, including QT prolonging drugs, antihypertensives, CNS depressants, antacids, and lithium.

Q9: Can Sulpiride be used to increase breast milk production?

A: While sulpiride can increase prolactin levels and has been used off-label as a galactagogue, its use for this purpose should be carefully considered and discussed with a physician due to potential side effects.

Q10: What should patients be advised regarding lifestyle while taking Sulpiride?

A: Patients should avoid alcohol while taking Sulpiride. They should also be cautious about driving or operating machinery due to the potential for drowsiness and impaired reaction time. They should protect their skin from bright sunlight.