Sulpiride

Sulpiride's primary use in medicine is in the management of the symptoms of schizophrenia.[1] It has been used as both a monotherapy and adjunctive therapy (in case of treatment-resistance) in schizophrenia.[1][9][10][11][12][13] It has also been used in the treatment of dysthymia.[14] There is evidence, although low quality, that Sulpiride could accelerate antidepressant response in patients with major depressive disorder.[15] There is also evidence of its efficacy in treating panic disorder.[16][17] Sulpiride is indicated for the treatment of vertigo in some countries.[18] In Japan, Sulpiride is both approved as a treatment for schizophrenia and for major depressive disorder (low dose).[19][20]

Contraindications[1]

• Hypersensitivity to sulpiride
• Pre-existing breast cancer or other prolactin-dependent tumors
• Phaeochromocytoma
• Intoxication with other centrally-active drugs
• Concomitant use of levodopa
• Acute porphyria
• Comatose state or CNS depression
• Bone-marrow suppression

Cautions[1]

• Pre-existing Parkinson's disease
• Patients under 18 years of age (insufficient clinical data)
• Pre-existing severe heart disease/bradycardia, or hypokalemia (predisposing to long QT syndrome and severe arrhythmias)
• Patients with pre-existing epilepsy. Anticonvulsant therapy should be maintained
• Lithium use — increased risk of neurological side effects of both drugs

Sulpiride is usually well tolerated, producing few adverse effects. Their incidences are as follows:[1][9][21][22][23][24][25][26][27]

Common (>1%) adverse effects

• Dizziness
• Headache
• Extrapyramidal side effects

- Tremor

- Dystonia

- Akathisia — a sense of inner restlessness that presents itself with the inability to stay still

- Parkinsonism

• Somnolence (not a very prominent adverse effect considering its lack of α₁ adrenergic, histamine and muscarinic acetylcholine receptor affinity)
• Insomnia
• Weight gain or loss
• Hyperprolactinemia (elevated plasma levels of the hormone, prolactin which can, in turn lead to sexual dysfunction, galactorrhea, amenorrhea, gynecomastia, etc.)
• Nausea
• Vomiting
• Nasal congestion
• Anticholinergic adverse effects such as:

- Dry mouth

- Constipation

- Blurred vision

• Impaired concentration

Rare (<1% incidence) adverse effects

• Tardive dyskinesia — a rare, often permanent movement disorder that, more often than not, results from prolonged treatment with antidopaminergic agents such as antipsychotics. It presents with slow (hence tardive), involuntary, repetitive and purposeless movements that most often affect the facial muscles.
• Neuroleptic malignant syndrome — a rare, life-threatening complication that results from the use of antidopaminergic agents. Its incidence increases with concomitant use of lithium (medication) salts
• Blood dyscrasias — rare, sometimes life-threatening complications of the use of a number of different antipsychotics (most notably clozapine) which involves abnormalities in the composition of a person's blood (e.g. having too few white blood cells per unit volume of blood). Examples include:

- Agranulocytosis — a significant drop in white blood cell count, leaving individuals wide open to life-threatening opportunistic infections

- Neutropenia

- Leucopenia

- Leukocytosis[28]

• Seizures
• Torsades de pointes

Unknown incidence adverse effects include

• QTc interval prolongation which can lead to potentially fatal arrhythmias.
• Cholestatic jaundice[29]
• Elevated liver enzymes
• Primary biliary cirrhosis[30]
• Allergic reactions
• Photosensitivity — sensitivity to light
• Skin rashes
• Depression
• Catatonia
• Palpitations
• Agitation
• Diaphoresis — sweating without a precipitating factor (e.g. increased ambient temperature)
• Hypotension — low blood pressure
• Hypertension — high blood pressure
• Venous thromboembolism (probably rare)

Sulpiride has a relatively low order of acute toxicity. Substantial amounts may cause severe but reversible dystonic crises with torticollis, protrusion of the tongue, and/or trismus. In some cases all the classical symptoms typical of severe Parkinson's disease may be noted; in others, over-sedation/coma may occur. The treatment is largely symptomatic. Some or all extrapyramidal reactions may respond to the application of anticholinergic drugs such as biperiden or benzatropine. All patients should be closely monitored for signs of long QT syndrome and severe arrhythmias.

Sulpiride neigher inhibits nor stimulates cytochrome P450 family (CYP) of oxidizing enzymes in human, thus would not cause clinically significant interactions with other drugs,[4] which are metabolized by CYPs. However, the risk or severity of adverse effects can be increased when sulpiride is combined with other drugs, but this is not related to substrates, inducers and inhibitors of CYPs.

Sulpiride was discovered as a result of a research program by Justin-Besançon and C. Laville at Laboratoires Delagrange who were working to improve the anti-dysrhythmic properties of procainamide; the program led first to metoclopramide and later to sulpiride.[35][36] Laboratoires Delagrange was acquired by Synthelabo in 1991[37][38] which eventually became part of Sanofi.[39]

Sulpiride has been studied for use as a hormonal contraceptive in women in whom conventional oral contraceptives are contraindicated and to potentiate progestogen-only contraceptives.[42][43] The contraceptive effects of sulpiride are due to its prolactin-releasing and antigonadotropic effects and the hyperprolactinemia–amenorrhea state that it induces.[42][43]