brands

Class

• Neuroscience-based Nomenclature: dopamine receptor antagonist (D-RAn)
• Atypical antipsychotic (benzamide; possibly a dopamine stabilizer and dopamine partial agonist)

AMISULPRIDE commonly prescribed for

(Bold for FDA approved)

How AMISULPRIDE works

• Theoretically blocks presynaptic dopamine 2 receptors at low doses

• Theoretically blocks postsynaptic dopamine 2 receptors at higher doses

• May be a partial agonist at dopamine 2 receptors, which would theoretically reduce dopamine output when dopamine concentrations are high and increase dopamine output when dopamine concentrations are low

• Blocks dopamine 3 receptors, which may contribute to its clinical actions

• Unlike other atypical antipsychotics, amisulpride does not have potent actions at serotonin 2A or serotonin 1A receptors

• Does have antagonist actions at serotonin 7 receptors and serotonin 2B receptors, which may contribute to antidepressant effects

How long until AMISULPRIDE works

• Psychotic symptoms can improve within 1 week, but it may take several weeks for full effect on behavior as well as on cognition and affective stabilization

• Classically recommended to wait at least 4–6 weeks to determine efficacy of drug, but in practice some patients require up to 16–20 weeks to show a good response, especially on negative or cognitive symptoms

Notable Side Effects

• Drug-induced parkinsonism

• Galactorrhea, amenorrhea

• Atypical antipsychotics may increase the risk for diabetes and dyslipidemia, although the specific risks associated with amisulpride are unknown

• Insomnia, sedation, agitation, anxiety

• Constipation, weight gain

• Tardive dyskinesia

• Risk of potentially irreversible involuntary dyskinetic movements may increase with cumulative dose and treatment duration

Life Threatening Side Effects

• Rare neuroleptic malignant syndrome may cause hyperpyrexia, muscle rigidity, delirium, and autonomic instability with elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure

• Rare seizures

• Dose-dependent QTc prolongation

• As a class, antipsychotics are associated with an increased risk of death and cerebrovascular events in elderly patients with dementia; not approved for treatment of dementia-related psychosis

weight gain

not usual

sedation

common

What to do about AMISULPRIDE side effects

• Wait

• Wait

• Wait

• Lower the dose

• For drug-induced parkinsonism, add an anticholinergic agent

• Beta blockers, benzodiazepines, or serotonin 2A antagonists (e.g., mirtazapine, cyproheptadine) may reduce akathisia

• Take more of the dose at bedtime to help reduce daytime sedation

• Weight loss, exercise programs, and medical management for high BMIs, diabetes, dyslipidemia

• Metformin may help prevent or reverse antipsychotic-induced weight gain

• Switch to another atypical antipsychotic

usual dosage range

• Schizophrenia: 400–800 mg/day in 2 doses

• Negative symptoms only: 50–300 mg/day

• Dysthymia: 50 mg/day

Dosage Forms

• Different formulations may be available in different markets

• Tablet 50 mg, 100 mg, 200 mg, 400 mg

long term use

• Amisulpride is used for both acute and chronic schizophrenia treatment

• Should periodically reevaluate long-term usefulness in individual patients, but treatment may need to continue for many years

habit forming

• No

Renal Impairment

• Use with caution; drug may accumulate

• Amisulpride is eliminated by the renal route; in cases of severe renal insufficiency, the dose should be decreased and intermittent treatment or switching to another antipsychotic should be considered

Hepatic Impairment

• Use with caution, but dose adjustment not generally necessary

Cardiac Impairment

• Amisulpride produces a dose-dependent prolongation of QTc interval, which may be enhanced by the existence of bradycardia, hypokalemia, congenital or acquired long QTc interval, which should be evaluated prior to administering amisulpride

• Use with caution if treating concomitantly with a medication likely to produce prolonged bradycardia, hypokalemia, slowing of intracardiac conduction, or prolongation of the QTc interval

• Avoid amisulpride in patients with a known history of QTc prolongation, recent acute myocardial infarction, and uncompensated heart failure

Elderly

• Some patients may be more susceptible to sedative and hypotensive effects

• Although atypical antipsychotics are commonly used for behavioral disturbances in dementia, no agent has been approved for treatment of elderly patients with behavioral symptoms of dementia such as agitation

Children and Adolescents

• Efficacy and safety not established under age 18

Pregnancy

• Although animal studies have not shown teratogenic effect, amisulpride is not recommended for use during pregnancy

• There is a risk of abnormal muscle movements and withdrawal symptoms in newborns whose mothers took an antipsychotic during the third trimester; symptoms may include agitation, abnormally increased or decreased muscle tone, tremor, sleepiness, severe difficulty breathing, and difficulty feeding

• Psychotic symptoms may worsen during pregnancy and some form of treatment may be necessary

Breast Feeding

Unknown if amisulpride is secreted in human breast milk, but all psychotropics are assumed to be secreted in breast milk

• Recommended either to discontinue drug or bottle feed