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 dementia-related psychosis

• Elderly patients with dementia-related psychosis treated with atypical antipsychotics are at an increased risk of death compared to placebo, and also have an increased risk of cerebrovascular events

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

• Amisulpride may be preferable to anticonvulsant mood stabilizers if treatment is required during pregnancy

Breast Feeding

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

✽ Recommended either to discontinue drug or bottle feed

AMISULPRIDE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Not as clearly associated with weight gain as some other atypical antipsychotics

• For patients who are responsive to low dose activation effects that reduce negative symptoms and depression

Potential Disadvantages

• Patients who have difficulty being compliant with twice daily dosing

• Patients for whom elevated prolactin may not be desired (e.g., possibly pregnant patients; pubescent girls with amenorrhea; postmenopausal women with low estrogen who do not take estrogen replacement therapy)

• Patients with severe renal impairment

Primary Target Symptoms

• Positive symptoms of psychosis

• Negative symptoms of psychosis

• Depressive symptoms

Pearls

✽ Efficacy has been particularly well demonstrated in patients with predominantly negative symptoms

✽ The increase in prolactin caused by amisulpride may cause menstruation to stop

• Some treatment-resistant patients with inadequate responses to clozapine may benefit from amisulpride augmentation of clozapine

• Risks of diabetes and dyslipidemia not well studied, but does not seem to cause as much weight gain as some other atypical antipsychotics

• Has atypical antipsychotic properties (i.e., antipsychotic action without a high incidence of extrapyramidal symptoms), especially at low doses, but not a serotonin dopamine antagonist

• Mediates its atypical antipsychotic properties via novel actions on dopamine receptors, perhaps dopamine stabilizing partial agonist actions on dopamine 2 receptors

• May be more of a dopamine 2 antagonist than aripiprazole, but less of a dopamine 2 antagonist than other atypical or conventional antipsychotics

• Low dose activating actions may be beneficial for negative symptoms in schizophrenia

• Very low doses may be useful in dysthymia

• Compared to sulpiride, amisulpride has better oral bioavailability and more potency, thus allowing lower dosing, less weight gain, and fewer extrapyramidal symptoms

• Compared to other atypical antipsychotics with potent serotonin 2A antagonism, amisulpride may have more extrapyramidal symptoms and prolactin elevation, but may still be classified as an atypical antipsychotic, particularly at low doses

• Patients have very similar antipsychotic responses to any conventional antipsychotic, which is different from atypical antipsychotics where antipsychotic responses of individual patients can occasionally vary greatly from one atypical antipsychotic to another

• Patients with inadequate responses to atypical antipsychotics may benefit from determination of plasma drug levels and, if low, a dosage increase even beyond the usual prescribing limits

• Patients with inadequate responses to atypical antipsychotics may also benefit from a trial of augmentation with a conventional antipsychotic or switching to a conventional antipsychotic

• However, long-term polypharmacy with a combination of a conventional antipsychotic with an atypical antipsychotic may combine their side effects without clearly augmenting the efficacy of either

• For treatment-resistant patients, especially those with impulsivity, aggression, violence, and self-harm, long-term polypharmacy with 2 atypical antipsychotics or with 1 atypical antipsychotic and 1 conventional antipsychotic may be useful or even necessary while closely monitoring

• In such cases, it may be beneficial to combine 1 depot antipsychotic with 1 oral antipsychotic

• Although a frequent practice by some prescribers, adding two conventional antipsychotics together has little rationale and may reduce tolerability without clearly enhancing efficacy

THE ART OF SWITCHING