LUMATEPERONE

Class

• Atypical antipsychotic (serotonin– dopamine antagonist; second-generation antipsychotic; also a mood stabilizer)

LUMATEPERONE commonly prescribed for

(Bold for FDA approved)

How LUMATEPERONE works

• Blocks serotonin 2A receptors, causing enhancement of dopamine release in certain brain regions and thus reducing motor side effects and possibly improving cognitive and affective symptoms

• Blocks postsynaptic dopamine 2 receptors, reducing positive symptoms of psychosis and stabilizing affective symptoms

• Binds as a partial agonist at presynaptic dopamine 2 receptors

• Interactions at a myriad of other neurotransmitter receptors may contribute to lumateperone’s efficacy

• Binds to dopamine 1 receptors, with preclinical data showing dopamine-1- dependent activation of AMPA receptors leading to activation of the mTOR pathway, a mechanism that has been associated with antidepressant effects

• Also has affinity for the serotonin reuptake pump (SERT, serotonin transporter)

How long until LUMATEPERONE works

• Psychotic and manic 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

• Sedation, dry mouth, nausea

• Tardive dyskinesia (reduced risk compared to conventional antipsychotics)

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

Life Threatening Side Effects

• Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients taking atypical antipsychotics

• 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

• 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

unusual

sedation

common

What to do about LUMATEPERONE side effects

• Wait

• Wait

• Wait

• Take in the evening to help reduce daytime sedation

• Anticholinergics may reduce drug-induced parkinsonism when present

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

• 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

• 42 mg once daily

Dosage Forms

• Capsule 42 mg

long term use

• Studied in clinical trials for up to 1 year

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

habit forming

• No

Renal Impairment

• Dose adjustment not necessary

Hepatic Impairment

• Mild impairment (Child–Pugh score between 5 and 6): no dose adjustment necessary

• Not recommended for use in patients with moderate to severe impairment

Cardiac Impairment

• Use in patients with cardiac impairment has not been studied, so use with caution because of risk of orthostatic hypotension

• Use with caution if patient is taking concomitant antihypertensive or alpha 1 antagonist

Elderly

• 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

• 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

• Consider pimavanserin for dementia-related psychosis or Parkinson’s disease psychosis instead of an atypical antipsychotic

Children and Adolescents

• Safety and efficacy have not been established

• Children and adolescents using lumateperone may need to be monitored more often than adults

Pregnancy

• Controlled studies have not been conducted in pregnant women

• In rats and rabbits, administration of lumateperone during organogenesis did not result in malformations at doses 2.4 and 9.7 times, respectively, the maximum recommended human dose (MRHD) of 42 mg

• In rats, administration of lumateperone during organogenesis through lactation resulted in lower pup survival at 4.9 times the MRHD, but not at 2.4 times the MRHD

• 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 lumateperone is secreted in human breast milk, but all psychotropics are assumed to be secreted in breast milk

• Recommended either to discontinue drug or formula feed

• Infants of women who choose to breast feed while on lumateperone should be monitored for possible adverse effects