LURASIDONE

brands

Class

• Neuroscience-based Nomenclature: dopamine, serotonin receptor antagonist (DS-RAn)
• Atypical antipsychotic (serotonin– dopamine antagonist; second-generation antipsychotic; also a potential mood stabilizer)

LURASIDONE commonly prescribed for

(Bold for FDA approved)

How LURASIDONE works

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

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

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

• Potently blocks serotonin 7 receptors, which may be beneficial for mood, sleep, cognitive impairment, and negative symptoms in schizophrenia, and also in bipolar disorder and major depressive disorder

• Partial agonist at serotonin 1A receptors, and antagonist actions at serotonin 7 and alpha 2A and alpha 2C receptors, which may be beneficial for mood, anxiety, and cognition in a number of disorders

• Lacks potent actions at dopamine D1, muscarinic M1, and histamine H1 receptors, theoretically suggesting less propensity for inducing cognitive impairment, weight gain, or sedation compared to other agents with these properties

How long until LURASIDONE works

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

• For psychosis, 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

• For bipolar depression, onset of therapeutic actions usually not immediate, but often delayed 2–4 weeks

Notable Side Effects

• Dose-dependent sedation

• Akathisia

• Nausea

• Dose-dependent hyperprolactinemia

• May increase risk for diabetes and dyslipidemia

• 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

• Tachycardia, first-degree atrioventricular block

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

• 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 LURASIDONE side effects

• Wait

• Wait

• Wait

• Anticholinergics may reduce drug-induced parkinsonism when present

• Dose reduction may reduce akathisia when present

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

• Consider changing to nighttime dosing (with evening meal)

• 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

• 40–80 mg/day for schizophrenia

• Some patients with schizophrenia may benefit from doses up to 160 mg/day

• 20–60 mg/day for bipolar depression

• Some patients with bipolar depression may benefit from doses up to 120 mg/day

Dosage Forms

• Tablet 20 mg, 40 mg, 60 mg, 80 mg, 120 mg

long term use

• Not extensively studied past 52 weeks, but long-term maintenance treatment is often necessary for schizophrenia

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

habit forming

• No

Renal Impairment

• Moderate and severe impairment: initial 20 mg/day; maximum dose 80 mg/day

Hepatic Impairment

• Moderate impairment: initial 20 mg/day; maximum dose 80 mg/day

• Severe impairment: initial 20 mg/day; maximum dose 40 mg/day

Cardiac Impairment

• Use in patients with cardiac impairment has not been studied, so use with caution because of risk of orthostatic hypotension, although low potency at alpha 1 receptors suggests this risk may be less than for some other antipsychotics

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

• Lurasidone does not have a warning for QTc prolongation

Elderly

In general, no dose adjustment is necessary for elderly patients

• However, some elderly patients may tolerate lower doses better

• 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 dementiarelated psychosis or Parkinson’s disease psychosis instead of an atypical antipsychotic

Children and Adolescents

• Approved for schizophrenia in adolescents ages 13 and older

• Although lurasidone can be initiated at 40 mg/day, often a good idea to initiate at 20 mg to test for tolerability before raising dose to 40 mg, especially in children and in small body weight adolescents

• Approved for bipolar depression in bipolar I disorder in adolescents ages 10 and older

• Little or no weight gain documented in long-term studies up to 2 years

• Children and adolescents using lurasidone may need to be monitored more often than adults and may tolerate lower doses better

Pregnancy

• Effective June 30, 2015, the FDA requires changes to the content and format of pregnancy and lactation information in prescription drug labels, including the elimination of the pregnancy letter categories; the Pregnancy and Lactation Labeling Rule (PLLR or final rule) applies only to prescription drugs and will be phased in gradually for drugs approved on or after June 30, 2001

• Controlled studies have not been conducted in pregnant women

• Animal studies do not show adverse effects; not teratogenic in rats and rabbits at doses up to 1.5–6 times the maximum recommended human dose

• 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

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

Breast Feeding

• Unknown if lurasidone 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 unless the potential benefit to the mother justifies the potential risk to the child

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