RISPERIDONE

brands

Class

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

RISPERIDONE commonly prescribed for

(Bold for FDA approved)

How RISPERIDONE 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 cognitive and affective symptoms

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

• Specifically, serotonin 7 antagonist properties may contribute to antidepressant actions

How long until RISPERIDONE 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

• May increase risk for diabetes and dyslipidemia

• Dose-dependent drug-induced parkinsonism, akathisia

• Dose-related hyperprolactinemia

• Dose-dependent dizziness, insomnia, anxiety, sedation, fatigue, headache

• Nausea, constipation, abdominal pain, dry mouth, dyspepsia, weight gain

• Tachycardia, dose-dependent sexual dysfunction

• Tardive dyskinesia (reduced risk compared to conventional antipsychotics)

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

• Rare orthostatic hypotension, usually during initial dose titration

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

common

sedation

common

What to do about RISPERIDONE side effects

• Wait

• Wait

• Wait

• Take at bedtime 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

• Oral: 2–8 mg/day for acute psychosis and bipolar disorder

• Oral: 0.5–2.0 mg/day for children and elderly

• Risperdal Consta: 12.5–50 mg every 2 weeks (intramuscular) (see Depot Formulations after Pearls for dosing and use)

• Rykindo: 25–50 mg every 2 weeks (intramuscular) (see Depot Formulations after Pearls for dosing and use)

• Perseris: 90 or 120 mg every month (subcutaneous) (see Depot Formulations after Pearls for dosing and use)

• Uzedy: 50–125 mg every month or 100–250 mg every 2 months (see Depot Formulations after Pearls for dosing and use)

Dosage Forms

• Tablets 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg, 6 mg

• Orally disintegrating tablets 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg

• Liquid 1 mg/mL

• Risperdal Consta (risperidone microspheres) 12.5 mg, 25 mg, 37.5 mg, 50 mg

• Rykindo (risperidone microspheres) 12.5 mg, 25 mg, 37.5 mg, 50 mg

• Perseris (risperidone subcutaneous) 90 mg, 120 mg

• Uzedy (risperidone subcutaneous) 50 mg, 75 mg, 100 mg, 125 mg, 150 mg, 200 mg, 250 mg

long term use

• Approved to delay relapse in long-term treatment of schizophrenia

• Often used for long-term maintenance in bipolar disorder and various behavioral disorders

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

habit forming

• No

Renal Impairment

• Oral: initial 0.5 mg twice a day for first week; increase to 1 mg twice a day during second week; dosage increases above 1.5 mg twice a day should occur at least 1 week apart

• Risperdal Consta: patient should demonstrate tolerability of at least 2 mg/ day orally prior to initiation; should be dosed at 25 mg every 2 weeks; oral administration should be continued for 3 weeks after the first injection

• Rykindo: patient should demonstrate tolerability of at least 2 mg/day orally prior to initiation; should be dosed at 25 mg every 2 weeks; oral administration should be continued for 7 days after the first injection

• Perseris: has not been studied in this population; recommended to titrate patients to at least 3 mg/day of oral risperidone and establish efficacy/tolerability prior to initiating the monthly injection

Hepatic Impairment

• Oral: initial 0.5 mg twice a day for first week; increase to 1 mg twice a day during second week

• Risperdal Consta: patient should demonstrate tolerability of at least 2 mg/day orally prior to initiation; should be dosed at 25 mg every 2 weeks; oral administration should be continued for 3 weeks after the first injection

• Rykindo: patient should demonstrate tolerability of at least 2 mg/day orally prior to initiation; should be dosed at 25 mg every 2 weeks; oral administration should be continued for 7 days after the first injection

• Perseris: has not been studied in this population; recommended to titrate patients to at least 3 mg/day of oral risperidone and establish efficacy/tolerability prior to initiating the monthly injection

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

• When administered to elderly patients with atrial fibrillation, may increase the chances of stroke

Elderly

• Initial 0.5 mg orally twice a day; increase by 0.5 mg twice a day; titrate once a week for doses above 1.5 mg twice a day

• Risperdal Consta: recommended dose is 25 mg every 2 weeks; oral administration should be continued for 3 weeks after the first injection

• Perseris: not studied in this population

• Some 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 dementia-related psychosis or Parkinson’s disease psychosis instead of an atypical antipsychotic

Children and Adolescents

• Oral risperidone is approved for use in schizophrenia (ages 13 and older), mania/ mixed episodes (ages 10 and older), and irritability associated with autism (ages 5–16)

• Risperidone is the most frequently used atypical antipsychotic in children and adolescents

• Clinical experience and early data suggest risperidone is safe and effective for behavioral disturbances in children and adolescents

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

Pregnancy

• Controlled studies have not been conducted in pregnant women

• 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

• Early findings of infants exposed to risperidone in utero do not show adverse consequences

• When administered to pregnant rats and rabbits, risperidone was not teratogenic at doses up to 6 times the maximum recommended human dose (MRHD); increased stillbirths and decreased birth weight occurred at 1.5 times the MRHD when administered to pregnant rats

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

• Effects of hyperprolactinemia on the fetus are unknown

Breast Feeding

• Some drug is found in mother’s breast milk

• Recommended either to discontinue drug or formula feed

• Infants of women who choose to breast feed while on risperidone should be monitored for possible adverse effects; sedation, failure to thrive, jitteriness, and drug-induced parkinsonism (tremor and abnormal muscle movements) have been reported