brands

Class

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

PALIPERIDONE commonly prescribed for

(Bold for FDA approved)

How PALIPERIDONE 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 paliperidone’s efficacy

• Serotonin 7 antagonist properties may contribute to antidepressant actions

How long until PALIPERIDONE works

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

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

Notable Side Effects

• Dose-dependent drug-induced parkinsonism

• Hyperprolactinemia

• May increase risk for diabetes and dyslipidemia

• Sedation

• Tachycardia

• Hypersalivation

• Dose-dependent orthostatic hypotension

• Injection site reactions

• 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

common

sedation

common

What to do about PALIPERIDONE side effects

• Wait

• Wait

• Wait

• 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

• 6 mg/day (oral)

• 1-month injectable maintenance dose: 117 mg/month (range 39–234 mg/month (see Paliperidone Palmitate section after Pearls for dosing and use)

• 3-month injectable maintenance dose: 273–819 mg/3 months (see Paliperidone Palmitate section after Pearls for dosing and use)

• 6-month injectable maintenance dose: based on the previous once-a-month or every-3-month product dose

Dosage Forms

• Tablet (extended-release) 1.5 mg, 3 mg, 6 mg, 9 mg

• 1-month injection 39 mg, 78 mg, 117 mg, 156 mg, 234 mg

• 3-month injection 273 mg, 410 mg, 546 mg, 819 mg

• 6-month injection 1092 mg, 1560 mg

long term use

• Approved for maintenance in schizophrenia

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

habit forming

• No

Renal Impairment

• For mild impairment, maximum recommended dose 6 mg/day

• For moderate impairment, initial and maximum recommended dose 3 mg/day

• For severe impairment, initial dose 1.5 mg/ day; maximum recommended dose 3 mg/ day

Hepatic Impairment

• No dose adjustment necessary for mild to moderate impairment

• Use in individuals with severe hepatic impairment has not been studied

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

• 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

• Safety and efficacy have not been established under age 12

• Adolescents <51 kg: initial 3 mg/day; recommended 3–6 mg/day; maximum 6 mg/day

• Adolescents >51 kg: initial 3 mg/day; recommended 3–12 mg/day; maximum 12 mg/day

• Children and adolescents using paliperidone 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

• When administered to rats during the period of organogenesis, there were no treatmentrelated effects at doses up to 10 times the maximum recommended human dose

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

• Paliperidone 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 paliperidone should be monitored for possible adverse effects; sedation, failure to thrive, jitteriness, and drug-induced parkinsonism (tremor and abnormal muscle movements) have been reported