CARIPRAZINE

brands

Class

• Neuroscience-based Nomenclature: dopamine, serotonin receptor partial agonist and antagonist
• Dopamine partial agonist (dopamine– serotonin partial agonist, dopamine stabilizer, atypical antipsychotic, thirdgeneration antipsychotic; sometimes included as a second-generation antipsychotic; also a potential mood stabilizer)

CARIPRAZINE commonly prescribed for

(Bold for FDA approved)

How CARIPRAZINE works

• Partial agonism at dopamine 2 receptors

• Theoretically reduces dopamine output when dopamine concentrations are high, thus improving positive symptoms and mediating antipsychotic actions

• Theoretically increases dopamine output when dopamine concentrations are low, thus improving cognitive, negative, and mood symptoms

• Preferentially binds to dopamine 3 over dopamine 2 receptors at low doses; the clinical significance is unknown but could theoretically contribute to cariprazine’s efficacy for negative symptoms. Dopamine 3 partial agonism could theoretically be useful for treating cognition, mood, emotions, and reward/substance use

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

• Cariprazine also has high affinity for the serotonin 1A (partial agonist) and 2B (antagonist) receptors

• 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

How long until CARIPRAZINE 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 full antipsychotic 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

• Akathisia, extrapyramidal symptoms, restlessness

• Gastrointestinal distress

• Sedation

• Tardive dyskinesia (reduced risk compared to conventional antipsychotics)

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

• Side effects may theoretically appear several weeks after initiating cariprazine because plasma levels and major active metabolites accumulate over time

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

• As a class, antidepressants have been reported to increase the risk of suicidal thoughts and behaviors in children and young adults

weight gain

unusual

sedation

not usual

What to do about CARIPRAZINE 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

• Schizophrenia: 1.5–6 mg once daily

• Bipolar mania: 3–6 mg once daily

• Bipolar depression: 1.5–3 mg once daily

• Major depressive disorder (adjunct): 1.5–3 mg once daily

Dosage Forms

• Capsule 1.5 mg, 3 mg, 4.5 mg, 6 mg

long term use

• Approved for maintenance treatment of schizophrenia in adults

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

habit forming

• No

Renal Impairment

• Mild to moderate impairment (creatinine clearance <30 mL/minute): no dose adjustment necessary

• Severe or end-stage: not recommended

Hepatic Impairment

• Mild to moderate impairment (Child– Pugh score between 5 and 9): no dose adjustment necessary

• Severe: not recommended

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 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 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 cariprazine 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

• In rats, administration of cariprazine during organogenesis caused malformations, lower pup survival, and developmental delays at exposures less than the human exposure at the maximum recommended human dose (MRHD) (6 mg/day); cariprazine was not teratogenic in rabbits at doses up to 4.6 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 cariprazine 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 cariprazine should be monitored for possible adverse effects