ARIPIPRAZOLE

brands

Class

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

ARIPIPRAZOLE commonly prescribed for

(Bold for FDA approved)

How ARIPIPRAZOLE 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

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

• Actions at dopamine 3 receptors could theoretically contribute to aripiprazole’s efficacy

• Partial agonism at serotonin 1A receptors may be relevant at clinical doses

• 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

• Blockade of serotonin type 2C and 7 receptors as well as partial agonist actions at serotonin 1A receptors may contribute to antidepressant actions

How long until ARIPIPRAZOLE 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

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

Notable Side Effects

• Dizziness, insomnia, akathisia, activation

• Nausea, vomiting

• Constipation

• Headache, asthenia

• Orthostatic hypotension, occasionally during initial dosing

• 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

• Rare impulse control problems

• 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

unusual

What to do about ARIPIPRAZOLE side effects

• Wait

• Wait

• Wait

• Reduce the dose

• 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: 15–30 mg/day for schizophrenia and mania

• Oral: 2–10 mg/day for augmenting SSRIs/ SNRIs in depression

• Oral: 5–15 mg/day for autism

• Oral: 5–20 mg/day for Tourette’s syndrome

• Depot formulations: see Depot Formulations after Pearls for dosing and use

Dosage Forms

• Tablet 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg

• Orally disintegrating tablet 10 mg, 15 mg

• Oral solution 1 mg/mL

• Injection 9.75 mg/1.3 mL

• Depot (Abilify Maintena) 300 mg, 400 mg

• Depot (Abilify Asimtufii) 720 mg, 960 mg

• Depot (Aristada) 441 mg, 662 mg, 882 mg, 1064 mg

• Single-dose injection (Initio) 675 mg

long term use

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

• Approved for long-term maintenance in bipolar disorder

• Often used for long-term maintenance in 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

• Dose adjustment not necessary

Hepatic Impairment

• Dose adjustment not necessary

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

• Dose adjustment generally not necessary, but 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

• Approved for use in schizophrenia (ages 13 and older), manic/mixed episodes (ages 10 and older), irritability associated with autism (ages 6–17), and treatment of Tourette’s syndrome (ages 6–18)

• Clinical experience and early data suggest aripiprazole may be safe and effective for behavioral disturbances in children and adolescents, especially at lower doses

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

• May be more risk of weight gain in children than in adults

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

• In animal studies, aripiprazole demonstrated developmental toxicity, including possible teratogenic effects, at doses higher than the maximum recommended human dose

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

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

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 aripiprazole should be monitored for possible adverse effects