Version July 2025
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Aripiprazole is not approved for the treatment of patients with dementia-related psychosis.
Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients older than 24 years of age; there was a reduction in risk with antidepressant use in patients 65 years of age and older. Closely monitor all antidepressant-treated patients for clinical worsening and for the emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber. The safety and efficacy of aripiprazole tablets with sensor have not been established in pediatric patients.
Dosage guidance:
Safety: Antipsychotics are not indicated for use in catatonia and may worsen psychosis and increase risk for neuroleptic malignant syndrome in patients with catatonia (Ref).
Clinical considerations: For treatment of psychiatric disorders, consult a psychiatry specialist for all management decisions; select antipsychotic carefully based on patient preference, clinical characteristics, history, comorbidities, and adverse effect profile (Ref).
Agitation/Aggression (acute, severe) associated with psychiatric disorders (eg, schizophrenia, bipolar disorder), substance intoxication, or other organic causes (alternative agent) (off-label use) :
Note: Antipsychotics are appropriate when psychosis is suspected to be the primary cause of agitation/aggression. Other agents are used preferentially in some intoxications (eg, stimulants) or alcohol withdrawal. Depending on presentation, may combine with a benzodiazepine (Ref).
Oral: Initial: 10 to 15 mg; may repeat based on response and tolerability every 2 hours up to 30 mg/day (Ref).
Agitation/Aggression and psychosis associated with dementia, severe or refractory (alternative agent) (off-label use):
Note: For short-term adjunctive use while addressing underlying causes of severe symptoms (Ref).
Oral: Initial: 2 to 5 mg once daily; may increase dose based on response and tolerability in 5 mg increments at intervals ≥1 week up to 15 mg once daily. In patients without a clinically significant response after an adequate trial (eg, up to 4 weeks), taper and withdraw therapy. Only continue in patients with a demonstrated benefit and attempt to taper and withdraw at regular intervals; first taper attempt should occur ≤4 months of initiation (Ref).
Note: Patients with dementia with Lewy bodies are at increased risk for severe adverse reactions; caution is required even with low doses (Ref).
Bipolar disorder:
Oral: Acute mania or episodes with mixed features (labeled use), acute hypomania (off-label use), and maintenance treatment (labeled use, formulation specific) as monotherapy or adjunctive therapy: Initial: 10 to 15 mg once daily; may increase dose based on response and tolerability in 5 to 10 mg/day increments at intervals of ≥1 week up to a maximum of 30 mg/day (Ref). Note: Some experts suggest higher initial doses of up to 30 mg/day (Ref). Although the manufacturer's labeling recommends waiting ≥2 weeks before increasing dose due to long half-life of aripiprazole, it may be appropriate to increase dose at 1 week for some patients (Ref). For maintenance treatment, continue dose and combination regimen that was used to achieve control of the acute episode (Ref).
IM, ER injectable suspension (aripiprazole monohydrate) (alternative agent): Note: Establish tolerability with oral aripiprazole prior to initiation of ER injection; due to the prolonged half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.
Monthly injection (Abilify Maintena):
Single injection start: IM: 400 mg once monthly (doses should be separated by ≥26 days). Continue (overlap) oral aripiprazole or other oral antipsychotic for 14 days during initiation of the ER injection.
Double injection start: IM: Initial: Administer a single oral aripiprazole 20 mg dose, plus two 400 mg injections in separate injection sites (eg, right deltoid and left gluteal muscle). Maintenance: 400 mg once monthly (doses should be separated by ≥ 26 days) (Canadian product monograph).
Dosage adjustment of monthly ER injection for adverse effects: Consider reducing dose to 300 mg once monthly.
Missed doses of monthly ER injection:
Second or third doses missed:
>4 weeks but <5 weeks since last dose: Administer next dose as soon as possible.
>5 weeks since last dose: Administer oral aripiprazole for 14 days with next injection or administer 1 oral aripiprazole dose of 20 mg plus 2 aripiprazole 400 mg IM injections in separate injection sites (eg, right deltoid and left gluteal muscle) (Canadian product monograph); adjust oral dose as needed based on response and tolerability.
Fourth or subsequent doses missed:
>4 weeks but <6 weeks since last dose: Administer next dose as soon as possible.
>6 weeks since last dose: Administer oral aripiprazole for 14 days with next injection or administer 1 oral aripiprazole dose of 20 mg plus 2 aripiprazole 400 mg IM injections in separate injection sites (eg, right deltoid and left gluteal muscle) (Canadian product monograph); adjust oral dose as needed based on response and tolerability.
Every-2-months injection (Abilify Asimtufii):
IM: 960 mg once every 2 months (56 days); may be given up to 2 weeks before or 2 weeks after the 2-month schedule timepoint. Continue (overlap) oral aripiprazole or other oral antipsychotic for 14 days during initiation of every-2-months ER injection. When converting from monthly injection (Abilify Maintena), administer every-2-months injection in place of the next monthly injection; do not overlap with oral aripiprazole (Ref).
Dosage adjustment of every-2-months ER injection for adverse effects: Consider reducing dose to 720 mg every 2 months.
Missed doses of every-2-months ER injection:
>8 weeks and <14 weeks since last dose: Administer next dose as soon as possible then resume the once every-2-months schedule.
>14 weeks since last dose: Administer oral aripiprazole for 14 days with next injection.
Delusional disorder (off-label use):
Note: Dosing based on expert opinion:
Oral: Initial: 2 to 5 mg once daily; gradually increase to 10 mg/day; if needed, may further increase dose at intervals of ≥1 week based upon response and tolerability up to 30 mg/day (Ref).
Delusional infestation (delusional parasitosis) (alternative agent) (off-label use):
Oral: Initial: 2 to 5 mg once daily; may increase dose gradually based on response and tolerability in 2 mg increments at intervals ≥2 weeks up to 15 mg/day (Ref). Some patients may require doses up to 30 mg/day for optimal response. After achieving adequate response, maintain for ≥1 to 12 months before attempting to taper and discontinue (Ref).
Huntington disease–associated chorea (alternative agent) (off-label use):
Oral: Initial: 2 mg once daily; may increase dose gradually based on response and tolerability up to a usual range of 7.5 to 15 mg/day (Ref).
Major depressive disorder (unipolar), treatment resistant (adjunctive therapy with antidepressant):
Oral: Initial: 2 to 5 mg/day; may increase dose based on response and tolerability in 5 mg increments at intervals ≥1 week up to a manufacturer's maximum of 15 mg/day. A further increase up to 20 mg/day may be necessary in some patients for optimal response (Ref). Although the manufacturer's labeling recommends waiting ≥2 weeks before increasing dose due to long half-life of aripiprazole, it may be appropriate to increase dose at 1 week for some patients (Ref).
Obsessive-compulsive disorder, treatment resistant (adjunctive therapy to antidepressants) (off-label use):
Oral: Initial: 5 mg once daily; may increase dose gradually based on response and tolerability in 5 mg increments at intervals ≥1 week up to 15 mg/day (Ref).
Schizophrenia:
Oral: Initial: 5 to 10 mg once daily typically; however, some patients may benefit from 15 mg once daily initially. If this is a first episode of psychosis, consider initiating at a reduced dose (2 to 5 mg/day) because these patients will be more sensitive to adverse effects. May increase daily dose based on response and tolerability in increments of 5 to 10 mg no sooner than every 3 days; monitor for akathisia during titration. Usual dose range: 10 to 15 mg/day; use lowest effective maintenance dose. Maximum: 30 mg/day (Ref).
IM, ER injectable suspension (aripiprazole monohydrate):
Monthly injection (Abilify Maintena):
Note: Establish tolerability using oral aripiprazole prior to initiating long-acting IM injection; due to the prolonged half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability. This formulation should be administered no sooner than every 26 days (approximately every month).
Initial dosage:
Option 1: Single injection start: IM: 400 mg once. Initiate maintenance dosing ~1 month after first IM dose.
Oral overlap: Following the initial IM dose, continue oral aripiprazole for 14 days, and then discontinue oral aripiprazole. If patient is currently stabilized on a different oral antipsychotic, continue oral treatment with that antipsychotic for 14 days, and then discontinue oral antipsychotic.
Option 2: Double injection start: IM: Administer two 400 mg injections in separate injection sites (eg, right deltoid and left gluteal muscle) on the same day. Initiate maintenance ~1 month after first 2 IM doses (Canadian product monograph).
Oral overlap: Oral: Administer a single oral aripiprazole 20 mg dose on the same day as the 2 IM injections. No further oral overlap is needed (Canadian product monograph).
Maintenance dose:
IM: 400 mg every ~1 month. Maximum dose: 400 mg every ~1 month (Ref). May decrease to 300 mg every ~1 month based on tolerability.
Missed doses of monthly IM injection:
Second or third doses missed:
More than 4 weeks but <5 weeks since last dose: Administer next monthly injection as soon as possible. Resume monthly injections no sooner than 26 days later.
More than 5 weeks since last dose:
Single injection option: Administer next monthly injection as soon as possible and administer oral aripiprazole for 14 days (starting on injection day). Adjust daily oral dose as needed based on response and tolerability. Resume monthly injections no sooner than 26 days later.
Double injection option: Administer two aripiprazole 400 mg IM injections in separate injection sites (eg, right deltoid and left gluteal muscle) plus one oral aripiprazole dose of 20 mg as soon as possible. Resume monthly injections no sooner than 26 days later (Canadian product monograph).
Fourth or subsequent doses missed:
More than 4 weeks but <6 weeks since last dose: Administer next dose as soon as possible.
More than 6 weeks since last dose:
Single injection option: Administer next monthly injection as soon as possible and administer oral aripiprazole for 14 days (starting on injection day). Adjust daily oral dose as needed based on response and tolerability. Resume monthly injections no sooner than 26 days later.
Double injection option: Administer two aripiprazole 400 mg IM injections in separate injection sites (eg, right deltoid and left gluteal muscle) plus one oral aripiprazole dose of 20 mg as soon as possible. Resume monthly injections no sooner than 26 days later (Canadian product monograph).
2-month injection (Abilify Asimtufii):
Note: Establish tolerability using oral aripiprazole prior to initiating long-acting IM injection; due to the prolonged half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability. This formulation should be administered every 56 days (approximately every 2 months).
Initial dosage:
Scenario 1: Not previously receiving monthly injection (Abilify Maintena): IM: 960 mg once. Initiate maintenance dosing ~2 months after initial IM dose.
Oral overlap: Following the initial ER dose, continue oral aripiprazole for 14 days, and then discontinue oral aripiprazole. If patient is currently stabilized on a different oral antipsychotic, continue oral treatment with that antipsychotic for 14 days, and then discontinue oral antipsychotic.
Scenario 2: Converting from monthly injection (Abilify Maintena): IM: Administer 960 mg of Abilify Asimtufii in place of the next monthly Abilify Maintena injection. Initiate maintenance dosing ~2 months after initial Abilify Asimtufii dose.
Oral overlap: It is not necessary to overlap oral aripiprazole following the initial Abilify Asimtufii injection (Ref).
Maintenance dose: IM: 960 mg once every ~2 months. May administer each maintenance dose 6 to 8 weeks after previous IM dose. May decrease to 720 mg every ~2 months based on tolerability. Maximum dose: 960 mg every ~2 months (Ref).
Dosage adjustment in known poor CYP2D6 metabolizers: Initial and maintenance dose: 720 mg every ~2 months.
Missed doses of 2-month ER injection:
More than 8 weeks but <14 weeks since last dose: Administer next Abilify Asimtufii injection as soon as possible. Resume regular maintenance injections no sooner than ~2 months later.
More than 14 weeks since last dose: Administer next Abilify Asimtufii injection as soon as possible and administer oral aripiprazole for 14 days (starting on injection day). Adjust daily oral dose as needed based on response and tolerability. Resume regular maintenance injections no sooner than ~2 months later.
Tourette syndrome (off-label use): Oral: Initial: 2.5 mg once daily; may increase dose based on response and tolerability in 2.5 mg increments at intervals ≥3 days up to 30 mg/day (Ref).
Dosing conversions:
Orally disintegrating tablets to oral tablet: Orally disintegrating tablets may be substituted for the oral tablet on a mg-per-mg basis.
Oral solution to oral tablet: Oral solution may be substituted for the oral tablet on a mg-per-mg basis, up to 25 mg. Patients receiving 30 mg tablets should be given 25 mg oral solution.
Dosage adjustment based on CYP2D6 metabolizer status:
Oral: Aripiprazole dose should be reduced to 50% of the usual dose in known CYP2D6 poor metabolizers; subsequently adjust dose for favorable response and tolerability. Do not adjust dose for patients taking aripiprazole as adjunctive treatment for unipolar major depressive disorder.
IM, ER injectable suspension (aripiprazole monohydrate):
Monthly injection (Abilify Maintena):
Single injection start: Reduce aripiprazole dose to 300 mg once monthly in known CYP2D6 poor metabolizers; subsequently adjust dose according to response and tolerability.
Double injection start: Reduce initial 2 aripiprazole doses to 300 mg each and reduce monthly aripiprazole dose to 300 mg once monthly in known CYP2D6 poor metabolizers; subsequently adjust dose according to response and tolerability (Canadian product monograph).
Every-2-months injection (Abilify Asimtufii): Reduce aripiprazole dose to 720 mg every 2 months in known CYP2D6 poor metabolizers.
Discontinuation of therapy:
Oral: In the treatment of chronic psychiatric disease switching therapy rather than discontinuation is generally advised if side effects are intolerable or treatment is not effective. If patient insists on stopping treatment, gradual dose reduction (ie, over several weeks to months) is advised to detect a re-emergence of symptoms and to avoid withdrawal reactions (eg, agitation, alternating feelings of warmth and chill, anxiety, diaphoresis, dyskinesias, GI symptoms, insomnia, irritability, myalgia, paresthesia, psychosis, restlessness, rhinorrhea, tremor, vertigo) unless discontinuation is due to significant adverse effects. Monitor closely to allow for detection of prodromal symptoms of disease recurrence (Ref).
Long-acting injection: Switching to other treatments is generally advised if side effects are intolerable or treatment is not effective. However, if a patient insists on stopping treatment, gradual dose reduction to avoid withdrawal reactions is generally not needed with long-acting injectable antipsychotics. The risk of withdrawal symptoms from discontinuation of long-acting injectables is low because the rate of drug elimination is slow. Monitor closely to allow for detection of prodromal symptoms of disease recurrence (Ref).
Switching antipsychotics: An optimal universal strategy for switching antipsychotic drugs has not been established. Strategies include: Cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic) and abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose). In patients with schizophrenia at high risk of relapse, the current medication may be maintained at full dose as the new medication is increased (ie, overlap); once the new medication is at therapeutic dose, the first medication is gradually decreased and discontinued over 1 to 2 weeks (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed (highly protein bound; large Vd): No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Unlikely to be dialyzed (highly protein bound; large Vd): No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
The liver dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST, FCCP; Jeong Park, PharmD, MS, BCTXP, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD.
Liver impairment prior to treatment initiation:
Initial or dose titration in patients with preexisting liver cirrhosis:
Child-Turcotte-Pugh class A to C: IM, Oral: Initial: Use lowest recommended indication-specific dose; may titrate, if necessary, based on response and tolerability (Ref).
Liver impairment developing in patients already receiving aripiprazole :
Acute worsening of liver function (eg, requiring hospitalization):
Child-Turcotte-Pugh class A to C: IM, Oral: No dosage adjustment necessary; however, consider discontinuation of aripiprazole therapy in patients with suspected aripiprazole-induced liver injury (Ref).
Note: Avoid for behavioral problems associated with dementia or delirium unless alternative nonpharmacologic therapies have failed and patient may harm self or others. If used, consider deprescribing attempts to assess continued need and/or lowest effective dose. Of note, use in certain indications may be appropriate (eg, schizophrenia, bipolar disorder) (Ref). For psychiatric disorders, consult a psychiatry specialist for all management decisions (Ref).
All indications: Refer to adult dosing. Dosages in the lower range of recommended adult dosing are generally sufficient. Titrate dosage slowly and monitor carefully (Ref).
(For additional information see "Aripiprazole (oral and long-acting injectable [Abilify Maintena]): Pediatric drug information")
Dosage guidance:
Dosage form information: Oral solution may be substituted for the oral tablet on a milligram-per-milligram basis, up to 25 mg (eg, patients receiving 30 mg tablets should be given 25 mg oral solution). Approved pediatric indications may vary amongst generics; refer to product labeling.
Bipolar I disorder; acute mania or episodes with mixed features: Note : Due to decreased risk of extrapyramidal symptoms, second-generation antipsychotics including aripiprazole have replaced first-generation antipsychotics for treatment as monotherapy or in combination with other agents (Ref).
Children ≥10 years and Adolescents <18 years: Orally disintegrating tablet, oral solution, tablets (Abilify): Oral: Initial: 2 mg once daily for 2 days, followed by 5 mg once daily for 2 days with a further increase to target dose of 10 mg once daily; subsequent dose increases may be made in 5 mg increments, up to a maximum daily dose: 30 mg/day.
Conduct disorder (CD); aggression: Limited data available: Children ≥6 years and Adolescents: Oral: Initial: 1 to 2.5 mg once daily; may titrate at weekly intervals in 2.5 mg/day increments to clinical effectiveness; maximum daily dose: 15 mg/day.
Dosing based on two open-label, prospective studies (Ref) (n=43; age: 6 to 17 years) which evaluated pharmacokinetics and effectiveness in patients with a primary diagnosis of CD (with or without comorbid attention-deficit/hyperactivity disorder); results showed improvement in CD symptom scores with only minor improvements in cognition.
Irritability, associated with autistic disorder: Children ≥6 years and Adolescents <18 years: Orally disintegrating tablets; oral film (Opipza), oral solution, tablets (Abilify): Oral: Initial: 2 mg once daily for 7 days, followed by 5 mg once daily; subsequent dose increases may be made in 5 mg increments every ≥7 days, up to a maximum daily dose: 15 mg/day.
Schizophrenia: Note : Second-generation antipsychotics (including aripiprazole) are generally the preferred initial treatment in management of pediatric patients with schizophrenia due to decreased risk of extrapyramidal symptoms and tardive dyskinesia (Ref).
Adolescents 13 to <18 years: Orally disintegrating tablets; oral film (Opipza), oral solution, tablets (Abilify): Oral: Initial: 2 mg once daily for 2 days, followed by 5 mg once daily for 2 days with a further increase to target dose of 10 mg once daily; subsequent dose increases may be made in 5 mg increments up to a maximum daily dose: 30 mg/day. Note: A daily dose of 30 mg/day was not found to be more effective than the 10 mg/day dose.
Tourette syndrome, tic disorder:
Children ≥6 years and Adolescents:
Patient weight <50 kg: Orally disintegrating tablets, oral film (Opipza), oral solution, tablets (Abilify): Oral: Initial: 2 mg once daily for 2 days, then increase to target dose of 5 mg/day; in patients not achieving optimal control, dose may be further titrated at weekly intervals up to 10 mg/day.
Patient weight ≥50 kg: Orally disintegrating tablets, oral film (Opipza), oral solution, tablets (Abilify): Oral: Initial: 2 mg once daily for 2 days, then increase to 5 mg/day for 5 days, then increase to target dose of 10 mg/day on day 8 of therapy; in patients not achieving optimal control, dose may be further titrated at weekly intervals in 5 mg/day increments up to 20 mg/day.
Dosage adjustment based on CYP2D6 metabolizer status:
Children ≥6 years and Adolescents: Oral: Initial: Aripiprazole dose should be reduced to 50% of the usual dose in known CYP2D6 poor metabolizers; subsequently adjust dose for favorable response and tolerability.
Discontinuation of therapy: Children and Adolescents: American Academy of Child and Adolescent Psychiatry (AACAP), American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), National Institute for Health and Care Excellence (NICE), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid withdrawal symptoms and minimize the risk of relapse (Ref); risk for withdrawal symptoms may be highest with highly anticholinergic or dopaminergic antipsychotics (Ref). When stopping antipsychotic therapy in patients with schizophrenia, the CPA guidelines recommend a gradual taper over 6 to 24 months and the APA guidelines recommend reducing the dose by 10% each month (Ref). Continuing antiparkinsonism agents for a brief period after discontinuation may prevent withdrawal symptoms (Ref). When switching antipsychotics, three strategies have been suggested: Cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic), overlap and taper (maintaining the dose of the first antipsychotic while gradually increasing the new antipsychotic, then tapering the first antipsychotic), and abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose). Evidence supporting ideal switch strategies and taper rates is limited and results are conflicting (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥6 years and Adolescents: Oral: No dosage adjustment required.
Children ≥6 years and Adolescents: Oral: No dosage adjustment required.
Both activating effects (eg, akathisia, restlessness) and sedating effects (eg, sedated state, drowsiness) may occur with aripiprazole and may lead to nonadherence or discontinuation. Individual patient experience can vary depending on the person's sensitivity toward activation or sedation and the dose used (Ref).
Mechanism: Dose-related; sedation is believed to be due to H1 antagonism leading to potential CNS depressant effects; aripiprazole is considered to display modest antagonism at H1 receptors (Ref).
Risk factors:
• Young age (in general, children and adolescents appear to be at higher risk for sedation due to antipsychotics compared to adults (Ref); in studies that included aripiprazole in children and adolescents, younger age has been associated with activating symptoms and higher age has been associated with sedating symptoms) (Ref)
• Specific antipsychotic (aripiprazole is generally considered to be minimally sedating at usual therapeutic doses in comparison with other antipsychotics) (Ref)
Angioedema may occur with use of aripiprazole (Shirk 2021 33970023).
Mechanism: Unknown; both a nonallergic and allergic mechanism have been proposed with antipsychotic-induced angioedema, including IgE-related hypersensitivity, kinin-dependent processes, or C1-esterase inhibition deficiencies (Ref).
Onset: Varied; onset following aripiprazole use has been described within several doses (Ref). When angioedema has occurred following use of other antipsychotics, onset has occurred within minutes to years (Ref).
Risk factors:
• Cross-reactivity: The risk of cross-reactivity between antipsychotics as it relates to angioedema events is not well established; however, cross-reactivity has been described between clozapine and olanzapine, haloperidol and iloperidone, and haloperidol and aripiprazole (Ref).
Antipsychotics are associated with dyslipidemia in adult and pediatric patients, which is a component of the metabolic syndrome observed with this pharmacologic class. Aripiprazole is associated with a low risk of causing lipid abnormalities; however, hypertriglyceridemia and hypercholesterolemia have been observed (Ref).
Mechanism: The mechanism is not entirely understood and is likely multifactorial (Ref).
Onset: Varied; metabolic alterations from antipsychotics can develop in as short as 3 months after initiation (Ref).
Risk factors:
• Schizophrenia (regardless of medication use) is associated with a higher rate of morbidity/mortality compared to the general population, primarily due to cardiovascular disease (Ref)
• Specific antipsychotic: Clozapine and olanzapine are associated with a high risk of hyperlipidemia while aripiprazole and ziprasidone are associated with the lowest risk (Ref)
Aripiprazole may cause extrapyramidal symptoms (EPS), also known as drug-induced movement disorders, particularly akathisia in all ages (Ref). Antipsychotics can cause 4 main EPS: Drug-induced parkinsonism, akathisia, acute dystonia, and tardive dyskinesia (Ref). EPS presenting as dysphagia, esophageal motility disorder, or pulmonary aspiration have also been reported with antipsychotics, which may not be recognized as EPS (Ref).
Mechanism: EPS: Dose-related; due to antagonism of dopaminergic D2 receptors in nigrostriatal pathways (as either antagonists or as a partial agonist, such as aripiprazole) (Ref). Akathisia: Mechanism not completely understood, but possibly associated with the low activity of dopaminergic projections from the midbrain to the ventral striatum and imbalance between the dopamine and serotonin neurotransmitter system (Ref). Tardive dyskinesia: Time-related (delayed); results from chronic exposure to dopamine 2 receptor antagonists leading to up-regulation of these receptors over time; aripiprazole has partial agonistic activity at the D2 receptor; however, it has one of the highest D2 receptor affinities among the antipsychotic agents (Ref).
Onset:
Antipsychotics in general:
Acute dystonia: Rapid; in the majority of cases, dystonia usually occurs within the first 5 days after initiating antipsychotic therapy (and even with the first dose, particularly in patients receiving parenteral antipsychotics) or a dosage increase (Ref).
Drug-induced parkinsonism: Varied; onset may be delayed from days to weeks, with 50% to 75% of cases occurring within 1 month and 90% within 3 months of antipsychotic initiation, a dosage increase, or a change in the medication regimen (such as adding another antipsychotic agent or discontinuing an anticholinergic medication) (Ref).
Akathisia: Varied; may begin within several days after antipsychotic initiation but usually increases with treatment duration, occurring within 1 month in up to 50% of cases and within 3 months in 90% of cases (Ref).
Tardive dyskinesia: Delayed; symptoms usually appear after 1 to 2 years of continuous exposure to a dopamine 2 receptor antagonist, and almost never before 3 months, with an insidious onset, evolving into a full syndrome over days and weeks, followed by symptom stabilization and then a chronic waxing and waning of symptoms (Ref).
Esophageal dysfunction (associated with EPS): Varied; ranges from weeks to months following initiation (Ref).
Risk factors:
EPS (in general):
• Prior history of EPS (Ref)
• Higher doses (Ref)
• Younger age (in general, children and adolescents are usually at higher risk for EPS compared to adults) (Ref)
• Specific antipsychotic: Aripiprazole is usually associated with a lower risk of EPS, with the possible exception of akathisia (Ref)
Acute dystonia:
• Males (Ref)
• Young age (Ref)
Drug-induced parkinsonism:
• Females (Ref)
• Older patients (Ref)
Akathisia:
• Higher antipsychotic dosages (Ref)
• Polypharmacy (Ref)
• Mood disorders (Ref)
• Females (Ref)
• Older patients (Ref)
Tardive dyskinesia:
• Age >55 years (Ref)
• Cognitive impairment (Ref)
• Concomitant treatment with anticholinergic medications (Ref)
• Diabetes (Ref)
• Diagnosis of schizophrenia or affective disorders (Ref)
• Female sex (Ref)
• Greater total antipsychotic exposure (especially first-generation antipsychotics) (Ref)
• History of extrapyramidal symptoms (Ref)
• Substance misuse or dependence (Ref)
• Race (White or African descent). Note: Although early literature supported race as a potential risk factor for tardive dyskinesia (Morgenstern 1993), newer studies have challenged this assertion (Ref).
Esophageal dysfunction (associated with EPS):
• Certain comorbidities such as neurologic degenerative disease, dementia, stroke, Parkinson disease, or myasthenia gravis (Ref)
• Older adults >75 years of age (may be risk factor due to age related muscle atrophy, cognitive impairment, reduced esophageal peristalsis) (Ref)
Leukopenia and neutropenia have been reported with aripiprazole (Ref). Agranulocytosis has been reported with other atypical antipsychotics and, per the manufacturer's labeling, has also been reported with aripiprazole.
Mechanism: Non–dose-related; likely idiosyncratic (Ref).
Onset: Varied; in general, drug-induced neutropenia usually manifests after 1 or 2 weeks of exposure and agranulocytosis usually appears 3 to 4 weeks following initiation of therapy; however, the onset may be insidious (Ref).
Risk factors:
• History of drug-induced leukopenia/neutropenia and preexisting low white blood cell count/absolute neutrophil count
• Older adults (Ref)
Antipsychotics are associated with hyperglycemia, to varying degrees, which is a component of the metabolic syndrome observed with this pharmacologic class. Aripiprazole is associated with a low risk of causing metabolic alterations; however, glycemic abnormalities ranging from mild insulin resistance or hyperglycemia to new-onset diabetes mellitus, diabetes mellitus with hyperosmolar coma, and diabetic ketoacidosis, including fatal cases, have been observed (Ref).
Mechanism: The mechanism is not entirely understood and is likely multifactorial (Ref).
Onset: Varied; new-onset diabetes has been observed within first 3 months to a median onset of 3.9 years (Ref).
Risk factors:
Antipsychotics in general:
• African American race (Ref)
• Males (Ref)
• Age <35 years (Ref)
• Preexisting obesity, poor exercise habits, or other risk factors for diabetes, including family history of diabetes (Ref)
• Exposure to other agents that also increase the risk of hyperglycemia (Ref)
• Type 2 diabetes mellitus: Extended exposure (mean: 17.2 months) in pediatric patients 10 to 18 years (Ref)
• Specific antipsychotic: Metabolic disturbances appear to be the greatest with clozapine and olanzapine and lowest with aripiprazole (Ref)
Aripiprazole has been associated with an increased risk of developing impulse control disorders, which primarily manifests as pathological gambling, although other reported behaviors include hypersexuality, compulsive buying, compulsive eating, and/or other intense urges (Ref).
Mechanism: Non–dose-related; may be due to aripiprazole’s partial dopamine agonist activity in brain circuits regulating reward pathways such as the mesolimbic circuitry (Ref).
Onset: Varied; case reports and case series of aripiprazole-associated pathological gambling suggest that the onset occurs between a few days and a few months after initiation, with some cases occurring only after an increase in dosage (Ref).
Risk factors:
• History of impulse control disorders and gambling behaviors (Ref)
• The depot formulation (aripiprazole lauroxil) may be associated with an increased risk compared to oral aripiprazole (Ref)
Aripiprazole-induced liver injury has been reported in case reports and evaluated in a retrospective registry which identified liver injury as mixed (eg, jaundice with transaminitis) or isolated hepatocellular injury and deemed as serious in 26.8% of cases (Ref). Liver injury resolved in ~78% of cases with therapy discontinuation (Ref).
Mechanism: Unknown; idiosyncratic (Ref).
Onset: Varied; most cases of any aripiprazole-induced liver injury occurred within 40 days of continuous use. Severe cases occurred within 90 days with most of those cases occurring between 15 to 40 days (Ref).
Risk factors:
• Increased dose (eg, >30 mg/day) (Ref)
• Male birth gender (Ref)
• Concurrent use of CYP3A4 or CYP2D6 inhibitors (Ref)
• Concurrent use of known hepatotoxic agents (eg, alcohol) (Ref)
• Age ≤44 years (Ref)
Older adults with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo (Ref). In addition, an increased incidence of cerebrovascular effects (eg, cerebrovascular accident, transient ischemic attacks), including fatalities, have been reported in placebo-controlled aripiprazole trials in older adults with dementia-related psychosis, per the manufacturer's labeling. Of note, aripiprazole is not approved for the treatment of dementia-related psychosis.
Mechanism: Unknown; possible mechanisms include arrhythmia, cardiac arrest, and extrapyramidal effects that may increase the risk of falls, aspirations, and pneumonia (Ref).
Risk factors:
Antipsychotics in general:
• Higher antipsychotic dosage (Ref)
• Dementia-related psychosis (eg, Lewy body dementia, Parkinson disease dementia)
• Older adults
All antipsychotics have been associated with neuroleptic malignant syndrome (NMS) in all ages. First-generation antipsychotic-associated NMS seems to occur at a higher frequency, severity, and lethality compared to second-generation antipsychotic-associated NMS (Ref). There are case reports of NMS with aripiprazole, including monotherapy. Some data suggest that NMS induced by certain second-generation antipsychotics, including aripiprazole, may present with milder or atypical features more frequently compared to NMS induced by other agents; these atypical features include less intense extrapyramidal symptoms or less extreme fever (Ref).
Mechanism: Non–dose-related; idiosyncratic. Believed to be due to a reduction in CNS dopaminergic tone, along with the dysregulation of autonomic nervous system activity (Ref).
Onset: Varied; in general, most patients develop NMS within 2 weeks of initiating an antipsychotic, and in some patients, prodromal symptoms emerge within hours of initiation; once the syndrome starts, the full syndrome usually develops in 3 to 5 days (Ref). However, there are many cases of NMS occurring months after stable therapy, including a report of NMS developing 1 year after treatment with aripiprazole (Ref).
Risk factors:
Antipsychotics in general:
• Males (twice as likely to develop NMS compared to females) (Ref)
• Dehydration (Ref)
• High-dose antipsychotic treatment (Ref)
• Concomitant lithium or benzodiazepine (potential risk factors) (Ref)
• Catatonia (Ref)
• Polypharmacy (Ref)
• Pharmacokinetic interactions (Ref)
• Intramuscular administration (Ref)
• Rapid dosage escalation (Ref)
• Psychomotor agitation (Ref)
Antipsychotics have been associated with sexual disorder in both males and females. Antipsychotic treatment has been associated with effects on all phases of sexual activity (libido, arousal, and orgasm); however, many patients with schizophrenia experience more frequent sexual dysfunction, with or without antipsychotic treatment. Conversely, there are also case reports of hypersexuality ,related to impulse control disorders, occurring with use (Ref).
Mechanism: Antipsychotic-induced sexual dysfunction has been attributed to many potential mechanisms, including dopamine receptor antagonism, dopamine D2 receptor antagonism in the hypothalamic infundibular system causing hyperprolactinemia, histamine receptor antagonism, cholinergic receptor antagonism, and alpha-adrenergic receptor antagonism. Of note, in adults, aripiprazole is associated with a minimal risk of causing hyperprolactinemia (Ref).
Risk factors:
• Hyperprolactinemia (although a correlation with sexual dysfunction has been observed, a relationship has not been confirmed) (Ref)
• Schizophrenia (the prevalence of antipsychotic-induced sexual dysfunction in patients with schizophrenia is high [~50% to 60% compared with 31% of males in the general population]) (Ref)
• Specific antipsychotic: Aripiprazole is associated with lower rates of sexual dysfunction relative to other antipsychotics (Ref)
Antipsychotics may impair the body's ability to regulate core body temperature, which may cause a potentially life-threatening heatstroke during predisposing conditions such as a heat wave or strenuous exercise. There are also several case reports of potentially life-threatening hypothermia associated with aripiprazole use (Ref).
Mechanism: Non–dose-related; idiosyncratic. Exact mechanism is unknown; however, body temperature is regulated by the hypothalamus with complex involvement of the dopamine, serotonin, and norepinephrine neurotransmitters. D2 antagonism may cause an increase in body temperature, while 5-HT2A (serotonin) receptor antagonism and 5-HT1 receptor agonism may cause a decrease in body temperature. Aripiprazole is a partial agonist at D2 receptors, an antagonist at 5-HT2A receptor, and a partial agonist at 5-HT1A receptor. In addition, antagonism of peripheral alpha-adrenergic receptors has also been suggested as a factor in the hypothermic effect, by inhibiting peripheral responses to cooling (vasoconstriction and shivering) (Ref).
Onset: Hypothermia: Varied; antipsychotic-induced hypothermia cases indicate a typical onset in the period shortly after initiation of therapy or a dosage increase (first 7 to 10 days) (Ref).
Risk factors:
Heat stroke:
• Psychiatric illness (regardless of medication use) (Ref)
• Dehydration (Ref)
• Strenuous exercise (Ref)
• Heat exposure (Ref)
• Concomitant medications possessing anticholinergic effects (Ref)
Hypothermia:
• In general, predisposing risk factors include: Older adults, cerebrovascular accident, preexisting brain damage, hypothyroidism, malnutrition, shock, sepsis, adrenal insufficiency, diabetes, disability, burns, exfoliative dermatitis, benzodiazepine use, alcohol intoxication, kidney or liver failure (Ref)
• Schizophrenia (regardless of antipsychotic use) (Ref)
Aripiprazole may cause significant weight gain (increase of >7% from baseline), particularly in pediatric patients, which is a component of the metabolic syndrome observed with this pharmacologic class (Ref).
Mechanism: Dose-related (Ref); multiple proposed mechanisms, including actions at serotonin, dopamine, histamine, and muscarinic receptors, with differing effects explained by differing affinity of antipsychotics at these receptors (Ref). Aripiprazole displays a low affinity for histamine H1 receptors, which may account for the relatively low risk of weight gain associated with aripiprazole (Ref).
Onset: Varied; antipsychotic-induced weight gain usually occurs rapidly in the initial period following initiation, then gradually decreases and flattens over several months with patients continuing to gain weight in the long term (Ref).
Risk factors:
• Family history of obesity (Ref)
• Parental BMI (Ref)
• Children and adolescents (Ref)
• Rapid weight gain in the initial period: Younger age, lower baseline BMI, more robust response to antipsychotic, and increase in appetite; rapid weight gain of >5% in the first month has been observed as the best predictor for significant long-term weight gain (Ref)
• Duration of therapy (although weight gain plateaus, patients continue to gain weight over time) (Ref)
• Schizophrenia (regardless of medication) is associated with a higher prevalence of obesity compared to the general population due to components of the illness such as negative symptoms, sedentary lifestyles, and unhealthy diets (Ref)
• Specific antipsychotic: In adults, aripiprazole is considered to have a minimal or low risk for weight gain; clozapine and olanzapine are considered to have high propensity (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults receiving monotherapy unless otherwise indicated.
IM:
>10%:
Endocrine & metabolic: Decreased HDL cholesterol (14%), hypercholesterolemia (4% to 22%), increased LDL cholesterol (10% to 14%), increased serum triglycerides (7% to 27%), weight gain (17% to 22%) (table 1)
|
Drug (Aripiprazole) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Aripiprazole) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
22% |
9% |
Adults |
IM injection |
Schizophrenia |
144 |
141 |
≥7% of body weight |
|
17% |
7% |
Adults |
IM injection |
Schizophrenia |
167 |
172 |
≥7% of body weight |
Nervous system: Akathisia (2% to 12%) (table 2), headache (12%)
|
Drug (Aripiprazole) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Aripiprazole) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
2% |
0% |
Adults |
IM injection |
Agitation associated with schizophrenia or bipolar mania |
501 |
220 |
|
12% |
4% |
Adults |
IM injection |
Schizophrenia |
N/A |
N/A |
|
11% |
4% |
Adults |
IM injection |
Schizophrenia |
167 |
172 |
1% to 10%:
Cardiovascular: Orthostatic hypotension (≤3%), tachycardia (2%)
Endocrine & metabolic: Increased serum glucose (8%), weight loss (4%)
Gastrointestinal: Abdominal distress (2%), constipation (10%), diarrhea (3%), nausea (9%), vomiting (3%), xerostomia (4%)
Hematologic & oncologic: Neutropenia (6%) (table 3)
|
Drug (Aripiprazole) |
Placebo |
Population |
Dosage Form |
Indication |
|---|---|---|---|---|
|
6% |
2% |
Adults |
IM injection |
Schizophrenia |
Local: Injection-site reaction (≥1%; including bleeding at injection site, bruising at injection site, erythema at injection site, induration at injection site, inflammation at injection site, injection-site pruritus, rash at injection site, swelling at injection), pain at injection site (5%)
Nervous system: Anxiety (≥1%), dizziness (4% to 8%), drowsiness (7%) (table 4), extrapyramidal reaction (10%), fatigue (2%), insomnia (≥1%), restlessness (≥1%), sedated state (3% to 5%), tremor (3%)
|
Drug (Aripiprazole) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Aripiprazole) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
7% |
4% |
Adults |
IM injection |
Agitation associated with schizophrenia or bipolar mania |
501 |
220 |
Neuromuscular & skeletal: Arthralgia (4%), back pain (4%), dystonia (2%), musculoskeletal pain (3%), myalgia (4%)
Respiratory: Nasal congestion (2%), upper respiratory tract infection (4%)
<1%:
Cardiovascular: Abnormal T waves on ECG, bradycardia, chest discomfort, decreased blood pressure, hypertension, orthostatic dizziness, presyncope, prolonged QT interval on ECG, sinus tachycardia, syncope
Endocrine & metabolic: Decreased serum cholesterol, decreased serum triglycerides, hyperinsulinism, hyperprolactinemia, increased libido, obesity
Gastrointestinal: Bruxism, decreased appetite, dysgeusia, dyspepsia, upper abdominal pain
Genitourinary: Delayed ejaculation, glycosuria, pollakiuria, urinary incontinence
Hematologic & oncologic: Thrombocytopenia
Hepatic: Abnormal hepatic function tests, hepatotoxicity
Hypersensitivity: Hypersensitivity reaction, swollen tongue
Nervous system: Abnormal gait, aggressive behavior, agitation, hypersomnia, irritability, lethargy, memory impairment, panic attack, psychotic reaction, seizure, trismus
Neuromuscular & skeletal: Bradykinesia, dystonia (oromandibular), increased creatinine phosphokinase in blood specimen, joint stiffness, muscle twitching, rhabdomyolysis
Ophthalmic: Blurred vision, oculogyric crisis
Respiratory: Nasopharyngitis
Miscellaneous: Fever
Oral:
>10%:
Endocrine & metabolic: Increased serum glucose (children, adolescents: 3% to 5%; adults: 18%), weight gain (children, adolescents: 3% to 26%; adults: 2% to 8%) (table 5)
|
Drug (Aripiprazole) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Aripiprazole) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
26% |
7% |
Children, adolescents |
Oral |
Irritability associated with autistic disorder |
209 |
98 |
≥7% of body weight |
|
5% |
2% |
Children, adolescents |
Oral |
Schizophrenia or bipolar mania |
381 |
187 |
≥7% of body weight |
|
3% |
1% |
Children, adolescents |
Oral |
Schizophrenia, bipolar mania, autistic disorder, or Tourette disorder |
732 |
370 |
N/A |
|
20% |
8% |
Children, adolescents |
Oral |
Tourette disorder |
105 |
66 |
≥7% of body weight |
|
2% |
3% |
Adults |
Oral |
Bipolar mania |
719 |
598 |
≥7% of body weight |
|
8% |
3% |
Adults |
Oral |
Schizophrenia |
852 |
379 |
≥7% of body weight |
Gastrointestinal: Constipation (children, adolescents: 2%; adults: 11%), nausea (children, adolescents, adults: 8% to 15%), vomiting (children, adolescents, adults: 8% to 14%)
Local: Application-site rash (MyCite patch: 12%)
Nervous system: Agitation (19%), akathisia (children, adolescents, adults: 3% to 13%) (table 6), anxiety (17%), drowsiness (children, adolescents: 10% to 26%; adults: 5% to 13%) (table 7), extrapyramidal reaction (children, adolescents: 6% to 27%; adults: 5% to 16%), fatigue (children, adolescents: 4% to 22%; adults: 6%), headache (children, adolescents: 10% to 12%; adults: 27%), insomnia (18%), sedated state (children, adolescents: 9% to 21%; adults: ≤13%), tremor (children, adolescents, adults: 5% to 12%)
|
Drug (Aripiprazole) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Aripiprazole) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
3% |
9% |
Children, adolescents |
Oral |
Autistic disorder |
N/A |
N/A |
|
10% |
2% |
Children, adolescents |
Oral |
Bipolar mania |
197 |
97 |
|
6% |
4% |
Children, adolescents |
Oral |
Schizophrenia, bipolar mania, autistic disorder, or Tourette disorder |
732 |
370 |
|
4% |
6% |
Children, adolescents |
Oral |
Tourette disorder |
N/A |
N/A |
|
9% |
6% |
Adolescents |
Oral |
Schizophrenia |
N/A |
N/A |
|
13% |
4% |
Adults |
Oral |
Bipolar mania |
917 |
753 |
|
8% |
4% |
Adults |
Oral |
Schizophrenia |
N/A |
N/A |
|
10% |
4% |
Adults |
Oral |
Schizophrenia or bipolar mania |
1,843 |
1,166 |
|
Drug (Aripiprazole) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Aripiprazole) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|---|
|
10% |
4% |
Children, adolescents |
N/A |
Oral |
Autistic disorder |
212 |
101 |
N/A |
|
26% |
3% |
Children, adolescents |
30 mg |
Oral |
Bipolar mania |
N/A |
N/A |
N/A |
|
23% |
3% |
Children, adolescents |
N/A |
Oral |
Bipolar mania |
197 |
97 |
N/A |
|
19% |
3% |
Children, adolescents |
10 mg |
Oral |
Bipolar mania |
N/A |
N/A |
N/A |
|
16% |
4% |
Children, adolescents |
N/A |
Oral |
Schizophrenia, bipolar mania, autistic disorder, or Tourette disorder |
732 |
370 |
N/A |
|
13% |
1% |
Children, adolescents |
N/A |
Oral |
Tourette disorder |
121 |
72 |
N/A |
|
22% |
6% |
Adolescents |
30 mg |
Oral |
Schizophrenia |
N/A |
N/A |
N/A |
|
11% |
6% |
Adolescents |
10 mg |
Oral |
Schizophrenia |
N/A |
N/A |
N/A |
|
13% |
7% |
Adults |
30 mg |
Oral |
Schizophrenia |
N/A |
N/A |
Including sedation |
|
9% |
7% |
Adults |
10 mg |
Oral |
Schizophrenia |
N/A |
N/A |
Including sedation |
|
9% |
7% |
Adults |
15 mg |
Oral |
Schizophrenia |
N/A |
N/A |
Including sedation |
|
8% |
7% |
Adults |
20 mg |
Oral |
Schizophrenia |
N/A |
N/A |
Including sedation |
|
5% |
3% |
Adults |
N/A |
Oral |
Schizophrenia or bipolar mania |
1,843 |
1,166 |
N/A |
1% to 10%:
Cardiovascular: Orthostatic hypotension (children, adolescents, adults: ≤4%)
Dermatologic: Skin rash (children, adolescents, adults: ≤2%)
Endocrine & metabolic: Decreased HDL cholesterol (children, adolescents: 4%), hypercholesterolemia (children, adolescents: 1%), increased serum triglycerides (children, adolescents, adults: 5% to 10%), inhibitor of prolactin secretion (≥1%), weight loss (≥1%)
Gastrointestinal: Abdominal distress (children, adolescents, adults: 2% to 3%), anorexia (≥1%), decreased appetite (children, adolescents: 5% to 7%), diarrhea (children, adolescents: 4%), dyspepsia (9%), increased appetite (children, adolescents: 7%), sialorrhea (children, adolescents: 4% to 8%), stomach discomfort (3%), upper abdominal pain (children, adolescents: 3%), xerostomia (5%)
Genitourinary: Urinary incontinence (≥1%)
Nervous system: Asthenia (children, adolescents: 2%; adults: ≥1%), dizziness (children, adolescents, adults: 3% to 10%), drooling (children, adolescents: 3% to 9%), irritability (children, adolescents: 2%), lethargy (children, adolescents: 3% to 5%), pain (3%), restlessness (5% to 6%) (table 8)
|
Drug (Aripiprazole) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Aripiprazole) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
6% |
3% |
Adults |
Oral |
Bipolar mania |
917 |
753 |
|
5% |
3% |
Adults |
Oral |
Schizophrenia or bipolar mania |
1,843 |
1,166 |
Neuromuscular & skeletal: Dystonia (children, adolescents: 2%) (table 9), limb pain (4%), muscle rigidity (children, adolescents: 2%), muscle spasm (2%), myalgia (2%), stiffness (children, adolescents, adults: 2% to 4%)
|
Drug (Aripiprazole) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Aripiprazole) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
2% |
1% |
Children and adolescents |
Oral |
Schizophrenia, bipolar mania, autistic disorder, or Tourette disorder |
732 |
370 |
Ophthalmic: Blurred vision (children, adolescents, adults: 3% to 8%)
Respiratory: Cough (3%), epistaxis (children, adolescents: 2%), nasopharyngitis (children, adolescents: 6% to 9%), pharyngolaryngeal pain (3%)
Miscellaneous: Fever (children, adolescents: 4% to 9%)
<1%:
Cardiovascular: Acute cardiorespiratory failure, acute myocardial infarction, angina pectoris, atrial fibrillation, atrial flutter, atrioventricular block, bradycardia, chest pain, hypertension, hypotension, ischemic heart disease, orthostatic dizziness, palpitations, peripheral edema, prolonged QT interval on ECG, syncope
Dermatologic: Alopecia, hyperhidrosis, pruritus, skin photosensitivity, urticaria
Endocrine & metabolic: Amenorrhea, change in libido, elevated glycosylated hemoglobin, gynecomastia, hypoglycemia, hypokalemia, hyponatremia, increased lactate dehydrogenase, increased serum prolactin, menstrual disease
Gastrointestinal: Gastroesophageal reflux disease
Genitourinary: Anorgasmia, erectile dysfunction, mastalgia, nocturia, priapism, urinary retention
Hematologic & oncologic: Thrombocytopenia
Hepatic: Hepatitis, increased gamma-glutamyl transferase, increased liver enzymes, increased serum bilirubin, jaundice
Hypersensitivity: Facial edema, hypersensitivity reaction
Nervous system: Aggressive behavior, akinesia, ataxia, catatonia, choreoathetosis, cogwheel rigidity, delirium, homicidal ideation, hypertonia, impaired mobility, memory impairment, myasthenia, myoclonus, parkinsonism, seizure, somnambulism, speech disturbance, tic disorder
Neuromuscular & skeletal: Bradykinesia, hypokinesia, increased creatinine phosphokinase in blood specimen, rhabdomyolysis
Ophthalmic: Diplopia, photophobia
Renal: Increased blood urea nitrogen
Respiratory: Dyspnea, nasal congestion
Frequency not defined (any route or population):
Endocrine & metabolic: Hirsutism
Gastrointestinal: Esophageal motility disorder, tongue spasm
Nervous system: Sleep talking
Respiratory: Pulmonary aspiration
Postmarketing (any route or population):
Cardiovascular: Pericarditis (Ref), torsades de pointes (Ref)
Endocrine & metabolic: Diabetes mellitus (new onset) (Ref), diabetes mellitus with hyperosmolar coma (Ref), diabetic ketoacidosis (Ref), hyperglycemia (Ref), hypertriglyceridemia (Ref), insulin resistance (Ref)
Gastrointestinal: Dysphagia (Ref), fecal incontinence, hiccups (Ref)
Genitourinary: Sexual disorder (Ref)
Hematologic & oncologic: Agranulocytosis, leukopenia (Ref), neutropenia (Ref), transient neutropenia (pseudoneutropenia) (Ref)
Hypersensitivity: Anaphylaxis, angioedema (Ref), drug reaction with eosinophilia and systemic symptoms (Ref)
Nervous system: Cerebrovascular accident, hypothermia (Ref), impulse control disorder (including compulsive buying, compulsive eating, hypersexuality, pathological gambling) (Ref), neuroleptic malignant syndrome (Ref), suicidal ideation (Ref), suicidal tendencies (Ref), transient ischemic attacks
Neuromuscular & skeletal: Orofacial dyskinesia (including onset with drug withdrawal) (Ref), tardive dyskinesia (Ref)
Respiratory: Hypersensitivity pneumonitis (Ref), sleep apnea (obstructive) (Ref)
Hypersensitivity (eg, anaphylaxis, pruritus, urticaria) to aripiprazole or any component of the formulation.
Disease-related concerns:
• Bariatric surgery: In persons receiving oral dosage forms, document presurgical assessment of the indication for use, symptoms, and goals of therapy to enable postsurgical assessment. A single case report described increased exposure to aripiprazole after converting a 5 mg dose from the oral tablet to oral solution following Roux-en-Y gastric bypass (Kuzin 2023). Monitor for continued efficacy after bariatric surgery and consider switching to an alternate medication or dosage form if symptom management is not achieved with current therapy.
• Cardiovascular disease: Use with caution in patients with cardiac disease, cerebrovascular disease, prior myocardial infarction, ischemic heart disease, or conditions that predispose to hypotension.
• Parkinson disease: Use with caution in patients with Parkinson disease; antipsychotics may aggravate motor disturbances (APA [Keepers 2020]; APA [Reus 2016]).
• Seizures: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold. Elderly patients may be at increased risk of seizures due to an increased prevalence of predisposing factors.
Dosage form specific issues:
• Lactose: Tablets may contain lactose; avoid use in patients with galactose intolerance or glucose-galactose malabsorption.
• Phenylalanine: Orally disintegrating tablets may contain phenylalanine.
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP ["Inactive" 1997]; Zar 2007).
• Product interchangeability: Injection: There are 2 ER aripiprazole formulations available for IM administration: aripiprazole monohydrate (Abilify Maintena and Abilify Asimtufii) and aripiprazole lauroxil (Aristada and Aristada Initio); formulations and product brands vary in dose strength and frequency of administration.
• Tablet with sensor: The ability of aripiprazole tablets with sensor to improve patient compliance or modify aripiprazole dosage has not been established. The use of aripiprazole tablets with sensor to track drug ingestion in “real time” or during an emergency is not recommended because detection may be delayed or not occur.
Pediatric psychiatric disorders are frequently serious disorders which present with variable symptoms that do not always match adult diagnostic criteria. Conduct a thorough diagnostic evaluation and carefully consider risks of psychotropic medication before initiation in pediatric patients with schizophrenia, bipolar disorder, irritability associated with autistic disorder, or Tourette disorder. Medication therapy for pediatric patients with these disorders is indicated as part of a total treatment program that frequently includes educational, psychological, and social interventions. Long-term usefulness of aripiprazole should be periodically re-evaluated in patients receiving the drug for extended periods of time.
Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Shehab 2009).
Oral solution contains fructose 200 mg and sucrose 400 mg per mL.
Aripiprazole tablets are also available with an embedded device that tracks drug ingestion using a smartphone app (Abilify Mycite). Abilify MyCite is a drug-device combination product comprised of aripiprazole tablets embedded with an Ingestible Event Marker (IEM) sensor and packaged with a wearable sensor patch intended to track drug ingestion.
Abilify MyCite Kit is packaged with seven 1-component patches (electronic recording component is contained in each patch).
Abilify MyCite Starter Kit is packaged with 1 sensor pod and 7 adhesive patches (electronic recording component is contained in the pod).
Abilify MyCite Maintenance Kit is packaged with 7 adhesive patches (for use with the sensor pod supplied separately).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Film, Oral:
Opipza: 2 mg (1 ea, 30 ea); 5 mg (1 ea, 30 ea); 10 mg (1 ea, 30 ea)
Prefilled Syringe, Intramuscular:
Abilify Maintena: 300 mg (extended release) (1 ea); 400 mg (extended release) (1 ea)
Prefilled Syringe, Intramuscular [preservative free]:
Abilify Asimtufii: 720 mg/2.4 mL (extended release) (2.4 mL); 960 mg/3.2 mL (extended release) (3.2 mL) [contains polyethylene glycol (macrogol)]
Solution, Oral:
Generic: 1 mg/mL (150 mL)
Suspension Reconstituted ER, Intramuscular:
Abilify Maintena: 300 mg (extended release) (1 ea); 400 mg (extended release) (1 ea)
Suspension Reconstituted ER, Intramuscular [preservative free]:
Abilify Maintena: 300 mg (extended release) (1 ea); 400 mg (extended release) (1 ea)
Tablet, Oral:
Abilify: 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg [contains corn starch, fd&c blue #2 (indigo carm) aluminum lake]
Abilify MyCite: 2 mg [DSC], 5 mg [DSC], 10 mg [DSC], 15 mg [DSC], 20 mg [DSC], 30 mg [DSC] [contains corn starch, fd&c blue #2 (indigo carm) aluminum lake]
Generic: 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg
Tablet Disintegrating, Oral:
Generic: 10 mg, 15 mg
Tablet Therapy Pack, Oral:
Abilify MyCite Maintenance Kit: 2 mg (30 ea); 5 mg (30 ea); 10 mg (30 ea); 15 mg (30 ea); 20 mg (30 ea); 30 mg (30 ea) [contains corn starch, fd&c blue #2 (indigo carm) aluminum lake]
Abilify MyCite Starter Kit: 2 mg (30 ea); 5 mg (30 ea); 10 mg (30 ea); 15 mg (30 ea); 20 mg (30 ea); 30 mg (30 ea) [contains corn starch, fd&c blue #2 (indigo carm) aluminum lake]
May be product dependent
Film (Opipza Oral)
2 mg (per each): $75.82
5 mg (per each): $83.82
10 mg (per each): $91.82
Prefilled Syringe (Abilify Asimtufii Intramuscular)
720MG/2.4ML (per mL): $2,178.33
960MG/3.2ML (per mL): $2,178.33
Prefilled Syringe (Abilify Maintena Intramuscular)
300 mg (per each): $2,614.00
400 mg (per each): $3,485.33
Solution (ARIPiprazole Oral)
1 mg/mL (per mL): $2.08 - $7.07
Suspension Reconstituted ER (Abilify Maintena Intramuscular)
300 mg (per each): $2,614.00
400 mg (per each): $3,485.33
Tablet Therapy Pack (Abilify MyCite Maintenance Kit Oral)
2 mg (per each): $67.98
5 mg (per each): $67.98
10 mg (per each): $67.98
15 mg (per each): $67.98
20 mg (per each): $67.98
30 mg (per each): $67.98
Tablet Therapy Pack (Abilify MyCite Starter Kit Oral)
2 mg (per each): $67.98
5 mg (per each): $67.98
10 mg (per each): $67.98
15 mg (per each): $67.98
20 mg (per each): $67.98
30 mg (per each): $67.98
Tablet, orally-disintegrating (ARIPiprazole Oral)
10 mg (per each): $41.87 - $41.89
15 mg (per each): $41.87 - $41.89
Tablets (Abilify Oral)
2 mg (per each): $23.35
5 mg (per each): $23.35
10 mg (per each): $23.35
15 mg (per each): $23.35
20 mg (per each): $33.02
30 mg (per each): $33.02
Tablets (ARIPiprazole Oral)
2 mg (per each): $0.09 - $32.11
5 mg (per each): $0.11 - $32.11
10 mg (per each): $0.14 - $32.11
15 mg (per each): $0.18 - $32.11
20 mg (per each): $0.25 - $45.41
30 mg (per each): $0.26 - $45.41
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension Reconstituted ER, Intramuscular:
Abilify Maintena: 300 mg (extended release) (1 ea); 400 mg (extended release) (1 ea)
Tablet, Oral:
Abilify: 2 mg, 5 mg [contains corn starch, fd&c blue #2 (indigo carm) aluminum lake]
Abilify: 10 mg, 15 mg, 20 mg, 30 mg [contains corn starch]
Generic: 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg
IM: Extended release: For IM use only; do not administer SUBQ or IV.
Monthly injection (Abilify Maintena): Inject slowly into deltoid or gluteal muscle using the appropriate provided needle; for nonobese patients, use the 1-inch (25 mm) needle with deltoid administration or the 1.5-inch (38 mm) needle with gluteal administration; for obese patients, use the 1.5-inch (38 mm) needle with deltoid administration or the 2-inch (51 mm) needle with gluteal administration. Do not massage muscle after administration. Rotate injection sites between the 2 deltoid or gluteal muscles.
Every-2-months injection (Abilify Asimtufii): Inject slowly into gluteal muscle using the appropriate provided needle; for nonobese patients, use the 22-gauge, 1.5-inch (38 mm) needle; for obese patients, use the 21-gauge, 2-inch (51 mm) needle. Do not massage muscle after administration.
Oral: Administer with or without food.
Oral film: Apply film on top of tongue; allow to dissolve in saliva and swallow without water or other liquids. Do not chew, cut, or split the film; do not swallow an undissolved film. Apply only 1 film at a time; if more than 1 film is needed for the dosage, allow each film to completely dissolve before administering another.
Orally disintegrating tablet: Remove from foil blister by peeling back (do not push tablet through the foil). Place tablet in mouth immediately upon removal. Tablet dissolves rapidly in saliva and may be swallowed without liquid. If needed, can be taken with liquid. Do not split tablet.
Tablet with sensor: Swallow tablets whole; do not divide, crush, or chew. Each tablet is embedded with an ingestible event marker (IEM). The patch that accompanies the tablets is a wearable sensor that detects a signal from the IEM sensor after the tablet is ingested and transmits data to a smartphone within 30 minutes to 2 hours of ingestion. If the detection system fails (ie, tablet is not detected after ingestion), do not repeat the dose. Before use, ensure that the patient is capable and willing to use smartphones and apps, that the app is compatible with the patient's specific smartphone, and that the smartphone is paired with the patch prior to use. There are 2 types of patches; refer to corresponding instructions for use within the app. Apply the 1-component patch only when instructed by the app to the left side of the body just above the lower edge of the rib cage. Apply the 2-component patch only when instructed by the app to the left or right side of the body just above the lower edge of the rib cage. Do not place the patch in areas where the skin is scraped, cracked, inflamed, or irritated, or in a location that overlaps the area of the most recently removed patch. Instruct patients to keep the patch on when showering, swimming, or exercising. The patch should be changed weekly or sooner as needed. The app will prompt patient to change the patch and will direct patient to apply and remove the patch correctly. Patients undergoing an MRI need to remove their patch and replace with a new one as soon as possible. If there is skin irritation, instruct patients to remove the patch. Refer to the information provided in the product packaging and electronic instructions for use with the Mycite app.
Oral: May administer all dosage forms without regard to food.
Orally disintegrating tablet: Do not remove tablet from blister pack until ready to administer; do not push tablet through foil (tablet may become damaged); peel back foil to expose tablet; use dry hands to remove tablet and place immediately on tongue. Tablet dissolves rapidly in saliva and may be swallowed without liquid; if needed, tablet can be taken with liquid. Do not split tablet.
Oral film (Opipza): Wash and completely dry hands. Remove correct number of pouches for prescribed dose from carton. Open only one pouch at a time, remove film and lay entire film on top of tongue, then close mouth. Film will dissolve as it mixes with saliva and can then be swallowed in normal manner. Do not rinse mouth with liquid. If film tears or dissolves (eg, wet hands) prior to placement on tongue, discard film and open a new pouch. If >1 film is required for dose, allow previous film to completely dissolve before opening another pouch. Do not split or cut film, chew, or swallow whole.
Oral solution: Administer with an accurate measuring device (calibrated oral syringe or measuring cup); do not use a household teaspoon or tablespoon to measure dose (overdosage may occur).
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Abilify: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/021436s046s050lbl.pdf#page=66
Abilify Asimtufii: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/217006s002lbl.pdf#page=40
Abilify Maintena: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/202971s019lbl.pdf#page=46
Abilify MyCite: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/207202s009lbl.pdf#page=48
Oral:
Bipolar disorder: As monotherapy or as an adjunct to lithium or valproate for acute treatment of mania or episodes with mixed features associated with bipolar disorder (tablet, orally disintegrating tablet, and oral solution only) and maintenance treatment (tablet with sensor only) of bipolar disorder.
Irritability associated with autistic disorder: Treatment of irritability associated with autistic disorder (tablet, orally disintegrating tablet, oral film, and oral solution only) in children and adolescents.
Major depressive disorder (unipolar), treatment resistant: Adjunctive treatment of unipolar major depressive disorder in patients with an inadequate response to prior antidepressant therapy.
Schizophrenia: Treatment of schizophrenia.
Tourette disorder: Treatment of Tourette disorder (tablet, orally disintegrating tablet, oral film, and oral solution only) in children and adolescents.
Injection: Extended release:
Bipolar disorder: Maintenance monotherapy treatment of bipolar disorder.
Schizophrenia: Treatment of schizophrenia.
Agitation/aggression (acute, severe) associated with psychiatric disorders (eg, schizophrenia, bipolar disorder), substance intoxication, or other organic causes; Agitation/aggression and psychosis associated with dementia, severe or refractory; Delusional disorder; Delusional infestation (delusional parasitosis); Huntington disease-associated chorea; Obsessive-compulsive disorder, treatment resistant; Tourette syndrome
Abilify may be confused with Ambien
ARIPiprazole may be confused with proton pump inhibitors (dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, RABEprazole)
Beers Criteria: Antipsychotics are identified in the Beers Criteria as potentially inappropriate medications to be avoided in patients 65 years and older due to an increased risk of stroke and a greater rate of cognitive decline and mortality in patients with dementia. Evidence also suggests there may be an increased risk of mortality with use independent of dementia. Avoid antipsychotics for behavioral problems associated with dementia or delirium unless alternative nonpharmacologic therapies have failed and patient may harm self or others. In addition, antipsychotics should be used with caution in older adults due to their potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults. Use of antipsychotics may be appropriate for labeled indications, including schizophrenia, bipolar disorder, Parkinson disease psychosis, adjunctive therapy for major depressive disorder, or for short-term use as an antiemetic (Beers Criteria [AGS 2023]).
Antipsychotics are identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) due to an increased risk of falls. Initiation is not recommended for treatment of sleep disorder. Some disease states of concern include dementia, Parkinson disease, sleep disorder, dysphagia, and coronary, cerebral, or peripheral vascular disease (O’Mahony 2023).
There are two ER formulations available for IM administration: Aripiprazole monohydrate (Abilify Maintena) and aripiprazole lauroxil (Aristada and Aristada Initio).
Substrate of CYP2D6 (Major), CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Agents With Seizure Threshold Lowering Potential: May increase adverse/toxic effects of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Ajmaline: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Amifampridine: Agents With Seizure Threshold Lowering Potential may increase neuroexcitatory and/or seizure-potentiating effects of Amifampridine. Risk C: Monitor
Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor
Amisulpride (Oral): May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk of neuroleptic malignant syndrome or increased QTc interval may be increased. Risk C: Monitor
Anti-Parkinson Agents (Dopamine Agonist): Antipsychotic Agents (Second Generation [Atypical]) may decrease therapeutic effects of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider avoiding atypical antipsychotic use in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider Therapy Modification
Antidiabetic Agents: Hyperglycemia-Associated Agents may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor
Armodafinil: May decrease serum concentration of ARIPiprazole. Risk C: Monitor
Artemether and Lumefantrine: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Asenapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Benperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Benzgalantamine-Galantamine: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor
Benzodiazepines: ARIPiprazole may increase CNS depressant effects of Benzodiazepines. ARIPiprazole may increase hypotensive effects of Benzodiazepines. Specifically, orthostatic hypotension may be increased. Risk C: Monitor
Blonanserin: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Blonanserin. Specifically, the risk of seizures may be increased. Risk C: Monitor
Blood Pressure Lowering Agents: May increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor
Bornaprine: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, tardive dyskinesia symptoms may be potentiated. Risk C: Monitor
Brexpiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Bromopride: May increase adverse/toxic effects of Antipsychotic Agents. Risk X: Avoid
Bromperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Bromperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Cabergoline: May decrease therapeutic effects of Antipsychotic Agents. Risk X: Avoid
Cariprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
Clothiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
CloZAPine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of CloZAPine. Specifically, the risk of seizures may be increased. Risk C: Monitor
CYP2D6 Inhibitors (Moderate): May increase serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy, indication, or dosage form. Consult full interaction monograph for specific recommendations. Risk C: Monitor
CYP2D6 Inhibitors (Strong): May increase serum concentration of ARIPiprazole. Management: Aripiprazole dose reductions or avoidance are required for indications other than major depressive disorder. Dose adjustments vary based on formulation, initial starting dose, and the additional use of CYP3A4 inhibitors. See interact monograph for details Risk D: Consider Therapy Modification
CYP3A4 Inducers (Moderate): May decrease serum concentration of ARIPiprazole. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of ARIPiprazole. Management: For indications other than major depressive disorder: double the oral aripiprazole dose over 1 to 2 weeks and closely monitor. Avoid use of strong CYP3A4 inducers for more than 14 days with extended-release injectable aripiprazole. Risk D: Consider Therapy Modification
CYP3A4 Inhibitors (Moderate): May increase serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy, indication, or dosage form. Consult full interaction monograph for specific recommendations. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of ARIPiprazole. Management: Aripiprazole dose reductions are required for indications other than major depressive disorder. Dose reductions vary based on formulation, initial starting dose, CYP2D6 genotype, and use of CYP2D6 inhibitors. See full interaction monograph for details. Risk D: Consider Therapy Modification
Deutetrabenazine: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased. Risk C: Monitor
Dexmethylphenidate-Methylphenidate: Antipsychotic Agents may increase adverse/toxic effects of Dexmethylphenidate-Methylphenidate. Dexmethylphenidate-Methylphenidate may increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk of extrapyramidal symptoms may be increased when these agents are combined. Risk C: Monitor
Donepezil: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor
DroPERidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of DroPERidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Flupentixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
FluPHENAZine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Grapefruit Juice: May increase serum concentration of ARIPiprazole. Risk C: Monitor
Guanethidine: Antipsychotic Agents may decrease therapeutic effects of Guanethidine. Risk C: Monitor
Haloperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Huperzine A: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor
Iloperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Iohexol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Lithium: May increase neurotoxic effects of Antipsychotic Agents. Lithium may decrease serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. Risk C: Monitor
Loxapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Loxapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Lumateperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Lurasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Mavorixafor: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk X: Avoid
Metergoline: Antipsychotic Agents may decrease therapeutic effects of Metergoline. Metergoline may decrease therapeutic effects of Antipsychotic Agents. Risk C: Monitor
Methotrimeprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Methotrimeprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Metoclopramide: May increase adverse/toxic effects of Antipsychotic Agents. Risk X: Avoid
MetyroSINE: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk for extrapyramidal symptoms and excessive sedation may be increased. Risk C: Monitor
Molindone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor
OLANZapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Paliperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Peginterferon Alfa-2b: May decrease serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Periciazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Perphenazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Pimozide: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pimozide. Specifically, the risk of seizures may be increased. Risk C: Monitor
Pipamperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pipamperone. Specifically, the risk of seizures may be increased. Risk X: Avoid
Piribedil: Antipsychotic Agents may decrease therapeutic effects of Piribedil. Piribedil may decrease therapeutic effects of Antipsychotic Agents. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended. Risk X: Avoid
Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor
Prochlorperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Promazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
QUEtiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Quinagolide: Antipsychotic Agents may decrease therapeutic effects of Quinagolide. Risk C: Monitor
RisperiDONE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of RisperiDONE. Specifically, the risk of seizures may be increased. Risk C: Monitor
Rivastigmine: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor
Serotonergic Agents (High Risk): May increase adverse/toxic effects of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
Sertindole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sertindole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor
Sulpiride: Antipsychotic Agents may increase adverse/toxic effects of Sulpiride. Risk X: Avoid
Tetrabenazine: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk for NMS and extrapyramidal symptoms may be increased. Risk C: Monitor
Thioridazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Thiothixene: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor
Trifluoperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Trimeprazine: May increase CNS depressant effects of ARIPiprazole. Trimeprazine may increase serum concentration of ARIPiprazole. Risk C: Monitor
Ziprasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Ziprasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Ingestion of oral formulations with a high-fat meal delays time to peak plasma level. Management: Administer without regard to meals.
Evaluate pregnancy status and provide preconception counseling prior to initiating treatment in patients who could become pregnant (APA [Keepers 2020]; BAP [McAllister-Williams 2017]; CANMAT [Yatham 2018]). Patients effectively treated may continue their current antipsychotic medication when planning a pregnancy unless contraindications exist (ACOG 2023; BAP [McAllister-Williams 2017]); the lowest effective dose and avoidance of polytherapy is recommended (BAP [Barnes 2020]; BAP [McAllister-Williams 2017]; CANMAT [Yatham 2018]). Management of mental health conditions in patients who could become pregnant should be based on a shared decision-making process that considers the possibility of pregnancy during treatment and the risks of discontinuing antipsychotic therapy (ACOG 2023; BAP [McAllister-Williams 2017]; CANMAT [Yatham 2018]).
Antipsychotic agents may be associated with sexual dysfunction. Some second generation (atypical) antipsychotics (SGAs) may cause hyperprolactinemia, resulting in menstrual disorders or impaired spermatogenesis. Consider changing to a medication that is prolactin-sparing in patients with clinical symptoms. Contraception should be provided if pregnancy is not desired as unintended pregnancies may occur when changing to a prolactin-sparing medication (APA [Keepers 2020]; BAP [McAllister-Williams 2017]).
Aripiprazole crosses the placenta; aripiprazole and the active metabolite dehydro-aripiprazole can be detected in the cord blood at delivery (Nguyen 2011; Watanabe 2011; Windhager 2014).
Outcome data following exposure to second generation (atypical) antipsychotics (SGAs) as a class do not show a significant increased risk of major congenital malformations (BAP [Barnes 2020]), however, specific outcomes vary due to differences in study design (BAP [McAllister-Williams 2017]; Cuomo 2018; Ellfolk 2021; Ennis 2015; Freeman 2021; Galbally 2018; Huybrechts 2023; Terrana 2015; Viguera 2021; Wang 2021). Aripiprazole is one of the SGAs with more limited data for first-trimester exposure (BAP [McAllister-Williams 2017]); additional studies are needed for individual agents and specific outcomes (BAP [Barnes 2020]). Data related to the long-term effects of in utero antipsychotic exposure on infant neurodevelopment and behavior are limited (BAP [McAllister-Williams 2017]; Straub 2022, Swetlik 2024).
Antipsychotic use during the third trimester of pregnancy increases the risk for extrapyramidal symptoms and/or withdrawal symptoms in newborns following delivery (Viguera 2023). Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor. These effects may require prolonged hospitalization or resolve within hour or days without specific treatment. Tapering the dose late in pregnancy to reduce the risk of symptoms is not recommended (APA [Keepers 2020]).
Atypical antipsychotics are associated with metabolic changes and the risk varies by specific agent. Available studies that evaluated the risk of developing gestational diabetes mellitus (GDM) during antipsychotic therapy have conflicting results, possibly due to differences in study design (ACOG 2023; Uguz 2019). Pregnant patients with diabetes mellitus or GDM may continue antipsychotic treatment (ACOG 2023). Consider the metabolic risks of the specific antipsychotic if treatment is initiated for the first time during pregnancy (Heinonen 2022). Screening for GDM should continue as part of standard prenatal care; early screening is not needed due to psychiatric medication exposure (ACOG 2023; BAP [McAllister-Williams 2017]).
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of aripiprazole may be altered. Clearance can increase and plasma concentrations can decrease as pregnancy progresses; dose adjustments may be required (Westin 2018; Windhager 2014; Zheng 2021).
Untreated and undertreated mental health conditions are associated with adverse pregnancy outcomes (ACOG 2023). Adverse obstetric and neonatal outcomes are associated with schizophrenia; however, comparisons between treated and untreated pregnancies are limited (BAP [McAllister-Williams 2017]). Untreated bipolar disorder is associated with fetal growth restriction, preterm birth, adverse neurodevelopment, and may increase the risk of postpartum psychosis, worsening mood, and postpartum hospitalization. Untreated or undertreated depression is associated with preterm birth, low birth weight, preeclampsia, postpartum depression, and impaired infant attachment (associated with long-term developmental effects). Discontinuing effective medications during pregnancy increases the risk of symptom relapse (ACOG 2023).
Patients effectively treated for schizophrenia or bipolar disorder pre-pregnancy may use the same medication during pregnancy unless contraindications exist (ACOG 2023; APA [Keeper2020]). SGAs are better tolerated and have fewer extrapyramidal adverse effects than first-generation (typical) antipsychotics (ACOG 2023). SGAs are not considered a first-line medication for depression in pregnant patients who are treatment naive or who do not have a history of effective treatment in the past (ACOG 2023; BAP [McAllister-Williams 2017]). Long-acting/depot preparations should not be initiated during pregnancy, but may be continued when the risk of recurrence is high (BAP [Barnes 2020]).
Management of mental health conditions should be made as part of a shared decision-making process (ACOG 2023; BAP [McAllister-Williams 2017]). Treatment should not be withheld or discontinued based only on pregnancy status (ACOG 2023).
When medications are used, the lowest effective dose of a single agent is recommended. Optimize dosing prior to changing a medication or adding additional agents whenever possible. Close monitoring for symptom improvement with a validated screening tool during pregnancy is recommended. Manage side effects as needed (ACOG 2023).
Data collection to monitor pregnancy and infant outcomes following exposure to psychiatric medications is ongoing. Encourage pregnant patients 45 years of age and younger with a history of psychiatric illness to enroll in the National Pregnancy Registry for Psychiatric Mediations (1-866-961-2388 or https://womensmentalhealth.org/research/pregnancyregistry/).
Aripiprazole and the active metabolite dehydro-aripiprazole are present in breast milk (Nordeng 2014).
Multiple reports evaluated the presence of aripiprazole in breast milk (Lutz 2010; Nordeng 2014; Schlotterbeck 2007; Watanabe 2011).
• A case report describes the presence of aripiprazole in breast milk in a lactating patient, 6 days after delivery. Aripiprazole 6 mg/day was initiated at 22 weeks' gestation and gradually increased to 18 mg/day by 34 weeks' gestation. Delivery was at 35 weeks. Breast milk concentrations of aripiprazole were 38.7 ng/mL; time of sampling was not noted (Watanabe 2011).
• The presence of aripiprazole in breast milk was evaluated in one patient at 8 and 10 weeks postpartum following a dose of 10 mg/day beginning 9 weeks' gestation. Samples were obtained prior to and 2, 3, 6, 9, 12, and 24 hours after the maternal dose. The mean daily breast milk concentrations (based on AUC) at 8 weeks postpartum were aripiprazole 52.6 ng/mL and dehydro-aripiprazole 8.8 ng/mL. At 10 weeks postpartum, mean concentrations were 53.6 ng/mL and 6.3ng/mL for aripiprazole and dehydro-aripiprazole, respectively. Using mean breast milk concentrations of 56 ng/mL (aripiprazole) and 8.8 ng/mL (dehydro-aripiprazole), authors of the study calculated the estimated infant dose via breast milk to be 47 mcg/day, providing a relative infant dose (RID) of 8.3%. The infant was partially breastfed. Concentrations of aripiprazole peaked in breast milk ~3 to 4 hours after the maternal dose (Nordeng 2014). In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000); however, some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Anderson 2021).
• Breast milk was sampled in a lactating patient requiring antipsychotic treatment at 6 months postpartum. Aripiprazole 10 mg was administered for 3 days, then increased to 15 mg on day 4. Aripiprazole breast milk concentrations were 13 ng/mL on treatment day 15, and 14 ng/mL on treatment day 16. Aripiprazole breast milk concentrations were ~20% of those in the maternal plasma (Schlotterbeck 2007).
• Aripiprazole was not detected (<10 ng/mL) in the breast milk of one patient when sampled 3 and 27 days postpartum. The patient was taking aripiprazole 15 mg daily, initiated prior to pregnancy. Breast milk on day 27 was obtained 4, 10, and 24 hours after the maternal dose. Although aripiprazole and dehydro-aripiprazole were present in maternal plasma, they were not detected in breast milk (Lutz 2010).
Decreased breast milk supply and inability to breastfeed has been described in case reports of patients taking aripiprazole (Frew 2015; Komaroff 2021; Mendhekar 2006; Nordeng 2014; Sahoo 2023; Yskes 2018). This was resolved after aripiprazole was discontinued in 2 patients (Frew 2015; Yskes 2018). Maternal prolactin levels were evaluated in 2 reports and found to be decreased (Komaraff 2021; Nordeng 2014).
Drowsiness, irritability, motor abnormalities, poor feeding, sedation, and slowed development have been reported in infants exposed to antipsychotics via breast milk. Monitor breastfed infants, especially those who are premature or of low birth weight, or when other sedative drugs are also prescribed (BAP [Barnes]; BAP [McAllister-Williams 2017]). Also monitor infants exposed to aripiprazole via breast milk for dehydration and appropriate weight gain.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. When medications are used, using the lowest effective dose and avoiding use of multiple medications is recommended. Consider sedative properties when initiating an antipsychotic medication for the first time postpartum (BAP [Barnes 2020]). Because aripiprazole may lower postpartum prolactin levels and cause lactation failure in some patients, breastfeeding during therapy should be evaluated as part of a shared decision-making process; patients may need additional assistance to initiate and maintain breastfeeding (Naughton 2023).
Some products may contain phenylalanine.
|
Frequency of Antipsychotic Monitoring for Aripiprazolea,b | ||
|---|---|---|
|
Monitoring parameter |
Frequency of monitoring |
Comments |
|
Adherence |
Every visit |
|
|
Blood chemistries (electrolytes, renal function, liver function, TSH) |
Annually |
|
|
CBC |
As clinically indicated |
Check frequently during the first few months of therapy in patients with preexisting low WBC or history of drug-induced leukopenia/neutropenia |
|
Extrapyramidal symptoms |
Every visit; 4 weeks after initiation and dose change; annually. Use a formalized rating scale at least annually or every 6 months if high riskc |
|
|
Fall risk |
Every visit |
|
|
Fasting plasma glucose/HbA1c |
4 months after initiation; annually |
Check more frequently than annually if abnormal. Follow diabetes guidelines. |
|
Lipid panel |
4 months after initiation; annually |
Check more frequently than annually if abnormal. Follow lipid guidelines. |
|
Mental status and alertness |
Every visit |
|
|
Metabolic syndrome history |
Annually |
Evaluate for personal and family history of obesity, diabetes, dyslipidemia, hypertension, or cardiovascular disease |
|
Prolactin |
Ask about symptoms at every visit until dose is stable. Check prolactin level if symptoms are reported. |
Hyperprolactinemia symptoms: Changes in menstruation, libido, gynecomastia, development of galactorrhea, and erectile and ejaculatory function |
|
Tardive dyskinesia |
Every visit; annually. Use a formalized rating scale at least annually or every 6 months if high riskd |
|
|
Vital signs (BP, orthostatics, temperature, pulse, signs of infection) |
Every visit (at least weekly during first 3 to 4 weeks of treatment); 4 weeks after dose change. |
|
|
Weight/Height/BMI |
8 and 12 weeks after initiation and dose change; quarterly |
Consider monitoring waist circumference at baseline and annually, especially in patients with or at risk for metabolic syndrome. Consider changing antipsychotic if BMI increases by ≥1 unit. Some experts recommend checking weight and height at every visit. |
|
a For all monitoring parameters, it is appropriate for check at baseline and when clinically relevant (based on symptoms or suspected adverse reactions) in addition to the timeline. b ADA 2004; APA [Keepers 2020]; de Hert 2011; Gugger 2011; manufacturer’s labeling. c Risk factors for extrapyramidal symptoms (EPS) include prior history of EPS, high doses of antipsychotics, young age (children and adolescents at higher risk than adults), and dopaminergic affinity of individual antipsychotic. d Risk factors for tardive dyskinesia include age >55 years; females; White or African ethnicity; presence of a mood disorder, intellectual disability, or CNS injury; and past or current EPS. | ||
Timing of serum samples: Draw trough just before next dose (Hiemke 2018).
Therapeutic reference range: 100 to 350 ng/mL (SI: 223 to 780.5 nmol/L) (Hiemke 2018). Note: Dosing should be based on therapeutic response as opposed to serum concentrations, however therapeutic drug monitoring can be used to confirm adherence (APA [Keepers 2020]).
Laboratory alert level: 1,000 ng/mL (SI: 2,230 nmol/L) (Hiemke 2018).
Aripiprazole is a quinolinone antipsychotic which exhibits high affinity for D2, D3, 5-HT1A, and 5-HT2A receptors; moderate affinity for D4, 5-HT2C, 5-HT7, alpha1 adrenergic, and H1 receptors. It also possesses moderate affinity for the serotonin reuptake transporter; has no affinity for muscarinic (cholinergic) receptors. Aripiprazole functions as a partial agonist at the D2 and 5-HT1A receptors, and as an antagonist at the 5-HT2A receptor (de Bartolomeis 2015).
Note: In pediatric patients 10 to 17 years of age, the pharmacokinetic parameters of aripiprazole and dehydro-aripiprazole have been shown to be similar to adult values when adjusted for weight.
Onset of action: Oral:
Bipolar disorder, acute mania: Initial effects may be observed within days of treatment with continued improvements over 1 to 2 weeks (Goikolea 2013; Tohen 2000; Welten 2016).
Major depressive disorder, unipolar: Initial effects may be observed within 1 week with continued improvements over 6 to 12 weeks (Wen 2014).
Schizophrenia: Initial effects may be observed within 1 to 2 weeks of treatment with continued improvements through 4 to 6 weeks (Agid 2003; Levine 2010). Due to its long half-life and active metabolite, it may take longer for aripiprazole to reach steady state at a therapeutic dose, resulting in delayed efficacy and tolerability issues compared to other antipsychotics (APA [Keepers 2020]).
Absorption:
Oral: Well absorbed.
IM long-acting injectable: Slow, prolonged.
Distribution: Vd: 4.9 L/kg.
Protein binding: ≥99%, primarily to albumin.
Metabolism: Hepatic dehydrogenation, hydroxylation, and N-dealkylation via CYP2D6, CYP3A4 to dehydro-aripiprazole (active metabolite) (Sheehan 2010).
Bioavailability:
Orally disintegrating tablets: 87% (bioequivalent to tablets).
Oral film: Oral film to tablet ratio of geometric mean for peak concentration under fasting conditions is 114% and AUC is 106% and under fed conditions is 91% and 95%, respectively.
Oral solution: Oral solution to tablet ratio of geometric mean for peak concentration is 122% and for AUC is 114%.
Tablet: 87%.
Half-life elimination:
Oral: Aripiprazole: 75 hours (CYP2D6 poor metabolizers: 146 hours); dehydro-aripiprazole (active metabolite): 94 hours.
Monthly IM long-acting injectable: Terminal t1/2: ~30 to 47 days (dose dependent).
Time to peak, plasma:
Oral: 3 to 5 hours; high-fat meals delay time to peak by 3 hours for aripiprazole and 12 hours for dehydro-aripiprazole (active metabolite).
Oral film: 1.5 hours; high-fat meals delay time to peak to 6 hours for aripiprazole.
IM long-acting injectable:
Monthly injection (Abilify Maintena): After multiple doses, 4 days with deltoid administration and 5 to 7 days with gluteal administration.
Every-2-months injection (Abilify Asimtufii): After multiple doses, a flat plasma concentration profile is maintained from days 1 through 49.
Excretion: Feces (55%, ~18% of the total dose as unchanged drug; 37% of the total dose as changed drug); urine (25%, <1% of the total dose as unchanged drug; 25% of the total dose as changed drug) (Sheehan 2010).
Altered kidney function: In severe renal impairment (CrCl <30 mL/minute), Cmax increased by 36% (aripiprazole) and 53% (dehydro-aripiprazole), but AUC was 15% lower for aripiprazole and 7% higher for dehydro-aripiprazole.
Hepatic function impairment: AUC increased by 31% in mild hepatic impairment and by 8% in moderate impairment, and decreased by 20% in severe impairment.
Older adult: In patients ≥65 years of age who were administered a single oral dose, clearance was 20% lower than that observed in younger patients.
Sex: Cmax and AUC are 30% to 40% higher in women than in men.
CYP 2D6 metabolizers: 60% higher exposure to aripiprazole and active metabolites in poor CYP 2D6 metabolizers compared to extensive metabolizers (Sheehan 2010).
