Drug Monograph
Aripiprazole
Abilify, Abilify Maintena, Abilify MyCite, Aristada (lauroxil prodrug)
Pharmacokinetic Profile
Half-Life
75 h (parent); 94 h (active metabolite)
Metabolism
Hepatic (CYP2D6, CYP3A4)
Protein Binding
>99% (albumin)
Bioavailability
87% (oral)
Volume of Distribution
404 L (4.9 L/kg)
Clinical Information
Drug Class
Atypical Antipsychotic (D2 Partial Agonist)
Available Doses
2, 5, 10, 15, 20, 30 mg tablets; 1 mg/mL solution; 9.75 mg/1.3 mL IM
Route
Oral, Intramuscular
Renal Adjustment
None required
Hepatic Adjustment
None required
Pregnancy
Category C; neonatal EPS risk with 3rd trimester use
Lactation
Present in breast milk; may reduce milk supply
Schedule / Legal Status
Not a controlled substance
Generic Available
Yes
Black Box Warning
Yes (dementia mortality; suicidality in youth)
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Schizophrenia | Adults and adolescents ≥13 years | Monotherapy | FDA Approved |
| Bipolar I disorder — acute manic/mixed episodes | Adults and pediatric patients ≥10 years | Monotherapy or adjunctive to lithium/valproate | FDA Approved |
| Major depressive disorder | Adults | Adjunctive to antidepressants | FDA Approved |
| Irritability associated with autistic disorder | Pediatric patients 6–17 years | Monotherapy | FDA Approved |
| Tourette’s disorder | Pediatric patients 6–18 years | Monotherapy | FDA Approved |
| Agitation in schizophrenia or bipolar mania | Adults (IM formulation) | Acute IM injection | FDA Approved |
Aripiprazole was first approved in 2002 and remains one of the most broadly indicated atypical antipsychotics. Its unique pharmacological profile as a dopamine D2 partial agonist distinguishes it from older second-generation agents that function primarily as D2 antagonists. The drug is available in multiple formulations including oral tablets, orally disintegrating tablets, oral solution, acute intramuscular injection, and long-acting injectable preparations (Abilify Maintena, Abilify Asimtufii, Aristada).
Off-Label Uses
Anxiety disorders — Open-label data suggest potential benefit, particularly as augmentation to SSRI therapy. Evidence quality: Low.
Treatment-resistant depression — Used as augmentation beyond the standard adjunctive MDD indication; some clinicians use doses above the approved 15 mg ceiling. Evidence quality: Moderate.
Psychosis in dementia — Occasionally used when non-pharmacological approaches fail, although the FDA boxed warning specifically advises against this use due to increased mortality. Evidence quality: Moderate (efficacy) / High (risk).
Antipsychotic-induced tardive dyskinesia — Case reports and small series suggest improvement after switching to aripiprazole. Evidence quality: Very low.
Dosing
Adult Dosing by Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Schizophrenia — acute episode or new diagnosis | 10–15 mg/day | 10–15 mg/day | 30 mg/day | Doses above 15 mg have not shown superior efficacy (FDA PI) Steady state reached in ~14 days |
| Schizophrenia — relapse prevention | 15 mg/day | 15 mg/day | 30 mg/day | Demonstrated efficacy in maintenance trials; reassess periodically |
| Bipolar I mania — monotherapy | 15 mg/day | 15 mg/day | 30 mg/day | May increase based on clinical response |
| Bipolar I mania — adjunct to lithium or valproate | 10–15 mg/day | 15 mg/day | 30 mg/day | Monitor lithium/valproate levels concurrently |
| MDD — adjunctive to antidepressant | 2–5 mg/day | 5–10 mg/day | 15 mg/day | Titrate by ≤5 mg at ≥1-week intervals Lower doses than schizophrenia |
| Acute agitation (IM) — schizophrenia or bipolar mania | 9.75 mg IM | N/A | 30 mg/day IM | Range 5.25–15 mg per injection; wait ≥2 h between doses Switch to oral as soon as possible |
Pediatric Dosing by Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Schizophrenia — adolescent (13–17 years) | 2 mg/day | 10 mg/day | 30 mg/day | Titrate: 2 mg → 5 mg (day 3) → 10 mg (day 5); 30 mg not more effective than 10 mg |
| Bipolar I mania — pediatric (10–17 years) | 2 mg/day | 10 mg/day | 30 mg/day | Same titration schedule as schizophrenia; monotherapy or adjunctive |
| Autism-related irritability (6–17 years) | 2 mg/day | 5–10 mg/day | 15 mg/day | Increase by ≤5 mg at ≥1-week intervals |
| Tourette’s disorder — body weight <50 kg (6–18 years) | 2 mg/day | 5 mg/day | 10 mg/day | Target 5 mg after 2 days; may increase to 10 mg at ≥1-week intervals |
| Tourette’s disorder — body weight ≥50 kg (6–18 years) | 2 mg/day | 10 mg/day | 20 mg/day | 2 mg × 2 days → 5 mg × 5 days → 10 mg target on day 8 |
CYP450 Dose Adjustments
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Known CYP2D6 poor metabolizer | Half of usual dose | Half of usual max | Reduced clearance prolongs exposure | |
| Co-prescribed strong CYP3A4 or CYP2D6 inhibitor | Half of usual dose | Half of usual max | Restore original dose when inhibitor withdrawn | |
| CYP2D6 poor metabolizer + strong CYP3A4 inhibitor | Quarter of usual dose | Quarter of usual max | Double impairment of clearance | |
| Co-prescribed strong CYP3A4 inducer (e.g., carbamazepine) | Double usual dose | Double usual max | Increase over 1–2 weeks; reduce back over 1–2 weeks when inducer stopped | |
Clinical Pearl: Dosing
For the MDD adjunctive indication, aripiprazole doses are substantially lower (2–15 mg) than those used in schizophrenia (10–30 mg). This reflects the partial agonist pharmacology: in hyperdopaminergic states (psychosis), higher occupancy is needed for functional antagonism, while in hypodopaminergic states (depression), modest D2 partial agonism at lower doses can augment monoaminergic transmission.
Pharmacology
Mechanism of Action
Aripiprazole is classified as a third-generation antipsychotic due to its distinctive receptor profile. Unlike traditional antipsychotics that block dopamine D2 receptors outright, aripiprazole functions as a high-affinity partial agonist at D2 and D3 receptors. In conditions of dopaminergic excess (such as the mesolimbic pathway in psychosis), aripiprazole competes with dopamine and attenuates signalling. In regions of dopaminergic deficit (such as the mesocortical pathway), it provides modest agonist tone that may address negative symptoms and cognitive impairment. Additionally, aripiprazole acts as a partial agonist at serotonin 5-HT1A receptors, an antagonist at 5-HT2A receptors, and has moderate affinity for histamine H1 and adrenergic alpha-1 receptors. This balanced receptor engagement accounts for its relatively favourable metabolic and extrapyramidal side-effect profile compared with many other antipsychotics.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Bioavailability 87%; Tmax 3–5 h (oral), 1 h (IM); food does not affect extent of absorption | Can be administered without regard to meals; IM provides faster peak levels for acute agitation |
| Distribution | Vd = 404 L (4.9 L/kg); >99% protein-bound (albumin); crosses blood-brain barrier | Extensive tissue distribution; high D2 occupancy (>90%) at clinical doses persists for days after discontinuation |
| Metabolism | Hepatic via CYP3A4 and CYP2D6; active metabolite dehydro-aripiprazole (~40% of parent exposure) | CYP2D6 poor metabolizers have ~60% reduced clearance; requires dose reduction. No direct glucuronidation; smoking does not affect levels |
| Elimination | t½ = 75 h (parent), 94 h (dehydro-aripiprazole); steady state by day 14; excretion ~60% faeces, ~25% urine (minimal unchanged drug) | Long half-life means missed doses have less immediate impact but also means adverse effects persist after discontinuation; no renal or hepatic dose adjustment needed |
Side Effects
≥10%
Very Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Nausea | 15% | Most common GI complaint; usually transient and dose-related; onset often in first 1–2 weeks |
| Headache | 12–27% | Rates vary by indication and trial; placebo rates are also high (15–25%), so drug-attributable headache is modest; typically mild and self-limiting |
| Insomnia | 18% | Activating profile of D2 partial agonism; morning dosing may help; distinct from sedating antipsychotics |
| Akathisia | 12% | Dose-related inner restlessness; higher in bipolar mania (~15%) than schizophrenia (~8%); frequently limits tolerability |
| Anxiety | 17% | May overlap with akathisia; careful clinical assessment needed to differentiate from underlying disorder |
| Restlessness | 12% | Related to akathisia spectrum; may present as subjective motor discomfort |
| Constipation | 11% | Less prominent than with highly anticholinergic antipsychotics; dietary and hydration measures usually sufficient |
| Dizziness | 10% | Related to alpha-1 antagonism; advise caution with position changes particularly during initiation |
1–10%
Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Somnolence / Sedation | 8% | More prominent in paediatric populations (up to 24% in autism trials); dose-related |
| Vomiting | 8% | Typically occurs early in treatment and resolves; more common in children |
| Extrapyramidal symptoms (non-akathisia) | 6% | Includes tremor, dystonia, and parkinsonian features; lower than many other antipsychotics |
| Tremor | 5% | Fine postural tremor; generally mild; consider dose reduction if bothersome |
| Fatigue | 6% | Distinguished from somnolence; may improve with time on treatment |
| Blurred vision | 3% | Reported mainly in the MDD adjunctive trials; usually transient |
| Weight gain | 2–5% | Mean gain +0.3 kg in short-term adult monotherapy trials (median 3–4 weeks); higher with longer exposure (~1.5 kg at 8 weeks); more pronounced in antipsychotic-naive youth; less than olanzapine or quetiapine |
| Dyspepsia | 4% | Upper GI discomfort; taking with food may help |
| Musculoskeletal stiffness | 4% | Part of EPS spectrum; usually responds to dose reduction |
Serious
Serious (Regardless of Frequency)
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Neuroleptic malignant syndrome (NMS) | Very rare | Days to weeks after initiation or dose change | Immediate discontinuation; ICU-level supportive care; monitor CK, renal function, temperature |
| Tardive dyskinesia | Rare (<1%) | Months to years of treatment | Consider discontinuation if clinically appropriate; may be irreversible; use AIMS for screening |
| Pathological gambling and compulsive behaviours | Rare | Variable; reported at any time during treatment | Dose reduction or discontinuation; proactively screen all patients; believed related to D3 agonism |
| Hyperglycaemia / new-onset diabetes | Uncommon (~1–2%) | Weeks to months | Monitor fasting glucose at baseline and periodically; risk lower than with olanzapine or clozapine |
| Cerebrovascular adverse events (elderly dementia patients) | Uncommon | Variable | Aripiprazole not approved for dementia-related psychosis; avoid use in this population |
| Seizures | Rare (0.1%) | Any time | Use with caution in patients with seizure history or conditions lowering seizure threshold |
| Leukopenia / Neutropenia / Agranulocytosis | Rare | First months of therapy | Monitor CBC in patients with pre-existing low WBC or drug-induced leukopenia history; discontinue if significant decline |
| Anaphylaxis / Angioedema | Very rare | Any time | Emergency treatment; permanent discontinuation; contraindicated in known hypersensitivity |
| Suicidal thoughts and behaviours (youth on adjunctive MDD therapy) | See boxed warning | Early weeks of treatment or dose changes | Close monitoring in all patients <25 years; family education; smallest prescription quantity |
Discontinuation
Discontinuation Rates
Adults (Schizophrenia Short-Term Trials)
11% vs 15% placebo
Top reasons: Lack of efficacy, akathisia, insomnia, agitation
Pediatric Patients
7–11% vs 7–17% placebo
Top reasons: Somnolence, EPS, weight gain, behavioural activation
| Reason for Discontinuation | Incidence | Context |
|---|---|---|
| Akathisia | 0.3–1.2% | Low discontinuation rate despite relatively high incidence; many patients tolerate with dose adjustment |
| EPS / Tremor | <1% | Rarely treatment-limiting; more common in children |
| Nausea / Vomiting | <1% | GI adverse effects usually self-limiting |
| Insomnia | <1% | Consider morning dosing before discontinuing |
Managing Akathisia
Akathisia is the most clinically significant tolerability barrier with aripiprazole. Management strategies include dose reduction (often the first and most effective step), switching to evening dosing, or adding a short course of a beta-blocker (propranolol 20–80 mg/day) or benzodiazepine. When akathisia occurs with concomitant SSRI use, a pharmacokinetic interaction via CYP2D6 inhibition should be considered, and the aripiprazole dose may need halving.
Drug Interactions
Aripiprazole is metabolised primarily by CYP2D6 and CYP3A4. It does not significantly inhibit or induce major CYP enzymes at clinical doses, so it is unlikely to alter the levels of co-administered medications. However, drugs that modulate CYP2D6 or CYP3A4 activity can substantially change aripiprazole exposure and require dose adjustment.
Major
Ketoconazole / Itraconazole
MechanismStrong CYP3A4 inhibition
EffectApproximately doubles aripiprazole AUC, increasing risk of dose-dependent side effects
ManagementReduce aripiprazole to half of usual dose; restore full dose when azole discontinued
FDA PI
Major
Fluoxetine / Paroxetine
MechanismStrong CYP2D6 inhibition
EffectIncreased aripiprazole levels; higher risk of akathisia and EPS
ManagementReduce aripiprazole to half of usual dose; particularly relevant in adjunctive MDD treatment
FDA PI
Major
Carbamazepine / Rifampin
MechanismStrong CYP3A4 induction
EffectSubstantially reduces aripiprazole plasma levels, risking therapeutic failure
ManagementDouble aripiprazole dose over 1–2 weeks; reduce back when inducer stopped
FDA PI
Major
Quinidine
MechanismStrong CYP2D6 inhibition
EffectElevated aripiprazole exposure similar to CYP2D6 poor-metaboliser phenotype
ManagementReduce aripiprazole to half of usual dose
FDA PI
Moderate
Benzodiazepines
MechanismAdditive CNS depression
EffectEnhanced sedation, orthostatic hypotension, and respiratory depression (IM co-administration)
ManagementMonitor closely when using both for acute agitation; avoid IV lorazepam within 1 h of IM aripiprazole
FDA PI
Moderate
Antihypertensives
MechanismAdditive alpha-1 blockade / hypotensive effects
EffectIncreased risk of orthostatic hypotension and syncope
ManagementMonitor blood pressure; consider slower aripiprazole titration in patients on multiple antihypertensives
Lexicomp
Moderate
Lithium / Valproate
MechanismNo significant pharmacokinetic interaction; pharmacodynamic overlap
EffectApproved combination for bipolar mania; additive sedation possible
ManagementNo dose adjustment needed; monitor for additive CNS effects and metabolic parameters
FDA PI
Minor
Sertraline / Citalopram / Escitalopram
MechanismWeak-to-moderate CYP2D6 inhibition (sertraline); minimal CYP effect (citalopram/escitalopram)
EffectMild increase in aripiprazole exposure with sertraline; negligible with citalopram
ManagementNo routine dose adjustment; monitor for akathisia especially at higher aripiprazole doses
LexicompMonitoring
-
Fasting Glucose & HbA1c
Baseline, 12 weeks, then annually
Routine All atypical antipsychotics carry metabolic risk. Aripiprazole has a more favourable glucose profile than olanzapine or clozapine, but monitoring remains standard of care per APA/ADA consensus guidelines. -
Lipid Panel
Baseline, 12 weeks, then annually
Routine Fasting total cholesterol, LDL, HDL, and triglycerides. Aripiprazole-associated dyslipidaemia is less common than with other second-generation agents. -
Body Weight & BMI
Baseline, monthly for 3 months, then quarterly
Routine Track weight trajectory particularly in antipsychotic-naive patients and adolescents. Clinically significant gain (≥7% baseline) occurred in up to 33% of paediatric patients over 26 weeks. -
Blood Pressure
Baseline, then periodically
Routine Orthostatic measurements at initiation; aripiprazole can cause postural hypotension via alpha-1 blockade. -
Extrapyramidal Symptoms
Each visit
Routine Use AIMS for tardive dyskinesia screening at least every 6–12 months; use Barnes Akathisia Scale if restlessness symptoms reported. -
Compulsive Behaviours
Each visit
Routine Proactively ask about new gambling, shopping, eating, or sexual urges. Patients may not volunteer this information. Dose reduction or discontinuation required if identified. -
CBC with Differential
If signs of infection or pre-existing low WBC
Trigger-Based Frequent monitoring during first few months for patients with a history of drug-induced leukopenia. Discontinue if ANC falls significantly without other explanation. -
Suicidality Assessment
Weekly for first 4 weeks, then at dose changes
Trigger-Based Particularly important in patients <25 years receiving adjunctive aripiprazole for MDD per the boxed warning. Educate family and caregivers to report concerning behavioural changes.
Contraindications & Cautions
Absolute Contraindications
- Known hypersensitivity to aripiprazole — reactions have ranged from urticaria to anaphylaxis (FDA PI)
Relative Contraindications (Specialist Input Recommended)
- Dementia-related psychosis in elderly patients — increased mortality risk; not an approved indication; prescribing requires exceptional clinical justification and documented informed consent
- Known CYP2D6 poor metaboliser receiving concomitant strong CYP3A4 inhibitor — markedly reduced clearance may lead to toxicity even at standard doses; requires quarter-dose or alternative agent
- Active pathological gambling or history of impulse-control disorders — aripiprazole’s D3 agonism may exacerbate compulsive behaviours; weigh alternatives carefully
Use with Caution
- Cardiovascular or cerebrovascular disease — orthostatic hypotension risk
- History of seizures or conditions that lower the seizure threshold
- Conditions predisposing to aspiration — dysphagia reported with all antipsychotics
- Diabetes or risk factors for diabetes — monitor glucose even though aripiprazole has a relatively favourable metabolic profile
- Patients at risk for falls — somnolence, motor instability, and orthostatic hypotension increase fall risk
- Extreme heat exposure — antipsychotics can impair thermoregulation
FDA Boxed Warning
Increased Mortality in Elderly Patients with Dementia-Related Psychosis
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration 10 weeks) in this population showed a death rate of 4.5% in drug-treated patients versus 2.6% in placebo-treated patients. Aripiprazole is not approved for dementia-related psychosis.
FDA Boxed Warning
Suicidal Thoughts and Behaviours in Youth
Antidepressants (including aripiprazole when used adjunctively for MDD) increased the risk of suicidal thinking and behaviour in children, adolescents, and young adults (18–24 years) in short-term studies. All patients started on antidepressant therapy should be monitored closely for clinical worsening, suicidality, and unusual behavioural changes, particularly during the initial months or at dose adjustments.
Patient Counselling
Purpose of Therapy
Aripiprazole works by rebalancing dopamine activity in the brain. Depending on the condition being treated, it may reduce hallucinations and disordered thinking (schizophrenia), stabilise mood and reduce manic episodes (bipolar disorder), enhance the effectiveness of an antidepressant (depression), or reduce irritability and behavioural outbursts (autism, Tourette’s). The full benefit typically emerges over 2–4 weeks, although some improvement may be noticed within the first week.
How to Take
Take aripiprazole once daily at the same time each day, with or without food. If a dose is missed, take it as soon as remembered unless it is almost time for the next dose. Do not stop the medication suddenly without consulting a prescriber, as abrupt discontinuation may lead to withdrawal-like symptoms. The orally disintegrating tablet should be placed on the tongue and allowed to dissolve; it can be taken without water.
Akathisia (Inner Restlessness)
Tell patient
Some patients experience a feeling of needing to keep moving or an inability to sit still. This is a recognised side effect and not a worsening of the psychiatric condition. It is most likely to occur in the first 1–2 weeks and often improves with dose adjustment.
Call prescriber
If restlessness is severe, persistent, or causing significant distress. Do not stop the medication without guidance.
Insomnia & Activation
Tell patient
Unlike many antipsychotics, aripiprazole can be activating rather than sedating. If sleep difficulties occur, morning dosing is preferred. Practising good sleep hygiene and avoiding caffeine in the afternoon may help.
Call prescriber
If insomnia persists for more than 2 weeks or if agitation, racing thoughts, or increased energy suggest a mood change.
Gambling & Compulsive Urges
Tell patient
Aripiprazole has been associated with new or intensified urges to gamble, shop excessively, binge eat, or engage in other compulsive behaviours. These urges may be hard to resist and may not feel medication-related.
Call prescriber
Immediately if any new compulsive urges develop. The prescriber may reduce the dose or switch to an alternative medication.
Dizziness & Falls
Tell patient
The medication can cause lightheadedness, especially when standing up quickly. Rise slowly from sitting or lying positions, particularly during the first few days of treatment. Stay well hydrated.
Call prescriber
If fainting occurs or if dizziness is persistent and interferes with daily activities.
Weight & Metabolic Health
Tell patient
While aripiprazole generally causes less weight gain than many other antipsychotics, some patients may gain weight. Maintaining a balanced diet and regular physical activity is important. Blood sugar and cholesterol will be monitored periodically.
Call prescriber
If experiencing increased thirst, frequent urination, or unexplained weight gain of more than 3 kg.
Mood Changes & Suicidality (MDD Indication)
Tell patient
When used alongside an antidepressant, there is a small increased risk of worsening depression or suicidal thoughts, particularly in young adults. Family members should be aware of warning signs including withdrawal, agitation, or talking about self-harm.
Call prescriber
Immediately if new or worsening thoughts of self-harm, panic attacks, or marked behavioural changes emerge.
Sources
Regulatory (PI / SmPC)
- Otsuka America Pharmaceutical, Inc. ABILIFY (aripiprazole) Prescribing Information. Revised January 2025. FDA Label Primary source for all dosing, indications, contraindications, adverse reaction incidence data, and drug interaction guidance used in this monograph.
- Otsuka America Pharmaceutical, Inc. ABILIFY MAINTENA (aripiprazole) Prescribing Information. 2023. FDA Label Reference for long-acting injectable formulation safety and dosing data.
- OPIPZA (aripiprazole) Oral Film Prescribing Information. 2025. FDA Label Most recently approved formulation; adverse reaction data from pooled aripiprazole clinical trial database.
Key Clinical Trials
- Potkin SG, Saha AR, Kujawa MJ, et al. Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs. placebo in patients with schizophrenia and schizoaffective disorder. Arch Gen Psychiatry. 2003;60(7):681-690. doi:10.1001/archpsyc.60.7.681 Pivotal RCT establishing efficacy versus placebo with comparative data against risperidone including EPS rates.
- Vieta E, Bourin M, Sanchez R, et al. Effectiveness of aripiprazole v. haloperidol in acute bipolar mania: double-blind, randomised, comparative 12-week trial. Br J Psychiatry. 2005;187:235-242. doi:10.1192/bjp.187.3.235 Head-to-head trial demonstrating comparable antimanic efficacy with superior EPS tolerability profile.
- Berman RM, Marcus RN, Swanink R, et al. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2007;68(6):843-853. doi:10.4088/jcp.v68n0604 Key trial supporting the adjunctive MDD indication with dose-response and akathisia incidence data.
Guidelines
- American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia, 3rd edition. Am J Psychiatry. 2021;178(suppl). doi:10.1176/appi.books.9780890424841 Current APA guideline positioning aripiprazole among first-line oral antipsychotic options for schizophrenia.
- American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27(2):596-601. doi:10.2337/diacare.27.2.596 Establishes metabolic monitoring standards for all atypical antipsychotics including aripiprazole.
Mechanistic / Basic Science
- Burris KD, Molski TF, Xu C, et al. Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. J Pharmacol Exp Ther. 2002;302(1):381-389. doi:10.1124/jpet.102.033175 Foundational study characterising the D2 partial agonist mechanism that underpins aripiprazole’s unique pharmacology.
- Grunder G, Carlsson A, Wong DF. Mechanism of new antipsychotic medications: occupancy is not just antagonism. Arch Gen Psychiatry. 2003;60(10):974-977. doi:10.1001/archpsyc.60.10.974 Conceptual framework for understanding dopamine partial agonism and functional selectivity in antipsychotic action.
Pharmacokinetics / Special Populations
- Boulton DW, Kollia G, Mallikaarjun S, et al. Pharmacokinetics and tolerability of intramuscular, oral and intravenous aripiprazole in healthy subjects and in patients with schizophrenia. Clin Pharmacokinet. 2008;47(7):475-485. doi:10.2165/00003088-200847070-00006 Comprehensive PK characterisation across formulations including IM bioavailability and Tmax data.
- Kim JR, Sohn S, Yoon YR, et al. Population pharmacokinetic modelling of aripiprazole and its active metabolite, dehydroaripiprazole, in psychiatric patients. Br J Clin Pharmacol. 2008;66(6):802-810. doi:10.1111/j.1365-2125.2008.03223.x Population PK model confirming CYP2D6 genotype impact on clearance with metabolite kinetics in real-world psychiatric populations.
- Grunder G, Fellows C, Carlsson A, et al. Brain and plasma pharmacokinetics of aripiprazole in patients with schizophrenia. Am J Psychiatry. 2008;165(8):988-995. doi:10.1176/appi.ajp.2008.07101574 PET study demonstrating high D2/D3 receptor occupancy across brain regions at clinical doses with slow dissociation.