ARIPIPRAZOLE
Generic Name
Aripiprazole
Brand Names
Abilify
Aristada (long-acting injection)
Abilify Maintena (monthly intramuscular injection)
Abilify MyCite (tablet with ingestible sensor for adherence tracking)
Available as oral tablets, orally disintegrating tablets, oral solution, and injectable forms
Drug Class
Atypical antipsychotic (Second-generation antipsychotic)
Dopamine D2 receptor partial agonist
Serotonin-dopamine activity modulator (SDAM)
Mechanism of Action
Aripiprazole acts as a partial agonist at dopamine D2 and D3 receptors, leading to functional modulation of dopaminergic activity
It also acts as a partial agonist at serotonin 5-HT1A receptors and an antagonist at 5-HT2A receptors
This mechanism stabilizes dopaminergic and serotonergic activity—reducing dopamine in areas of excess (e.g., mesolimbic pathway in schizophrenia) while enhancing it where deficient (e.g., mesocortical pathway)
Minimal activity on histamine and muscarinic receptors accounts for its favorable side effect profile (less sedation and anticholinergic effects)
Indications
FDA-Approved and Global Indications
Schizophrenia (adults and adolescents aged 13–17 years)
Bipolar I disorder
• Acute manic and mixed episodes (adults, adolescents)
• Maintenance treatment
Major depressive disorder (as adjunct)
Irritability associated with autistic disorder
Tourette’s disorder (children aged 6–18 years)
Agitation associated with schizophrenia or bipolar I disorder (intramuscular injection)
Off-Label Uses
Borderline personality disorder
Obsessive-compulsive disorder
Delusional disorder
Treatment-resistant depression
Anxiety disorders
Post-traumatic stress disorder
Tics and movement disorders
Behavioral symptoms in dementia (caution advised)
Delirium in hospitalized patients
Dosage and Administration
Oral Formulations
Initial dose depends on indication and age group
Schizophrenia (Adults)
Start: 10–15 mg once daily
Target dose: 10–30 mg/day
Max: 30 mg/day
Can be taken with or without food
Schizophrenia (Adolescents 13–17 years)
Start: 2 mg/day → titrate to 10 mg/day over several days
Max: 30 mg/day
Bipolar I Disorder (Adults)
Acute mania: 15 mg/day as monotherapy or adjunct to lithium/valproate
Maintenance: Continue effective dose
Max: 30 mg/day
Bipolar I Disorder (Children 10–17 years)
Start: 2 mg/day → increase to 10 mg/day
Max: 30 mg/day
Major Depressive Disorder (Adjunctive)
Start: 2–5 mg/day
Adjust based on response, typical range 5–15 mg/day
Max: 15 mg/day
Irritability in Autism (Aged 6–17)
Start: 2 mg/day → target: 5–15 mg/day
Max: 15 mg/day
Tourette’s Disorder (Aged 6–18)
Start: 2 mg/day
Usual target: 5–10 mg/day
Max: 20 mg/day
Intramuscular Short-Acting (IM) for Agitation
Initial: 9.75 mg IM (range 5.25–15 mg)
May repeat dose every 2 hours if needed
Max: 30 mg/day
Long-Acting Injectables
Abilify Maintena (monthly injection)
Dose: 400 mg IM monthly (gluteal or deltoid)
Overlap oral aripiprazole for 14 days
Aristada (every 4, 6, or 8 weeks)
Doses: 441 mg, 662 mg, 882 mg, or 1064 mg depending on frequency
Oral overlap required for 21 days
Pharmacokinetics
Bioavailability (oral): ~87%
Peak plasma: 3–5 hours
Metabolism: liver via CYP3A4 and CYP2D6 to active metabolite (dehydro-aripiprazole)
Half-life: 75 hours (aripiprazole), 94 hours (active metabolite)
Steady-state: 10–14 days
Protein binding: >99%
Excretion: feces and urine
Contraindications
Hypersensitivity to aripiprazole or any formulation ingredients
Caution in patients with known cardiovascular disease or history of seizures
Warnings and Precautions
Increased mortality in elderly patients with dementia-related psychosis (Boxed Warning)
Risk of suicidal thoughts and behavior (especially in depression)
Neuroleptic malignant syndrome
Tardive dyskinesia (risk increases with duration and dose)
Metabolic changes: hyperglycemia, dyslipidemia, weight gain (less than other atypicals)
Orthostatic hypotension
Impulse control disorders: reports of pathological gambling, hypersexuality
Seizures—caution in seizure-prone individuals
Risk of akathisia, especially early in treatment
Monitor for behavioral changes, agitation, aggression, or suicidal ideation
Adverse Effects
Very Common
Akathisia
Headache
Anxiety
Insomnia
Nausea
Constipation
Weight gain (modest)
Common
Dizziness
Somnolence
Agitation
Tremor
Blurred vision
Restlessness
Fatigue
Dry mouth
Increased appetite
Less Common
Tardive dyskinesia
Hyperprolactinemia (less than risperidone)
Neuroleptic malignant syndrome
Seizures
QT prolongation (rare)
Rare
Suicidal ideation or behavior (mostly in youth)
Impulse control issues
Hypersensitivity reactions
Priapism
Severe hyperglycemia or ketoacidosis
Pregnancy and Lactation
Pregnancy
Category C (old FDA system)
Animal studies showed adverse fetal effects
Use only if benefits outweigh risks
Neonatal extrapyramidal or withdrawal symptoms reported with late pregnancy exposure
Avoid in 3rd trimester unless no alternatives
Lactation
Excreted in breast milk
Use caution if breastfeeding—monitor infant for sedation, irritability, or feeding problems
Alternative antipsychotics may be preferred
Drug Interactions
CYP2D6 or CYP3A4 inhibitors (e.g. fluoxetine, paroxetine, ketoconazole)
May increase plasma levels—lower aripiprazole dose
CYP3A4 inducers (e.g. carbamazepine, phenytoin, rifampin)
May reduce efficacy—consider dose adjustment
Antihypertensives
Additive hypotensive effect
CNS depressants (benzodiazepines, alcohol, opioids)
Additive sedation and cognitive impairment
Dopaminergic drugs (e.g. levodopa)
May reduce effects of aripiprazole
SSRIs/SNRIs
Can be co-administered for depression but monitor for serotonin syndrome
QT-prolonging drugs (e.g. amiodarone, erythromycin)
Risk of QT prolongation, though aripiprazole is relatively low risk
Monitoring Parameters
Mental status, mood changes, suicidal ideation
Weight, BMI, waist circumference
Fasting glucose and lipid panel
Blood pressure and heart rate
Extrapyramidal symptoms (EPS), akathisia, tremors
Tardive dyskinesia (AIMS scale)
Signs of neuroleptic malignant syndrome
Serum prolactin (if galactorrhea, gynecomastia, or amenorrhea occurs)
Adherence (especially in outpatient and long-term therapy)
Counseling Points
Take at the same time daily, with or without food
Do not abruptly stop the medication—risk of relapse
May cause dizziness or drowsiness—avoid driving until effects known
May take several weeks to show full benefit
Report restlessness, unusual urges, muscle stiffness, or fever
Limit alcohol consumption
Notify doctor if pregnant or planning pregnancy
Inform dentist or surgeon about this medication before any procedure
Keep tablets dry and out of reach of children
Report any mood changes or suicidal thoughts immediately
Comparative Notes
Aripiprazole vs Risperidone
Lower risk of prolactin elevation and sedation
Less weight gain
More akathisia
No significant QT prolongation
Aripiprazole vs Olanzapine
Better metabolic profile (less weight gain, hyperlipidemia)
Less sedating
Olanzapine has higher antipsychotic efficacy in some trials
Aripiprazole vs Quetiapine
Aripiprazole is activating (akathisia risk), quetiapine is sedating
Both are approved as adjuncts in depression
Quetiapine more useful for sleep disorders, aripiprazole more for negative symptoms
Aripiprazole in Treatment-Resistant Depression
Used as augmentation with SSRIs or SNRIs
Low-dose initiation (2–5 mg/day)
Monitored for emergence of akathisia or agitation
Legal and Regulatory Status
Prescription-only
FDA-approved for multiple psychiatric disorders
Available in most countries under centralized marketing authorizations
Long-acting injectable formulations require administration by healthcare providers
Included in WHO Model List of Essential Medicines for schizophrenia
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