Aripiprazole, marketed under the trade names Abilify among others, is an atypical antipsychotic medication used primarily in the treatment of psychiatric conditions.
Brand names
- USA: Abilify, Abilify Maintena, Aristada
- Europe: Abilify, Abilify Maintena
Generic versions are available in both regions under various manufacturer names.
Mechanism of action
- Partial agonist at D2 and 5-HT1A receptors
- Antagonist at 5-HT2A receptors
- Unique “dopamine system stabilizer”
- Moderate affinity for histamine and alpha-adrenergic receptors
Pharmacokinetics
- Bioavailability: 87%
- Peak plasma levels: 3-5 hours
- Half-life: 75 hours
- Steady state achieved in 14 days
- Metabolized primarily by CYP2D6 and CYP3A4
Dosage forms
Here’s a detailed breakdown of Aripiprazole dosage forms in the USA and Europe:
United States (FDA-approved forms)
1. Oral Tablets:
- 2 mg (white)
- 5 mg (blue)
- 10 mg (pink)
- 15 mg (yellow)
- 20 mg (white)
- 30 mg (pink)
2. Orally Disintegrating Tablets (ABILIFY DISCMELT):
- 10 mg
- 15 mg
- Available with vanilla flavor
- Dissolves on tongue within seconds
3. Oral Solution:
- 1 mg/mL concentration
- Clear, colorless liquid
- Available in 150 mL bottles
4. Long-acting Injectable Forms:
- ABILIFY MAINTENA: 300 mg and 400 mg monthly injection (powder for reconstitution)
- ARISTADA: Available in:
- 441 mg monthly
- 662 mg monthly
- 882 mg monthly or every 6 weeks
- 1064 mg every 2 months
European Union (EMA-approved forms)
1. Oral Tablets:
- 5 mg
- 10 mg
- 15 mg
- 30 mg
2. Orodispersible Tablets:
- 10 mg
- 15 mg
- 30 mg
3. Oral Solution:
- 1 mg/mL concentration
4. Long-acting Injectable:
ABILIFY MAINTENA: 300 mg and 400 mg monthly injection. Available as:
- Powder and solvent for suspension
- Pre-filled dual chamber syringe
Storage requirements
Oral Tablets/Orodispersible:
Store at room temperature (20-25°C)
- Protect from moisture
- Keep in original container
Oral Solution:
- Store at room temperature
- Discard 6 months after opening
Injectable Forms:
- Store at room temperature
- Protect from light
- Use immediately after reconstitution
Key Differences Between Regions:
- More injectable options available in USA (ARISTADA)
- Slightly different tablet strength selections
- Additional orodispersible strengths in Europe
- Same storage requirements across regions
How does it work?
Aripiprazole functions as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors, and as an antagonist at 5-HT2A receptors. This unique profile means it can both stimulate and block these neurotransmitter pathways depending on the baseline level of neurotransmitter activity. By modulating dopamine and serotonin, aripiprazole helps in stabilizing mood, reducing psychotic symptoms, and managing certain aspects of cognitive function.
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Dopamine modulation
As a partial agonist at D2 receptors, aripiprazole can reduce dopamine activity in areas where it is too high (like the mesolimbic pathway associated with psychosis) but increase it where it’s low (such as in the prefrontal cortex, which might be beneficial in cognitive enhancement).
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Serotonin effects
Its action at serotonin receptors helps in mood stabilization and potentially reduces some of the side effects associated with pure dopamine antagonism.
Indications
Aripiprazole is approved for:
- Schizophrenia: To manage positive symptoms (hallucinations, delusions) and to a lesser extent, negative symptoms (social withdrawal, lack of motivation).
- Bipolar disorder: Both for manic and mixed episodes as well as for maintenance treatment to prevent recurrence.
- Major depressive disorder: As an adjunct treatment to antidepressants when standard therapy does not provide sufficient response.
- Irritability and anger in Autistic Disorder: Used mostly in young patients.
- Tourette’s syndrome: To reduce tics.
Off-label uses commonly include:
- Anxiety disorders
- Obsessive-compulsive disorder
- Personality disorders
- Aggression in dementia
- Treatment-resistant depression
Dosage and administration
- Oral: Available in tablets, orally disintegrating tablets, and liquid form. Dosage starts low and is titrated up based on response and tolerance, typically ranging from 10 to 30 mg per day for adults.
- Injection: Long-acting injectable forms are available for maintenance treatment, administered every 4 weeks or monthly, offering a compliance advantage over daily oral medications.
Dosing guidelines
Schizophrenia:
- Adults: Initial 10-15 mg once daily, target 10-30 mg/day
- Adolescents: Start 2 mg/day, gradually increase to 10 mg/day
- Maximum dose: 30 mg/day
Bipolar Disorder:
- Acute mania: Start 15 mg/day, can increase to 30 mg/day
- Maintenance: 15-30 mg/day
- Bipolar disorder in children (10-17 years): Start 2 mg/day, target 10 mg/day
Major Depression (Adjunctive):
- Start 2-5 mg/day
- Gradually increase to 5-15 mg/day based on response
- Maximum 15 mg/day
Administration
- Can be taken with or without food
- Available in tablets, oral solution, and long-acting injectable
- Tablets can be crushed if needed
- Evening dosing may help with sedation
Treatment duration
- Chronic conditions require long-term treatment
- Gradual discontinuation recommended
- Monitor for withdrawal symptoms
Side effects
Side Effects:
Common side effects of Aripiprazole (>10%):
- Akathisia
- Headache
- Nausea/vomiting
- Insomnia
- Restlessness
- Weight gain (less than other antipsychotics)
- Somnolence
Less Common (1-10%):
- Anxiety
- Dizziness
- Constipation
- Tremor
- Blurred vision
- Sexual dysfunction
Rare but Serious Aripiprazole side effects:
- Tardive dyskinesia
- Neuroleptic malignant syndrome
- QT prolongation
- Metabolic changes
- Orthostatic hypotension
Contraindications and precautions
It’s contraindicated in patients with a known hypersensitivity to the drug.
Use with caution in patients with a history of seizures, cardiovascular disease, or Parkinson’s disease due to potential worsening of symptoms or interactions with other medications.
Drug interactions
Aripiprazole can interact with many drugs, particularly those affecting the cytochrome P450 liver enzymes (CYP2D6 and CYP3A4), which can alter its serum levels. Medications like ketoconazole, fluoxetine, or carbamazepine can either increase or decrease aripiprazole’s metabolism, necessitating dosage adjustments.
Strong CYP3A4 inhibitors:
- Reduce aripiprazole dose by 50%
- Monitor for side effects
Strong CYP2D6 inhibitors:
- Reduce dose by 50%
- Examples: fluoxetine, paroxetine
CYP3A4 inducers:
- May require dose increase
- Examples: carbamazepine, rifampin
Patient monitoring
Baseline:
- Complete blood count
- Metabolic panel
- Lipid profile
- ECG (if cardiac risk factors)
- Weight and BMI
- Blood pressure
- Abnormal involuntary movement scale (AIMS)
Ongoing:
- Metabolic monitoring every 3-6 months
- Weight monitoring monthly initially
- AIMS evaluation every 6 months
- Annual lipid and glucose testing
- Regular blood pressure checks
Special populations
Elderly:
- Start at lower doses (2-5 mg/day)
- Higher risk of orthostatic hypotension
- Monitor cognitive effects
Pregnancy:
- Category C
- Risk/benefit assessment needed
- Monitor neonates for withdrawal symptoms
Renal/Hepatic Impairment:
- No initial dose adjustment needed in mild-moderate impairment
- Use caution in severe impairment
Aripiprazole vs other Antipsychotics: pharmacological and clinical distinctions
Aripiprazole vs. Risperidone
Mechanism of action
Aripiprazole functions as a partial D2 agonist, creating a “stabilizing” effect on dopamine systems. This results in fewer extrapyramidal symptoms and less prolactin elevation. Risperidone, in contrast, works as a potent D2 antagonist with strong 5-HT2A blocking properties, leading to more complete dopamine blockade.
Side effect profile
- Aripiprazole: Lower weight gain, minimal prolactin elevation, less sedation
- Risperidone: Higher prolactin elevation, moderate weight gain, greater risk of extrapyramidal symptoms
Clinical usage patterns
- Aripiprazole often serves as first-line treatment for younger patients and those concerned about metabolic effects.
- Risperidone shows particular strength in acute psychosis control and aggressive behaviors.
Aripiprazole vs. Olanzapine
Metabolic impact
Olanzapine carries significantly higher risk of:
- Weight gain (often 7% or more of body weight)
- Diabetes development
- Lipid abnormalities
Aripiprazole shows minimal metabolic effects.
Sedation Profiles:
- Olanzapine: Strong sedation, useful in acute agitation
- Aripiprazole: Minimal sedation, better for day functioning
Clinical selection factors
Olanzapine often preferred for:
- Acute psychotic episodes requiring rapid control
- Patients with sleep disturbance
- Treatment-resistant cases
Aripiprazole preferred for:
- Young patients
- First-episode psychosis
- Long-term maintenance
Aripiprazole vs. Quetiapine
Receptor binding
Quetiapine shows:
- Strong antihistamine effects
- Significant alpha-blocking properties
- Weaker D2 binding
Making it more sedating but with fewer movement disorders.
Clinical applications
Quetiapine excels in:
- Mood disorders
- Elderly patients
- Sleep disturbance
Aripiprazole better suited for:
- Primary psychotic disorders
- Long-term maintenance
- Patients requiring cognitive clarity
Aripiprazole vs. Haloperidol
Generational differences
Haloperidol (first-generation):
- Strong D2 blockade
- High EPS risk
- Minimal weight gain
- Limited receptor profile
Aripiprazole (third-generation):
- Partial agonist properties
- Better tolerability
- Broader receptor activity
- Lower EPS risk
Usage patterns
Haloperidol remains valuable for:
- Acute agitation control
- Injectable forms for emergency use
- Cost-effective treatment
Aripiprazole preferred for:
- Maintenance therapy
- Better quality of life
- Reduced side effect burden
Clinical considerations for choosing Aripiprazole
Patient factors:
- Young age
- First episode
- Metabolic risk factors
- Need for cognitive clarity
- Long-term treatment plans
Patient factors favoring other antipsychotics:
Risperidone:
- Acute psychosis
- Aggression control
- Cost considerations
Olanzapine:
- Treatment resistance
- Need for rapid sedation
- History of good response
Quetiapine:
- Mood symptoms
- Sleep problems
- Elderly patients
Haloperidol:
- Acute emergencies
- Limited treatment duration
- Resource-limited settings
Monitoring requirements
Aripiprazole:
- Less frequent metabolic monitoring
- Regular movement disorder screening
- Activation side effects
Other Agents:
- More frequent metabolic screening (especially olanzapine)
- Prolactin monitoring (risperidone)
- Blood pressure monitoring (quetiapine)
- EPS monitoring (haloperidol)