Abilify
Abilify
Generic Name
Abilify
Mechanism
- Partial agonist at D₂ & 5‑HT₁A receptors: Modulates dopaminergic and serotonergic neurotransmission, producing antipsychotic and antidepressant effects without full blockade that leads to classic EPS.
- Antagonist at 5‑HT₂A receptors: Contributes to antipsychotic efficacy and mitigates extrapyramidal side effects.
- Secondary activity: Low affinity for histamine H₁, α₁‑adrenergic, and muscarinic M₁ receptors, accounting for minimal sedation and anticholinergic burden.
Pharmacokinetics
| Parameter | Detail |
| Absorption | Oral bioavailability 70–75 %; peak plasma concentration 1–4 h post‑dose (immediate‑release). |
| Distribution | Protein‑binding ~93 %; crosses the blood–brain barrier efficiently. |
| Metabolism | Hepatic CYP3A4 & CYP2D6; active metabolites (dehydroaripiprazole). |
| Elimination | Renally excreted (≈25 %) and biliary. |
| Half‑life | ~75 h (immediate‑release) to ~94 h (extended‑release). |
| Food effects | No clinically relevant impact on absorption. |
Indications
- Schizophrenia (adult patients)
- Bipolar I disorder – manic and mixed episodes; maintenance therapy
- Major depressive disorder – adjunctive therapy to SSRIs/SNRIs
- Irritability associated with autism spectrum disorder (approved in adults and children ≥6 y)
- Off‑label: catatonia, tic disorders, and certain anxiety syndromes
Contraindications
- Hypersensitivity to aripiprazole or any excipient
- Severe uncontrolled agitation or delirium (risk for neuroleptic malignant syndrome)
- Known QTc prolongation (e.g., congenital long‑QT) due to rare bradycardic effects
- History of severe movement disorders that may worsen EPS
- Pregnancy Category B: caution; potential teratogenicity in animal studies; use only if benefits outweigh risks
> Warnings
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• Neuroleptic malignant syndrome: rare, but require vigilance for fever, rigidity, autonomic instability.
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• Metabolic syndrome: minimal weight gain but monitor waist circumference, lipids, and glucose.
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• Extrapyramidal symptoms (EPS): akathisia most frequent; monitor for dystonia, tremor.
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• Hypersalivation: paradoxical effect due to alpha‑1 blockade.
Dosing
| Form | Typical Starting Dose | Titration | Maintenance | Administration Notes |
| Oral Immediate‑Release (OIR) | 10 mg once daily (max 30 mg) | ↑5 mg q‑week; max 30 mg/d | 10–20 mg/d | Take with or without food; avoid large alcohol intake |
| Oral Extended‑Release (OXR) | 5 mg once daily (max 30 mg) | ↑5 mg q‑week; max 30 mg/d | 10–20 mg/d | Must maintain consistent dosing time; do not crush/split tablets |
| Intramuscular (IM) | 5–10 mg/24 h (for acute agitation) | Adjust after 48 h | Transition to oral | Use long‑acting formulation for maintenance (e.g., 300 mg monthly) |
| Injection (IV) – rare | 1–2 mg over 15 min | Follow protocol | Use only in specific emergencies (e.g., catatonia) | Monitor vital signs continuously |
> Key point: Aripiprazole has a low abuse potential; oral forms are not classified as controlled substances in the U.S.
Adverse Effects
| Category | Adverse Effect |
| Neuropsychiatric | Akathisia, anxiety, insomnia (rare), somnolence (low due to H₁ minimal) |
| Movement | Extrapyramidal symptoms (tremor, dystonia) – dose‑dependent |
| Metabolic | Weight gain (<5 % over baseline generally), dyslipidemia (↑ triglycerides), hyperglycemia |
| Cardiovascular | QTc prolongation (rare), orthostatic hypotension (low), increased risk of arrhythmia in predisposed |
| Gastrointestinal | Dry mouth, nausea, constipation (rare) |
| Other | Elevated prolactin (rare vs first‑generation), hypersalivation (paradoxical) |
Monitoring
- Baseline and periodic: ECG (QTc), weight, BMI, waist circumference
- Metabolic panel: fasting glucose, HbA1c, lipid profile annually
- Liver function tests: AST/ALT, bilirubin ±3 months
- Extrapyramidal: Barnes Akathisia Rating Scale (at baseline and 1–2 weeks)
- Adverse drug reactions: patient diary; report symptoms of sedation, orthostatic hypotension
Clinical Pearls
- Partial agonist uniqueness: Offers antipsychotic benefit while preserving dopaminergic tone, reducing EPS risk—ideal for patients with prior antipsychotic intolerance.
- Rapid Onset in Acute Settings: IM formulation can provide relief within 24–48 h; useful for catatonic stupor or severe agitation.
- Low Interaction with CYP3A4/2D6 inhibitors: Avoid strong inhibitors (ketoconazole, clarithromycin) or strong inducers (rifampin, carbamazepine) to prevent subtherapeutic levels.
- Adjuvant for Depression: Add 10–30 mg oral daily to SSRIs/SNRIs to boost response rates without significantly increasing metabolic burden.
- Cognitive Decline in Elderly: Preferred over typical antipsychotics due to minimal cholinergic blockade; however, still monitor for falls and delirium.
- Women of Childbearing Age: Use barrier contraception; although pregnancy category B, data limited; consult obstetricians.
- Drug‑Drug Interactions: Be cautious with CYP2D6 metabolites like dextromethorphan (increase serotonin syndrome risk).
- Tapering: Should be gradual (≤5 mg weekly) to reduce relapse risk and mitigate akathisia flare.
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• Abilify provides a flexible, well‑tolerated pharmacologic armamentarium across multiple psychiatric indications. Its distinct partial agonist mechanism and metabolic profile make it a preferred choice for clinicians seeking efficacy with a lower risk of classic antipsychotic side effects.