What is Abilify (aripiprazole)?

Aripiprazole (Abilify): A Comprehensive Overview

Aripiprazole (Abilify) is an atypical antipsychotic medication with a unique pharmacological profile, acting primarily as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors, and as an antagonist at serotonin 5-HT2A receptors. 1

Mechanism of Action

• Aripiprazole differs from other atypical antipsychotics by functioning as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors, rather than primarily as an antagonist 1
• This unique mechanism is described as "functionally selective," allowing for more targeted receptor activity 1
• Aripiprazole also acts as an antagonist at serotonin 5-HT2A receptors, contributing to its efficacy and side effect profile 1, 2

FDA-Approved Indications

• Schizophrenia in adults and adolescents (13-17 years) 3
• Bipolar I disorder (manic and mixed episodes) in adults and pediatric patients (≥13 years) 4
• Adjunctive treatment of major depressive disorder in adults 5
• Irritability associated with autism 5

Dosing Information

• For schizophrenia in adults: Starting and target dose is 10-15 mg/day, with an effective dose range of 10-30 mg/day 3
• For adolescents with schizophrenia (13-17 years): Target dose is 10 mg/day, starting at 2 mg/day and titrating up 3
• Dosage adjustments are recommended for patients who are CYP2D6 poor metabolizers or taking CYP3A4 inhibitors or CYP2D6 inhibitors 3
• Oral solution can be substituted for tablets on a mg-per-mg basis up to 25 mg 3

Formulations Available

• Oral tablets in various strengths 3
• Oral solution 3
• Long-acting injectable (LAI) formulations:
  • Aripiprazole monohydrate LAI (Abilify Maintena®) 6, 2
  • Aripiprazole lauroxil LAI (Aristada®) 2

Efficacy

• Effective in treating positive and negative symptoms of schizophrenia, with rapid onset of action (within one week) 1
• In bipolar disorder, effective for treating manic episodes in adults and adolescents (≥13 years) 4
• As adjunctive therapy to antidepressants, demonstrated clinically meaningful efficacy for major depressive disorder 5
• Long-acting injectable formulations have shown efficacy in maintenance treatment of schizophrenia, with comparable effectiveness to oral formulations 6, 2

Safety and Adverse Effects

• Generally well-tolerated compared to other antipsychotics 2
• Common side effects include:
  • Nausea, vomiting, constipation, headache, dizziness, anxiety, insomnia, and blurred vision 3
  • Akathisia (inner sense of restlessness) 3, 2
• Metabolic profile:
  • Lower risk of metabolic disturbances compared to some other atypical antipsychotics 6, 2
  • May cause weight gain, but typically less than other atypical antipsychotics 5
  • Can affect blood glucose levels; monitoring recommended in patients with diabetes or risk factors 3
• Neurological effects:
  • Risk of extrapyramidal symptoms, though generally at lower rates than first-generation antipsychotics 2
  • Akathisia and tremor occur at higher rates than placebo (10-11%) 2
• Unique effects:
  • Associated with reduced serum prolactin levels (unlike many other antipsychotics) 2
  • Favorable QTc interval profile 2

Special Considerations

• Unusual urges: Some patients may experience compulsive behaviors such as gambling, binge eating, compulsive shopping, and sexual urges 3
• Risk of orthostatic hypotension and falls, particularly in elderly patients 3
• May impair judgment, thinking, or motor skills; caution advised when operating machinery or vehicles 3
• Pregnancy considerations: May cause extrapyramidal and/or withdrawal symptoms in neonates; pregnancy registry available 3
• Heat exposure and dehydration: Patients should be advised to avoid overheating and dehydration 3

Use in Special Populations

• Pediatric use: Approved for adolescents (≥13 years) with schizophrenia or bipolar disorder, with weight-based dosing recommended 3, 4
• CYP2D6 poor metabolizers: Recommended to administer half the usual dose 3
• Patients taking CYP3A4 or CYP2D6 inhibitors: Dose adjustments required 3

Combination Therapy

• When switching from other antipsychotics to aripiprazole, gradual discontinuation of the previous antipsychotic is recommended to minimize withdrawal effects 3
• In treatment-resistant cases, combination with other antipsychotics may be considered, though monotherapy is generally preferred 7
• Combining aripiprazole with partial dopamine agonists may be beneficial in reducing residual symptoms while minimizing side effects 8

Aripiprazole represents an important option in the antipsychotic armamentarium with its unique mechanism of action and generally favorable side effect profile, particularly regarding metabolic and cardiovascular effects.