What are the potential side effects of Abilify (aripiprazole) in patients with a history of psychiatric conditions, such as schizophrenia, bipolar disorder, or major depressive disorder?

Abilify (Aripiprazole) Side Effects

Most Common Side Effects

The most frequently reported side effect of Abilify is akathisia (restlessness), occurring in 8-10% of adult patients compared to 4% with placebo, making it the only side effect occurring at twice the rate of placebo in schizophrenia trials. 1

Neurological Side Effects

• Akathisia is the most prominent side effect, particularly dose-dependent at 30 mg doses 1
• Extrapyramidal symptoms (EPS) occur in 13% of adults (vs 12% placebo), but are significantly more common in adolescents at 25% (vs 7% placebo) 1
• Tremor affects 5% of adults and shows dose-response relationship in adolescents (2% at 10mg, 11.8% at 30mg) 1
• Somnolence/sedation occurs in 5-7% of adults, with dose-dependent increases at 30mg (12.6%) 1
• Headache (27%), dizziness (10%), and lethargy are common neurological complaints 1

Psychiatric and Behavioral Side Effects

• Agitation (19%), insomnia (18%), anxiety (17%), and restlessness (5%) are frequently reported 1
• Compulsive behaviors including pathological gambling, hypersexuality, and uncontrollable urges were recognized by the FDA in 2016 as serious side effects 2
• Behavioral activation or nausea occurred in 15.5% of hospitalized patients, with women three times more likely to experience adverse effects 3

Gastrointestinal Side Effects

• Nausea and vomiting (11%), constipation (11%), dyspepsia (9%), and dry mouth (5%) are common 1
• These effects are typically transient and resolve with continued treatment 4

Metabolic Side Effects

Aripiprazole has a uniquely favorable metabolic profile compared to other antipsychotics, with minimal propensity for weight gain, dyslipidemia, or diabetes. 5, 6, 4

• Weight gain is minimal (3% of pediatric patients vs 1% placebo) 1
• No clinically significant changes in glucose, lipids, or metabolic parameters in 26-week trials 5
• When used to augment other antipsychotics, aripiprazole may actually reduce weight gain, dyslipidemia, and metabolic dysfunction caused by those medications 7, 8

Endocrine Side Effects

• Aripiprazole may reduce prolactin levels rather than elevate them, distinguishing it from most antipsychotics 8
• Reduced hyperprolactinemia and sexual dysfunction when combined with other antipsychotics 7, 9
• No clinically significant QTc interval prolongation 5

Serious but Rare Side Effects

Life-Threatening Complications

• Neuroleptic Malignant Syndrome (NMS): Rare but potentially fatal, characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability 1
• Tardive dyskinesia: Potentially irreversible involuntary movements, though incidence is very low (0.2%, similar to placebo) 1
• Suicidality risk: Increased in patients under 24 years old when used for depression (14 additional cases per 1000 patients under 18) 1

Pediatric-Specific Considerations

Adolescents (13-17 years) experience significantly higher rates of extrapyramidal symptoms compared to adults. 1

• Extrapyramidal disorder (21.6% at 30mg vs 5% placebo), somnolence (21.6% at 30mg vs 6% placebo), and tremor (11.8% at 30mg vs 2% placebo) show clear dose-response relationships 1
• Fatigue (10%), increased appetite (7%), and sedation (9%) are more common in pediatric patients 1
• Discontinuation rates due to adverse effects are 5% in adolescents vs 2% with placebo 1

Critical Clinical Pitfalls

• Do not overlook akathisia, as it is the most common reason for treatment discontinuation and may be mistaken for worsening agitation or anxiety 7, 1
• Screen for history of impulse control disorders before prescribing, as aripiprazole can precipitate pathological gambling and compulsive behaviors 2
• Monitor for behavioral activation in patients with mood disorders, as symptoms like agitation, irritability, and restlessness may represent precursors to suicidality 1
• Adjust dosing for body weight, particularly in obese patients who may require higher mg/kg doses for adequate therapeutic effect 3
• Consider CYP2D6 metabolizer status, as poor metabolizers and elderly patients require lower doses 8

Comparative Safety Profile

Aripiprazole demonstrates superior metabolic safety compared to other atypical antipsychotics, with placebo-level incidence of weight gain and metabolic syndrome. 5, 6, 4

• EPS rates are significantly lower than haloperidol in long-term trials 5
• When combined with clozapine, aripiprazole reduces clozapine-induced metabolic side effects while maintaining efficacy 7, 8, 9
• The overall safety profile is favorable, though akathisia remains a limiting factor in some patients 6