What are the common and serious adverse effects of aripiprazole, and what monitoring is recommended for adults, children, elderly, and pregnant or nursing patients?

Aripiprazole Side Effects

Common Adverse Effects

Aripiprazole is generally well-tolerated, but clinicians must monitor for several common side effects that can impact adherence and quality of life.

In Adults

• Nausea, vomiting, and constipation are among the most frequently reported gastrointestinal effects 1
• Akathisia (inner restlessness/need to move) occurs commonly and may be mistaken for anxiety or worsening psychiatric symptoms 1
• Headache, dizziness, and insomnia are reported frequently, particularly during initial titration 1
• Anxiety and restlessness can emerge, especially early in treatment 1
• Blurred vision may occur but typically resolves with continued treatment 1
• Upper respiratory illness and general fatigue are documented 1

In Children and Adolescents

• Sedation/somnolence is the most common side effect in pediatric populations 1
• Extrapyramidal symptoms (EPS) occur at a mean incidence of 17.1% in youth, significantly higher than previously appreciated 2
• Weight gain and appetite changes (both increased and decreased) are frequently observed 1
• Uncontrolled movements including tremor, muscle stiffness, and restlessness occur more commonly than in adults 1
• Increased salivation or drooling is particularly notable in younger patients 1
• Headache, nausea, vomiting, and stuffy nose are common 1

A critical pitfall: The pediatric population shows significantly higher rates of acute EPS (dystonia, akathisia, Parkinsonism) compared to adults, with tremor and parkinsonism being significantly more common than placebo 2. This contradicts the assumption of a universally favorable side-effect profile in youth.

Serious Adverse Effects Requiring Immediate Attention

Neuroleptic Malignant Syndrome (NMS)

• Presents with high fever, muscle rigidity, confusion, sweating, and changes in pulse/heart rate/blood pressure 1
• This is a rare but potentially fatal condition requiring immediate medical intervention 1
• Discontinue aripiprazole immediately if NMS is suspected 1

Tardive Dyskinesia

• Uncontrolled movements of face, tongue, or other body parts that may be irreversible 1
• Risk persists even after discontinuation of the medication 1
• Elderly patients are at particularly high risk 1

Metabolic Complications

• Hyperglycemia and diabetes: Aripiprazole can cause significant blood sugar elevations, potentially leading to diabetic ketoacidosis, coma, or death 1
• Warning signs include: excessive thirst, increased urination, extreme hunger, weakness, fatigue, nausea, confusion, or fruity-smelling breath 1
• Increased cholesterol and triglycerides require monitoring 1
• Weight gain should be tracked regularly, though aripiprazole causes less weight gain than olanzapine or quetiapine 1

Cardiovascular Effects

• Orthostatic hypotension with lightheadedness or fainting when rising from sitting/lying positions 1
• Increased fall risk due to sedation, dizziness, decreased blood pressure, and slowed motor skills 1
• QTc prolongation is possible, particularly when combined with other QT-prolonging medications 3

Cerebrovascular Events

• Stroke risk in elderly patients (cerebrovascular problems) that can be fatal 1
• This is particularly concerning in patients with dementia-related psychosis 4

Hematologic Effects

• Low white blood cell count increases infection risk 1

Neurological Complications

• Seizures (convulsions) can occur 1
• Difficulty swallowing may lead to aspiration of food or liquid into the lungs 1

Behavioral and Impulse Control Disorders

• Pathological gambling, compulsive shopping, binge eating, and compulsive sexual urges have been reported 1
• These urges may resolve with dose reduction or discontinuation 1
• Patients and families must be counseled about this risk and instructed to report any unusual urges immediately 1

Temperature Dysregulation

• Impaired body temperature regulation, especially with exercise or heat exposure 1
• Patients must maintain adequate hydration, avoid heavy clothing, and drink plenty of water 1

Monitoring Recommendations

For All Patients on Aripiprazole

Baseline Assessment:

• Body mass index (BMI), waist circumference, blood pressure 5
• Fasting glucose and fasting lipid panel 5
• Pregnancy test in females of childbearing potential 1

Ongoing Monitoring:

• BMI monthly for 3 months, then quarterly 5
• Blood pressure, fasting glucose, and lipids at 3 months, then annually 5
• Regular assessment for movement disorders (akathisia, tremor, dystonia) 1
• Evaluation for behavioral changes including suicidal ideation, agitation, anxiety, or unusual urges 1

Special Population Considerations

Children and Adolescents

• More frequent monitoring for EPS given the 17.1% incidence rate 2
• Close observation for behavioral activation (restlessness, impulsivity, aggression) 5
• Weight and metabolic parameters require particularly vigilant tracking due to higher vulnerability 5

Elderly Patients

• Aripiprazole shows modest efficacy for dementia-related psychosis but carries increased mortality risk as a class effect 4
• Should only be used in selected patients resistant to non-pharmacological treatment with severe, persisting psychotic symptoms causing significant morbidity 4
• Lower starting doses (2.5-5 mg) are appropriate, with slower titration 6
• Monitor closely for falls, orthostatic hypotension, and cerebrovascular events 1, 4
• Sedation and postural hypotension are common but often resolve without intervention 7
• Indication for continuing treatment should be revised regularly 4

Patients with Diabetes or Metabolic Risk Factors

• Check blood sugar before starting aripiprazole and during treatment 1
• Aripiprazole has fewer metabolic effects compared to haloperidol, clozapine, quetiapine, and risperidone 3
• Screen at baseline, rescreen at 12-16 weeks, then annually for patients on second-generation antipsychotics 3

Pregnancy and Nursing

• Advise patients to notify healthcare provider if pregnant or planning pregnancy 1
• Neonatal risks include: extrapyramidal symptoms, withdrawal symptoms (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, feeding disorder) 1
• Pregnancy registry available to monitor outcomes in exposed women 1
• Breastfeeding considerations should be discussed, though specific data are limited 1

Drug Interactions and Precautions

• Strong CYP450 inducers (rifampin, phenobarbital, carbamazepine, phenytoin) may decrease aripiprazole efficacy 3
• Patients should inform physicians of all medications including over-the-counter drugs due to interaction potential 1
• Avoid alcohol and other CNS depressants which may potentiate sedation and orthostatic hypotension 1

Critical Clinical Pitfalls to Avoid

1. Underestimating EPS risk in youth: The 17.1% incidence contradicts assumptions of minimal motor side effects 2
2. Failing to counsel about impulse control disorders: These can devastate patients' lives if unrecognized 1
3. Inadequate metabolic monitoring: Diabetes and dyslipidemia can develop insidiously 1
4. Overlooking fall risk in elderly: Combined effects of sedation, orthostatic hypotension, and motor slowing significantly increase injury risk 1
5. Continuing treatment without reassessment in dementia patients: Given increased mortality risk, ongoing indication must be justified 4
6. Ignoring early signs of NMS or tardive dyskinesia: These require immediate intervention 1
7. Inadequate hydration counseling: Temperature dysregulation can be dangerous, especially in hot weather or with exercise 1