Can Abilify (aripiprazole) lower the seizure threshold?

Aripiprazole and Seizure Threshold

Yes, Abilify (aripiprazole) can lower the seizure threshold, but it has a relatively low risk compared to many other antipsychotics. According to the FDA drug label, aripiprazole should be used cautiously in patients with a history of seizures or with conditions that lower the seizure threshold 1.

Evidence on Aripiprazole and Seizure Risk

The FDA drug label specifically states that in short-term, placebo-controlled trials with aripiprazole, seizures/convulsions occurred in 0.1% (3/2467) of adult patients treated with oral aripiprazole and in 0.1% (1/732) of pediatric patients (6 to 18 years) 1. This indicates a low but present risk.

Research evidence supports that aripiprazole has a relatively low seizure risk profile:

• Among second-generation antipsychotics, aripiprazole appears to pose a significantly lower risk of seizure induction compared to medications like clozapine 2.
• In a comprehensive review of antipsychotic medications and seizure threshold, aripiprazole was not identified among the high-risk agents 3.

Risk Stratification of Antipsychotics

Antipsychotics vary significantly in their potential to lower seizure threshold:

Higher Risk:

• Clozapine (highest risk among second-generation antipsychotics) 2, 4
• Chlorpromazine (highest risk among first-generation antipsychotics) 3, 4

Lower Risk:

• Aripiprazole 2
• Risperidone 2, 4
• Haloperidol 4
• Fluphenazine 4
• Pimozide 4

Patient-Specific Risk Factors

The risk of seizures with aripiprazole increases in patients with:

1. History of seizures or epilepsy 1
2. Conditions that lower seizure threshold 1
3. Age 65 years or older (conditions that lower seizure threshold may be more prevalent) 1
4. Concurrent use of other medications that lower seizure threshold 5

Clinical Recommendations

When prescribing aripiprazole to patients with seizure risk factors:

• Start with lower doses and titrate slowly 5
• Monitor closely for any signs of seizure activity, especially during dose adjustments
• Avoid combinations with other medications known to lower seizure threshold (e.g., certain antidepressants, other antipsychotics) 5
• Consider alternative antipsychotics with even lower seizure risk if the patient has a history of seizures
• Be particularly cautious in elderly patients, as the FDA label notes that conditions lowering seizure threshold may be more prevalent in patients 65 years or older 1

Important Precautions

• The risk of seizures with aripiprazole appears to be dose-dependent, as with other psychotropic medications 3
• Drug-drug interactions can increase seizure risk, particularly when multiple medications that lower seizure threshold are used concurrently 5
• Rapid dose titration may increase the risk of seizures 3

In summary, while aripiprazole can lower seizure threshold, it represents one of the safer options among antipsychotics for patients with seizure concerns. However, caution is still warranted, particularly in high-risk patients.