Is a total daily dose of 2 x 400mg (800mg) of Abilify (aripiprazole) safe?

Safety of 800mg Daily Dose of Abilify (Aripiprazole)

A total daily dose of 800mg of Abilify (aripiprazole) is not safe and far exceeds the maximum recommended therapeutic dose, posing significant risks for severe adverse effects.

Recommended Dosing for Aripiprazole

• The recommended therapeutic dose range for aripiprazole in schizophrenia is between 10-30 mg per day 1, 2
• Clinical evidence indicates that the optimal dose for aripiprazole is around 10 mg/day, with doses above 20 mg/day providing no additional benefit 2
• For treatment of delirium in adult patients, the recommended starting dose is only 5 mg per day with a maximum daily dose of 30 mg 3
• Third-generation antipsychotics like aripiprazole are typically administered once daily (q24h) at these therapeutic doses 3

Evidence Against High-Dose Aripiprazole

• Clinical trials have established that doses above 20 mg/day do not provide additional therapeutic benefit and may be associated with smaller improvements in symptom scores 2
• Even at low doses (2 mg), aripiprazole produces striatal dopamine D2 receptor occupancy exceeding 70%, which is already above the threshold needed for antipsychotic effect 2
• The mean doses achieved in clinical trials were significantly lower than 800 mg, with most studies using doses between 10-30 mg daily 4, 5

Potential Adverse Effects of Excessive Dosing

• At extremely high doses like 800 mg daily (20-80 times the recommended dose), severe adverse effects would be expected, including:
  • Increased risk of extrapyramidal symptoms (EPSs) 3
  • Severe headache, agitation, anxiety, insomnia, dizziness, and drowsiness 3
  • Potential for QTc prolongation and cardiac complications 3
  • Risk of severe drug-drug interactions, especially with cytochrome P450 2D6 and 3A4 inhibitors 3

Highest Reported Safe Doses

• The highest documented dose of aripiprazole in published literature was 60 mg/day in a case report of a patient with refractory schizophrenia who had previously been on olanzapine 6
• Even this 60 mg dose, which is far below 800 mg, was considered exceptionally high and outside standard practice 6
• This case was notable enough to warrant publication, indicating the unusual nature of such high dosing 6

Clinical Considerations

• Aripiprazole has a long half-life of approximately 75 hours, which can lead to drug accumulation with repeated dosing 4
• At steady state (achieved after about 14 days), drug concentrations can be 4 times higher than after initial dosing 4
• This pharmacokinetic profile makes extremely high doses particularly dangerous due to cumulative effects 4

Conclusion

• 800 mg of aripiprazole (2 x 400 mg) represents a potentially toxic dose that is approximately 27-80 times the recommended therapeutic dose
• No clinical evidence supports the safety or efficacy of aripiprazole at such extreme doses
• Such high doses would significantly increase the risk of severe adverse effects without providing additional therapeutic benefit