Should aripiprazole be administered in the morning or at night?

Aripiprazole Administration: Morning vs. Night

Aripiprazole should be administered in the morning due to its activating properties that can potentially disrupt sleep if taken at night.

Timing of Administration Based on FDA Labeling

The FDA label for aripiprazole states that it can be administered "once-a-day schedule without regard to meals" 1. While this indicates flexibility in administration timing, it doesn't specifically address the morning versus evening question. However, understanding aripiprazole's pharmacological profile helps determine the optimal timing.

Pharmacological Properties Affecting Timing

Aripiprazole has unique pharmacological properties that influence when it should be taken:

• It acts as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors 2
• It has antagonistic effects at serotonin 5-HT2A receptors 2
• The mean elimination half-life is approximately 75 hours 2
• Steady-state plasma concentrations are achieved by 14 days 1

Morning Administration Rationale

Morning administration is preferred for aripiprazole for several reasons:

1. Activating properties: Aripiprazole has activating effects that can cause insomnia and anxiety, which are among its most common side effects 3

2. Sleep disruption potential: Taking aripiprazole at night may increase the risk of sleep disturbances due to its activating properties 4

3. Consistent with other activating antipsychotics: Guidelines suggest that activating antipsychotics should be administered in the morning to avoid sleep disruption 5

When Evening Administration Might Be Considered

In certain clinical scenarios, evening administration might be considered:

• For patients experiencing excessive daytime sedation with morning dosing
• When treating conditions where the activating properties at night might be beneficial, such as in some cases of delayed sleep phase syndrome 4
• When managing specific side effects that may be better tolerated during sleep

Dosing Considerations

• Starting dose is typically 10-15 mg once daily 1
• No dosage titration is necessary for most patients 3
• Dosage adjustments are needed for:
  • CYP2D6 poor metabolizers (half the usual dose)
  • Patients taking CYP3A4 inhibitors or CYP2D6 inhibitors
  • Patients taking strong CYP3A4 inducers 1

Clinical Pearls and Pitfalls

• Common pitfall: Administering aripiprazole at night may worsen insomnia, which is already one of the most common side effects 3
• Important consideration: The long half-life (75 hours) means that the timing of administration may have less impact on steady-state levels than drugs with shorter half-lives 2
• Monitoring recommendation: Assess for sleep disturbances, anxiety, and agitation regardless of administration time
• Patient-specific factors: While morning administration is generally preferred, individual response should be monitored

Conclusion

Based on aripiprazole's pharmacological profile and side effect pattern, morning administration is generally recommended to minimize sleep disruption. The long half-life provides stable blood levels, but the activating properties make morning dosing preferable for most patients.