Which is the least sedating option between Latuda (lurasidone) and Abilify (aripiprazole)?

Aripiprazole (Abilify) is Less Sedating Than Lurasidone (Latuda)

Aripiprazole (Abilify) is the less sedating option between the two medications, making it preferable when sedation is a concern. 1, 2

Comparative Sedation Profiles

• Aripiprazole may be particularly useful when a less sedating antipsychotic is desired, as noted by clinical guidelines 2
• Aripiprazole is often selected for delirium management specifically when less sedation is desired compared to other antipsychotics 2
• Lurasidone, while having a favorable metabolic profile, is associated with sedation as one of its notable side effects 3
• Sedation is a well-recognized side effect of olanzapine and quetiapine, but aripiprazole has a lower sedation profile compared to these and other antipsychotics 4

Mechanism of Action Explaining Sedation Differences

• Aripiprazole's unique mechanism as a partial agonist at dopamine D2 and D3 receptors, rather than a full antagonist like most antipsychotics, contributes to its lower sedation profile 5
• Aripiprazole's partial agonism at serotonin 5-HT1A receptors and modest antagonism of 5-HT2A receptors creates a different side effect profile than lurasidone 5
• Lurasidone has potent blockade of the 5HT7 receptor, which may contribute to its different sedation profile 3

Side Effect Profiles Beyond Sedation

Aripiprazole (Abilify)

• Common side effects include headache, agitation, anxiety, insomnia, and dizziness 2
• Less likely to cause extrapyramidal symptoms (EPS) than first-generation antipsychotics, though risk increases at higher doses 2
• Generally does not increase bodyweight to a clinically relevant extent in short-term treatment, though long-term treatment (100 weeks) may lead to clinically significant weight gain in some patients 5
• Low risk of prolactin elevation, QT interval prolongation, and metabolic disturbances 5
• May cause emotional blunting, particularly manifesting as anxiety, agitation, and changes in emotional responsiveness 1

Lurasidone (Latuda)

• Has demonstrated positive effects on psychosis, mood, and cognition 3
• Does not appear to have significant adverse impact on metabolic profile (weight, glucose, or lipid metabolism) 3
• Associated with good cardiovascular tolerability without QT interval prolongation 3
• May have advantages in treating negative symptoms and cognitive and depressive symptoms associated with schizophrenia 3

Clinical Considerations for Medication Selection

• When treating patients at risk for arrhythmias, aripiprazole is favored as it has not been associated with QTc prolongation or torsade de pointes 4
• For patients with delirium, aripiprazole may offer benefit in symptomatic management with less sedation 4
• Lower doses of aripiprazole (5-10mg) are recommended for elderly patients, those with hepatic impairment, or poor metabolizers of cytochrome P450 2D6 2
• Medication adherence may be better with aripiprazole compared to other atypical antipsychotics, including ziprasidone and quetiapine 6

Practical Prescribing Considerations

• Starting with lower doses of aripiprazole (5-10mg) may help minimize side effects while maintaining therapeutic benefit 2
• Monitor for drug-drug interactions, especially with cytochrome P450 2D6 and 3A4 inhibitors or inducers, as these can alter aripiprazole levels and potentially affect sedation 1
• Consider dose reduction if emotional blunting occurs with aripiprazole 1
• For patients requiring antipsychotic treatment but where sedation would be problematic (e.g., outpatients who need to drive or work), aripiprazole would be the preferred choice 2

In conclusion, when sedation is a concern, aripiprazole (Abilify) is the better choice compared to lurasidone (Latuda) based on its pharmacological properties and clinical evidence.