Which antidepressant is least likely to cause sedation?

Sertraline is considered the antidepressant least likely to cause sedation due to its selective serotonin reuptake inhibitor (SSRI) classification. SSRIs generally have a favorable side effect profile regarding sedation, making them suitable for patients who may experience fatigue or lethargy from their medications. Unlike some other antidepressants, sertraline typically doesn't have sedative properties, which can be beneficial for individuals who need to maintain daytime alertness.

In contrast, mirtazapine can cause sedation, especially at lower doses, due to its antihistaminergic effects. Venlafaxine, while primarily an SNRI, can also lead to sedation, particularly at higher doses when noradrenergic activity is increased. Amitriptyline, a tricyclic antidepressant, is well-known for its sedative effects because of its potent antihistamine activity and its mechanism of action, which can lead to significant drowsiness.

The pharmacological profiles of these medications highlight sertraline's relative lack of sedative effects, making it the optimal choice for individuals concerned about sedation as a potential side effect of their treatment.