Which of the following antidepressants is considered the most sedating?

Doxepin is recognized as the most sedating antidepressant among the options provided. This sedative effect is primarily due to its strong antihistaminic properties, which lead to significant sedation. Doxepin is a tricyclic antidepressant (TCA) that can have a calming impact on the central nervous system, making it suitable for individuals who face challenges with sleep or anxiety alongside their depression.

While bupropion is known for its stimulating effects due to its norepinephrine-dopamine reuptake inhibition, duloxetine and venlafaxine, which are serotonin-norepinephrine reuptake inhibitors (SNRIs), are also less sedating than doxepin. Doxepin’s relatively higher sedative qualities make it favorable in certain clinical scenarios where sleep improvement is also a treatment goal.

In summary, doxepin’s effectiveness as a sedating antidepressant is attributed to its pharmacological profile, particularly its antihistaminic effects, distinguishing it from the other listed medications that do not offer the same level of sedation.