Which class of antidepressants is primarily associated with sedation?

The class of antidepressants primarily associated with sedation is the Tricyclic Antidepressants (TCAs). These medications, developed in the 1950s, tend to affect various neurotransmitter systems, including norepinephrine and serotonin. One of the common side effects of many TCAs is sedation, which can be beneficial for patients who also have insomnia or significant anxiety in addition to their depressive symptoms.

The sedation is largely due to their antihistaminic properties as TCAs can block histamine H1 receptors. This action contributes to their sedative effects, differentiating them from other classes of antidepressants. In contrast, SSRIs (Selective Serotonin Reuptake Inhibitors) are generally considered to be more activating and less sedating. Norepinephrine-Dopamine Reuptake Inhibitors (NDRIs) are also stimulating rather than sedating, and Monoamine Oxidase Inhibitors (MAOIs) don’t have the same level of sedation as TCAs; they can be activating depending on the specific agent and patient response. Thus, TCAs are the best-known class for their sedative properties.