Which of the following is associated with more side effects?

Tricyclic antidepressants (TCAs) are indeed associated with more side effects compared to other classes of antidepressants. This is primarily due to their mechanism of action, which affects several neurotransmitter systems, not just serotonin and norepinephrine. TCAs inhibit the reuptake of norepinephrine and serotonin, but they also have significant anticholinergic properties, which can lead to a variety of side effects such as dry mouth, constipation, urinary retention, blurred vision, and confusion, particularly in older adults.

In addition to anticholinergic effects, TCAs can also influence histamine receptors, leading to sedation, and they can block alpha-adrenergic receptors, which may cause hypotension. This broad spectrum of activity, while effective for depression and certain other conditions, increases the likelihood of experiencing adverse effects.

Other antidepressants like SSRIs, NDRIs, and SNRIs generally have a more targeted action with fewer side effects. For instance, SSRIs are mainly selective for serotonin reuptake, resulting in fewer anticholinergic effects. Similarly, SNRIs, while they affect both serotonin and norepinephrine, tend to have a better side effect profile than TCAs. NDRIs, which primarily affect