Trazodone

H1 and 5-HT2A mediated. Dose-dependent. At sleep doses (25-100mg), this is the therapeutic effect. At antidepressant doses, it becomes a tolerability problem. Next-day grogginess occurs in some patients, particularly at higher sleep doses. Taking the medication at least 7-8 hours before the alarm can help.

Alpha-1 mediated, clinically significant in vulnerable populations. The most important safety consideration in elderly and fall-risk patients. Present even at low sleep doses. Counsel patients to rise slowly from sitting or lying positions. Check orthostatic blood pressures when clinically indicated. This is the primary pharmacological difference between trazodone and mirtazapine for insomnia.

Rare, alpha-1 mediated, a urological emergency. Estimated incidence roughly 1 in 6,000 to 1 in 8,000. Can occur at any dose. Requires emergency treatment if sustained beyond 4 hours. All male patients must be counseled. This is non-negotiable regardless of how routine the prescription feels.

Multifactorial. Combination of orthostatic effects, sedation, and possible vestibular contributions. Taking with food slows absorption and may reduce peak dizziness.

Mild anticholinergic contribution. Less pronounced than with TCAs or olanzapine, but present.

Clinically relevant primarily at antidepressant doses (150mg+). At sleep doses, the risk is low but should be considered in patients with pre-existing QTc prolongation or those on multiple QTc-prolonging medications.

A relative advantage. Compared to mirtazapine or quetiapine, trazodone causes minimal weight gain. This is a meaningful advantage for patients who need a sedating sleep agent but are overweight or metabolically vulnerable.

At low doses, trazodone does not cause the sexual dysfunction associated with SSRIs. At antidepressant doses, sexual side effects can occur but are generally less prominent than with SSRIs.