An antidepressant became a go-to sleep drug despite a guideline against it
Trazodone was approved in 1981 to treat depression, yet much of its fame comes from a job it was never licensed for: helping people sleep. By the early 2000s it was the second most prescribed insomnia drug, even though a major sleep medicine body later advised against using it that way.
Chemically, trazodone is a phenylpiperazine in a class called serotonin antagonist and reuptake inhibitors, taken by mouth. Trials comparing it with older antidepressants such as amitriptyline found similar effectiveness against major depression, with milder side effects and low toxicity to the heart. Because it has little anticholinergic activity, the kind of action behind dry mouth, urinary trouble and constipation, it was welcomed for older patients when it arrived. It is now generic, and in 2023 it ranked 21st among all US prescriptions, with more than 24 million issued.
Its sedating quality cuts both ways. For agitated, anxious or sleepless patients relief can come quickly; for people already sluggish and low in energy, the drowsiness can be too much. It can also make blood pressure drop on standing, probably by blocking alpha-1 adrenergic receptors, which raises the risk of dizziness and falls. In older adults it has been linked to more falls and hip fractures.
The sleep story is where evidence gets thin. Reviews in the late 2010s, including a Cochrane review, concluded that low doses help with short-term insomnia, slightly improving how people rate their sleep and cutting night-time awakenings. They found no clear effect on how fast people fall asleep or on total sleep time, and rated the evidence low to moderate. Nothing yet informs long-term use. In 2017 the American Academy of Sleep Medicine recommended against it for insomnia, citing weak evidence and harms that might outweigh benefits.
Rarer risks draw close attention. Irregular heart rhythms have been reported, including in people with no history of heart disease. The manufacturer estimated abnormal erectile function in roughly one in 6,000 men treated. Like other antidepressants, it may raise suicidal thinking in young people, and stopping abruptly can trigger discontinuation symptoms. In overdose it appears safer than several older antidepressant classes; in one report, all nine deaths among 294 overdoses involved other sedating drugs taken as well.
Source: Trazodone
