Trazodone (Desyrel) was the first non-tricyclic / non-MAOI antidepressant approved in the US, predating the SSRIs. Many psychiatrists consider trazodone their first-line sleep medication. It is the author’s #1 most prescribed drug. It can be combined with any other medication. Low-dose Trazodone 50–75 mg can even be combined with an MAOI (Jacobsen, 1990). The author regards significantly prolonged QTc interval (over 490 msec or so) as the only contraindication.
Although it is approved as an antidepressant, trazodone is usually prescribed at low dose for insomnia, with no antidepressant benefit expected. It is seldom used as a stand-alone treatment for depression due to sedation and orthostatic hypotension if dosed at antidepressant strength. Trazodone is often prescribed as an adjunct to SSRIs. It may be helpful for reducing PTSD nightmares (Warner MD et al, 2001).
Trazodone induces and maintains sleep without causing tolerance. Its half-life of 3–6 hours is ideal for sleep without causing daytime drowsiness. The most common side effect is xerostomia—a mouth that’s “dry as a bone”. Most medications causing dry mouth do so as an anticholinergic effect. This is not the case with trazodone, which lacks anticholinergic effects.
It is a preferred sleep medication for those with obstructive sleep apnea (OSA) because it does not depress respiration. It does not cause weight gain or sexual side effects.
Many sedatives work by blocking H1 histamine receptors. Trazodone is sedating due to a combination of moderate H1 antihistamine effect plus antagonism of 5-HT2A and alpha-1 adrenergic receptors.
Priapism (painful prolonged erection) is a rare risk of Trazodone, and a medical emergency. Priapism is not considered a significant risk with any other psychotropic medication. Although the risk is low (1 in 6,000), think twice before prescribing trazodone to a man being discharged to jail, where prompt medical treatment for priapism might not be provided. Trazodone-induced priapism is likely attributable to antagonism of alpha-1 adrenoceptors, which interferes with the sympathetic control of penile detumescence.
Animal studies suggested trazodone could reduce the risk of dementia, but this does not appear to apply to humans (Brauer et al, 2019). At worst, trazodone does not contribute to dementia risk. Anticholinergic sleep medications like diphenhydramine (Benadryl) and doxylamine (Unisom) do increase risk of dementia.
The original trade name of trazodone was DESYREL, but no one calls it that because the generic name has such a nice ring to it. An extended-release version of trazodone branded as OLEPTRO (150, 300 mg) was available, but virtually no one prescribed it.
It is commonly misspelled as trazadone.
Dosing: Titrate slowly. The dose for insomnia is 25–200 mg, usually started at 50 mg, for routine or PRN use. For healthy adults, the author often prescribes 150 mg tablets with instructions to take ⅓ to 1 tab PRN which allows doses of 50, 75, 100, or 150 mg. QT prolongation may occur if the FDA max of 400 mg is exceeded. Antidepressant dosing is 300–600 mg, divided BID (as the label instructs) or taken all at HS which is better tolerated. 150 mg may be useful for depression for some patients.