Trazodone is an antidepressant medication used to treat major depressive disorder, anxiety disorders, and insomnia. It is a phenylpiperazine compound of the serotonin antagonist and reuptake inhibitor (SARI) class. The medication is taken orally. Common side effects include dry mouth, feeling faint, vomiting, and headache. More serious side effects may include suicide, mania, irregular heart rate, and pathologically prolonged erections. It is unclear if use during pregnancy or breastfeeding is safe. Trazodone also has sedating effects. Trazodone was approved for medical use in the United States in 1981. It is available as a generic medication. In 2023, it was the 21st most commonly prescribed medication in the United States and the fifth most common antidepressant, with more than 24 million prescriptions.
Medical uses
Depression The primary use of trazodone is the treatment of unipolar major depression with or without anxiety. Data from open and double-blind trials suggest that the antidepressant efficacy of trazodone is comparable to that of amitriptyline, doxepin, and mianserin. Furthermore, trazodone has shown anxiolytic properties, low cardiotoxicity, and relatively mild side effects. Because trazodone has minimal anticholinergic activity, it was especially welcomed as a treatment for geriatric patients with depression when it first became available. Three double-blind studies reported trazodone had antidepressant efficacy similar to that of other antidepressants in geriatric patients. Unfortunately, a side effect of trazodone, orthostatic hypotension, may cause dizziness and increase the risk of falling. This may have devastating consequences for elderly patients. Therefore, this side effect, along with sedation, often makes trazodone less acceptable for this population compared to newer compounds that share its lack of anticholinergic activity (but not the rest of its side effect profile). Still, trazodone is often helpful for geriatric patients with depression who have severe agitation and insomnia. Trazodone is usually used at a dosage of 150 to 300 mg/day for the treatment of depression. Lower doses have also been used to augment other antidepressants or when initiating therapy. Higher doses, up to 600 mg/day, have been used in more severe cases of depression (in hospitalized patients, for example). Trazodone is usually administered multiple times per day, but once-daily administration may be similarly effective.
Insomnia Low-dose trazodone is used off-label in the treatment of insomnia and is considered to be effective and safe for this indication. It may also be used to treat antidepressant-related insomnia. Trazodone was the second-most prescribed agent for insomnia in the early 2000s even though most studies of trazodone for the treatment of sleep disturbances have been in depressed individuals. Systematic reviews and meta-analyses published in the late 2010s, including a Cochrane review, found low-dose trazodone to be an effective medication for short-term treatment of insomnia in both depressed and euthymic people. Trazodone slightly improves subjective sleep quality (SMDTooltip standardized mean difference = –0.34 to –0.41) and reduces the number of nighttime awakenings (MD = –0.31, SMD = –0.51), on average. Conversely, it does not appear to affect sleep onset, total sleep time, time awake after sleep onset, or sleep efficiency. It appears to increase deep sleep—in contrast to certain other hypnotics. The quality of evidence of trazodone for short-term treatment of insomnia was rated as low to moderate. There is no evidence available at present to inform the long-term use of trazodone in the treatment of insomnia. The benefits of trazodone for insomnia must be weighed against potential adverse effects, such as morning grogginess, daytime sleepiness, cognitive and motor impairment, and postural hypotension, among others. Quality safety data on the use of trazodone as a sleep aid are currently lacking. Trazodone is used at low doses in the range of 50 to 150 mg/day for insomnia. Higher doses of 200 to 600 mg/day have also been studied. The American Academy of Sleep Medicine's 2017 clinical practice guidelines recommended against the use of trazodone in the treatment of insomnia due to inadequate evidence and due to harms potentially outweighing benefits.
Other disorders Trazodone is often used in the treatment of anxiety disorders—such as generalized anxiety disorder and panic disorder—as well as in post-traumatic stress disorder (PTSD) and obsessive–compulsive disorder (OCD). Trazodone is often used as an alternative to benzodiazepines in the treatment of anxiety disorders. However, use of trazodone in anxiety disorders is off-label and evidence of its effectiveness for these indications is variable and limited. Benefits for OCD appear to be mild. Trazodone has been used to treat sleep disturbances and nightmares in PTSD.
Combination with other antidepressants Trazodone is often used in combination with other antidepressants such as selective serotonin reuptake inhibitors in order to augment their antidepressant and anxiolytic effects and to reduce side effects such as sexual dysfunction, anxiety, and insomnia.
Available forms Trazodone is provided as the hydrochloride salt and is available in the form of 50 mg, 100 mg, 150 mg, and 300 mg oral tablets. In Italy, it is also available as an oral solution (Trittico 60 mg/mL) with a dosing pipette marked at 25 mg and 50 mg. An extended-release oral tablet formulation at doses of 150 mg and 300 mg is also available.
Side effects
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