What is the use of Trazodone (Triazolopyridine antidepressant)?

From the Guidelines

Trazodone should not be used as a treatment for sleep onset or sleep maintenance insomnia in adults, due to its adverse effect profile and lack of significant benefits compared to placebo, as recommended by the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guidelines 1.

Key Points

• The American Academy of Sleep Medicine clinical practice guideline suggests that clinicians not use trazodone as a treatment for sleep onset or sleep maintenance insomnia in adults, based on trials of 50 mg doses of trazodone 1.
• A systematic review reported no differences in sleep efficiency or rate of discontinuation due to adverse events between trazodone and placebo in patients diagnosed with chronic insomnia, although trazodone was more effective at improving subjective sleep quality 1.
• The work group advised against use of benzodiazepines or trazodone for treatment of chronic insomnia disorder, due to the widely known harms and adverse effects of benzodiazepines and the low-quality evidence supporting the efficacy of trazodone 1.
• Trazodone is primarily prescribed for depression and anxiety, and its use for insomnia is not recommended due to its adverse effect profile and lack of significant benefits compared to placebo.

Adverse Effects

• Common side effects of trazodone include drowsiness, dizziness, dry mouth, and occasionally priapism (prolonged erection) in men, which requires immediate medical attention.
• The medication should be taken with food to reduce stomach upset, and patients should avoid alcohol while using it.

Alternative Treatments

• Nonbenzodiazepine BZRAs, such as zolpidem, zaleplon, eszopiclone, and zopiclone, may be considered for the treatment of chronic insomnia disorder, but should be administered at the lowest effective dose and for the shortest possible duration, and patients should be counseled on the potential risks 1.
• Other treatments, such as cognitive behavioral therapy for insomnia (CBT-I), may also be effective for the treatment of chronic insomnia disorder.

From the FDA Drug Label

Trazodone Hydrochloride Tablets are indicated for the treatment of major depressive disorder (MDD) in adults. The primary use of Trazodone is for the treatment of major depressive disorder (MDD) in adults.

• Key points about Trazodone include:
  • It is a prescription medicine used to treat MDD in adults
  • It belongs to a class of medicines known as SSRIs (or selective serotonin reuptake inhibitors)
  • It is not known if Trazodone Hydrochloride Tablets are safe and effective in children 2
  • The mechanism of trazodone’s antidepressant action is not fully understood, but is thought to be related to its enhancement of serotonergic activity in the CNS 2

From the Research

Trazodone Overview

• Trazodone is a triazolopyridine serotonin receptor antagonist and reuptake inhibitor (SARI) antidepressant approved for major depressive disorder (MDD) in adults 3, 4.
• It has established efficacy comparable to other available antidepressants and is effective for a range of depression symptoms, including insomnia 3, 4.

Mechanism of Action and Efficacy

• Trazodone's pharmacodynamic properties allow it to avoid the side effects of insomnia, anxiety, and sexual dysfunction often associated with selective serotonin reuptake inhibitor antidepressants 3, 4.
• It is effective in controlling a wide range of symptoms of depression, including insomnia, and has a rapid onset of action 3, 4, 5.
• Trazodone has been shown to have antidepressant activity at a starting dose of 150 mg/day and results in statistically significant greater reduction in Hamilton Depression Rating Scale (HAM-D17) scores within 1 week of starting treatment compared to placebo or venlafaxine XR 5.

Side Effects and Tolerability

• The most common adverse effects of trazodone are somnolence, headache, dizziness, and xerostomia 3, 4, 6.
• Trazodone has minimal anticholinergic activity but may be associated infrequently with orthostatic hypotension, QT interval prolongation, cardiac arrhythmias, and rare episodes of priapism 3, 4.
• It has a low risk of anticholinergic side effects, weight gain, and sexual side effects, making it a well-tolerated antidepressant 7.

Clinical Guidance and Use

• Trazodone is usually well tolerated and has a low risk of side effects, making it an established medication for the treatment of a broad array of depressive symptoms 7.
• It may be helpful for patients with major depression and comorbid insomnia, anxiety, or psychomotor agitation 7.
• The appropriate antidepressant doses are usually 150-300 mg/day, and trazodone is often used to augment the antidepressant effect of another medication, such as addressing insomnia in a patient treated with an SSRI 7.