What is the use of Trazodone (an antidepressant medication)?

From the Guidelines

Trazodone should not be used as a first-line treatment for chronic insomnia disorder due to its adverse effect profile and low-quality evidence supporting its efficacy. The work group advised against the use of trazodone for treatment of chronic insomnia disorder, as the widely known harms and adverse effects of trazodone, including risk for dependency and diversion, falls and cognitive impairment in older patients, hypoventilation in patients with respiratory conditions, and neuromuscular diseases, were deemed to substantially outweigh the benefits 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.

Some key points to consider when discussing trazodone include:

• The typical dosage for depression ranges from 150-400mg daily, while lower doses of 25-100mg at bedtime are often used for sleep problems.
• Trazodone works by increasing serotonin levels in the brain while also blocking certain serotonin receptors and histamine receptors, which contributes to its sleep-promoting properties.
• Side effects may include drowsiness, dizziness, dry mouth, and occasionally priapism (prolonged erection) in men, which requires immediate medical attention.
• Patients should not stop taking trazodone suddenly as this may cause withdrawal symptoms; dosage should be gradually reduced under medical supervision.

However, the most recent and highest quality studies suggest that the risks associated with trazodone outweigh its benefits for the treatment of chronic insomnia disorder 1. Therefore, alternative treatments, such as cognitive behavioral therapy for insomnia (CBT-I) or other non-pharmacologic interventions, should be considered as first-line treatments for chronic insomnia disorder.

From the FDA Drug Label

Trazodone Hydrochloride Tablets are indicated for the treatment of major depressive disorder (MDD) in adults. Trazodone Hydrochloride Tablets are a prescription medicine used in adults to treat major depressive disorder (MDD). 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
  • It is used to treat MDD in adults
  • It belongs to a class of medicines known as SSRIs (or selective serotonin reuptake inhibitors) 2, 2 The mechanism of action of trazodone is not fully understood, but it is thought to be related to its enhancement of serotonergic activity in the CNS 2.

From the Research

Trazodone Overview

• Trazodone is a triazolopyridine derivative that belongs to the class of serotonin receptor antagonists and reuptake inhibitors (SARIs) 3.
• It is approved and marketed in several countries worldwide for the treatment of major depressive disorder (MDD) in adult patients 3.
• Trazodone has demonstrated comparable antidepressant activity to other drug classes, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and serotonin-noradrenaline (norepinephrine) reuptake inhibitors (SNRIs) 3.

Mechanism of Action and Efficacy

• The SARI action of trazodone may overcome the tolerability issues that are often associated with second-generation antidepressants such as SSRIs (i.e., insomnia, anxiety, and sexual dysfunction) 3.
• Trazodone is effective in controlling a wide range of symptoms of depression, while avoiding the negative effects on sleep seen with SSRI antidepressants 3.
• The drug has established efficacy that is comparable to other available antidepressants and is effective for a range of depression symptoms, including insomnia 4.

Adverse Effects and Tolerability

• The most common adverse effects reported with trazodone are drowsiness (somnolence/sedation), headache, dizziness, and dry mouth 3, 4.
• Other events reported, albeit with low incidence, include orthostatic hypotension, minimal anticholinergic activity, corrected QT interval prolongation, and torsade de pointes, cardiac arrhythmias, and rare occurrences of priapism and suicidal ideation 3.
• Trazodone is usually well tolerated and has a low risk of anticholinergic side effects, weight gain, and sexual side effects 5.

Clinical Guidance and Use

• Trazodone may be helpful for patients with major depression and comorbid insomnia, anxiety, or psychomotor agitation 5.
• The appropriate antidepressant doses are usually 150-300 mg/day and are often higher than the doses that are used when trazodone is prescribed to augment the antidepressant effect of another medication 5.
• Evidence of the role of trazodone in patients affected by major depressive disorder with anxiety symptoms, insomnia, agitation, cognitive deficits, alcohol use disorders, physical comorbidities, and suicide risk has been identified, showing the effectiveness of trazodone in different presentations of major depressive disorder 6.