What is Trazodone (Triazolopyridine antidepressant)?

From the Guidelines

Trazodone should not be used as a treatment for sleep onset or sleep maintenance insomnia in adults. This recommendation is based on the American Academy of Sleep Medicine's clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults, which suggests that clinicians not use trazodone as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults, based on trials of 50 mg doses of trazodone 1.

Key Points to Consider

• The guideline provides recommendations for various treatments, including orexin receptor agonists, BZD receptor agonists, zaleplon, zolpidem, benzodiazepines, melatonin agonists, heterocyclics, and over-the-counter preparations.
• For insomnia treatment, alternatives such as suvorexant, eszopiclone, zaleplon, zolpidem, triazolam, temazepam, and ramelteon are suggested, based on their respective trials and dosages.
• Trazodone's primary use is for depression and anxiety, and its use for insomnia is not recommended due to the lack of evidence supporting its effectiveness for this condition 1.

Clinical Implications

• Clinicians should consider the recommended treatments for insomnia, such as suvorexant, eszopiclone, and zolpidem, instead of trazodone.
• Patients with insomnia should be informed about the potential risks and benefits of available treatments and involved in the decision-making process.
• The American Academy of Sleep Medicine's guideline provides a comprehensive framework for the pharmacologic treatment of chronic insomnia in adults, and clinicians should refer to this guideline when making treatment decisions 1.

From the FDA Drug Label

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 Trazodone is both a selective serotonin reuptake inhibitor (SSRI) and a 5HT2 receptor antagonist Trazodone is also an antagonist at several other monoaminergic receptors including 5-HT2B, 5-HT2C, α1A, α2C receptors and it is a partial agonist at 5-HT1A receptor.

Trazodone is a medication that is used to treat major depressive disorder (MDD) in adults. It belongs to a class of medicines known as SSRIs (or selective serotonin reuptake inhibitors). The exact mechanism of its antidepressant action is not fully understood, but it is thought to be related to its enhancement of serotonergic activity in the CNS.

• Key points about trazodone include:
  • It is a selective serotonin reuptake inhibitor (SSRI) and a 5HT2 receptor antagonist.
  • It is also an antagonist at several other monoaminergic receptors.
  • It is a partial agonist at the 5-HT1A receptor.
  • It should be taken exactly as prescribed by a healthcare provider, shortly after a meal or light snack 2 2.

From the Research

Overview of Trazodone

• Trazodone is a triazolopyridine derivative that belongs to the class of serotonin receptor antagonists and reuptake inhibitors (SARIs) 3, 4, 5, 6, 7
• It is approved and marketed in several countries worldwide for the treatment of major depressive disorder (MDD) in adult patients 3

Efficacy and Mechanism of Action

• 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, 4, 5
• 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, 4, 5
• Trazodone is effective in controlling a wide range of symptoms of depression, including insomnia, which is one of the most common and bothersome symptoms of depression 4, 5, 6, 7

Adverse Effects and Tolerability

• The most common adverse effects reported with trazodone are drowsiness (somnolence/sedation), headache, dizziness, and dry mouth 3, 4, 5
• 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, 4, 5
• Trazodone has a low risk of anticholinergic side effects, weight gain, and sexual side effects 5

Clinical Use and Dosage

• The appropriate antidepressant doses of trazodone are usually 150-300 mg/day and are often higher than the doses used when trazodone is prescribed to augment the antidepressant effect of another medication 5
• Trazodone may be helpful for patients with major depression and comorbid insomnia, anxiety, or psychomotor agitation 5, 6
• The once-a-day formulation of trazodone has an improved tolerability profile compared to its conventional formulations and exhibits antidepressant activity at a starting dose of 150 mg/day 7