Trazodone is an FDA-approved antidepressant medication belonging to the serotonin antagonist and reuptake inhibitor (SARI) class, primarily indicated for the treatment of major depressive disorder (MDD). With its unique dual mechanism of action, it modulates serotonin levels while offering pronounced sedative effects, making it a versatile agent in both psychiatric and sleep medicine. Clinicians frequently prescribe it off-label for insomnia due to its favorable safety profile compared to traditional hypnotics. Its efficacy, tolerability, and low abuse potential position it as a cornerstone in managing depression with comorbid sleep disturbances.

Features

• Active ingredient: Trazodone hydrochloride
• Available formulations: 50 mg, 100 mg, 150 mg, and 300 mg oral tablets
• Pharmacologic class: Serotonin antagonist and reuptake inhibitor (SARI)
• Half-life: Approximately 5–9 hours for acute dosing; active metabolite (m-chlorophenylpiperazine) extends duration
• Bioavailability: ~85% when taken orally with food
• Excretion: Primarily renal (70–75%), with some fecal elimination

Benefits

• Promotes sustained sleep architecture by reducing sleep latency and decreasing nighttime awakenings
• Alleviates core symptoms of depression, including low mood, anhedonia, and psychomotor agitation
• Exhibits a lower risk of dependence and withdrawal compared to benzodiazepines and Z-drugs
• May improve anxiety symptoms often comorbid with depression
• Generally well-tolerated in long-term use with a favorable cardiovascular profile relative to older antidepressants
• Off-label utility in conditions such as fibromyalgia, alcohol dependence, and agitation in dementia

Common use

Trazodone is primarily prescribed for the treatment of major depressive disorder in adults. Its potent histaminergic blockade contributes to significant sedative effects, leading to widespread off-label use for insomnia—even in patients without depression. It is also used in generalized anxiety disorder, and emerging evidence supports its role in augmenting other antidepressants or managing agitation in neurological disorders. Its use is common among geriatric populations due to a comparatively lower side effect burden concerning anticholinergic and cardiovascular risks.

Dosage and direction

For depression, the initial adult dose is 150 mg/day in divided doses, which may be increased by 50 mg/day every three to four days. The maximum dose should not exceed 400 mg/day for outpatients or 600 mg/day for inpatients. For insomnia, doses typically range from 25 mg to 100 mg taken 30 minutes before bedtime. Dosage must be individualized based on clinical response, tolerability, hepatic and renal function, and concomitant medications. Administration with food may enhance absorption and reduce dizziness.

Precautions

Use with caution in patients with a history of cardiac disease, particularly arrhythmias, due to potential QT prolongation. Monitor for signs of hyponatremia or SIADH, especially in elderly patients. Priapism—a medical emergency—has been reported; discontinue immediately if prolonged or inappropriate erection occurs. May impair cognitive and motor performance; advise against driving or operating machinery until response is established. Avoid abrupt discontinuation to minimize withdrawal symptoms such as anxiety and agitation.

Contraindications

Hypersensitivity to trazodone or any component of the formulation. Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation due to risk of serotonin syndrome. Not recommended during the acute recovery phase after myocardial infarction. Severe hepatic or renal impairment may necessitate avoidance or significant dose reduction.

Possible side effect

Common adverse reactions include somnolence, dizziness, dry mouth, blurred vision, constipation, and headache. Less frequently, orthostatic hypotension, nausea, and fatigue may occur. Serious side effects include priapism (in males), serotonin syndrome, suicidal ideation (particularly in young adults), QT prolongation, and arrhythmias. Any unusual bleeding or bruising should be promptly evaluated.

Drug interaction

• Strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) may increase trazodone levels and risk of toxicity.
• Concomitant use with other serotonergic drugs (SSRIs, SNRIs, triptans) elevates serotonin syndrome risk.
• CNS depressants (alcohol, benzodiazepines, opioids) may exacerbate sedation and respiratory depression.
• Antihypertensives and nitrates can potentiate hypotensive effects.
• Trazodone may increase digoxin or phenytoin levels; monitor closely.

Missed dose

If a dose is missed, take it as soon as remembered unless it is nearly time for the next dose. Do not double the dose to catch up. Maintain regular dosing schedule to ensure stable serum concentrations and therapeutic effect.

Overdose

Symptoms may include severe sedation, vomiting, respiratory depression, priapism, seizures, or cardiac arrhythmias. Management is supportive and symptomatic: ensure airway protection, administer activated charcoal if presented early, and provide ECG monitoring. There is no specific antidote. Priapism requires urgent urological intervention to prevent permanent damage.

Storage

Store at room temperature (20–25°C or 68–77°F) in a tightly closed container, protected from light and moisture. Keep out of reach of children and pets. Do not use after the expiration date printed on the packaging.

Disclaimer

This information is intended for educational purposes and does not replace professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before starting, changing, or discontinuing any medication. Individual response to trazodone may vary based on health status, comorbidities, and concomitant therapies.

Reviews

Clinical studies and meta-analyses consistently support trazodone’s efficacy in improving sleep parameters and depressive symptoms, with particular praise for its utility in treatment-resistant insomnia. Patient reports often highlight improved sleep quality and mood stabilization, though some note initial drowsiness or dizziness. Its role in geriatric psychopharmacology is well-regarded due to a lower incidence of anticholinergic effects compared to tricyclic antidepressants. Long-term adherence is generally high owing to its balanced efficacy and tolerability profile.