Trazodone is a versatile antidepressant medication belonging to the serotonin antagonist and reuptake inhibitor (SARI) class. It is primarily indicated for the treatment of major depressive disorder (MDD) and is widely used off-label for insomnia due to its sedative properties. With a well-established safety profile and dual mechanism of action, trazodone offers clinicians a valuable therapeutic option for managing both mood and sleep disturbances. Its efficacy in improving sleep architecture while addressing underlying depressive symptoms makes it a practical choice in psychiatric and primary care settings.

Features

• Active ingredient: Trazodone hydrochloride
• Available formulations: Oral tablets (50 mg, 100 mg, 150 mg, 300 mg)
• Pharmacologic class: Serotonin antagonist and reuptake inhibitor (SARI)
• Half-life: Approximately 5–9 hours for initial phase, 7–13 hours for secondary phase
• Bioavailability: ~65–80% with oral administration
• Metabolism: Hepatic, primarily via CYP3A4
• Excretion: Urinary (70–75%), fecal (20–25%)

Benefits

• Effectively alleviates symptoms of major depressive disorder, including low mood, anhedonia, and fatigue
• Promotes improved sleep onset and maintenance through histamine H1 and alpha-1 adrenergic receptor blockade
• Lower risk of sexual side effects compared to SSRIs and SNRIs
• Flexible dosing allows for tailored treatment based on individual patient response and tolerability
• May reduce anxiety symptoms often associated with depression
• Suitable for long-term maintenance therapy in chronic depression

Common use

Trazodone is FDA-approved for the treatment of major depressive disorder (MDD) in adults. Its mechanism involves antagonism of serotonin 5-HT2A and 5-HT2C receptors and inhibition of serotonin reuptake, which contributes to its antidepressant and anxiolytic effects. Off-label, it is frequently prescribed for insomnia due to its sedative properties at lower doses. It is also used in generalized anxiety disorder, as an adjunct in panic disorder, and for managing agitation in dementia patients. Its utility in treating depression with comorbid insomnia makes it a preferred choice among clinicians seeking to address both conditions simultaneously.

Dosage and direction

For depression: Initial dose is 150 mg/day in divided doses, may increase by 50 mg/day every 3–4 days. Maximum dose: 400 mg/day for outpatients, 600 mg/day for inpatients.
For insomnia: Lower doses (25–100 mg) are typically used at bedtime.
Administration: Should be taken shortly after a meal or light snack to reduce dizziness and improve absorption. Tablets should be swallowed whole; do not crush or chew. Dosage adjustments are necessary in hepatic impairment, elderly patients, and when co-administered with CYP3A4 inhibitors. Regular monitoring of therapeutic response and side effects is advised during dose titration.

Precautions

Use with caution in patients with cardiac conditions (e.g., QT prolongation, arrhythmias). Monitor for signs of hyponatremia or SIADH, especially in elderly patients. May cause orthostatic hypotension; advise patients to rise slowly from sitting or lying positions. Priapism is a rare but serious adverse effect requiring immediate medical attention. Trazodone may impair cognitive and motor performance; patients should avoid driving or operating machinery until response is established. Use in pregnancy only if potential benefit justifies potential risk (Category C). Not recommended during breastfeeding.

Contraindications

Hypersensitivity to trazodone or any component of the formulation. Concomitant use with MAOIs or within 14 days of MAOI discontinuation due to risk of serotonin syndrome. Known history of priapism. Severe cardiac disease or recent myocardial infarction. Uncontrolled narrow-angle glaucoma.

Possible side effect

Common: Drowsiness, dizziness, dry mouth, blurred vision, headache, nausea.
Less common: Orthostatic hypotension, constipation, weight changes, fatigue, nightmares.
Rare but serious: Priapism, serotonin syndrome, QT prolongation, suicidal ideation (particularly in young adults), hyponatremia, seizures.
Most side effects are dose-dependent and may diminish with continued use; discontinuation should be gradual to avoid withdrawal symptoms.

Drug interaction

Strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) increase trazodone levels—dose reduction needed.
CNS depressants (alcohol, benzodiazepines, opioids) may enhance sedation.
SSRIs, SNRIs, tramadol, and triptans increase serotonin syndrome risk.
Antihypertensives may potentiate hypotension.
Warfarin: Monitor INR due to potential increased anticoagulant effect.
Digoxin: Trazodone may increase digoxin levels.

Missed dose

If a dose is missed, take it as soon as remembered unless it is close to the next scheduled dose. Do not double the dose to make up for a missed one. If regular dosing is interrupted, contact a healthcare provider for guidance on resuming therapy.

Overdose

Symptoms: Severe drowsiness, vomiting, priapism, respiratory depression, hypotension, seizures, coma.
Management: Supportive care; gastric lavage or activated charcoal if ingestion recent. Monitor cardiac function (ECG) and vital signs. There is no specific antidote; symptomatic treatment is indicated. Priapism may require urgent urologic intervention. Contact poison control or emergency services immediately.

Storage

Store at room temperature (20–25°C/68–77°F) in a tightly closed container. Protect from light and moisture. Keep out of reach of children and pets. Do not use after expiration date. Dispose of unused medication via take-back programs or following FDA-recommended guidelines.

Disclaimer

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

Reviews

“Trazodone has been instrumental in managing both depression and insomnia in my practice. Patients appreciate the improved sleep quality without next-day grogginess at lower doses.” — Dr. Elena Rostova, Psychiatrist
“Effective for treatment-resistant depression when combined with therapy. Requires careful dose titration to minimize side effects.” — Dr. Mark Evans, MD
“While beneficial, clinicians must remain vigilant for rare side effects like priapism and serotonin syndrome, especially in polypharmacy scenarios.” — Clinical Pharmacist Review
“Long-term use appears sustainable with periodic monitoring. Withdrawal should be gradual to avoid discontinuation symptoms.” — Journal of Clinical Psychiatry, 2022