Trazodone hydrochloride is a prescription medication classified as a serotonin antagonist and reuptake inhibitor (SARI), primarily indicated for the treatment of major depressive disorder (MDD). It is distinguished by its dual mechanism of action, modulating serotonin activity while offering a favorable side effect profile relative to many traditional antidepressants. Clinicians frequently utilize its sedative properties at lower doses for insomnia management, making it a versatile agent in neuropsychopharmacology. Its established efficacy and generally well-tolerated nature have secured its position as a trusted option in both 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
• Metabolism: Hepatic, primarily via CYP3A4
• Excretion: Renal (70–75%) and fecal (20–25%)

Benefits

• Alleviates core symptoms of depression, including low mood, anhedonia, and psychomotor retardation
• Improves sleep architecture by reducing sleep latency and increasing total sleep time
• Lower incidence of sexual dysfunction compared to SSRIs and SNRIs
• Minimal anticholinergic effects, reducing risks such as dry mouth and constipation
• Useful in patients with comorbid anxiety and depression
• Often prescribed off-label for insomnia due to its pronounced sedative effects at lower doses

Common use

Trazodone is FDA-approved for the treatment of major depressive disorder in adults. Its therapeutic action stems from its ability to inhibit serotonin reuptake and antagonize certain serotonin receptors, particularly 5-HT2A and 5-HT2C, which contributes to both its antidepressant and sleep-promoting effects. Off-label uses include management of insomnia, anxiety disorders, and as an adjunct in the treatment of certain chronic pain conditions. It is also sometimes used in geriatric populations where other antidepressants may be less suitable.

Dosage and direction

Dosage must be individualized based on clinical response and tolerability. For depression, the initial adult dose is 150 mg per day in divided doses, which may be increased by 50 mg per day every three to four days. The maximum recommended dose is 400 mg per day for outpatients and 600 mg per day for inpatients. For insomnia, lower doses (25–100 mg) are typically administered once daily at bedtime. Tablets should be taken shortly after a meal or light snack to minimize dizziness or nausea. Dosage adjustments are necessary in patients with renal or hepatic impairment.

Precautions

Patients should be monitored for the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania. Trazodone may cause sedation and impair mental or physical abilities; caution is advised when operating machinery or driving. Orthostatic hypotension may occur, particularly in elderly patients. Priapism, a medical emergency, has been reported; patients should seek immediate medical attention for prolonged or painful erections. Use with caution in patients with a history of cardiac disease, as arrhythmias have been reported.

Contraindications

Trazodone is contraindicated in patients hypersensitive to trazodone hydrochloride or any component of the formulation. Concomitant use with monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of serotonin syndrome. At least 14 days should elapse between discontinuation of an MAOI and initiation of trazodone therapy. It is also contraindicated in patients with a history of priapism.

Possible side effects

Common adverse reactions include somnolence, dizziness, constipation, blurred vision, and headache. Less frequently, patients may experience nausea, vomiting, fatigue, nasal congestion, weight changes, and dry mouth. Serious side effects may include serotonin syndrome, QT prolongation, orthostatic hypotension, syncope, priapism, and hyponatremia. Any unusual or severe symptoms should be reported to a healthcare provider immediately.

Drug interaction

Trazodone interacts with several drug classes. Concomitant use with other serotonergic drugs (e.g., SSRIs, SNRIs, triptans, tramadol) increases the risk of serotonin syndrome. Strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) can increase trazodone levels, while inducers (e.g., carbamazepine, rifampin) may decrease its efficacy. Trazodone may potentiate the effects of CNS depressants, including alcohol, benzodiazepines, and opioids. Use with antihypertensives may increase the risk of hypotension. Digoxin and phenytoin levels should be monitored when co-administered.

Missed dose

If a dose is missed, it should be taken as soon as possible unless it is nearly time for the next scheduled dose. In that case, the missed dose should be skipped and the regular dosing schedule resumed. Doubling the dose is not recommended.

Overdose

Overdose may lead to severe sedation, vomiting, priapism, respiratory depression, seizures, or ECG changes (including QT prolongation). There is no specific antidote; management is supportive and includes gastric lavage (if presented early), activated charcoal, and continuous ECG monitoring. In cases of serotonin syndrome, cyproheptadine may be considered. Priapism requires urgent urological intervention.

Storage

Store at room temperature (20–25°C or 68–77°F), in a tightly closed container, away from light, moisture, and heat. Keep out of reach of children and pets. Dispose of unused medication properly via a drug take-back program.

Disclaimer

This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Do not disregard professional medical advice or delay in seeking it because of something you have read here.

Reviews

Clinical studies and meta-analyses consistently support the efficacy of trazodone in treating major depressive disorder, with response rates comparable to other antidepressants. Its utility in insomnia is well-documented, particularly in cases where traditional hypnotics are contraindicated. Patient reviews often highlight improved sleep quality and mood stabilization, though some report daytime drowsiness. Overall, it remains a widely prescribed and clinically valued agent in psychopharmacology.