Trazodone

Trazodone hydrochloride is a serotonin antagonist and reuptake inhibitor (SARI) antidepressant medication with established efficacy in managing major depressive disorder and insomnia. Originally developed and approved by the FDA in 1981 for depression, its potent sedative properties—mediated through histamine H1 and alpha-1 adrenergic receptor blockade—have made it a widely prescribed off-label option for sleep initiation and maintenance. Unlike traditional benzodiazepines or Z-drugs, trazodone offers a favorable safety profile with lower abuse potential, making it a versatile agent in both psychiatric and primary care settings. Its dual mechanism addresses both mood dysregulation and sleep architecture disruption, providing comprehensive therapeutic benefit.

Features

• Active Ingredient: Trazodone hydrochloride
• Available Strengths: 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 (mCPP) extends duration
• Bioavailability: ~65% with oral administration, subject to first-pass metabolism
• Onset of Action: Sedative effects typically occur within 30–60 minutes; antidepressant effects may take 2–4 weeks
• Administration: Oral tablet, taken with or without food

Benefits

• Promotes rapid sleep onset and improves sleep continuity through histaminergic and adrenergic modulation
• Alleviates symptoms of depression including low mood, anhedonia, and psychomotor agitation via serotonergic activity
• Reduces nighttime awakenings and early morning insomnia without significant respiratory depression
• Lower risk of dependence and tolerance compared to conventional hypnotics
• May improve anxiety symptoms related to both depression and primary anxiety disorders
• Cost-effective generic availability improves accessibility for long-term therapy

Common use

Trazodone is FDA-approved for the treatment of major depressive disorder (MDD) in adults. Its most frequent off-label use is for the management of insomnia, particularly in individuals with comorbid depression or anxiety. It is also used in low doses (25–100 mg) as a sleep aid in patients without depression. In psychiatric practice, it may be adjunctively used for anxiety disorders, such as generalized anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). Geriatric patients often receive trazodone for sleep disturbances due to its favorable side effect profile relative to benzodiazepines.

Dosage and direction

For depression: Initial dose is 150 mg/day in divided doses, with increases of 50 mg/day every 3–4 days as tolerated. Maximum dose: 400 mg/day for outpatients; 600 mg/day for inpatients.
For insomnia: 25–100 mg taken 30 minutes before bedtime.
Dosage should be individualized based on clinical response, tolerability, hepatic function, and concomitant medications. Tablets should be swallowed whole with water; splitting or crushing is not recommended due to potential bitter taste and uneven dosing. Titration should be gradual to minimize orthostatic hypotension and sedation.

Precautions

• Use with caution in patients with cardiac disease due to risk of QT prolongation and arrhythmias
• Orthostatic hypotension may occur, particularly in elderly patients or those dehydrated
• Priapism (prolonged, painful erection) is a rare but serious adverse effect requiring immediate medical attention
• May impair cognitive and motor performance; advise against driving or operating machinery until effects are known
• Monitor for emergence of anxiety, agitation, panic attacks, insomnia, irritability, or suicidal ideation, particularly in young adults
• Abrupt discontinuation may lead to withdrawal symptoms including anxiety, agitation, and sleep disturbances

Contraindications

• Hypersensitivity to trazodone or any component of the formulation
• Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation
• History of priapism
• Acute recovery phase following myocardial infarction
• Severe hepatic or renal impairment without dose adjustment and close monitoring

Possible side effect

Common (≥1%):

• Sedation, somnolence
• Dizziness, lightheadedness
• Dry mouth
• Headache
• Nausea
• Blurred vision

Less common:

• Orthostatic hypotension
• Constipation
• Weight changes
• Confusion (especially in elderly)
• Nightmares or vivid dreams

Rare but serious:

• Priapism
• Serotonin syndrome
• QT prolongation
• Suicidal thoughts or behaviors
• Hyponatremia (especially in elderly)

Drug interaction

• MAOIs: Risk of serotonin syndrome; contraindicated
• CNS depressants (e.g., benzodiazepines, opioids, alcohol): Additive sedation and respiratory depression
• Strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir): Increased trazodone levels and risk of adverse effects
• Strong CYP3A4 inducers (e.g., carbamazepine, rifampin): Reduced trazodone efficacy
• Antihypertensives: Potentiated hypotension
• Serotonergic drugs (e.g., SSRIs, SNRIs, triptans): Increased risk of serotonin syndrome
• Antipsychotics and other QT-prolonging agents: Additive risk of arrhythmias

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 taking multiple doses per day, resume the regular dosing schedule. For bedtime dosing, if missed entirely, resume the next evening.

Overdose

Symptoms may include excessive sedation, vomiting, respiratory depression, hypotension, priapism, seizures, or ECG changes (e.g., QT prolongation). Priapism constitutes a urologic emergency. Management is supportive and symptomatic: ensure airway protection, administer activated charcoal if presented early, and provide cardiovascular monitoring. There is no specific antidote. Contact poison control (1-800-222-1222) or seek emergency medical attention immediately.

Storage

Store at controlled room temperature (20–25°C or 68–77°F). Keep in the original container, tightly closed, and protected from light and moisture. Do not store in bathrooms or damp areas. Keep out of reach of children and pets. Dispose of unused medication via drug take-back programs or following FDA flush guidelines if specified.

Disclaimer

This information is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before starting, changing, or stopping any medication. Individual response to trazodone may vary based on health status, genetics, and concomitant treatments. Not all uses described here may be approved in your country; follow local prescribing guidelines.

Reviews

Clinical studies and meta-analyses consistently support trazodone’s efficacy in improving sleep latency and maintenance, with particular benefit in depressed patients with insomnia. Patient reports often highlight improved sleep quality and mood stabilization, though some note morning grogginess or dry mouth. Long-term users appreciate the non-habit-forming nature compared to traditional sleep aids. Medical professionals value its dual-action profile and cost-effectiveness, though caution is advised regarding cardiac monitoring in at-risk populations.