Trazodone

What is Trazodone?

Trazodone is an antidepressant medication that belongs to a class of drugs called serotonin antagonist and reuptake inhibitors (SARIs). Originally developed and approved for treating major depressive disorder, it is now commonly prescribed off-label for insomnia due to its sedating properties. The medication works differently from other antidepressants and has a unique dual mechanism of action.

Uses

• Major depressive disorder: The primary FDA-approved use, particularly effective for patients with depression accompanied by anxiety or sleep disturbances
• Insomnia: Widely prescribed off-label for sleep disorders, especially in patients who cannot tolerate traditional sleep medications
• Anxiety disorders: Sometimes used as an adjunct treatment for generalized anxiety disorder and panic disorder
• Post-traumatic stress disorder (PTSD): May help with sleep disturbances and nightmares associated with PTSD
• Chronic pain: Occasionally used off-label for certain types of chronic pain conditions, particularly when sleep disturbance is a factor

How it works

Trazodone blocks serotonin reuptake, allowing more of this mood-regulating neurotransmitter to remain available in the brain. Additionally, it blocks certain serotonin receptors and histamine receptors, which contributes to its sedating effects. This dual mechanism makes it effective for both mood disorders and sleep problems, distinguishing it from other antidepressants.

Side effects

Common side effects:

• Drowsiness and sedation
• Dizziness and lightheadedness
• Dry mouth
• Headache
• Nausea
• Constipation
• Blurred vision
• Fatigue

Serious side effects requiring immediate medical attention:

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• Priapism (prolonged, painful erection lasting more than 4 hours)
• Irregular heartbeat or chest pain
• Severe allergic reactions with rash, swelling, or difficulty breathing
• Suicidal thoughts or behavior, especially in young adults
• Serotonin syndrome symptoms (confusion, fever, rapid heart rate, muscle rigidity)

Warnings and precautions

• Suicide risk: Like all antidepressants, trazodone carries an FDA black box warning for increased suicidal thoughts and behaviors in children, adolescents, and young adults under 25
• Cardiac conditions: Should be used cautiously in patients with heart disease, as it can cause changes in heart rhythm and blood pressure
• Pregnancy and breastfeeding: Classified as pregnancy category C; potential risks and benefits should be carefully weighed with healthcare providers
• Liver and kidney impairment: Dosage adjustments may be necessary for patients with hepatic or renal dysfunction
• Elderly patients: Increased sensitivity to side effects, particularly sedation and dizziness, which may increase fall risk

Interactions

• MAO inhibitors: Can cause dangerous serotonin syndrome; must allow adequate washout period between medications
• Other serotonergic drugs (SSRIs, SNRIs, tramadol): Increased risk of serotonin syndrome when combined
• Blood thinners (warfarin): Trazodone may increase bleeding risk by affecting platelet function
• CYP3A4 inhibitors (ketoconazole, ritonavir): Can increase trazodone levels, potentially causing increased side effects
• Digoxin: Trazodone may increase digoxin blood levels, requiring monitoring
• Alcohol and CNS depressants: Enhanced sedation and respiratory depression risk
• St. John’s Wort: May increase serotonin activity and risk of serotonin syndrome
• Phenytoin: Trazodone may increase phenytoin levels, requiring dose adjustments

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Dosage

For depression in adults, the typical starting dose is 150 mg daily in divided doses, which may be gradually increased to 300-400 mg daily as needed. For insomnia, much lower doses of 25-100 mg at bedtime are commonly used. Extended-release formulations may be taken once daily. Elderly patients typically start with lower doses due to increased sensitivity. Dosage should always be individualized and determined by a healthcare provider based on the specific condition being treated, patient response, and tolerance. Gradual dose reduction is recommended when discontinuing to avoid withdrawal symptoms.

Sources: FDA DailyMed drug labels (public domain), BNF, WHO Essential Medicines List. This article is for informational purposes only and does not constitute medical advice. Always consult your healthcare provider before starting or stopping any medication.

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