Important Safety Information — Trazodone

DRIFT Protocol

WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS

Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (ages 18-24) in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes.

Trazodone hydrochloride is not approved for use in pediatric patients.

Indications

Trazodone hydrochloride is a serotonin modulator indicated for the treatment of major depressive disorder (MDD). It is commonly used off-label at lower doses for the treatment of insomnia. Trazodone works by inhibiting serotonin reuptake and blocking certain serotonin receptors, producing both antidepressant and sedative effects.

Contraindications

Use within 14 days of stopping monoamine oxidase inhibitors (MAOIs), including MAOIs such as linezolid or intravenous methylene blue, because of an increased risk of serotonin syndrome
Known hypersensitivity to trazodone hydrochloride or any component of the formulation

Warnings and Precautions

Suicidality: Monitor all patients for clinical worsening, suicidal thoughts, and unusual behavioral changes, particularly during the initial months of therapy or when doses are changed.
Serotonin syndrome: A potentially life-threatening condition that can occur with serotonergic drugs, especially in combination with other serotonergic agents or MAOIs. Symptoms include agitation, hallucinations, tachycardia, hyperthermia, hyperreflexia, incoordination, nausea, vomiting, and diarrhea. Discontinue trazodone and any concomitant serotonergic agent immediately if symptoms develop.
QT prolongation and arrhythmias: Trazodone can prolong the QT/QTc interval. Avoid use in patients with known QT prolongation, recent myocardial infarction, or uncompensated heart failure. Use with caution in patients taking other QT-prolonging medications.
Priapism: Trazodone has been associated with priapism (prolonged, painful erections). Patients who experience an erection lasting more than 4 hours should seek immediate medical attention. Priapism may require surgical intervention and can result in permanent impotence if not treated promptly.
Orthostatic hypotension and syncope: Trazodone may cause a drop in blood pressure upon standing, particularly in elderly patients. Rise slowly from sitting or lying positions.
Bleeding risk: Concomitant use with antiplatelet agents or anticoagulants may increase the risk of bleeding.
Activation of mania/hypomania: May precipitate a manic episode in patients with bipolar disorder. Screen for bipolar disorder before initiating treatment.
CNS depression: May impair mental and physical abilities. Do not drive or operate machinery until you know how trazodone affects you.
Alcohol: Trazodone may enhance the effects of alcohol. Avoid alcohol during treatment.

Common Side Effects

Drowsiness / sedation
Dizziness / lightheadedness
Dry mouth
Nausea / vomiting
Headache
Blurred vision
Constipation
Fatigue
Nasal congestion
Muscle aches

Serious Side Effects

Seek medical attention immediately if you experience any of the following:

Suicidal thoughts or behavior, or worsening depression
Priapism (a painful erection lasting more than 4 hours)
Signs of serotonin syndrome: agitation, hallucinations, rapid heartbeat, fever, muscle rigidity, twitching, loss of coordination, nausea, vomiting, diarrhea
Fainting or severe dizziness upon standing
Irregular heartbeat or palpitations
Unusual bleeding or bruising
Signs of a manic episode: greatly increased energy, racing thoughts, unusually risky behavior, excessive happiness or irritability, talking more or faster than usual
Seizures
Signs of allergic reaction: rash, hives, difficulty breathing, swelling of face, lips, tongue, or throat

Drug Interactions

MAO inhibitors: Contraindicated within 14 days of MAOI use due to risk of serotonin syndrome.
CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir): May substantially increase trazodone plasma concentrations. Consider a lower dose of trazodone.
CYP3A4 inducers (e.g., carbamazepine): May reduce trazodone levels. Dose adjustment may be needed.
Other serotonergic drugs (SSRIs, SNRIs, triptans, buspirone, St. John's Wort, tramadol): Increased risk of serotonin syndrome.
Alcohol, barbiturates, and other CNS depressants: Enhanced sedative effects. Avoid or use with extreme caution.
Anticoagulants / antiplatelet agents (e.g., warfarin, aspirin, NSAIDs): May increase bleeding risk.
Digoxin and phenytoin: Trazodone may increase serum levels of these drugs. Monitor levels accordingly.
QT-prolonging drugs: Increased risk of arrhythmias. Avoid concurrent use with other QT-prolonging medications.

Use in Specific Populations

Pregnancy: There are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.
Lactation: Trazodone and its metabolites are found in human breast milk. Exercise caution when administering to a nursing woman.
Pediatric use: Not approved for use in pediatric patients. See boxed warning regarding suicidality.
Geriatric use: Elderly patients may be more susceptible to sedation and orthostatic hypotension. Start with lower doses and titrate carefully.
Hepatic impairment: Use with caution. Dose adjustment may be needed.