Last updated: October 29, 2014

Trade Names: Desyrel, Oleptro (an extended release formulation)

Drug Class: Antidepressant

Preparations: immediate release: 50-, 100-, 150-, 300 mg tablets; extended release: 150-, 300 mg tablets (bisectable)

Depression: Initially 150 mg/day in three divided doses; increase dose by 50 mg/day every week, if needed, to maximum of 400 mg/day. Extended release: 150 mg once daily initially can increase in 75 mg increments to maximum of 375 mg daily.
Fibromyalgia: As a sleep aid, the usual starting dose is 25–50 mg nightly. This can be increased by 50 mg per week (to as much as 150 mg) until maximum improvement in sleep is achieved without causing morning somnolence.

Indications: Treatment of depression or sleep disturbance in fibromyalgia

Mechanism of Action: Inhibits presynaptic uptake of serotonin

Contraindications: Hypersensitivity to trazodone

Precautions: May increase suicidality particularly in children and adolescents. Risk of serotonin syndrome. Sedating. Concomitant MAOI therapy is potentially dangerous. Allow at least a 14-day washout between trazodone and MAOI therapy. Prolongs QT interval. Use caution in cardiac, renal, and hepatic disease. Withdraw slowly to prevent discontinuation symptoms.

Pregnancy Risk: C

Adverse Effects
Common: Sedation, nausea, bad taste, dry mouth, dizziness, weight gain
Less common: Weakness, diarrhea, constipation, nightmares, discontinuation symptoms (headache, GI symptoms, anxiety, agitation, sleep disturbance)
Uncommon: Rash, orthostatic symptoms (tachycardia, postural dizziness), arrhythmias, heart block, agitation, seizures, extrapyramidal effects, priapism, urinary retention, acute glaucoma, serotonin syndrome, bleeding, hyponatremia

Drug Interactions
Cytochrome P450 (CYP) 3A inhibitors (strong inhibitors include clarithromycin, telithromycin, ketoconazole, itraconazole, nefazodone and many HIV drugs; moderate inhibitors include aprepitant, diltiazem, verapamil, erythromycin, fluconazole, posaconazole, voriconazole, grapefruit juice): Increase trazodone concentrations
Potent CYP3A inducers (e.g., rifampin): Decrease trazodone concentrations
CNS depressants: Increased CNS depression
Phenytoin: Increased phenytoin levels reported
Digoxin: Increased digoxin levels reported
MAOI: Avoid (serotonin syndrome)
QT prolonging drugs:  May increase risk of  torsade
Serotonergic drugs: Increased risk of serotonin syndrome

Patient Instructions: May cause drowsiness; avoid alcohol. Keep medication away from children. Increased risk of suicide; contact physician for suicidal thoughts or change in behavior. Patients should be advised of the risk factors for serotonin syndrome and symptoms that may include mental changes (e.g., agitation, hallucinations, delirium, increased heart rate and labile blood pressure, dizziness, sweating, flushing, fever, tremor, rigidity, nausea, vomiting, diarrhea).  Slow taper for discontinuation to prevent withdrawal symptoms.

Comments: Maximum effect for depression may be delayed for 6 weeks. Sometimes used for sedative effect to correct sleep disorders caused by SSRIs.

Clinical Pharmacology: Well absorbed; 90% protein bound; hepatic metabolism by CYP3A (major) and CYP2D6 (minor)  with half-life of 5–9 hours

Cost: $

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