Yes

Antidepressant, Serotonin Reuptake Inhibitor/Antagonist

Treatment of depression

C

Hypersensitivity to trazodone or any component of the formulation

Priapism, including cases resulting in permanent dysfunction, has occurred with the use of trazodone. Not recommended for use in a patient during the acute recovery phase of MI. Trazodone should be initiated with extreme caution in patients who are receiving concurrent or recent therapy with a MAOI. May cause sedation, resulting in impaired performance of tasks requiring alertness (ie, operating machinery or driving). Sedative effects may be additive with other CNS depressants and ethanol. The degree of sedation is very high relative to other antidepressants. May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disease. May increase the risks associated with electroconvulsive therapy. This agent should be discontinued, when possible, prior to elective surgery. Therapy should not be abruptly discontinued in patients receiving high doses for prolonged periods.

>10%:

Central nervous system: Dizziness, headache, sedation

Gastrointestinal: Nausea, xerostomia

1% to 10%:

Cardiovascular: Syncope, hypertension, hypotension, edema

Central nervous system: Confusion, decreased concentration, fatigue, incoordination

Gastrointestinal: Diarrhea, constipation, weight gain or loss

Neuromuscular & skeletal: Tremor, myalgia

Ocular: Blurred vision

Respiratory: Nasal congestion

<1%: Tachycardia, bradycardia, agitation, seizures, extrapyramidal reactions, rash, priapism, urinary retention, hepatitis

Symptoms of overdose include drowsiness, vomiting, hypotension, tachycardia, incontinence, coma, priapism

Following initiation of essential overdose management, toxic symptoms should be treated. Ventricular arrhythmias often respond to lidocaine 1.5 mg/kg bolus followed by 2 mg/minute infusion with concurrent systemic alkalinization (sodium bicarbonate 0.5-2 mEq/kg I.V.). Seizures usually respond to diazepam I.V. boluses (5-10 mg for adults up to 30 mg or 0.25-0.4 mg/kg/dose for children up to 10 mg/dose). If seizures are unresponsive or recur, phenytoin or phenobarbital may be required. Hypotension is best treated by I.V. fluids and by placing the patient in the Trendelenburg position.

CYP2D6 and 3A3/4 enzyme substrate

Trazodone in combination with other psychotropics (low potency antipsychotics) may result in additional hypotension

Trazodone in combination with ethanol may result in additive sedation and impairment of motor skills

Fluoxetine may inhibit the metabolism of trazodone resulting in elevated plasma levels

Inhibits reuptake of serotonin, causes adrenoreceptor subsensitivity, and induces significant changes in 5HT presynaptic receptor adrenoreceptors. Trazodone also significantly blocks histamine (H1) and alpha₁ adrenergic receptors.

Onset of effect: Therapeutic effects take 1-3 weeks to appear

Protein binding: 85% to 95%

Metabolism: In the liver

Half-life: 4-7.5 hours, 2 compartment kinetics

Time to peak serum concentration: Within 30-100 minutes, prolonged in the presence of food (up to 2.5 hours)

Elimination: Primarily in urine and secondarily in feces

Oral: Therapeutic effects may take up to 4 weeks to occur; therapy is normally maintained for several months after optimum response is reached to prevent recurrence of depression

Adolescents: Initial: 25-50 mg/day; increase to 100-150 mg/day in divided doses

Adults: Initial: 150 mg/day in 3 divided doses (may increase by 50 mg/day every 3-7 days); maximum: 600 mg/day

Elderly: 25-50 mg at bedtime with 25-50 mg/day dose increase every 3 days for inpatients and weekly for outpatients, if tolerated; usual dose: 75-150 mg/day

Alcohol: Avoid use

Plasma levels do not always correlate with clinical effectiveness

Therapeutic: 0.5-2.5 mg/mL

Potentially toxic: >2.5 mg/mL

Toxic: >4 mg/mL

No information available to require special precautions

>10% of patients will experience dry mouth; trazodone elicits anticholinergic effects, but occur much less frequently than with tricyclic antidepressants; more than 10% of patients will have significant dry mouth especially in the elderly which could contribute to periodontal diseases and oral discomfort

Take exactly as directed (do not increase dose or frequency); may take 2-4 weeks to achieve desired results; may cause physical and/or psychological dependence. Take after meals. Avoid excessive alcohol, caffeine, and other prescription or OTC medications not approved by prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience drowsiness, lightheadedness, dizziness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); postural hypotension (use caution when climbing stairs or changing position from lying or sitting to standing); nausea, dry mouth (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, or dietary fruit and fiber may help); or diarrhea (buttermilk, yogurt, or boiled milk may help). Report persistent dizziness or headache; muscle cramping, tremors, or altered gait; blurred vision or eye pain; chest pain or irregular heartbeat; or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.

Dosing after meals may decrease lightheadedness and postural hypotension; use side rails on bed if administered to the elderly; observe patient's activity and compare with admission level; assist with ambulation; sitting and standing blood pressure and pulse

Tablet, as hydrochloride: 50 mg, 100 mg, 150 mg, 300 mg

Battistella PA, Ruffilli R, Cernetti R, et al, "A Placebo-Controlled Crossover Trial Using Trazodone in Pediatric Migraine," Headache, 1993, 33(1):36-9.

Bayer AJ, Pathy MSJ, and Ankier SI, "Pharmacokinetic and Pharmacodynamic Characteristics of Trazodone in the Elderly," Br J Clin Pharmacol, 1983, 16:371-6.

Fishbain DA, "Priapism Associated With Trazodone Therapy," J Urol, 1989, 142(3):831.

Gerson SC, Plotkin DA, and Jarvik LF, "Antidepressant Drug Studies, 1964-1986: Empirical Evidence for Aging Patients," J Clin Psychopharmacol, 1988, 8(5):311-21.

Lesar T, Kingston R, Dahms R, et al, "Trazodone Overdose," Ann Emerg Med, 1982, 12(4):221-3.

Reeves RR and Bullen JA, "Serotonin Syndrome Produced by Paroxetine and Low-Dose Trazodone," Psychosomatics, 1995, 36(2):159-60.

Zmitek A, "Trazodone-Induced Mania," Br J Psychiatry, 1987, 151:274-5.

Zubieta JK and Alessi NE, "Acute and Chronic Administration of Trazodone in the Treatment of Disruptive Behavior Disorders in Children," J Clin Psychopharmacol, 1992, 12(5):346-51.