Dosing Tips

• Start low and go slow

✽ Patients can have carryover sedation, ataxia, and intoxicated-like feeling if dosed too aggressively, particularly when initiating dosing

✽ Do not discontinue trials if ineffective at low doses (<50 mg) as many patients with difficult cases may respond to higher doses (150–300 mg, even up to 600 mg in some cases)

• For relief of daytime anxiety, can give part of the dose in the daytime if not too sedating

• Although use as a monotherapy for depression is usually in divided doses due to its short half-life, use as an adjunct is often effective and best tolerated once daily at bedtime

Overdose

• Rarely lethal; sedation, vomiting, priapism, respiratory arrest, seizure, EKG changes

Long-Term Use

• Safe

Habit Forming

• No

How to Stop

• Taper is prudent to avoid withdrawal effects, but tolerance, dependence, and withdrawal effects have not been reliably demonstrated

Pharmacokinetics

• Metabolized by CYP450 3A4

• Half-life is biphasic; first phase is approximately 3–6 hours; second phase is approximately 5–9 hours

Drug Interactions

• Tramadol increases the risk of seizures in patients taking an antidepressant

• Fluoxetine and other SSRIs may raise trazodone plasma levels

• Trazodone may block the hypotensive effects of some antihypertensive drugs

• Trazodone may increase digoxin or phenytoin concentrations

• Trazodone may interfere with the antihypertensive effects of clonidine

• Generally, do not use with MAO inhibitors, including 14 days after MAOIs are stopped

• Reports of increased and decreased prothrombin time in patients taking warfarin and trazodone

Other Warnings/Precautions

• Possibility of additive effects if trazodone is used with other CNS depressants

• Treatment should be discontinued if prolonged penile erection occurs because of the risk of permanent erectile dysfunction

• Advise patients to seek medical attention immediately if painful erections occur lasting more than one hour

• Generally, priapism reverses spontaneously, while penile blood flow and other signs being monitored, but in urgent cases, local phenylephrine injections or even surgery may be indicated

• Use with caution in patients with history of seizures

• Use with caution in patients with bipolar disorder unless treated with concomitant mood-stabilizing agent

• When treating children, carefully weigh the risks and benefits of pharmacological treatment against the risks and benefits of nontreatment with antidepressants and make sure to document this in the patient’s chart

• Distribute the brochures provided by the FDA and the drug companies

• Warn patients and their caregivers about the possibility of activating side effects and advise them to report such symptoms immediately

• Monitor patients for activation of suicidal ideation, especially children and adolescents

Do Not Use

• If patient is taking an MAO inhibitor, but see Pearls

• If there is a proven allergy to trazodone

TRAZODONE: SPECIAL POPULATIONS

Renal Impairment

• No dose adjustment necessary

Hepatic Impairment

• Drug should be used with caution

Cardiac Impairment

• Trazodone may be arrhythmogenic

• Monitor patients closely

• Not recommended for use during recovery from myocardial infarction

Elderly

• Elderly patients may be more sensitive to adverse effects and may require lower doses

• Reduction in the risk of suicidality with antidepressants compared to placebo in adults age 65 and older

Children and Adolescents

• Carefully weigh the risks and benefits of pharmacological treatment against the risks and benefits of nontreatment with antidepressants and make sure to document this in the patient’s chart

• Monitor patients face-to-face regularly, particularly during the first several weeks of treatment

• Use with caution, observing for activation of known or unknown bipolar disorder and/or suicidal ideation, and inform parents or guardians of this risk so they can help observe child or adolescent patients

• Safety and efficacy have not been established, but trazodone has been used for behavioral disturbances, depression, and night terrors

• Children require lower initial dose and slow titration

• Boys may be even more sensitive to having prolonged erections than adult men