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traZODone

Drug class: Serotonin Modulators
VA class: CN609
CAS number: 25332-39-2

Medically reviewed by Drugs.com on Mar 17, 2022. Written by ASHP.

Warning

    Suicidality
  • Antidepressants increased risk of suicidal thinking and behavior (suicidality) compared with placebo in children, adolescents, and young adults (18–24 years of age) with major depressive disorder and other psychiatric disorders; balance this risk with clinical need. Trazodone is not approved for use in pediatric patients. (See Pediatric Use under Cautions.)

  • In pooled data analyses, risk of suicidality was not increased in adults >24 years of age and was reduced in adults ≥65 years of age with antidepressants compared with placebo.

  • Depression and certain other psychiatric disorders are themselves associated with an increased risk of suicide.

  • Appropriately monitor and closely observe all patients who are started on trazodone therapy for clinical worsening, suicidality, or unusual changes in behavior; involve family members and/or caregivers in this process. (See Worsening of Depression and Suicidality Risk under Cautions.)

Introduction

Antidepressant; serotonin modulator.

Uses for traZODone

Major Depressive Disorder

Management of major depressive disorder with or without anxiety.

Effective in both inpatient and outpatient settings.

Schizophrenic Disorder

Has been used for the short-term management of depressive episodes in patients with schizophrenia [off-label].

Alcohol Dependence

Has been used as adjunctive therapy for the management of alcohol dependence [off-label].

Anxiety States

Has been used for the management of anxiety states [off-label].

traZODone Dosage and Administration

General

  • Individualize dosages according to individual requirements and response.

  • Monitor for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustments. (See Worsening of Depression and Suicidality Risk under Cautions.)

  • Sustained therapy may be required; use lowest effective dose and monitor periodically for need for continued therapy.

Administration

Oral Administration

Administer orally after a meal or a light snack.

If drowsiness occurs, administer a major portion of the daily dosage at bedtime or reduce dosage.

Dosage

Available as trazodone hydrochloride; dosage is expressed in terms of the salt.

Adults

Major Depressive Disorder
Oral

Initially, 150 mg daily, given in divided doses. Daily dosage may be increased in 50-mg increments every 3 or 4 days based on patient’s response and tolerance.

Prescribing Limits

Adults

Major Depressive Disorder
Outpatients
Oral

Maximum 400 mg daily.

Hospitalized Patients
Oral

Maximum 600 mg daily.

Cautions for traZODone

Contraindications

  • Known hypersensitivity to trazodone or any ingredient in the formulation.

Warnings/Precautions

Warnings

Worsening of Depression and Suicidality Risk

Possible worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs. However, suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.

Appropriately monitor and closely observe patients receiving trazodone for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments. (See Boxed Warning and also see Pediatric Use under Cautions.)

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality. Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if severe, abrupt in onset, or not part of patient’s presenting symptoms. If decision is made to discontinue therapy, taper trazodone dosage as rapidly as is feasible but consider risks of abrupt discontinuance.

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.

Observe these precautions for patients with psychiatric (e.g., major depressive disorder, obsessive-compulsive disorder) or nonpsychiatric disorders.

Bipolar Disorder

May unmask bipolar disorder. Trazodone is not approved for use in treating bipolar depression.

Screen for risk of bipolar disorder by obtaining detailed psychiatric history (e.g., family history of suicide, bipolar disorder, depression) prior to initiating therapy.

Priapism

Risk of developing priapism; may require surgical or pharmacologic (e.g., epinephrine) intervention and result in impotence or permanent impairment of erectile function.

Perform pharmacologic or surgical interventions under the supervision of a urologist or a physician familiar with the procedure; procedures should not be initiated without a urologic consultation if priapism persists for >24 hours.

Discontinue immediately if prolonged or inappropriate erections occur.

Cardiovascular Effects

Possible cardiac arrhythmias (e.g., PVCs, VT); use with caution in patients with preexisting cardiovascular disease.

Do not use during initial recovery phase of MI.

Hypotension, including orthostatic hypotension and syncope, reported.

Concomitant administration of antihypertensive therapy may require a reduction in dosage of the antihypertensive agent(s).

General Precautions

Elective Surgery

Discontinue several days prior to surgery requiring general anesthesia whenever possible.

CNS Effects

Drowsiness reported in up to 50% of patients.

Performance of activities requiring mental alertness and physical coordination may be impaired.

Electroconvulsive Therapy (ECT)

Effects of concomitant use with ECT have not been systematically evaluated; avoid concomitant use.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether trazodone is distributed into milk; caution advised.

Pediatric Use

Safety and efficacy not established in children <18 years of age.

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during the first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and others). However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation. No suicides occurred in these pediatric trials.

Carefully consider these findings when assessing potential benefits and risks of trazodone in a child or adolescent for any clinical use. (See Suicidality in the Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Common Adverse Effects

Drowsiness, dry mouth, dizziness or lightheadedness, headache, blurred vision, nausea or vomiting.

Interactions for traZODone

Metabolized by CYP3A4.

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors or inducers of CYP3A4: Potential pharmacokinetic interaction (altered plasma trazodone concentrations).

Specific Drugs

Drug

Interaction

Comments

Anesthetics, general

Experience limited

Discontinue trazodone for as long as clinically feasible prior to elective surgery

Antifungals, azoles (e.g., itraconazole, ketoconazole)

Substantially increased plasma trazodone concentrations possible, with potential for adverse effects

If used concomitantly, consider reduction in trazodone dosage

Carbamazepine

Substantially decreased plasma concentrations of trazodone and active metabolite, m-chlorophenylpiperazine

Closely monitor during concomitant use; increase trazodone dosage if necessary

CNS depressants (e.g., alcohol, anesthetics, barbiturates, opiates or other analgesics, other sedatives)

Additive CNS depressant effects (e.g., sedation)

Use with caution

Digoxin

Increased serum digoxin concentrations

Monitor for digoxin toxicity

Fluoxetine

Increased plasma trazodone concentrations

Potential for serotonin syndrome

Observe for adverse effects; monitor trazodone concentrations; adjust dosages as needed

Hypotensive agents

Potential additive hypotensive effects

Adjust dosages as needed

Indinavir

Substantially increased plasma trazodone concentrations possible, with potential for adverse effects

If used concomitantly, consider reduction in trazodone dosage

MAO inhibitors

Limited experience

Initiate trazodone therapy cautiously if MAO inhibitors are discontinued shortly before or are to be given concomitantly with trazodone

Nefazodone

Substantially increased plasma trazodone concentrations possible, with potential for adverse effects

If used concomitantly, consider reduction in trazodone dosage

Phenytoin

Increased serum phenytoin concentrations

Ritonavir

Increased peak plasma concentration, AUC, and half-life and decreased clearance of trazodone; increased incidence of adverse effects of trazodone also observed

If used concomitantly, consider reduction in trazodone dosage

Serotonergic agents (e.g., buspirone, dextropropoxyphene, phenelzine)

Potential for serotonin syndrome

Caution

Warfarin

Increased or decreased PT

traZODone Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely absorbed from the GI tract; peak plasma concentration usually attained within 1–2 hours.

Onset

Antidepressant effects evident within 1 week; optimal antidepressant effects usually attained after 2–4 weeks.

Food

Food reduces peak plasma concentrations, delays time to peak plasma concentration, and increases extent of absorption.

Distribution

Extent

Distribution into human body tissues and fluids not determined.

Widely distributed; crosses the blood-brain barrier and the placenta in animals.

Distributed into milk in rats; not known whether trazodone is distributed into milk in humans.

Plasma Protein Binding

89–95%.

Elimination

Metabolism

Extensively metabolized in the liver via hydroxylation, oxidation, N-oxidation, and splitting of the pyridine ring. In vitro studies indicate metabolism by CYP3A4 to an active metabolite, m-chlorophenylpiperazine; other metabolic pathways not well characterized.

Elimination Route

Excreted principally in urine (70–75%) as metabolites and in feces via biliary elimination.

Half-life

5–9 hours.

Stability

Storage

Oral

Tablets

Room temperature. Protect from temperatures >40°C.

Actions

  • Mechanism of action as an antidepressant is presumed to be linked to potentiation of serotonergic activity in the CNS resulting from inhibition of reuptake of serotonin (5-HT) at the presynaptic neuronal membrane.

  • Does not influence reuptake of dopamine or norepinephrine; does not inhibit MAO; does not stimulate the CNS; exhibits little anticholinergic activity.

  • Produces varying degrees of sedation resulting from its central α1-adrenergic and/or histamine blocking activity.

Advice to Patients

  • Importance of providing copy of written patient information (medication guide) each time trazodone is dispensed. Importance of advising patients to read the patient information before taking trazodone.

  • Risk of suicidality; importance of patients, caregivers, and families being alert to and immediately reporting emergence of suicidality, worsening depression, or unusual changes in behavior, especially during the first few months of therapy or during periods of dosage adjustment. (See Worsening of Depression and Suicidality Risk under Cautions.)

  • Importance of men discontinuing the drug and notifying clinician if prolonged or inappropriate penile erection occurs.

  • Risks associated with concomitant use with alcohol, barbiturates, and other CNS depressants.

  • Potential for drug to impair mental alertness or physical coordination; avoid driving or operating machinery until effects on individual are known.

  • Importance of taking trazodone shortly after a meal or light snack to enhance absorption and to minimize risk of dizziness/lightheadedness.

  • Importance of continuing trazodone therapy even if improvement is evident within 2 weeks, unless directed otherwise by their clinician.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

traZODone Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

150 mg*

Trazodone Hydrochloride Dividose (with povidone; scored)

Sandoz

300 mg*

Trazodone Hydrochloride Tablets

Barr

Tablets, film-coated

50 mg*

100 mg*

AHFS DI Essentials™. © Copyright 2022, Selected Revisions March 27, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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Frequently asked questions

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