What is the usage and precautions for Trazodone (an antidepressant medication) in an adult patient with a history of mental health issues, possibly with conditions such as depression, insomnia, anxiety disorders, heart disease, or liver disease?

Trazodone: Clinical Overview

FDA-Approved Indication

Trazodone is FDA-approved exclusively for the treatment of major depressive disorder (MDD) in adults, not for insomnia. 1

Efficacy for Depression

• Trazodone demonstrates comparable antidepressant efficacy to tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs) in treating MDD 2, 3
• In head-to-head trials, trazodone showed no significant differences in efficacy compared to other second-generation antidepressants including SSRIs, SNRIs, and other agents like bupropion and nefazodone 4
• Trazodone is particularly effective for depression accompanied by anxiety, agitation, and insomnia symptoms 5
• The therapeutic dosage range for depression is 150-300 mg/day for monotherapy, with maximum tolerated doses of 300-400 mg/day in elderly patients and up to 600 mg/day in younger adults 3, 6

Mechanism of Action

• Trazodone is classified as a serotonin receptor antagonist and reuptake inhibitor (SARI), with a triazolopyridine structure distinct from other antidepressants 2, 3
• Its antidepressant action occurs primarily through serotonin reuptake inhibition with 5HT2A receptor antagonism, which may prevent SSRI-associated side effects like insomnia, anxiety, and sexual dysfunction 2, 7

Off-Label Use for Insomnia: Critical Guideline Position

The American Academy of Sleep Medicine explicitly recommends AGAINST trazodone for sleep onset or sleep maintenance insomnia. 8

• Despite widespread off-label prescribing for insomnia, clinical trials show only modest improvements in sleep parameters with no improvement in subjective sleep quality 8
• The 2009 NIH State-of-Science Conference on Insomnia concluded there is no systematic evidence for effectiveness of antidepressants including trazodone for insomnia treatment, and warned that risks outweigh benefits 4
• Low-dose trazodone (typically 25-100 mg) is commonly prescribed off-label as a hypnotic, but this practice lacks strong evidence-based support 2, 7

Common Adverse Effects

The most frequently reported side effects include:

• Somnolence/sedation (most common) 2, 3
• Headache 2, 3
• Dizziness 2, 3
• Dry mouth (xerostomia) 2, 3

Serious Adverse Effects and Warnings

Cardiovascular Risks

• Orthostatic hypotension, particularly in elderly patients or those with pre-existing heart disease 2, 3, 6
• QT interval prolongation and potential for torsade de pointes 2, 3
• Cardiac arrhythmias 2, 3

Other Serious Risks

• Priapism (rare but serious): Requires immediate medical attention 2, 3, 6, 5
• Suicidal ideation: Black box warning for increased suicidal thoughts/actions in children, teenagers, and young adults, particularly within the first few months of treatment 1
• Minimal anticholinergic activity compared to TCAs, but still present 2, 3

Contraindications and Drug Interactions

Absolute Contraindications

• Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 2 weeks of MAOI discontinuation 1

Significant Drug Interactions

• Triptans (migraine medications) 1
• Other psychotropic medications (tricyclics, lithium, SSRIs, SNRIs, buspirone, antipsychotics) 1
• Tramadol 1
• Tryptophan or St. John's Wort 1
• NSAIDs, aspirin, warfarin (increased bleeding risk) 1
• Phenytoin 1
• Diuretics 1

Special Population Considerations

Pregnancy and Breastfeeding

• Trazodone passes into breast milk; discuss risks/benefits with patients 1
• Pregnant patients should be informed about the National Pregnancy Registry for Antidepressants (1-844-405-6185) 1

Elderly Patients

• Maximum tolerated doses are lower (300-400 mg/day vs. 600 mg/day in younger adults) 6
• Increased risk of orthostatic hypotension and falls 6
• May be better tolerated than older tricyclic antidepressants with fewer anticholinergic and cardiovascular effects 6

Cardiovascular Disease

• Can be used successfully in patients with depression and pre-existing cardiovascular disease, but requires close monitoring for orthostatic hypotension and arrhythmias 6

Administration Guidelines

• Take shortly after a meal or light snack to optimize absorption and reduce side effects 1
• Tablets should be swallowed whole or broken in half along the score line; do not chew or crush 1
• If drowsiness occurs, timing or dosage adjustments may be necessary 1
• Do not discontinue abruptly—consult healthcare provider before stopping 1

Safety Precautions

• Avoid driving or operating heavy machinery until effects are known, as trazodone can impair thinking and motor skills 1
• Avoid alcohol and other CNS depressants, which can worsen sedation and dizziness 1
• Monitor for new or worsening depression, suicidal thoughts, anxiety, agitation, panic attacks, insomnia, irritability, aggression, or unusual behavioral changes 1

Overdose Safety

• Trazodone is relatively safe in overdose compared to tricyclic antidepressants 6, 5
• In case of overdose, contact Poison Control (1-800-222-1222) or seek emergency care immediately 1

Clinical Positioning

For depression treatment: Trazodone is an effective option comparable to other antidepressants, with particular advantages for patients who cannot tolerate anticholinergic effects or who have prominent anxiety, agitation, and insomnia as part of their depressive syndrome 4, 2, 3, 5

For insomnia treatment: Despite common off-label use, trazodone is explicitly not recommended by sleep medicine guidelines due to insufficient evidence of efficacy and potential for adverse effects 4, 8