Is it safe to give trazodone to a patient?

Can You Give Trazodone?

Yes, trazodone can be given, but it should NOT be used as first-line therapy for insomnia and requires careful patient selection with attention to cardiac risk factors, particularly QT prolongation, arrhythmias, and priapism risk. 1

Primary Indication and FDA Approval

• Trazodone is FDA-approved specifically for the treatment of major depressive disorder, not insomnia 1
• Despite this, it has become the second most commonly prescribed agent for insomnia due to its sedating properties 2

Critical Safety Contraindications

Before prescribing trazodone, you must screen for absolute contraindications:

• Do not use with MAOIs (including linezolid or IV methylene blue) - this is an absolute contraindication due to serotonin syndrome risk 1
• Avoid in patients with known QT prolongation or those taking QT-prolonging drugs (Class 1A antiarrhythmics like quinidine, Class 3 antiarrhythmics like amiodarone, certain antipsychotics like ziprasidone, certain antibiotics like gatifloxacin) 1
• Avoid in patients with cardiac arrhythmias, particularly those with premature ventricular contractions, ventricular couplets, or history of torsade de pointes 1
• Not recommended during initial recovery phase of myocardial infarction 1

When Trazodone May Be Appropriate

For Depression:

• Trazodone is effective as an antidepressant at doses of 150-400 mg daily in divided doses 3
• It may be particularly useful in elderly patients who cannot tolerate anticholinergic effects of tricyclic antidepressants 4
• It has fewer cardiovascular side effects than older tricyclics and is relatively safe in overdose 3

For Insomnia (Third-Line Only):

• The American Academy of Sleep Medicine recommends AGAINST using trazodone as first or second-line therapy for insomnia 5
• Trazodone should only be considered after cognitive behavioral therapy for insomnia (CBT-I) and FDA-approved hypnotics (benzodiazepine receptor agonists like zolpidem, eszopiclone, zaleplon, or ramelteon) have failed 5
• It may be appropriate when comorbid depression is present, though low doses (25-50 mg) used for insomnia are inadequate for treating major depression 5
• Evidence for efficacy in insomnia is very limited, with most studies being small and conducted in depressed populations 2

Dosing Guidelines

• For insomnia: Start at 25-50 mg at bedtime 5, 6
• For depression: Start at 150 mg daily in divided doses, with therapeutic range of 150-400 mg/day 3
• Elderly patients: Use lower starting doses (25-50 mg) and maximum tolerated doses of 300-400 mg/day 4
• Must be taken on a regular schedule, NOT as needed - inconsistent use leads to inadequate therapeutic effect 6
• Take on an empty stomach to maximize effectiveness 5
• Tablets should be swallowed whole or broken in half along score line; do not crush or chew 1

Dose Adjustments for Organ Impairment

• Hepatic impairment: Requires dose reduction 5
• Renal impairment: Use with caution and consider dose adjustments 5

Critical Monitoring Requirements

Serotonin Syndrome Risk:

Monitor for agitation, hallucinations, confusion, tachycardia, hypertension, hyperthermia, hyperreflexia, tremor, rigidity, and diaphoresis, especially when combining with:

• Other serotonergic drugs (SSRIs, SNRIs, triptans, tramadol, fentanyl, lithium, buspirone, St. John's Wort) 1
• Fluvoxamine (which inhibits CYP3A4 metabolism of trazodone) 7

Cardiac Monitoring:

• Monitor for arrhythmias, particularly in patients with preexisting cardiac disease 1
• Torsade de pointes has been reported at doses as low as 100 mg 1
• Watch for orthostatic hypotension and syncope 1

Priapism Warning:

• Men with erections lasting >4 hours must immediately discontinue trazodone and seek emergency care 1
• Use with extreme caution in men with conditions predisposing to priapism (sickle cell anemia, multiple myeloma, leukemia) or anatomical penile deformities 1

Bleeding Risk:

• Trazodone increases bleeding risk, particularly when combined with NSAIDs, aspirin, antiplatelet drugs, or anticoagulants 1
• Monitor coagulation indices carefully in patients taking warfarin 1

Common Side Effects

• Most common: Drowsiness, dizziness, blurred vision, tiredness, diarrhea, stuffy nose, swelling 1
• Morning "hangover effect": Excessive sedation may occur, particularly with higher doses or drug interactions 7
• Minimal anticholinergic effects compared to tricyclic antidepressants 7, 4

Drug Interactions Requiring Caution

• CYP3A4 inhibitors (itraconazole, clarithromycin, voriconazole, fluvoxamine) increase trazodone levels and QT prolongation risk 1, 7
• Antihypertensives: May require dose reduction due to additive hypotensive effects 1
• Other sedating medications: Use with caution due to additive sedation 5
• Benzodiazepines: Risk of oversedation 5

Special Populations

• Elderly: Higher risk of falls due to orthostatic hypotension and sedation; start with lower doses 5, 4
• Pregnancy and nursing: Should be avoided 5
• Bipolar disorder: May precipitate manic/hypomanic episodes 1

Treatment Algorithm for Insomnia

1. First-line: Cognitive behavioral therapy for insomnia (CBT-I) 5
2. Second-line pharmacologic: Benzodiazepine receptor agonists (zolpidem, eszopiclone, zaleplon, temazepam) or ramelteon 5
3. Third-line: Trazodone, only after first and second-line treatments have failed OR when comorbid depression/anxiety is present 5

Mandatory Patient Education

• Treatment goals and expectations 5
• Risk of daytime drowsiness and psychomotor impairment - do not drive or operate machinery until effects are known 1
• Do not drink alcohol or take other sedating medications without discussing with provider 1
• Allow appropriate sleep time (7-8 hours) 5
• Report any prolonged erections immediately 1
• Do not stop abruptly - taper to avoid withdrawal symptoms (anxiety, agitation, sleep problems) 6, 1

Follow-Up Requirements

• Assess effectiveness and side effects every few weeks initially 5
• Use lowest effective maintenance dose 5
• Taper when conditions allow 5
• Monitor for tolerance development 2

Common Pitfalls to Avoid

• Do not use as first-line therapy for primary insomnia - evidence does not support this practice 5
• Do not prescribe as needed - requires regular dosing schedule 6
• Do not combine two sedating antidepressants 5
• Do not use solely as sleep aid without addressing underlying depression or anxiety 6
• Do not prescribe without attempting CBT-I or FDA-approved hypnotics first 5
• Do not discontinue abruptly - always taper 6