Clinical Overview
Trazodone XR (Oleptro) is an extended-release formulation of trazodone indicated specifically for major depressive disorder. Note: Oleptro is no longer marketed in the United States; availability may vary by region. Immediate-release trazodone remains available. Unlike immediate-release trazodone which is commonly used off-label for insomnia at low doses, the XR formulation is designed to provide sustained antidepressant levels throughout the day while potentially reducing sedation and other side effects.
Primary Clinical Applications
Trazodone XR is indicated for major depressive disorder in adults. The extended-release formulation allows for once-daily dosing and may provide more consistent antidepressant effects compared to immediate-release trazodone, while potentially reducing the sedation that limits daytime use of the immediate-release formulation.
Mechanism and Clinical Benefits
Trazodone XR primarily blocks serotonin reuptake and antagonizes serotonin 5-HT2A receptors, with additional activity at alpha-1 adrenergic and histamine H1 receptors. The extended-release formulation provides sustained drug levels, potentially improving antidepressant efficacy while reducing peak-related side effects like excessive sedation.
Clinical Considerations
The XR formulation requires different dosing than immediate-release trazodone and should be taken on an empty stomach. It may cause less sedation than immediate-release trazodone but still carries risks of orthostatic hypotension, priapism, and cardiac effects. The medication should not be crushed or chewed as this destroys the extended-release properties.
Prescribing Information
Dosing & Administration
Major Depressive Disorder – Adults:
- Initial: 150 mg once daily in the evening
- Titration: May increase by 75 mg daily every 3 days
- Range: 150-375 mg once daily
- Maximum: 375 mg once daily
Elderly:
- Initial: 150 mg once daily
- Titrate slowly based on response and tolerance
- Monitor closely for orthostatic hypotension
Administration:
- Take once daily in the evening on an empty stomach
- Swallow tablets whole, do not crush, chew, or split
- Take at least 2 hours after eating
- Consistent timing each day
Indications
- Treatment of major depressive disorder in adults
Contraindications
- Hypersensitivity to trazodone
- Use with MAOIs (within 14 days)
- Use with linezolid or IV methylene blue
Warnings & Precautions
- Boxed Warning: Increased risk of suicidal thoughts and behavior in patients under 25 years
- Priapism: Rare but serious risk requiring immediate medical attention
- Orthostatic hypotension: Monitor blood pressure, especially during initiation
- Cardiac arrhythmias: Use caution in patients with cardiac disease
- Serotonin syndrome: Risk with concurrent serotonergic drugs
- Angle-closure glaucoma: May precipitate acute attack
- Bleeding risk: Increased with anticoagulants
Drug Interactions
- MAOIs: Contraindicated – minimum 14-day washout
- CYP3A4 inhibitors: May increase trazodone levels
- CYP3A4 inducers: May decrease trazodone effectiveness
- CNS depressants: Enhanced sedation
- Anticoagulants: Increased bleeding risk
- Digoxin, phenytoin: Increased levels reported
Adverse Reactions
Common (≥5%):
- Somnolence, dizziness, constipation, blurred vision
- Dry mouth, fatigue
Advantages of XR formulation:
- Once-daily dosing
- Potentially less sedation than immediate-release
- More consistent drug levels
Serious:
- Priapism, orthostatic hypotension, cardiac arrhythmias
- Serotonin syndrome
Special Populations
- Cardiac Disease: Use caution, monitor for arrhythmias
- Hepatic Impairment: Use caution, may require dose reduction
- Pregnancy: Category C – use only if benefits outweigh risks
- Empty stomach requirement: Must take 2+ hours after eating for proper absorption
Medical Disclaimer: This information is for educational purposes only and is not intended as medical advice. Always consult with qualified healthcare professionals before making any treatment decisions. Individual patient circumstances may vary significantly.
