Introduction
Oleptro (trazodone hydrochloride) is an antidepressant medication approved by the FDA in 2010 for the treatment of major depressive disorder (MDD). It belongs to the serotonin antagonist and reuptake inhibitor (SARI) class of antidepressants. Unlike conventional immediate-release trazodone formulations, Oleptro features an extended-release delivery system designed to provide sustained plasma concentrations with once-daily dosing, potentially improving tolerability and adherence.
Mechanism of Action
Oleptro exerts its antidepressant effects primarily through dual mechanisms:
- Potent antagonism of serotonin 5-HT2A receptors
- Inhibition of serotonin reuptake transporter (SERT)
This unique pharmacological profile increases serotonin availability in the synaptic cleft while blocking postsynaptic 5-HT2A receptors, which may contribute to its antidepressant efficacy with potentially fewer sexual side effects compared to selective serotonin reuptake inhibitors (SSRIs). Additional weak antagonism at α1-adrenergic receptors and histamine H1 receptors contributes to its sedative properties.
Indications
FDA-approved indications:- Major depressive disorder (MDD) in adults
- Insomnia (particularly for sleep maintenance)
- Anxiety disorders
- Fibromyalgia (as adjunctive therapy)
Dosage and Administration
Initial dosage: 150 mg once daily at bedtime Dosage titration: May increase by 75 mg/day every 3 days Maximum dosage: 375 mg/day Special populations:- Geriatric patients: Initial dose 75 mg daily, with cautious titration
- Hepatic impairment: Reduce dose by 50% in moderate to severe impairment
- Renal impairment: No specific dosage adjustment required, but use with caution
- Administration: Should be taken whole, not crushed or chewed, with food to minimize dizziness
Pharmacokinetics
Absorption: Bioavailability approximately 85%; food increases absorption by 20% Distribution: Volume of distribution 0.9-1.3 L/kg; protein binding 89-95% Metabolism: Extensive hepatic metabolism via CYP3A4; active metabolite m-chlorophenylpiperazine (mCPP) Elimination: Half-life approximately 10 hours; renal excretion (70-75%), fecal excretion (20-25%) Steady-state: Achieved within 4 days of repeated dosingContraindications
- Hypersensitivity to trazodone or any component of the formulation
- Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation
- Patients who have experienced priapism while taking trazodone
Warnings and Precautions
Black Box Warning: Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults (ages 18-24) with major depressive disorder and other psychiatric disorders Additional warnings:- Serotonin syndrome: Risk increased with concomitant serotonergic drugs
- QT prolongation: May occur at higher doses; avoid in patients with known QT prolongation
- Priapism: Requires immediate medical attention (reported incidence 1:6000 men)
- Orthostatic hypotension: Particularly in elderly patients
- Activation of mania/hypomania: In patients with bipolar disorder
- CNS depression: May impair mental/physical abilities required for hazardous tasks
- Discontinuation syndrome: Taper gradually when discontinuing treatment
Drug Interactions
Major interactions:- MAOIs: Risk of serotonin syndrome (contraindicated)
- Strong CYP3A4 inhibitors (ketoconazole, ritonavir): Increase trazodone levels 2-4 fold
- Strong CYP3A4 inducers (carbamazepine, rifampin): Decrease trazodone levels significantly
- Other CNS depressants (alcohol, benzodiazepines, opioids): Additive sedation
- Digoxin, phenytoin: Trazodone may increase levels of these drugs
- Warfarin: May potentiate anticoagulant effect
Adverse Effects
Common (≥5%):- Somnolence/sedation (23-40%)
- Dizziness (10-20%)
- Constipation (8-10%)
- Blurred vision (6-9%)
- Headache (5-8%)
- Priapism (medical emergency)
- Serotonin syndrome
- QT prolongation and torsades de pointes
- Orthostatic hypotension and syncope
- Hyponatremia (SIADH)
- Mania/hypomania
- Suicidal ideation
Monitoring Parameters
Baseline:- Comprehensive metabolic panel (including sodium)
- ECG (in patients with cardiac risk factors)
- Depression rating scales (PHQ-9, MADRS)
- Suicide risk assessment
- Therapeutic response and adverse effects at 2-4 weeks
- Blood pressure (especially orthostatic measurements)
- Mental status changes, especially in first few months
- Signs of serotonin syndrome or priapism
- Periodic ECG monitoring in patients at risk for QT prolongation
Patient Education
- Take medication at bedtime due to sedative effects
- Do not crush, chew, or break tablets
- Avoid alcohol and other CNS depressants
- Rise slowly from sitting/lying position to prevent dizziness
- Report any prolonged or painful erections immediately
- Do not stop medication abruptly without medical supervision
- Be aware of potential for drowsiness affecting driving/operating machinery
- Inform all healthcare providers about trazodone use
- Report worsening depression or suicidal thoughts promptly
- Use effective contraception; notify provider if pregnancy is planned or suspected
References
1. FDA Prescribing Information: Oleptro (trazodone hydrochloride) Extended-Release Tablets. 2010. 2. Sheehan DV, et al. Efficacy and tolerability of extended-release trazodone in major depressive disorder. J Clin Psychiatry. 2009;70(5):588-596. 3. Stahl SM. Mechanism of action of trazodone: a multifunctional drug. CNS Spectr. 2009;14(10):536-546. 4. Jayamaha JE, et al. The safety and efficacy of trazodone in the treatment of major depressive disorder. Neuropsychiatr Dis Treat. 2016;12:2387-2393. 5. Fagiolini A, et al. Trazodone extended-release for the treatment of major depressive disorder. Expert Opin Pharmacother. 2013;14(13):1819-1827. 6. Lexicomp Online®. Trazodone monograph. Wolters Kluwer Clinical Drug Information. 2023. 7. Micromedex® Healthcare Series. Trazodone drug information. IBM Watson Health. 2023.