Trazodone

# Trazodone ## Overview - **Classification**: Serotonin Antagonist and Reuptake Inhibitor (SARI) - **Mechanism**: Weakly inhibits serotonin reuptake; blocks alpha-1 adrenergic, histamine H1, and 5-HT2A/2C receptors. This contributes to its sedative and antidepressant effects. ## Primary Indications 1. **Major Depressive Disorder (MDD)** - Treatment of unipolar depression. 2. **Insomnia** - Off-label use for sleep disturbance. ## Adult Dosing ### Standard Dosing **Major Depressive Disorder (MDD)** - **Dose**: Initially **50-100 mg/day**. - **Frequency**: Divided doses or a single dose at bedtime. - **Route**: Oral. - **Titration**: Increase by **50 mg/day** every 3-4 days as tolerated. - **Maintenance**: **150-300 mg/day** (divided doses or at bedtime). - **Maximum Dose**: **400 mg/day** (outpatient), **600 mg/day** (inpatient). **Insomnia (Off-label)** - **Dose**: Initially **25-50 mg**. - **Frequency**: Once daily at bedtime. - **Route**: Oral. - **Maximum Dose**: Typically **100 mg** for sleep. ### Dose Adjustments - **Renal Impairment**: No specific adjustments provided. Use with caution. - **Hepatic Impairment**: Use with caution. Consider lower initial doses and slower titration. - **Elderly Patients**: Start with lower doses (e.g., **25-50 mg/day**) and titrate slowly due to increased sensitivity and risk of adverse effects like orthostatic hypotension. ## Pediatric Dosing ### Neonates (0-28 days) - **Dose**: Not recommended. - **Special Notes**: Safety and efficacy not established. High risk for adverse effects. ### Infants (1-12 months) - **Dose**: Not recommended. - **Special Notes**: Safety and efficacy not established. Consider non-pharmacological interventions. ### Children (1-12 years) - **Dose**: Generally **not recommended** for depression. - **Off-label for Insomnia**: Some sources suggest **0.5-2 mg/kg/day** at bedtime. - **Frequency**: Once daily at bedtime. - **Maximum**: **50-75 mg/day**. - **Special Notes**: Use with extreme caution. Monitor closely for adverse effects. ### Adolescents (13-18 years) - **Dose**: Generally **not recommended** for depression. - **Off-label for Insomnia**: Similar to lower adult doses, **25-50 mg** at bedtime. - **Frequency**: Once daily at bedtime. - **Maximum**: **100 mg/day**. - **Special Notes**: Risk of increased suicidal thoughts and behaviors if used for MDD. ## Safety Information ### Contraindications - **Absolute**: Concomitant use with MAOIs or within **14 days** of stopping an MAOI. - **Absolute**: Recovery period immediately following a myocardial infarction. - **Absolute**: Hypersensitivity to trazodone. ### Common Adverse Effects - **Very Common (>10%)**: Drowsiness, dizziness, dry mouth, nausea, headache. - **Common (1-10%)**: Blurred vision, constipation, orthostatic hypotension, fatigue, confusion. - **Serious but Rare**: Priapism, serotonin syndrome, cardiac arrhythmias (QT prolongation), suicidal ideation, hepatotoxicity. ### Key Drug Interactions - **MAOIs**: Risk of serotonin syndrome. **Contraindicated**. - **CYP3A4 Inhibitors (e.g., ketoconazole)**: Increased trazodone levels and toxicity risk. Consider dose reduction. - **CYP3A4 Inducers (e.g., carbamazepine)**: Decreased trazodone levels and efficacy. May require dose increase. - **CNS Depressants (e.g., alcohol)**: Increased sedation. Avoid concurrent use. - **Drugs that prolong QT interval**: Increased risk of arrhythmias. Use with caution. - **Anticoagulants (e.g., warfarin)**: Potential for increased bleeding. Monitor INR. ## Monitoring & Follow-up - **Before Treatment**: Baseline cardiovascular assessment (ECG if risk factors), CBC, liver function tests (LFTs). - **During Treatment**: Monitor for orthostatic hypotension, excessive sedation, cardiac symptoms. - **Clinical Signs**: Worsening depression, suicidal ideation, priapism, signs of serotonin syndrome (agitation, hyperthermia, rigidity). ## Clinical Pearls - 💡 **Timing**: Administer at bedtime for insomnia and to minimize daytime sedation for depression. Take with food to enhance absorption and reduce nausea/lightheadedness. - 💡 **Priapism Risk**: Counsel male patients about the rare but serious risk of priapism. Seek immediate medical attention if erection lasts >4 hours. - 💡 **Titration**: Start low and go slow, especially in elderly patients, to minimize side effects like orthostatic hypotension and excessive sedation. - 💡 **"Trazodone Hangover"**: Warn patients about potential morning drowsiness/grogginess, especially during initial therapy or dose increases. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.