DESYREL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DESYREL (DESYREL).
Selective serotonin reuptake inhibitor (SSRI) that potentiates serotonergic activity by blocking serotonin reuptake at the presynaptic neuron. Also has secondary antagonistic effects at 5-HT2A receptors, contributing to its antidepressant and anxiolytic effects.
| Metabolism | Hepatic via CYP3A4 isoenzyme to active metabolite m-chlorophenylpiperazine (m-CPP). |
| Excretion | Primarily renal (approximately 75% as metabolites, less than 1% unchanged); fecal excretion accounts for about 20%. |
| Half-life | Terminal elimination half-life is approximately 5-11 hours (mean 7 hours); for elderly patients, half-life may be prolonged. |
| Protein binding | Approximately 85-90% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | 20-40 L/kg (0.2-0.4 L/kg); large Vd indicates extensive tissue distribution. |
| Bioavailability | Oral: approximately 70-80% (due to first-pass metabolism). |
| Onset of Action | Antidepressant effects: 1-3 weeks after oral administration; Sedative effects: within 30-60 minutes. |
| Duration of Action | Antidepressant effects: sustained with continuous dosing; Sedative effects: 4-6 hours. |
Initial dose: 150 mg orally once daily, increased by 50 mg/day every 3-4 days. Maximum: 400 mg/day. For severe depression, up to 600 mg/day in hospitalized patients.
| Dosage form | TABLET |
| Renal impairment | GFR 10-50 mL/min: Administer 50-75% of normal dose. GFR <10 mL/min: Administer 50% of normal dose. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50%. Child-Pugh Class C: Avoid use. |
| Pediatric use | Not approved for use in children <18 years. If used, typical dose: 1.5-3 mg/kg/day orally in divided doses, maximum 6 mg/kg/day. |
| Geriatric use | Initial dose: 25-50 mg orally once daily, titrate slowly. Maximum: 300 mg/day. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DESYREL (DESYREL).
| Breastfeeding | Unknown M/P ratio. Desyrel and its active metabolite m-chlorophenylpiperazine are excreted into breast milk in low concentrations. Case reports show no adverse effects in infants, but theoretical risk of sedation. AAP considers trazodone compatible with breastfeeding; monitor infant for drowsiness. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Limited human data, animal studies show fetal toxicity (increased fetal resorptions, cardiovascular anomalies) at doses 4-9x MRHD. Second trimester: No specific malformation pattern, but risk of preterm birth. Third trimester: Neonatal withdrawal syndrome (irritability, feeding difficulties, respiratory depression) if used near term. |
■ FDA Black Box Warning
WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of Trazodone or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber.
| Serious Effects |
["Concurrent use with MAOIs (including linezolid or intravenous methylene blue) due to risk of serotonin syndrome","Hypersensitivity to trazodone or any component of the formulation","Recent myocardial infarction (within 6 weeks)"]
| Precautions | ["Clinical worsening and suicide risk","Serotonin syndrome","QT prolongation (especially with higher doses or in patients with risk factors)","Priapism (rare but requires immediate medical attention)","Hyponatremia (SIADH)","Activation of mania/hypomania","Psychomotor impairment (may impair ability to drive or operate machinery)","Increased risk of bleeding (especially with NSAIDs or anticoagulants)","Angle-closure glaucoma (due to mydriatic effect)"] |
Loading safety data…
| Fetal Monitoring | Maternal: Baseline and periodic liver function tests, CBC with differential, ECG if cardiac risk factors. Fetal: Serial ultrasounds for growth restriction; nonstress test/biophysical profile in third trimester if continued use. Neonatal: Monitor for neurobehavioral adaptation syndrome (poor feeding, jitteriness, respiratory distress) for 48-72 hours postpartum. |
| Fertility Effects | In men: Trazodone may cause priapism, potentially impairing fertility. In women: No direct effects on ovulation or conception; hyperprolactinemia from serotonin modulation is rare. Animal studies no impact on fertility at clinically relevant doses. |