Of course. Here is a comprehensive, evidence-based drug monograph for Desyrel formatted as a complete blog post.
*Introduction
Desyrel (trazodone hydrochloride) is an antidepressant medication belonging to the class of serotonin antagonist and reuptake inhibitors (SARIs). Initially approved by the FDA in 1981 for the treatment of major depressive disorder (MDD), its use has expanded in clinical practice, particularly for its sedative properties at lower doses. It is distinct from more common antidepressants like SSRIs and SNRIs due to its unique mechanism of action.
Mechanism of Action
Trazodone's primary mechanism of action is the potent inhibition of serotonin reuptake and antagonism of serotonin 5-HT2A and 5-HT2C receptors. Unlike SSRIs, which primarily block the serotonin transporter (SERT), trazodone's strong 5-HT2A receptor blockade is thought to contribute significantly to its antidepressant and, more notably, its sedative effects. It is also an antagonist at histamine H1 and alpha-1 adrenergic receptors, which contributes to its sedative and hypotensive side effects, respectively. It has negligible affinity for muscarinic cholinergic receptors, resulting in a low incidence of anticholinergic side effects.
Indications
* FDA-Approved Indication: * Major Depressive Disorder (MDD) * Common Off-Label Uses: * Insomnia (primary or comorbid with depression/anxiety) * Anxiety disorders (e.g., generalized anxiety disorder) * Sedation in delirium or agitation * Augmentation in partial response to SSRI therapy
Dosage and Administration
* Major Depressive Disorder: The initial dose is 150 mg per day in divided doses. The dose may be increased by 50 mg per day every 3 to 4 days. The maximum dose for outpatients should not exceed 400 mg per day in divided doses. Inpatients may be administered up to 600 mg per day in divided doses. * Insomnia (Off-Label): Much lower doses are typically used, ranging from 25 mg to 100 mg administered 30 minutes before bedtime. * Administration: Should be taken shortly after a meal or light snack to reduce the incidence of dizziness and lightheadedness. * Special Populations: * Geriatric Patients: Use a lower initial dose (e.g., 25-50 mg at bedtime) due to increased sensitivity and a higher risk of sedation, falls, and SIADH. * Hepatic Impairment: Use with caution and consider lower doses due to reduced clearance. * Renal Impairment: Use with caution; dose reduction may be necessary. * Pediatric Patients: Not typically first-line; use requires careful risk-benefit assessment due to black box warning (see below).
Pharmacokinetics
* Absorption: Well absorbed from the GI tract. Peak plasma concentrations occur approximately one hour after fasting administration and two hours when taken with food. * Distribution: Widely distributed in the body. It is 85-95% protein-bound. * Metabolism: Extensively metabolized in the liver primarily via the cytochrome P450 3A4 (CYP3A4) isoenzyme. Its active metabolite, meta-chlorophenylpiperazine (mCPP), contributes to both efficacy and side effects. * Elimination: Eliminated primarily in the urine (70-75%) and feces (20-25%). The elimination half-life of trazodone is biphasic, with an initial phase of 3-6 hours and a second phase of 5-9 hours.
Contraindications
* Known hypersensitivity to trazodone or any components of the formulation. * Concomitant use with, or within 14 days of stopping, monoamine oxidase inhibitors (MAOIs) due to the risk of serotonin syndrome. * Patients who are in the acute recovery phase after a myocardial infarction.
Warnings and Precautions
* Suicidal Thoughts and Behaviors (Black Box Warning): Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. Closely monitor all patients for clinical worsening, suicidality, or unusual changes in behavior. * Serotonin Syndrome: Risk is increased with concomitant use of other serotonergic drugs (e.g., other antidepressants, tramadol, triptans). Symptoms include mental status changes, autonomic instability, neuromuscular symptoms, and GI symptoms. * Cardiovascular Effects: Can cause hypotension and dizziness. Priapism, a prolonged and painful penile erection unrelated to sexual stimulation, is a medical emergency that requires immediate treatment. It occurs in approximately 1 in 6000 males. * QT Prolongation: Has been shown to prolong the QT interval. Avoid use in patients with known QT prolongation or conditions predisposing to it, and with other drugs that prolong the QT interval. * Activation of Mania/Hypomania: May occur in patients with bipolar disorder. Screen patients for bipolar disorder prior to initiation. * Discontinuation Syndrome: Abrupt discontinuation may lead to symptoms such as anxiety, agitation, and insomnia. Taper dose gradually.
Drug Interactions
* Strong CYP3A4 Inhibitors (e.g., ketoconazole, itraconazole, clarithromycin): May significantly increase trazodone levels, increasing the risk of adverse effects (e.g., sedation, hypotension, QT prolongation). Avoid concomitant use or consider a lower trazodone dose. * CYP3A4 Inducers (e.g., carbamazepine, rifampin): May decrease trazodone levels, reducing efficacy. * Central Nervous System Depressants (e.g., alcohol, benzodiazepines, opioids): Concomitant use can potentiate sedation and impair cognitive/motor performance. * Other Serotonergic Drugs (e.g., SSRIs, SNRIs, tramadol, linezolid): Increase the risk of serotonin syndrome. * Antihypertensives & Alpha-Blockers: May potentiate hypotensive effects. * Digoxin & Phenytoin: Trazodone may increase levels of these drugs.
Adverse Effects
* Common (>10%): Somnolence/sedation, dizziness, headache, dry mouth, nausea, constipation. * Serious but Less Common: * Priapism (requires urgent medical attention) * Serotonin syndrome * Orthostatic hypotension and syncope * Suicidal ideation * QT prolongation and ventricular arrhythmias * Hyponatremia/SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion)
Monitoring Parameters
* Efficacy: Mood, sleep patterns, and anxiety symptoms using standardized scales (e.g., PHQ-9) and clinical interview. * Safety: * Signs of suicidality, especially at initiation and during dose changes. * Signs of serotonin syndrome. * Orthostatic blood pressure and heart rate, especially in elderly patients. * Electrolytes (for hyponatremia) in at-risk populations (elderly, those on diuretics). * ECG monitoring in patients with cardiac risk factors or on concomitant QT-prolonging drugs. * Adherence: Regular assessment of adherence and tolerability.
Patient Education
* Take this medication exactly as prescribed; do not stop abruptly. * It may take several weeks to feel the full antidepressant effect. * The medication commonly causes drowsiness and dizziness. Avoid driving or operating heavy machinery until you know how it affects you. * Avoid alcohol while taking this medication. * Rise slowly from a sitting or lying position to prevent dizziness. * For Male Patients: Immediately report any prolonged or painful erection (priapism), as it is a medical emergency. * Report any new or worsening depression, suicidal thoughts, anxiety, agitation, panic attacks, insomnia, or any unusual changes in behavior to your healthcare provider immediately. * Inform all your healthcare providers (including dentists) that you are taking trazodone.
References
1. FDA Prescribing Information for Desyrel (trazodone hydrochloride). (2023). Accessible via DailyMed. 2. Shelton, R. C. (2019). Serotonin and Norepinephrine Reuptake Inhibitors. In Handbook of Experimental Pharmacology. 3. Schatzberg, A. F., & DeBattista, C. (2021). Manual of Clinical Psychopharmacology (9th ed.). American Psychiatric Publishing. 4. Jaffer, K. Y., et al. (2017). Trazodone for Insomnia: A Systematic Review. Innovations in Clinical Neuroscience, 14(7-8), 24–34. 5. Stahl, S. M. (2021). Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (5th ed.). Cambridge University Press. 6. Lexicomp Online, Trazodone Monograph. Hudson, Ohio: Wolters Kluwer Clinical Drug Information, Inc.; [accessed 2023 Oct 27].