Generic Name
Brand Names
Generic formulations available worldwide
Drug Class
Serotonin antagonist and reuptake inhibitor (SARI)
Sedative-hypnotic (off-label)
Mechanism of Action
Trazodone functions through a dual mechanism
It inhibits serotonin reuptake (5-HT reuptake) by presynaptic neurons
Also acts as an antagonist at postsynaptic 5-HT2A and 5-HT2C receptors
This dual serotonergic effect leads to increased serotonin availability and modulation of receptor overstimulation
At low doses, its antihistaminergic (H1) and alpha-1 adrenergic antagonist effects dominate, causing sedation and hypotension
Minimal anticholinergic effects
No significant inhibition of norepinephrine or dopamine reuptake
Indications
Approved Uses
Major depressive disorder (MDD) in adults
May be used as monotherapy or adjunctive therapy
Off-Label Uses
Insomnia (commonly prescribed in low doses)
Post-traumatic stress disorder (PTSD)
Obsessive-compulsive disorder (OCD)
Schizophrenia (as adjunct)
Dosage and Administration
Major Depression (Adults)
Initial dose 150 mg/day in divided doses
Increase by 50 mg every 3 to 4 days
Maximum dose outpatient 400 mg/day
Maximum dose inpatient 600 mg/day
Extended-release (Oleptro)
Initial 150 mg once daily at bedtime
Can be increased by 75 mg every 3 days
Maximum dose 375 mg/day
Insomnia (Off-label use)
Common dose 25–100 mg once daily at bedtime
Sedative effects are prominent at lower doses
Geriatric Population
Start at lower doses (e.g. 25–50 mg/day) due to fall risk and sedation
Titrate slowly based on tolerability
Pediatric Use
Not approved for use in children under 18
Rarely used and only under psychiatric supervision
Use with caution
Lower initial doses and slower titration advised
Monitor for accumulation
Administration
Immediate-release tablets usually given after meals or snacks
Extended-release formulations should be swallowed whole and not crushed
Pharmacokinetics
Absorption
Well absorbed orally
Bioavailability 65–80%
Food increases absorption
Distribution
Extensively bound to plasma proteins (~90–95%)
Widely distributed in body tissues
Metabolism
Hepatic metabolism via CYP3A4
Major active metabolite: m-chlorophenylpiperazine (mCPP)
Elimination
Excreted via urine (~70%) and feces (~20%)
Elimination half-life ~5 to 13 hours (dose-dependent)
Biphasic with longer half-life in elderly or liver dysfunction
Contraindications
Known hypersensitivity to trazodone or its components
Concurrent use with MAO inhibitors or within 14 days of MAOI discontinuation
Initiation during recovery phase of myocardial infarction
Use with linezolid or IV methylene blue
Caution with use in patients at risk for QT prolongation
Warnings and Precautions
Suicidality
Increased risk of suicidal thoughts and behavior in adolescents and young adults
Monitor closely during initiation and dosage changes
Dose-dependent risk
Monitor ECG in patients with cardiac disease or electrolyte abnormalities
Avoid with other QT-prolonging drugs
Sedation and CNS Depression
May impair mental and physical abilities
Caution with driving or operating machinery
Orthostatic Hypotension
Due to alpha-1 adrenergic antagonism
Common in elderly and at higher doses
Priapism
Rare but serious adverse effect
Prolonged erections require emergency treatment
May necessitate discontinuation
Serotonin Syndrome
Possible when combined with other serotonergic agents
Symptoms include agitation, confusion, fever, tremor, hyperreflexia
Discontinue if suspected
Hepatotoxicity
Rare reports of liver enzyme elevations and hepatic failure
Monitor liver function tests if clinically indicated
Adverse Effects
Very Common
Sedation
Drowsiness
Dizziness
Dry mouth
Fatigue
Common
Headache
Nausea
Blurred vision
Constipation
Hypotension
Weight changes
Sweating
Less Common
Arrhythmias
Tachycardia
Confusion
Mania
Agitation
Tremor
Urinary retention
Rare but Serious
QT prolongation
Torsades de pointes
Priapism
Hepatitis
Hyponatremia
Seizures
Suicidal ideation
Overdose
Symptoms
Extreme sedation
Respiratory depression
Arrhythmias
Hypotension
Seizures
Coma
Management
Supportive care
Monitor cardiac and respiratory function
Activated charcoal if within 1–2 hours
No specific antidote
ECG monitoring required
Drug Interactions
Pharmacodynamic Interactions
MAO inhibitors → serotonin syndrome risk
SSRIs SNRIs triptans tramadol → additive serotonergic effects
Alcohol CNS depressants → enhanced sedation
Antihypertensives → increased hypotension risk
Anticholinergics → additive effects on cognition and dry mouth
Pharmacokinetic Interactions
CYP3A4 inhibitors (ketoconazole, ritonavir, erythromycin) → increased trazodone levels
CYP3A4 inducers (carbamazepine, phenytoin, rifampin) → decreased trazodone levels
Digoxin and phenytoin → may increase serum levels of both
Warfarin → increased INR monitoring recommended
Use in Special Populations
Pregnancy
Category C
Use only if benefits outweigh risks
Animal studies show adverse fetal effects
Human data limited
Monitor for withdrawal symptoms in neonates if used late in pregnancy
Lactation
Excreted in small amounts in breast milk
Consider risk-benefit; limited data
Geriatrics
Greater risk of falls and orthostatic hypotension
Start at lower doses
Monitor for sedation and cardiovascular effects
Renal/Hepatic Impairment
Start with lower doses
Use cautiously and monitor for accumulation
Monitoring Parameters
Mental status and mood changes
Blood pressure (especially orthostatic)
Signs of serotonin syndrome
ECG in high-risk populations
Suicidal ideation
Liver function (if symptoms develop)
Priapism or genital complaints
Comparative Pharmacology
Compared to SSRIs
Less sexual dysfunction
More sedating
More cardiovascular side effects
Used when SSRIs are poorly tolerated
Compared to mirtazapine
Both are sedating but mirtazapine has more appetite stimulation
Trazodone may be preferred if weight gain is undesirable
Compared to benzodiazepines for insomnia
Trazodone lacks dependency potential
Safer in patients with history of substance use
Compared to TCAs
Less anticholinergic effects
Lower seizure risk
Less cardiotoxic in overdose
Formulations Available
Tablets: 50 mg, 100 mg, 150 mg, 300 mg
Extended-release (Oleptro): 150 mg, 300 mg (withdrawn in some markets)
Available generically in most countries
Regulatory and Legal Status
Prescription-only medication
Approved by FDA for depression
Widely used off-label for insomnia
Not classified as a controlled substance
Included in many national formularies
No comments:
Post a Comment