Actions and Spectrum: 

trazodone is an antidepressant medication that belongs to the class of drugs known as serotonin receptor antagonists and reuptake inhibitors (SARIs). It is primarily used to treat major depressive disorder (MDD). Still, it is also used off-label to treat other conditions, such as anxiety disorders, obsessive-compulsive disorder (OCD), and insomnia. 

trazodone acts as a serotonin receptor antagonist and reuptake inhibitor, which means that it enhances the effects of serotonin in the brain by blocking its reuptake and increasing its release. Serotonin is a neurotransmitter that regulates mood, anxiety, and sleep, and enhancing its effects is believed to be the mechanism by which trazodone produces its therapeutic effects. 

In addition to its effects on serotonin, trazodone has sedative and hypnotic effects due to its antagonism of histamine H1 receptors, contributing to its use in treating insomnia. 

Trazodone also acts as an antagonist at the 5-HT2A receptor and a partial agonist at the 5-HT1A receptor, which may contribute to its anxiolytic and antidepressant effects. 

DRUG INTERACTION

Contraindicated  

Serious Use Alternative  

Monitor Closely  

Minor  

Frequency Defined 

>10% 

Blurred vision  

Dizziness  

Fatigue  

Headache  

Drowsiness  

Dry mouth  

Nausea/vomiting 

1-10% 

Constipation  

Edema  

Incoordination  

Nasal congestion  

Confusion  

Disorientation  

Orthostatic hypotension  

Syncope  

Ejaculation disorder  

Tremor  

Weight change  

Decreased libido 

<1% 

Priapism 

Sedation 

Acne 

Anemia 

Alopecia 

Anxiety 

Increased appetite 

Diplopia 

Vertigo 

Insomnia 

Urinary retention 

Black Box Warning: 

trazodone increases the risk of suicidal thoughts and alters behavior in young adults. The drug is not meant for pediatrics. 

Contraindication/Caution: 

Contraindications: 

• Hypersensitivity: trazodone should not be used by individuals with known hypersensitivity or allergy to trazodone or its ingredients. 
• Concomitant use with MAOIs: trazodone should not be used with MAO inhibitors, such as selegiline, isocarboxazid, phenelzine, and tranylcypromine, due to the risk of serotonin syndrome, a potentially life-threatening condition. 

Cautions: 

• Pregnancy and lactation: trazodone should be used cautiously during pregnancy and breastfeeding, as its safety has not been established in these populations. 
• Cardiovascular disease: trazodone may cause orthostatic hypotension or a drop in blood pressure upon standing, which may be of concern in individuals with cardiovascular disease. 
• Liver and kidney disease: trazodone may accumulate in the body in individuals with liver or kidney disease, requiring dose adjustments or careful monitoring. 
• Seizure disorder: trazodone may lower the seizure threshold in individuals with a history of seizures, making them more susceptible. 
• Elderly: trazodone should be used cautiously in elderly individuals, as they may be more susceptible to adverse effects such as sedation, dizziness, and falls. 

Pregnancy consideration:  

trazodone should be used during pregnancy only when very much required. 

Breastfeeding warnings:  

Use the drug cautiously during lactation. 

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: No evidence of risk to the fetus is found in animal reproduction studies, and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for a human product; Pregnant women must take care of the potential risks. 
• Category D: There is adequate data with sufficient evidence of human fetal risk from various platforms. However, despite potential dangers may be used only in emergencies for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. The drug is not for pregnant women. 
• Category N: No data for the drug under this category is available. 

Pharmacology: 

trazodone is an antidepressant medication that belongs to the class of drugs known as serotonin receptor antagonists and reuptake inhibitors (SARIs). It works by increasing serotonin levels in the brain, a neurotransmitter that regulates mood, anxiety, and sleep. 

The primary mechanism of action of trazodone is the inhibition of serotonin reuptake. This increases the concentration of serotonin in the synaptic cleft, which enhances the transmission of serotonin-mediated signals. Additionally, trazodone acts as an antagonist at the 5-HT2A receptor and a partial agonist at the 5-HT1A receptor. These actions contribute to the antidepressant and anxiolytic effects of trazodone. 

trazodone also has sedative and hypnotic effects due to its antagonism of histamine H1 receptors, which is responsible for its use in the treatment of insomnia. 

Pharmacodynamics: 

The pharmacodynamics of trazodone refers to how the drug interacts with the body and produces its therapeutic effects. trazodone is primarily used to treat depression, anxiety, and sleep disorders. 

trazodone acts as a serotonin receptor antagonist and reuptake inhibitor (SARI), which means that it enhances the effects of serotonin in the brain by blocking its reuptake and increasing its release. Serotonin is a neurotransmitter that regulates mood, anxiety, and sleep, and enhancing its effects is believed to be the mechanism by which trazodone produces its therapeutic effects. 

In addition to its effects on serotonin, trazodone has sedative and hypnotic effects due to its antagonism of histamine H1 receptors, contributing to its use in treating insomnia. 

trazodone also acts as an antagonist at the 5-HT2A receptor and a partial agonist at the 5-HT1A receptor, which may contribute to its anxiolytic and antidepressant effects. 

The therapeutic effects of trazodone are believed to result from a combination of these mechanisms of action. By enhancing the effects of serotonin and modulating its effects on various receptor subtypes, trazodone helps to regulate mood, reduce anxiety, and improve sleep quality. 

Pharmacokinetics: 

Absorption 

The drug is completely absorbed (absorption increases by food) 

The onset of the action takes in 6 weeks (antidepressant); 1-3 hours help in sleep  

A peak serum concentration is achieved in 30-100 min (up to 2.5 hours with food); and 9 hours (for extended-release) 

480-1620 ng/mL of concentration is dose-dependent 

Distribution 

Protein-bound is 85-95% 

Metabolism 

Metabolism occurs via hepatic P450 enzyme and CYP3A4 (major) and CYP2D6 (minor) 

Metabolites formed are l-m-chlorophenyl piperazine 

Elimination and Excretion 

The half-life is achieved in 7-10 hours 

75% is excreted in urine, and 25% is excreted in feces  

The drug is not dialyzable 

Administration: 

trazodone is typically administered orally in tablet form. The tablets should be swallowed whole with a full glass of water and may be taken with or without food. 

The recommended starting dose of trazodone for depression is usually 150 mg daily, divided into two or three doses. Dose may gradually increase to a maximum daily dose of 400 mg over time. For the treatment of insomnia, lower doses of trazodone, typically 25-50 mg, may be used at bedtime. 

trazodone should be taken at the same time(s) each day to maintain a steady level in the body. It is essential to follow the dosing instructions provided by your healthcare provider and stay within the recommended dose. 

trazodone may take several weeks to reach its full therapeutic effect, and it is essential to continue taking the medication as directed even if you feel better. 

Patient information leaflet 

Generic Name:  trazodone 

Pronounced: tra-zo-done 

Why do we use trazodone? 

trazodone is primarily used to treat major depressive disorder (MDD). Still, it is also used off-label to treat other conditions, such as anxiety disorders, obsessive-compulsive disorder (OCD), and insomnia. 

trazodone is an antidepressant medication that belongs to the class of drugs known as serotonin receptor antagonists and reuptake inhibitors (SARIs). It increases serotonin levels in the brain, a neurotransmitter that regulates mood, anxiety, and sleep. By enhancing serotonin’s effects, trazodone helps regulate mood, reduce anxiety, and improve sleep quality. 

In addition to its effects on serotonin, trazodone has sedative and hypnotic effects due to its antagonism of histamine H1 receptors, contributing to its use in treating insomnia. 

trazodone is generally well-tolerated, and it may be a good choice for patients who do not respond to other antidepressant medications or who experience intolerable side effects from other medications. It is also sometimes used with other medications, such as selective serotonin reuptake inhibitors (SSRIs), to augment their effects.