Active ingredient: Trazodone - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Antidepressants, Second-Generation
• Anti-anxiety Agents
• Serotonin Uptake Inhibitors

Dosage Forms

• Tablet

Brands / Synonyms

Beneficat; Bimaran; Desirel; Desyrel; Molipaxin; Pragmazone; Sideril; Thombran; Tombran; Trazalon; Trazodil; Trazodon; Trazodona [Inn-Spanish]; Trazodona [Spanish]; Trazodone; Trazodone Hcl; Trazodone Hydrochloride; Trazodonum [Inn-Latin]; Trazodonum [Latin]; Trazolan; Trazonil; Trialodine; Trittico

Indications

For the treatment of depression.

Pharmacology

Trazodone is an antidepressant and hypnotic chemically unrelated to tricyclic, tetracyclic, or other known antidepressant agents. The mechanism of trazodone's antidepressant action in man is not fully understood. In animals, trazodone selectively inhibits serotonin uptake by brain synaptosomes and potentiates the behavioral changes induced by the serotonin precursor, 5-hydroxytryptophan. Cardiac conduction effects of trazodone in the anesthetized dog are qualitatively dissimilar and quantitatively less pronounced than those seen with tricyclic antidepressants. Trazodone is not a monoamine oxidase inhibitor and, unlike amphetamine-type drugs, does not stimulate the central nervous system. In man, trazodone is well absorbed after oral administration without selective localization in any tissue. Since the clearance of trazodone from the body is sufficiently variable, in some patients trazodone may accumulate in the plasma.

Mechanism of Action

Trazodone binds at 5-HT2 receptor, it acts as a serotonin agonist at high doses and a serotonin antagonist at low doses. Like fluoxetine, trazodone's antidepressant activity likely results from blockage of serotonin reuptake by inhibiting serotonin reuptake pump at the presynaptic neuronal membrane. If used for long time periods, postsynaptic neuronal receptor binding sites may also be affected. The sedative effect of trazodone is likely the result of alpha-adrenergic blocking action and modest histamine blockade at H1 receptor. It weakly blocks presynaptic alpha2-adrenergic receptors and strongly inhibits postsynaptic alpha1 receptors. Trazodone does not affect the reuptake of norepinephrine or dopamine within the CNS.

Absorption

Well absorbed following oral administration.

Toxicity

LD₅₀=96mg/kg (i.v. in mice)

Biotrnasformation / Drug Metabolism

Hepatic

Contraindications

DESYREL is contraindicated in patients hypersensitive to DESYREL.

Drug Interactions

In vitro drug metabolism studies suggest that there is a potential for drug interactions when trazodone is given with CYP3A4 inhibitors. Ritonavir, a potent CYP3A4 inhibitor, increased the C_max, AUC, and elimination half- life, and decreased clearance of trazodone after administration of ritonavir twice daily for 2 days. Adverse effects including nausea, hypotension, and syncope were observed when ritonavir and trazodone were coadministered. It is likely that ketoconazole, indinavir, and other CYP3A4 inhibitors such as itraconazole or nefazodone may lead to substantial increases in trazodone plasma concentrations, with the potential for adverse effects. If trazodone is used with a potent CYP3A4 inhibitor, a lower dose of trazodone should be considered.

Carbamazepine reduced plasma concentrations of trazodone when co-administered. Patients should be closely monitored to see if there is a need for an increased dose of trazodone when taking both drugs.

Increased serum digoxin or phenytoin levels have been reported to occur in patients receiving DESYREL concurrently with either of those two drugs.

It is not known whether interactions will occur between mono-amine oxidase (MAO) inhibitors and DESYREL. Due to the absence of clinical experience, if MAO inhibitors are discontinued shortly before or are to be given concomitantly with DESYREL, therapy should be initiated cautiously with gradual increase in dosage until optimum response is achieved.

Therapeutic Interactions

Concurrent administration with electroshock therapy should be avoided because of the absence of experience in this area.

There have been reports of increased and decreased prothrombin time occurring in warfarinized patients who take DESYREL.