Trazodone

BRAND NAMES:

Desyrel: Desyrel contains trazodone with available dosage ranges from 50 mg, 100 mg, 150 mg, and 300mg. It is used for major depression disorder.

MECHANISM OF ACTION:

Trazodone is a triazolopyridine derivative that works as an antidepressant by inhibiting serotonin transporters and type 2 receptors. Trazodone reduces serotonin reuptake and blocks histamine and α-1-adrenergic receptors. The medication also causes considerable alterations in the 5-HT presynaptic receptor adrenoreceptors. Trazodone's mechanism of action is not entirely understood, which explains its off-label usage. Trazodone belongs to the SARI drug class, which also includes phenylpiperazine, etoperidone, lorpiprazole, and mepiprazole.

Clinical studies have shown that trazodone is as effective as other pharmaceutical classes for treating severe depressive disorders, including tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin-norepinephrine receptor inhibitors. Furthermore, trazodone is more tolerable than second-generation SSRIs, which have been linked to insomnia, anxiety, and sexual dysfunction. Trazodone's unique ability to block SERT, 5-HT2A, and 5-HT2C receptors simultaneously avoids the sexual dysfunction, and insomnia that are common side effects of SSRI and SNRI medication.

Trazodone lowers neurotransmitters related to arousal, including serotonin, noradrenaline, dopamine, acetylcholine, and histamine. Low-dose trazodone has a relaxing impact on sleep by blocking the 5-HT-2A receptor, H1 receptor, and alpha-1-adrenergic receptors. Furthermore, a recent study on human astrocytes demonstrated that trazodone helps reduce inflammatory mediator release and normalize trophic and metabolic support during inflammation of neurons, which is associated with significant depression.

PHARMACOKINETICS:

Absorption: Trazodone's bioavailability is nearly 100%, and peak plasma concentrations are often reached within an hour of oral dosing.

Distribution: Trazodone has a volume distribution of 0.8 to 1.5 L/kg and protein binding 89 to 95%.

Metabolism:CYP3A4 substantially metabolizes trazodone to produce m-chlorophenyl piperazine, an active metabolite.

Elimination: Trazodone is generally excreted via urine. Trazodone has a terminal elimination half-life of 5 to 9 hours.

DOSAGE AND ADMINISTRATION:

Trazodone is taken orally. In the United States, trazodone hydrochloride oral tablets are available in strengths of 50, 100, 150, and 300 mg. It can be given after meals to reduce lightheadedness and postural hypotension.

Dosage for major depressive disorder:

Immediate-release formulation: Take 50 to 100 mg orally twice or three times per day. Begin with 25 to 50 mg two or three times per day, then increase by 50 mg every three or four days to a maximum of 400 mg daily for outpatients and 600 mg daily for inpatients. To quit, the dose should be gradually reduced. The research looked at the utilization of trazodone extended-release formulation after intravenous trazodone. They started with an evening dosage of 75 to 150 mg before sleep as a once-a-day extended-release dose. This regimen optimizes its role as an antidepressant, resulting in improved compliance. The dose can be raised every third day, up to 300 mg daily. In hospitalized patients, the dose may be increased to 600 mg per day. The findings of multi-drug regiment trials revealed that combining citalopram and fluoxetine with trazodone had no significant effect on blood levels and no increased risk of headache, sedation, or serotonin syndrome.

CONTRAINDICATIONS:

Patients using monoamine oxidase inhibitors, such as linezolid or intravenous methylene blue, should exercise caution when taking trazodone. MAO inhibitors decrease serotonin metabolism; thus, concomitant dosing raises blood levels of serotonin. To lessen the risk of serotonin syndrome, the patient must be MAOI-free for 14 days before starting therapy with trazodone. Furthermore, using other serotonergic medicines, such as triptans, TCA, or fentanyl, will raise serotonin levels. Trazodone should be used with care in individuals who have poor hepatic and renal function.

DRUG INTERACTIONS:

• CNS depressants: Trazodone may increase the CNS depression caused by alcohol and benzodiazepines, increasing the risk of falls and injury.
• CYP3A4 inhibitors: Reduce the dosage of trazodone owing to enhanced bioavailability. Clarithromycin administration enhanced the exposure, elimination half-life, and peak plasma levels of trazodone. Trazodone also lowers trazodone clearance, raising the risk of adverse effects.
• CYP3A4 Inducers: Carbamazepine, a CYP3A4 inducer, lowers the plasma levels of trazodone.

SIDE EFFECTS:

The common side effects of trazodone include

• Nightmares
• nervousness
• constipation
• vomiting
• nausea
• tiredness
• muscle pain
• dry mouth
• rash

TOXICITY:

Trazadone's hepatic and renal metabolism necessitates extra care for individuals with severe hepatic and renal impairments. While rare, serotonin syndrome can be fatal, manifesting as a combination of mental status changes, neuromuscular abnormalities, and autonomic instability. The initial clinical suspicion ranges from presenting tremor, clonus, or akathisia. The initial steps in treating this disease should be to stop taking serotonergic drugs, stay hydrated, and use anxiolytics to decrease agitation. Certain antidepressants, antibiotics, migraine drugs, antiemetics, and analgesics provide an increased risk. Trazodone administration may cause idiopathic drug-induced liver damage. The normal timescale is three months; however, recorded instances require liver transplantation.