Trazodone

Antidepressant Drug

Drug class: Atypical Antidepressants

Trazodone (TRITTICO)（中文：曲唑酮）

Pronunciation

Trazodone 50mg

Common Strengths of Trazodone

Trazodone are available in the following strengths:

• 50 mg, 75 mg, 100 mg, 150 mg

Drug Trade Names of Trazodone

• Trittico
• Desyrel

Drug Usage

• Major depressive disorder (MDD)
• Off-label uses: Anxiety, insomnia, alcohol dependence

Mechanism of Action

Trazodone is a serotonin antagonist and reuptake inhibitor (SARI). It works by:

• Antagonizing 5-HT_2A receptors
• Inhibiting serotonin reuptake
• Blocking histamine H1 and α1-adrenergic receptors

Route of Administration

Oral

Dosages

• Major depressive disorder (MDD):
  • Initial: 150 mg/day in divided doses
  • Maintenance: 150-400 mg/day
  • Maximum: 400 mg/day (outpatients), 600 mg/day (inpatients)

Trazodone can be used in patients with renal impairment without specific adjustments, careful monitoring and cautious titration are advised to ensure safety and efficacy.

Side Effects

Frequency	Adverse reactions
Common	Drowsiness or Fatigue: Especially when starting the medication. This effect may lesson over time.
	Dry Mouth: This can often be managed with sugar-free gum or candies.
	Nausea: This can sometimes be alleviated by taking trazodone with food.
	Headaches: Staying hydrated may help mitigate this side effect.
	Constipation: Increasing dietary fiber and fluid intake is recommended.
	Dizziness: Particularly when standing up quickly, which is related to orthostatic hypotension (a drop in blood pressure upon standing).
	Blurred Vision
	Weight Change: This can lead to either weight gain or loss, depending on the individual.
	Sexual Dysfunction: This may include problems with ejaculation or changes in libido.
Serious	Require immediate medical attention
	Priapism: A prolonged and painful erection that can cause permanent damage if not treated promptly.
	Serotonin Syndrome: A potentially life-threatening condition characterized by symptoms such as confusion, rapid hearbeat, and muscle rigidity, especially if taken with other serotonergic drugs.
	Allergic Reactions: Symptoms may include swelling of the face, lips, or throat, difficulty breathing, and hives.
	Suicidal Thoughts: Increased risk of suicidal ideation, particularly in young adults and adolescents, especially during the initial treatment phase or when doses are changed.
	Trazodone can cause QT prolongation, which may lead to serious heart arrhythmia.
	Unexplained Bruising or Bleeding-Confusion, tremor, skin reactions.

Pharmacokinetics

• Peak plasma concentration is typically reached within 1 to 2 hours when taken on an empty stomach. However, food can affect its absorption and a delay in the time to peak concentration.
• Extensive metabolism in the liver by the enzyme CYP3A4.
• The elimination half-life of trazodone varies between 5 to 9 hours. The half-life can be prolonged in elderly individuals.
• Excretion: Approximately 70% to 75% of trazodone is excreted in urine and about 21% is eliminated via feces.

Onset of Action:

• For Insomnia: Trazodone can start to exert its sedative effects within 30 minutes to 2 hours after oral administration.
• For Depression and Anxiety: The onset for these conditions is slower, typically taking 1 to 2 weeks to begin noticing effects, with full therapeutic benefits often taking 4 to 6 weeks to manifest.

Drug Precautions

Pregnancy

Use with caution; potential risks to the fetus

Breastfeeding

Use with caution; trazodone is excreted in breast milk

Children and Elderly

• Not recommended for children under 18 for depression
• Elderly may require lower doses due to decreased clearance

Monitoring Requirements

• Signs of suicidal thoughts or behaviors
• Blood pressure
• Liver function
• Signs of serotonin syndrome

Drug Inetractions

• Serotonergic Drugs: Combining trazodone with other medications that increase serotonin levels can lead to serotonin syndrome, a potentially life-threatening condition. This includes:
  • Buspirone
  • Fentanyl
  • Lithium
  • St.John's Wort
  • Triptans (e.e. simatriptan, zolmitriptan)

• CNS Depressants: Trazodone can enhance the sedative effects of other central nervous system depressants, such as:
  • Benzodiazepines (e.g. lorazepam, alprazolam)
  • Alcohol
  • Opioids (e.g. hydrocodone, oxycodone)

• Antidepressants: Caution is advised when combining trazodone with other antidepressants, especially SSRIs and SNRIs, as this can increase the risk of serotonin syndrome.

• Anticoagulants and Antiplatelet Drugs: Trazodone may increase the risk of bleeding when taken with:
  • Warfarin
  • NSAIDs
  • Aspirin

• CYP4A4 Inhibitors and Inducers: Trazodone is metabolized by the CYP3A4 enzyme, so drugs that inhibit or induce this enzyme can ater trazodone levels. For example:
  • Inhibitors (e.g. ketoconazole) may increase trazodone levels, necessitating a dose reduction
  • Inducers (e.g. rifampin) may decrease trazodone levels, potentially requiring an increase in dosage.

FAQ

How Should I Take the Tablet?

Take the tablets shortly after a meal or light snack. Tablets can be swallowed whole or broken in half along the score line. Do not crush or chew.

What Should I Avoid While Taking?

Avoid alcohol and operating heavy machinery until you know how trazodone affects you.

What Happens if I Miss a Dose?

Take the missed dose as soon as you remember unless it is almost time for your next dose. Do not doule doses.