Usage
- Trazodone is primarily prescribed for the treatment of major depressive disorder (MDD). It is also used off-label for insomnia, anxiety, and alcohol dependence.
- Pharmacological Classification: Trazodone is classified as a serotonin antagonist and reuptake inhibitor (SARI).
- Mechanism of Action: Trazodone primarily acts by inhibiting serotonin reuptake, increasing serotonin levels in the synaptic cleft. It also acts as an antagonist at 5-HT2A and 5-HT2C receptors and as an agonist at 5-HT1A receptors. This complex interaction with serotonin receptors contributes to its antidepressant and sedative effects.
Alternate Names
- Trazodone hydrochloride
- Brand Names: Desyrel®, Oleptro®, Trazorel®
How It Works
- Pharmacodynamics: Trazodone’s antidepressant effects are attributed to its SARI properties and receptor binding activities. It affects various neurotransmitters, primarily serotonin, but also histamine and alpha-adrenergic receptors. This combined action helps elevate mood, reduce anxiety, and promote sleep.
- Pharmacokinetics: Trazodone is well-absorbed orally and extensively metabolized in the liver, primarily by the CYP3A4 enzyme. It is eliminated through both renal and hepatic pathways. It reaches steady-state levels in about two days.
- Mode of Action: Trazodone inhibits serotonin reuptake by blocking the serotonin transporter (SERT) and antagonizes 5-HT2A and 5-HT2C receptors. It also acts as a 5-HT1A receptor agonist.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Trazodone inhibits SERT, leading to increased serotonin levels. It antagonizes 5-HT2A and 5-HT2C receptors, and demonstrates some affinity for alpha-adrenergic and histamine H1 receptors.
- Elimination Pathways: Primarily hepatic metabolism (CYP3A4), followed by renal and biliary excretion.
Dosage
Standard Dosage
Adults:
- Depression: Initial dose is 150 mg/day, divided into multiple doses, taken after a meal or light snack. The dose can be increased by 50 mg/day every 3-4 days, as needed, up to a maximum of 400 mg/day for outpatients and 600 mg/day for inpatients.
- Insomnia (off-label): 25-150 mg at bedtime.
- Anxiety: 75-300 mg/day.
Children:
- Trazodone is generally not recommended for children under 18 years old due to limited safety and efficacy data. Some studies suggest dosing based on body weight, but this requires careful consideration and monitoring by a physician.
Special Cases:
- Elderly Patients: Initial dose should be reduced (e.g., 100 mg/day) and increased gradually based on tolerance and response. Doses above 100 mg as a single dose should generally be avoided.
- Patients with Renal Impairment: Caution is advised, particularly in severe renal impairment, but dosage adjustment is not usually required.
- Patients with Hepatic Dysfunction: Caution is recommended, particularly in severe hepatic impairment, due to trazodone’s extensive hepatic metabolism. Liver function monitoring might be considered.
- Patients with Comorbid Conditions: Caution is advised in patients with cardiovascular disease, recent myocardial infarction, a history of priapism, or those taking other medications that prolong the QT interval. Careful consideration should be given to patients with bipolar disorder due to the risk of inducing mania or hypomania.
Clinical Use Cases
Trazodone is not typically indicated for use in clinical situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary use is in the treatment of depression.
Dosage Adjustments
Dose modifications are based on individual response, tolerability, age, and comorbidities. Consider renal and hepatic function, drug interactions, and the potential for drug-induced QT prolongation.
Side Effects
Common Side Effects:
- Drowsiness, dizziness, fatigue
- Headache, blurred vision
- Dry mouth, nausea, constipation
- Orthostatic hypotension
Rare but Serious Side Effects:
- Suicidal thoughts or behavior (especially in young adults)
- Serotonin syndrome (when combined with other serotonergic drugs)
- Cardiac arrhythmias (including QT prolongation)
- Priapism (prolonged erection)
- Severe allergic reactions
Long-Term Effects:
- Potential for withdrawal symptoms upon discontinuation (headache, nausea, and malaise), especially after prolonged use.
- Tolerance to sedative effects can develop over time.
Adverse Drug Reactions (ADR):
- Serotonin syndrome
- Cardiac arrhythmias (QT prolongation)
- Priapism
- Severe allergic reactions (e.g., anaphylaxis)
Contraindications
- Hypersensitivity to trazodone.
- Recent myocardial infarction.
- Concurrent use of MAOIs or within 14 days of stopping MAOIs.
- Alcohol intoxication or concomitant use of hypnotics.
Drug Interactions
- CYP450 Interactions: Trazodone is metabolized by CYP3A4. Inhibitors (e.g., ketoconazole, erythromycin) can increase trazodone levels, while inducers (e.g., rifampin, carbamazepine) can decrease levels.
- Other Interactions:
- Other serotonergic drugs (SSRIs, SNRIs, triptans): Increased risk of serotonin syndrome.
- Drugs that prolong the QT interval (e.g., antiarrhythmics, certain antibiotics): Increased risk of cardiac arrhythmias.
- CNS depressants (e.g., alcohol, benzodiazepines, opioids): Additive sedative effects.
- Antihypertensives: Enhanced hypotensive effects.
- Anticoagulants/antiplatelet drugs: Increased risk of bleeding.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: While there’s no definitive category, data suggests a potential risk, though limited. Close monitoring is needed if used during pregnancy.
- Fetal Risks: Potential for fetal harm, though limited data. Discuss risks and benefits with a physician.
- Breastfeeding: Trazodone passes into breast milk in small amounts. Monitor infants for adverse effects (e.g., drowsiness).
Drug Profile Summary
- Mechanism of Action: SARI, 5-HT2A/2C antagonist, 5-HT1A agonist.
- Side Effects: Drowsiness, dizziness, dry mouth, nausea, orthostatic hypotension. Serious side effects include serotonin syndrome, cardiac arrhythmias, and priapism.
- Contraindications: Hypersensitivity, recent MI, concurrent MAOI use.
- Drug Interactions: CYP3A4 inhibitors/inducers, other serotonergic drugs, QT-prolonging drugs, CNS depressants.
- Pregnancy & Breastfeeding: Potential risks; weigh benefits against risks. Close monitoring is essential.
- Dosage: Adults: 150-400 mg/day (outpatient); up to 600 mg/day (inpatient). Elderly: lower initial dose. Insomnia: 25-150 mg at bedtime. Anxiety: 75-300 mg/day.
- Monitoring Parameters: Blood pressure, heart rate, mental status, liver function tests (if indicated).
Popular Combinations
Trazodone is sometimes combined with other antidepressants (e.g., SSRIs) to address both mood and sleep disturbances in depression, or with benzodiazepines for short-term anxiety relief. However, caution is advised due to potential drug interactions.
Precautions
- General Precautions: Monitor for suicidality, serotonin syndrome, orthostatic hypotension, cardiac effects, and priapism. Screen for bipolar disorder before starting treatment.
- Specific Populations: Pregnancy (assess risk/benefit), breastfeeding (monitor infant), children (not recommended under 18), elderly (lower initial dose), and patients with hepatic/renal impairment (exercise caution).
- Lifestyle Considerations: Avoid alcohol and other CNS depressants. Caution when operating machinery or driving.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Trazodone?
A: Adults: Initially 150 mg/day divided, increasing as needed up to 400 mg/day (outpatients) or 600 mg/day (inpatients), taken after meals. Elderly: Start with a lower dose (e.g., 100 mg/day). Children: Generally not recommended under 18 years. Insomnia (off-label): 25-150mg at bedtime. Anxiety: 75-300 mg/day.
Q2: What are the most common side effects?
A: Drowsiness, dizziness, headache, dry mouth, blurred vision, nausea, constipation, and orthostatic hypotension.
Q3: What are the serious side effects to watch for?
A: Suicidal thoughts/behavior, serotonin syndrome, cardiac arrhythmias (QT prolongation), priapism, and severe allergic reactions.
Q4: What are the contraindications for using Trazodone?
A: Hypersensitivity, concurrent use of MAOIs, recent myocardial infarction, alcohol intoxication or concomitant use of hypnotics.
Q5: How does Trazodone interact with other medications?
A: It can interact with CYP3A4 inhibitors/inducers, other serotonergic medications, QT interval prolonging drugs, CNS depressants, and antihypertensives.
Q6: Can Trazodone be used during pregnancy or breastfeeding?
A: Use with caution during pregnancy and breastfeeding. Potential risks exist; the decision should be made in consultation with a physician, weighing the benefits against potential risks.
Q7: What should patients know about discontinuing Trazodone?
A: Trazodone should be tapered off gradually to avoid potential withdrawal symptoms such as headache, nausea, and malaise.
A: Primarily metabolized by CYP3A4 in the liver and eliminated through both renal and hepatic routes.
Q9: Can Trazodone be used to treat anxiety?
A: While primarily indicated for depression, trazodone is sometimes used off-label to treat anxiety, usually at a lower dose than that used for depression.
Q10: Is trazodone addictive?
A: There is no evidence suggesting that trazodone has addictive properties. However, abrupt discontinuation, especially after long-term use, can lead to withdrawal symptoms.
