Usage
Bupropion + Dextromethorphan Hydrobromide is prescribed for the treatment of major depressive disorder (MDD) in adults.
Pharmacological Classification: Atypical antidepressant; NMDA receptor antagonist and sigma-1 receptor agonist (dextromethorphan), aminoketone antidepressant and CYP2D6 inhibitor (bupropion).
Mechanism of Action: This combination therapy works through multiple pathways. Dextromethorphan acts primarily as an NMDA receptor antagonist, modulating glutamatergic neurotransmission, and also as a sigma-1 receptor agonist. Bupropion is a norepinephrine and dopamine reuptake inhibitor (NDRI) and also inhibits CYP2D6, increasing dextromethorphan levels. The combined effect is thought to enhance the availability of glutamate, potentially improving mood and alleviating depressive symptoms, while also weakly affecting norepinephrine and dopamine levels.
Alternate Names
The combination is not known by any other generic names. It is sometimes abbreviated as DXM/BUP.
Brand Name: Auvelity
How It Works
Pharmacodynamics: Dextromethorphan primarily antagonizes NMDA receptors and agonizes sigma-1 receptors. Bupropion inhibits the reuptake of norepinephrine and dopamine. The combination is believed to primarily work by increasing glutamate availability, possibly influencing neuroplasticity and synaptic function related to mood regulation. Bupropion also contributes through its effects on norepinephrine and dopamine, potentially increasing motivation and reducing anhedonia.
Pharmacokinetics: Both drugs are orally administered and absorbed. Bupropion inhibits CYP2D6, which is the primary enzyme responsible for metabolizing dextromethorphan, resulting in increased dextromethorphan plasma concentrations. Both drugs and their metabolites are primarily eliminated through hepatic metabolism and renal excretion.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Dextromethorphan binds to and antagonizes NMDA receptors and binds to and activates sigma-1 receptors. Bupropion inhibits the reuptake of norepinephrine and dopamine and inhibits CYP2D6.
Elimination Pathways: Both drugs are predominantly metabolized by the liver and excreted through the kidneys.
Dosage
Standard Dosage
Adults:
Initial dose: One tablet (45 mg dextromethorphan hydrobromide and 105 mg bupropion hydrochloride) orally once daily in the morning for 3 days.
Maintenance dose: One tablet twice daily, taken at least 8 hours apart. Do not exceed two tablets per day.
Children:
The safety and efficacy of Auvelity have not been established in pediatric patients. Use is not recommended.
Special Cases:
- Elderly Patients: Clinical trials did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger adults. Close monitoring for adverse effects is recommended.
- Patients with Renal Impairment: Mild renal impairment: No dosage adjustment is required. Moderate renal impairment: Initial and maintenance dose is one tablet once daily in the morning. Severe renal impairment: Use is not recommended.
- Patients with Hepatic Dysfunction: Mild to moderate hepatic impairment: No dosage adjustment is required. Severe hepatic impairment: Use is not recommended.
- Patients with Comorbid Conditions: Carefully consider the patient’s other conditions. Pre-screening for seizure disorders, eating disorders (anorexia nervosa, bulimia), bipolar disorder, and recent discontinuation of alcohol or sedatives/hypnotics is essential due to increased risks. Monitor blood pressure closely, especially in patients with hypertension.
Clinical Use Cases
Auvelity is specifically indicated for MDD and not recommended for clinical use cases like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose modification is necessary when Auvelity is co-administered with strong CYP2D6 inhibitors. In such cases, the initial and maintenance dose should be one tablet once daily in the morning. Concomitant use with strong CYP2B6 inducers should be avoided.
Side Effects
Common Side Effects:
Dizziness, diarrhea, dry mouth, excessive sweating, headache, somnolence, sexual dysfunction (e.g., decreased libido, erectile dysfunction, anorgasmia).
Rare but Serious Side Effects:
Suicidal thoughts and behaviors (especially in young adults), serotonin syndrome, seizures, hypertension, hypersensitivity reactions (e.g., angioedema, Stevens-Johnson syndrome), neuropsychiatric reactions (hallucinations, delusions, paranoia).
Long-Term Effects:
The long-term effects of Auvelity are still being studied. Potential concerns include the development of tolerance, dependence, and chronic adverse effects like sexual dysfunction or cardiovascular issues.
Adverse Drug Reactions (ADR):
Serious ADRs include serotonin syndrome, seizures, severe hypertension, hypersensitivity reactions, and neuropsychiatric reactions. These require immediate medical attention.
Contraindications
- Seizure disorder
- Eating disorder (anorexia nervosa, bulimia)
- Concurrent or recent (within 14 days) use of MAOIs
- Treatment with linezolid or intravenous methylene blue
- Hypersensitivity to dextromethorphan or bupropion
Drug Interactions
Auvelity interacts with many drugs. Significant interactions include:
- MAOIs: Concurrent use is contraindicated due to the risk of hypertensive crisis and serotonin syndrome.
- CYP2D6 Inhibitors: Increase dextromethorphan levels; dose adjustment of Auvelity may be necessary.
- CYP2B6 Inducers: Decrease bupropion and dextromethorphan levels, potentially reducing efficacy.
- Drugs that lower seizure threshold: Increase seizure risk.
- Alcohol: May increase the risk of seizures and other side effects.
- Drugs with serotonergic effects: Increase the risk of serotonin syndrome.
Pregnancy and Breastfeeding
Pregnancy: Auvelity is not recommended during pregnancy due to potential fetal harm. Advise patients to use effective contraception. If pregnancy occurs, discontinue treatment and discuss potential risks with the patient.
Breastfeeding: Breastfeeding is not recommended during treatment and for 5 days after the final dose due to the excretion of bupropion in breast milk.
Drug Profile Summary
- Mechanism of Action: NMDA receptor antagonism, sigma-1 receptor agonism (dextromethorphan), NDRI, CYP2D6 inhibition (bupropion).
- Side Effects: Dizziness, diarrhea, dry mouth, sweating, headache, somnolence, sexual dysfunction. Serious side effects include suicidal thoughts, seizures, serotonin syndrome, hypertension, hypersensitivity reactions.
- Contraindications: Seizure disorder, eating disorders, MAOI use, linezolid or methylene blue treatment, hypersensitivity.
- Drug Interactions: MAOIs, CYP2D6 inhibitors, CYP2B6 inducers, alcohol, serotonergic drugs.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Adults: One tablet daily for 3 days, then one tablet twice daily. Max: 2 tablets/day.
- Monitoring Parameters: Blood pressure, mood changes, suicidal thoughts and behaviors, signs of serotonin syndrome, neuropsychiatric symptoms.
Popular Combinations
Currently, no established popular drug combinations exist for Auvelity due to its relatively recent introduction to clinical practice. Further research and clinical experience will likely reveal potential beneficial combinations over time.
Precautions
- General Precautions: Monitor blood pressure, screen for bipolar disorder, mania, or hypomania, assess for other medications containing bupropion or dextromethorphan.
- Pregnant Women: Avoid use.
- Breastfeeding Mothers: Avoid use.
- Children & Elderly: Not recommended for use in children. Use with caution in the elderly.
- Lifestyle Considerations: Avoid alcohol, discuss smoking cessation strategies. Caution regarding driving or operating machinery due to potential dizziness and somnolence.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Bupropion + Dextromethorphan Hydrobromide (Auvelity)?
A: The initial dose is one tablet daily in the morning for 3 days, followed by a maintenance dose of one tablet twice daily, taken at least 8 hours apart. The maximum dose is two tablets per day.
Q2: What are the common side effects of Auvelity?
A: Common side effects include dizziness, diarrhea, dry mouth, excessive sweating, headache, sleepiness, and sexual dysfunction.
Q3: Is Auvelity safe to use during pregnancy or breastfeeding?
A: No, Auvelity is not recommended during pregnancy or breastfeeding.
Q4: How does Auvelity work differently from other antidepressants?
A: Auvelity combines the mechanisms of an NMDA receptor antagonist (dextromethorphan) and an NDRI (bupropion), offering a multimodal approach to treating MDD.
Q5: Are there any specific contraindications for using Auvelity?
A: Yes. Contraindications include seizure disorders, eating disorders, concurrent or recent MAOI use, treatment with linezolid or intravenous methylene blue, and hypersensitivity to the components.
Q6: What are the signs of a potential adverse drug reaction to Auvelity?
A: Signs of an ADR include suicidal ideation, increased anxiety, manic symptoms, seizures, hypertension, allergic reactions, and serotonin syndrome (e.g., fever, confusion, muscle rigidity). Seek immediate medical attention if these occur.
Q7: How should I manage patients with renal or hepatic impairment who require Auvelity?
A: For moderate renal impairment, the dose should be reduced to one tablet daily. Auvelity is not recommended for severe renal or hepatic impairment.
Q8: Can Auvelity be used in conjunction with other antidepressants?
A: Combining Auvelity with other antidepressants requires careful consideration and monitoring due to potential drug interactions and increased risk of serotonin syndrome. Consult a psychiatrist for guidance in such cases.
Q9: What monitoring is needed during treatment with Auvelity?
A: Monitor blood pressure before and during treatment. Carefully observe for mood changes, suicidal ideation, and neuropsychiatric symptoms, especially early in treatment and after dosage adjustments.
Q10: What patient counseling points are important for Auvelity?
A: Inform patients about common side effects, the risk of suicidal thoughts and behaviors, the importance of avoiding alcohol, potential drug interactions, and the need for regular monitoring. Emphasize that they should not stop taking the medication abruptly.
