For patients battling major depressive disorder (MDD), finding the right medication can be a complex and often frustrating journey. Auvelity, a newer drug, has emerged as a promising treatment option. It combines dextromethorphan and bupropion to target different brain pathways involved in mood regulation. However, understanding auvelity side effects, dosage guidelines, and mechanisms is crucial for ensuring its safe and successful use. This guide includes Auvelity’s potential benefits, risks, and management strategies.

What is Auvelity?

Primarily used for the treatment of major depressive disorder, Auvelity is a combination medication. It contains two active ingredients:

• Dextromethorphan: An NMDA receptor antagonist that modulates neurotransmitter systems (serotonin, norepinephrine, and dopamine).
• Bupropion: A norepinephrine-dopamine reuptake inhibitor (NDRI), which works by increasing the availability of dopamine and norepinephrine in the brain, contributing to mood regulation.

How Does Auvelity Work?

Auvelity’s mechanism of action is unique because it combines the effects of both dextromethorphan and bupropion. Dextromethorphan helps regulate glutamate activity (a key neurotransmitter involved in mood and cognition), while bupropion increases dopamine and norepinephrine availability, which are key neurotransmitters associated with feelings of well-being and motivation.

• Enzymes involved: Bupropion is metabolized by CYP2B6, and Dextromethorphan by CYP2D6. Genetic variations in these enzymes can influence how quickly or slowly a person metabolizes the medication, which is why pharmacogenomic testing is recommended for personalized dosing.

Starting and Adjusting the Dose

Dosage Guidelines are crucial for minimising side effects and ensuring therapeutic effectiveness.

1. Initial Dose:

The starting dose is typically 45 mg of dextromethorphan and 105 mg of bupropion, taken once daily. Starting low helps the body adjust and minimizes side effects.

2. Dose Adjustment:

If the patient tolerates the medication well, then after 3 days, the dose may be increased by administering the same dosage twice a day. The maximum recommended dose is 105 mg dextromethorphan and 240 mg bupropion.

3. Gradual Dose Increase:

A gradual increase in dose helps reduce common side effects like nausea, dizziness, and insomnia, and ensures that the treatment is better tolerated.

 

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Side Effects of Auvelity: An Overview

Although Auvelity does not show side effects quite often, like any other medication, it can still show some side effects. These can be broken down into common, rare, and extremely rare categories.

Common Side Effects

• Dizziness
• Headaches
• Dry mouth
• Nausea and vomiting
• Fatigue
• Insomnia or vivid dreams
• Increased anxiety or nervousness

Duration: Most of the Auvelity side effects are temporary. As the body adjusts to the medication, they tend to decrease within 2-3 weeks.

Sexual Side Effects

Both men and women may experience sexual dysfunction. These include:

• Decreased libido
• Erectile dysfunction (for men)
• Delayed orgasm or anorgasmia

These side effects may persist for the duration of treatment but can often improve over time or with dosage adjustments. If these effects are bothersome, discuss potential alternatives with a healthcare provider.

Rare and Extremely Rare Side Effects

• Seizures (particularly at high doses or in susceptible individuals)
• Serotonin syndrome which presents as agitation, confusion, high blood pressure, and rapid heart rate.
• Severe allergic reactions, such as rashes or difficulty breathing.

Critical Side Effects and Their Management

While most patients tolerate Auvelity well, it is important to recognize and manage critical side effects, including:

1. Seizures:

With symptoms such as sudden loss of consciousness, muscle spasms, and jerking movements, seizures may be experienced, especially at high doses. If a seizure occurs, discontinue the medication immediately and seek medical attention.

2. Suicidal Thoughts:

Especially in young adults, there may be an increased risk of suicidal thoughts or behaviours in the first few weeks of treatment. Patients should be closely monitored for any mood changes or signs of worsening depression.

3. Serotonin Syndrome:

This rare but serious condition requires immediate medical intervention. Symptoms include agitation, confusion, rapid heart rate, and muscle rigidity.

Who Is at Greater Risk of Side Effects?

Some patients are at higher risk of experiencing adverse effects with Auvelity. These include:

• History of seizures: Due to the seizure risk associated with bupropion, this medication should be used cautiously or avoided in individuals with a history of seizures.
• Those with eating disorders: These conditions increase the risk of seizures.
• Patients with liver impairment: Bupropion and dextromethorphan are metabolised by the liver, and reduced liver function can increase the risk of side effects.
• Alcohol use disorder: Increased risk of seizures and other serious side effects, especially when combined with alcohol.

Managing Side Effects of Auvelity and Minimising Risk

To minimize the risk of side effects, the following strategies can be employed:

1. Pharmacogenomic Testing:

Testing can help identify how well a patient metabolizes the medication and allow for tailored dosing. This is especially helpful for patients with genetic variations in CYP2B6 or CYP2D6, which affect drug metabolism.

2. Gradual Dose Escalation:

Starting with a low dose and increasing gradually helps reduce the risk of side effects such as dizziness, nausea, and insomnia.

3. Monitoring:

Regular follow-up visits are essential to monitor for potential side effects, especially during the initial weeks of treatment.

4. Avoiding Alcohol:

Alcohol should be avoided as it can exacerbate side effects like dizziness and increase the risk of seizures.

Conclusion

Auvelity offers an innovative approach to treating major depressive disorder, but its side effects—including sexual dysfunction, seizures, and serotonin syndrome—require careful management. By starting with a low dose, utilising pharmacogenomic testing, and following gradual dose adjustments, doctors can help ensure that patients receive the maximum benefit from the medication while minimizing risk. Regular monitoring, especially in high-risk patients, is crucial for safe and effective treatment.

Disclaimer: This blog is only for informational purposes. Always consult a healthcare specialist before taking any medical action.