Comparing Spravato Vs Auvelity: MOA, Dose, Cost, Side Effects

Spravato (esketamine) and Auvelity (dextromethorphan/bupropion) are two medications approved by the U.S. Food and Drug Administration (FDA) for treating major depression disorder (MDD) in adults.

While they share a common goal, they work differently, are administrated differently, and have distinct approved uses.

This comparison highlights the commonalities and differences between Auvelity and Spravato, providing a detailed overview of their key features.

Comparing these two treatments helps patients and physicians understand how these options differ so that they can determine which one is best for them.

Mechanism of Action:

Auvelity and Spravato affect the brain’s glutamate system but work in different ways, leading to unique effects. Knowing how they work helps explain their differences.

Spravato (esketamine):
- Spravato primarily functions as an NMDA receptor antagonist. These receptors play a key role in learning, memory, and neuronal plasticity [ref].
- Spravato blocks these receptors, which changes glutamate activity. Glutamate is essential for the brain and mood.
- This action notably triggers a rapid increase in glutamate levels in specific brain regions, which is thought to underlie its fast-acting antidepressant effects.
Auvelity (dextromethorphan/bupropion):
Auvelity works in multiple ways by combining the effect of two active components:
- Dextromethorphan:
- - Like Spravato drug, dextromethorphan functions as an NMDA receptor antagonist [ref].
- - However, it serves as a sigma-1 receptor agonist, which is believed to regulate mood, stress response, and cognition [ref].
- - This dual mechanism may play a role in its therapeutic effects [ref].
- Bupropion:
  - Bupropion is a weak inhibitor of dopamine and norepinephrine reuptake, which leads to increased levels of these neurotransmitters in the brain.
  - It also enhances the effects of dextromethorphan, likely by increasing its bioavailability and possibility through other synergistic mechanisms [ref].
  - This combination is believed to be essential for Auvelity’s antidepressant efficacy.

Onset of Action:

Spravato (esketamine):
- One of the unique things about Spravato is how quickly it works. Many people notice major symptoms relief within hours of taking it.
- This fast effect is thought to come from how it directly affects glutamate levels in the brain.
Auvelity (dextromethorphan/bupropion):
- Unlike Spravato, Auvelity has a slower onset of action. Although some people may experience subtle changes sooner, significant antidepressant effects generally appear after about a week.
- This gradual response is more in line with traditional antidepressants, which often need several weeks of consistent use to achieve their full therapeutic effect.

Administration:

How a medication is administered can significantly impact its onset of action, side effects, and overall patient experience. Here’s how Spravato and Auvelity differ:

Spravato (esketamine):
- Spravato is given as a nasal spray that quickly enters the bloodstream through the nose. Because it can cause side effects like dissociation and high blood pressure, it must be given by a healthcare provider in a certified clinic. This helps ensure that any side effects are closely watched and managed.
Auvelity (dextromethorphan/bupropion):
- Auvelity is available as an oral tablet, providing a traditional and convenient administration option that patients can take at home.
- Because Auvelity is taken as a pill and needs to be digested and absorbed, it usually works more slowly than Spravato’s fast-acting nasal spray.

FDA-Approved Uses of Spravato vs Auvelity:

The FDA has approved Spravato and Auvelity for specific indications within the broader scope of Major Depressive Disorder (MDD). These differences show their unique benefits and the particular groups of patients they are meant to help.

Spravato (esketamine):
Spravato has a more specific approval. It is indicated for:
- Treatment-Resistant Depression (TRD):
- - This means it is specifically intended for adults with MDD who have not responded to at least two different antidepressant treatments at adequate duration and doses during the current episode of depression.
- - This differentiation is crucial since it limits the use of Spravato to people who have not found relief from alternative treatments.
- Major Depressive Disorder (MDD) with Suicidal Ideation or Behavior:
  - Spravato is also approved for MDD patients who have suicidal thoughts and behavior.
  - Its fast-acting effect makes it helpful in urgent situations where quick treatment is needed to stabilize the patient and reduce the risk of self-harm [ref].
Auvelity (dextromethorphan/bupropion):
Auvelity has a broader approval but with some key differences; it is approved for:
- Major Depressive Disorder (MDD):
  - This approach applies to a broader spectrum of MDD patients, not limited to those with treatment-resistant depression. It may be used as either a first-line or second-line treatment option.

Side Effects of Spravato vs Auvelity:

All medication comes with the risk of side effects. Here is a closer examination of the side effect profiles of Spravato and Auvelity:

Spravato (esketamine):
- Spravato has a more notable side effect profile that necessitates careful management, primarily because of its mechanism of action. The main side effects include:
Dissociation:
- A frequent side effect characterized by a sense of detachment from oneself, the surrounding environment, or the passage of time [ref]. Sedation: Drowsiness and fatigue are common side effects.
Increased Blood Pressure:
- Sparavato can temporarily raise blood pressure, so monitoring is necessary during and after administration to stay safe.
Additional possible side effects of Spravato may include vomiting, dizziness, nausea, headache, and anxiety.
Auvelity (dextromethorphan/bupropion):
Auvelity has a more manageable side effect profile. Commonly reported side effects are:
- Dizziness and mild nausea.
- Headache
- Constipation
- Dry mouth
- Insomnia and anxiety.

Dosing and Frequency

The timing and frequency of dosing play a critical role in determining the effectiveness of treatment and patient adherence.

Spravato (esketamine): Spravato is given in a healthcare setting following a specific dosing schedule.
- Initial Treatment: During the first month, Spravato is typically given twice a month.
- Maintenance Treatment: After the first month, the administration frequency is typically reduced to weekly or every other week, depending on the patient’s response and tolerance [ref].
Auvelity (dextromethorphan/bupropion): Auvelity’s dosing regimen is more straightforward and intended for at-home use.
- The standard dosage is one tablet twice daily, ensuring at least an 8-hour interval between doses.
- Many oral antidepressants follow a similar consistent daily dose schedule

Cost of Spravato vs Auvelity:

Spravato (esketamine):
- It is considerably more expensive, with monthly treatment costs ranging from $2,500 to $7,500. This high cost is due to the price of the medication itself, the need for administration in a medical setting, and the required monitoring. Insurance coverage for Spravato varies significantly.
Auvelity (dextromethorphan/bupropion):
- Auvelity is a more affordable option. The cost for a 30-tablet supply (150mg-45mg) is approximately $623.91.
- However, prices may fluctuate, and insurance coverage will influence individual out-of-pocket expenses.

Which is Better: Spravato or Auvelity?

Spravato and Auvelity each have distinct advantages and disadvantages, making the ideal choice dependent on the individual patient’s specific needs.

Spravato provides rapid relief, which is beneficial for severe depression or suicidal ideation. Still, it requires administration in a medical setting and has a higher risk of side effects, such as dissociation.

Auvelity is more convenient, taken orally at home, and has a more favorable effect profile but has a slower onset of action.

This medication is more suitable for patients who can tolerate a delayed response and do not require immediate relief.

The choice between Auvelity and Spravato should be guided by a healthcare professional’s evaluation of the patient’s unique needs, medical history, and individual risk factors.