Can Auvelity (dextromethorphan and bupropion) be used to treat panic attacks in a patient with major depressive disorder?

Auvelity for Panic Attacks: Not Indicated

Auvelity (dextromethorphan-bupropion) is not approved or recommended for panic attacks. This combination is FDA-approved exclusively for major depressive disorder in adults, and neither component has established efficacy for panic disorder 1, 2.

Why Auvelity Is Not Appropriate for Panic Attacks

Lack of Evidence for Panic Disorder

• Auvelity's clinical trials evaluated only major depressive disorder outcomes using the Montgomery-Åsberg Depression Rating Scale, with no assessment of panic symptoms or panic disorder 1, 3.
• Real-world data from 22,288 patients treated with Auvelity show it was prescribed for MDD, with 53.5% having comorbid mental health disorders including anxiety—but panic disorder was not specifically studied 4.

Bupropion's Anxiogenic Properties

• Bupropion can provoke or worsen anxiety symptoms, particularly at higher doses, due to its stimulating norepinephrine and dopamine reuptake inhibition 5.
• Clinical trials suggest bupropion may reduce anxiety only in the context of comorbid depression with mild-to-moderate anxiety, not for primary anxiety disorders like panic disorder 5.
• The activating properties of bupropion make it contraindicated in highly agitated patients and require careful monitoring for worsening anxiety 6.

Mechanism of Action Mismatch

• Auvelity works through NMDA receptor antagonism (dextromethorphan) and norepinephrine-dopamine reuptake inhibition (bupropion), neither of which targets the serotonergic pathways that are first-line for panic disorder 1, 2.

What Should Be Used Instead

First-Line Treatment for Panic Attacks

• SSRIs (sertraline, fluoxetine, paroxetine, escitalopram) are the established first-line pharmacologic treatment for panic disorder 7.
• Sertraline 50–200 mg daily is particularly preferred due to its optimal balance of efficacy, safety, and lower risk of QTc prolongation compared to other SSRIs 7.
• All SSRIs demonstrate equivalent efficacy for panic disorder, with treatment duration of 4–9 months minimum after satisfactory response 7.

Treatment Algorithm for Panic Disorder

1. Start sertraline 25–50 mg daily (use 25 mg in highly anxious patients to minimize initial activation) 7.
2. Titrate in 50 mg increments every 1–2 weeks up to 200 mg daily as needed 7.
3. Allow 6–8 weeks for adequate trial, including at least 2 weeks at maximum tolerated dose 7.
4. Add cognitive-behavioral therapy (CBT), as combination treatment is superior to either modality alone for panic disorder 7.
5. If inadequate response after 6–8 weeks at therapeutic doses, switch to another SSRI (escitalopram, fluoxetine) or venlafaxine XR 7.

Critical Safety Monitoring

• Monitor for treatment-emergent suicidality during the first 1–2 weeks, especially in patients under 24 years (FDA black box warning applies to all SSRIs) 7.
• Initial activation symptoms (heightened anxiety, restlessness) may occur with SSRIs but typically resolve within 2–4 weeks; temporary dose reduction can mitigate these effects 7.

When Auvelity Might Be Considered (But Not for Panic)

• Auvelity is appropriate only for major depressive disorder in adults, showing significant MADRS score reductions within 2 weeks and remission rates approaching 70% in long-term studies 1, 3.
• If a patient has both MDD and panic disorder, treat the panic disorder with an SSRI first, as addressing depression often improves comorbid anxiety symptoms 7.
• Auvelity could theoretically be added later if depression persists despite SSRI treatment, but this would be off-label for the panic component and requires monitoring for worsening anxiety 2, 5.

Common Pitfalls to Avoid

• Do not use bupropion-containing medications (including Auvelity) as first-line treatment for any primary anxiety disorder, as the stimulating properties can exacerbate panic symptoms 5.
• Do not discontinue SSRIs prematurely before 6–8 weeks, as full response may take this long; partial response at 4 weeks warrants continued treatment, not switching 7.
• Do not combine Auvelity with MAOIs due to serotonin syndrome risk from the bupropion component 6.