How to manage a patient with Functional Neurological Disorder (FND) dissociation episodes who is taking Auvelity (dextromethorphan/bupropion)?

Managing FND Dissociation Episodes in Patients Taking Auvelity

Auvelity should be used with extreme caution or discontinued in patients with FND experiencing dissociation episodes, as the dextromethorphan component may theoretically worsen dissociative states, and the bupropion component carries seizure risk that could be problematic in patients with altered consciousness during dissociative episodes.

Understanding the Core Problem

The combination of Auvelity (dextromethorphan-bupropion) and FND dissociation creates a complex clinical scenario:

• Dextromethorphan acts as an NMDA receptor antagonist, which is the same mechanism by which dissociative anesthetics like ketamine produce dissociative states 1, 2
• Patients with FND demonstrate elevated baseline dissociation susceptibility and experience significantly greater dissociative responses to triggers compared to healthy controls 3
• Bupropion lowers seizure threshold, and dissociative episodes in FND can sometimes be difficult to distinguish from non-epileptic seizures, creating diagnostic and safety concerns 4

Immediate Assessment Algorithm

When a patient on Auvelity presents with dissociation episodes, evaluate:

• Temporal relationship: Did dissociation episodes begin or worsen after starting Auvelity? If symptoms emerged within 2-8 weeks of initiation, the medication is more likely contributory 1, 5
• Severity of dissociative symptoms: Patients with FND show impaired interoceptive accuracy during acute dissociation, meaning they lose awareness of internal bodily states, which can be dangerous 3
• Presence of seizure-like activity: Bupropion-containing medications should be avoided in patients with seizure disorders and used with extreme caution in those at risk 4

Management Strategy

If Dissociation Episodes Are Mild and Infrequent

Continue Auvelity only if the antidepressant benefit clearly outweighs risks, with these modifications:

• Reduce to lowest effective dose (one tablet twice daily rather than two tablets twice daily) to minimize dextromethorphan exposure 4, 5
• Implement structured monitoring: Have patient track dissociation frequency, duration, and triggers in a daily log 4
• Initiate concurrent FND-specific speech and language therapy focused on grounding techniques and symptom education, as early intervention is crucial even when other symptoms are present 4

If Dissociation Episodes Are Moderate to Severe

Discontinue Auvelity and transition to an alternative antidepressant that does not have dissociative properties:

• Switch to bupropion monotherapy (without dextromethorphan) if the patient had good response to the antidepressant effects, as bupropion alone does not have NMDA antagonist properties 4, 2
• Consider SSRIs or SNRIs as alternatives, though these lack the rapid onset seen with Auvelity 1, 2
• Avoid other NMDA antagonists including memantine, ketamine, or high-dose dextromethorphan products 4

Critical Safety Considerations

Monitor for drug-drug interactions that could worsen dissociation:

• Avoid concurrent use of three or more CNS-active agents (antidepressants, antipsychotics, benzodiazepines, antiepileptics, opioids), as this combination increases fall risk and could exacerbate dissociative states 4
• The dextromethorphan-quinidine combination should be used with extreme caution in patients with behavioral symptoms, as it increases fall risk and drug interactions—this same caution applies to dextromethorphan-bupropion 4
• Be aware that Auvelity carries a boxed warning for suicidal thoughts in young adults, and dissociative episodes may mask or complicate assessment of suicidality 5

FND-Specific Therapeutic Interventions

Regardless of medication decisions, implement evidence-based FND management:

• Provide clear positive diagnosis explanation: Explain that dissociation in FND represents "a software problem, not hardware problem" where the brain has difficulty integrating sensory and motor signals, particularly during stress 4
• Demonstrate inconsistency of symptoms: Show the patient how dissociative symptoms may resolve during distraction, automatic tasks, or when attention is diverted—this is a positive diagnostic feature, not evidence of malingering 4
• Address perpetuating factors: Hypervigilance, excessive self-monitoring, and belief that symptoms indicate damage all worsen dissociation in FND 4

Common Pitfalls to Avoid

• Do not assume dissociation is purely psychiatric: Patients with FND have measurable neurophysiological changes including altered brain network connectivity and reduced heart rate variability during dissociative states 3, 6
• Do not continue Auvelity "to see if it improves" when dissociation is severe—the NMDA antagonist properties of dextromethorphan provide a plausible mechanism for worsening dissociation 1, 3
• Do not abruptly stop Auvelity without a transition plan: Taper gradually and have alternative antidepressant therapy ready, as depression itself can worsen FND symptoms 4, 5

When Auvelity May Be Continued

The only scenario where continuing Auvelity is reasonable:

• Dissociation episodes clearly predate Auvelity initiation by months to years, with no worsening after starting medication 3
• Patient has achieved remission of depression (which occurred in ~70% of long-term users), and depression was a major perpetuating factor for FND 1
• Patient is engaged in active FND-specific therapy with demonstrated improvement in dissociative symptoms despite continuing medication 4