Can Auvelity Cause Psychosis?
Yes, Auvelity (dextromethorphan/bupropion) can cause psychosis, and this risk is explicitly documented in the FDA drug label, which warns that patients treated with bupropion have experienced delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion. 1
FDA-Documented Psychiatric Risks
The FDA label for dextromethorphan-bupropion specifically states that depressed patients treated with this medication have had a variety of neuropsychiatric signs and symptoms, including:
In some cases, these symptoms resolved with dose reduction and/or withdrawal of treatment, and patients should be instructed to contact a healthcare professional if such reactions occur. 1
Mechanism and Component-Specific Risks
Dextromethorphan Component
Dextromethorphan itself carries documented risk for psychotic symptoms, particularly when combined with stimulants. 2 The combination of dextromethorphan with other agents can cause psychosis and manic-like symptoms, with risk substantially amplified when stimulants are combined. 2
Bupropion Component
Bupropion monotherapy has been linked to rare instances of psychosis, especially in patients with risk factors like substance use, older age, or history of head trauma. 3 Case reports document bupropion-induced psychotic episodes with persecutory delusions that resolved within one week after discontinuation and addition of antipsychotic medication. 3
The dopaminergic effects of bupropion are the primary mechanism underlying its ability to induce psychosis. 3
Activation of Mania/Hypomania
The FDA label explicitly warns that antidepressant treatment with bupropion can precipitate a manic, mixed, or hypomanic episode, with increased risk in patients with bipolar disorder or risk factors for bipolar disorder. 1
Prior to initiating Auvelity, screen patients for:
- History of bipolar disorder 1
- Family history of bipolar disorder 1
- Family history of suicide or depression 1
Clinical Management Algorithm
If Psychosis Develops:
Immediately discontinue Auvelity - This is the first-line intervention for suspected drug-induced psychosis. 2
Consider short-term antipsychotic therapy - Although there are no formal guidelines, case reports demonstrate that antipsychotics such as risperidone have been helpful in reversing bupropion-induced psychosis after discontinuation. 3
Monitor for resolution - Substance-induced psychosis typically resolves within a certain period after discontinuation of the offending agent. 2
Dose-Related Considerations:
Some patients experienced symptom resolution with dose reduction rather than complete discontinuation. 1 However, given the severity of psychotic symptoms, complete discontinuation is the safer initial approach.
Risk Factors to Consider
Patients at higher risk for psychosis with Auvelity include those with:
- Pre-existing psychiatric conditions (psychotic disorders, bipolar disorder, anxiety disorders) 2
- History of substance use 3
- Older age 3
- History of head trauma 3
- Some patients with a diagnosis of bipolar disorder have experienced these symptoms 1
Critical Clinical Pitfall
Do not assume psychotic symptoms are simply worsening depression or a new primary psychiatric disorder without first considering medication-induced psychosis. The FDA label notes that some patients who developed these symptoms had a diagnosis of bipolar disorder, suggesting the medication may unmask or precipitate underlying vulnerability. 1
Patient Education
Instruct patients to immediately contact a healthcare professional if they experience: