Dextromethorphan Bupropion Combination Tablet Suicide Attempt by Overdose: A Case Report

ABSTRACT

Dextromethorphan and bupropion in combination are approved to treat major depressive disorders in adults. This case report describes a patient with a history of treatment‐resistant depression who presented to the emergency department after overdosing on approximately 30 tablets of dextromethorphan‐bupropion 45–105 mg in a suicide attempt. The patient required intubation, gastrointestinal decontamination, and changes in her antidepressant medications. The patient reported no suicidality by the end of her hospitalization, and she was discharged on paroxetine 40 mg daily and quetiapine 200 mg at night. Clinicians should be cautious and vigilant when prescribing or considering these medications together, particularly in populations at risk of overdose.

Dextromethorphan and bupropion in combination are approved to treat major depressive disorders in adults. This case report describes a patient with a history of treatment‐resistant depression who presented to the emergency department after overdosing on approximately 30 tablets of dextromethorphan‐bupropion 45–105 mg in a suicide attempt. The patient required intubation, gastrointestinal decontamination, and changes in her antidepressant medications. The patient reported no suicidality by the end of her hospitalization, and she was discharged on paroxetine 40 mg daily and quetiapine 200 mg at night. Clinicians should be cautious and vigilant when prescribing or considering these medications together, particularly in populations at risk of overdose.

1. Introduction

The recommended initial treatment of depression in adults consists of psychotherapy and medications such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), bupropion, mirtazapine, trazodone, vilazodone, or vortioxetine [1, 2]. The first‐line medications primarily work by increasing the effects of monoamines, including serotonin, norepinephrine, and dopamine. Approximately 50% of patients respond to a first‐line antidepressant medication [3], and it is estimated that 30% of patients fail at least two antidepressants and therefore meet the criteria for treatment‐resistant depression [4]. New mechanisms to treat depression are of importance based on the prevalence of inadequate response to standard treatments. Combination treatments from agents of different medication classes are options in the treatment of major depressive disorder (MDD).

The FDA approved an extended‐release combination of dextromethorphan and bupropion in 2022 for the treatment of major depressive disorder in adults. Dextromethorphan is an N‐methyl D‐aspartate (NMDA) receptor antagonist and sigma‐1 receptor agonist, and bupropion is a norepinephrine and dopamine reuptake inhibitor. The novel mechanism differs from first‐line treatment options and presents an alternative option in the treatment of MDD. Additionally, dextromethorphan has a short half‐life of approximately 4 h, limiting its use as monotherapy in the treatment of MDD, but bupropion is a CYP2D6 inhibitor, which increases dextromethorphan's half‐life to 22 h [5]. Little evidence is available on overdoses of the combination. One case report describes an instance where a 22‐year‐old male intentionally ingested four dextromethorphan‐bupropion 45 mg–105 mg extended‐release tablets in an attempt to get high and then experienced visual and auditory hallucinations and slurred speech. Dextromethorphan and its metabolite, dextrorphan, act as NMDA receptor antagonists, with dextrorphan being more potent and likely responsible for the majority of the psychoactive effects [6]. Another case report describes a 20‐year‐old male with a history of depression who overdosed on a reported one bottle of dextromethorphan‐bupropion 45 mg–105 mg extended‐release tablets. Additionally, citalopram was present on chromatography analysis. The patient had a seizure upon arrival and was treated with lorazepam, followed by cyproheptadine and levetiracetam. The patient was later intubated and discharged to psychiatry [7].

Though little evidence is available on overdoses of this combination, stronger guidance is available for overdoses on dextromethorphan and bupropion separately. Treatment for both includes supportive care, given the lack of an antidote. Dextromethorphan toxicity treatment also includes activated charcoal if the patient presents within 1 h of overdose. Agitated patients may require benzodiazepines or physical restraints, and naloxone may be used to treat respiratory depression. Patients presenting with dextromethorphan‐induced hyperthermia can be managed with active cooling methods to address hyperthermia [8]. Bupropion overdose can be treated in multiple ways. Physical exam findings of patients presenting with a bupropion overdose are variable and may be non‐specific. Benzodiazepines or barbiturates can be used to treat seizures. Severe, life‐threatening overdoses may require anti‐epileptics in patients that present with seizures, anti‐arrhythmics for patients presenting with life‐threatening arrhythmias, and vasopressor support, and intravenous lipid emulsion (ILE) to treat cardiogenic shock [9].

2. Case Report

A 52‐year‐old female was brought into the emergency department (ED) following an intentional overdose of an estimated 30 tablets of dextromethorphan‐bupropion 45–105 mg. The patient's psychiatric history is as follows. She reported taking paroxetine with good effect for nearly 20 years. The medication stopped working for her in 2023, and multiple medications were trialed. The patient remembers trialing fluoxetine, bupropion, vortioxetine, adjunctive brexpiprazole, adjunctive quetiapine, and esketamine nasal spray. Additionally, the patient reports receiving eight sessions of transcranial magnetic stimulation. The patient lost her job in 2024, and depression continued to worsen since that time. The patient does report previous suicide attempts. She had overdosed on bupropion, attempted carbon monoxide poisoning through car exhaust, and cut her wrists.

The patient was transported to the emergency department via emergency medical services. Initially, she was noted to be lethargic but was still responsive to questions. The patient then had one episode of vomiting, with pill fragments seen in the vomitus, and was subsequently intubated for airway protection. Gastric lavage was attempted in the ED with poor return of gastric content. Poison control was then consulted and recommended gastrointestinal decontamination with activated charcoal and whole bowel irrigation. The patient received 50 g of activated charcoal, and whole bowel irrigation was initiated with polyethylene glycol. She tolerated approximately 500 mL of polyethylene glycol via NG tube; however, due to regurgitation, further irrigation was held. She remained hemodynamically stable throughout her care in the ED.

The patient remained stable upon arrival to the intensive care unit (ICU). Acetaminophen, alcohol, and salicylate levels were all negative. The patient's urine drug screen resulted and was positive for phencyclidine (PCP) and opiates; however, it is unclear if the patient received opiates in the field prior to intubation. Given the risk for seizures with large doses of bupropion, neurology was consulted and recommended frequent neurological checks and electroencephalogram (EEG) monitoring. Both remained negative, and subsequently, the patient did not receive any antiepileptics. The patient remained on propofol until arrival to the ICU and was then switched to low infusion rates of fentanyl and dexmedetomidine. The patient was maintained at a Richmond Agitation Sedation Scale (RASS) of 0 to −1 and had a negative Confusion Assessment Method for the ICU (CAM‐ICU), exhibiting no signs of agitation or hallucinations. The patient had minimal ventilator requirements: positive end expiratory pressure (PEEP) of 5 cm H₂O and fraction of inspired oxygen (FiO₂) of 40%. An attempt was made to extubate her on Day 1 of hospitalization; however, the patient had a negative cuff leak, was given one dose of dexamethasone 6 mg IV, and was successfully extubated on Day 2. Daily electrocardiograms (EKGs) were done during her ICU stay, which showed a QTc and QRS within normal limits, and the patient was not tachycardic or hypertensive. Behavioral health was consulted on Day 4 of hospitalization. Behavioral health recommended holding psychiatric medications, and the patient was medically cleared for transfer outside of the ICU. Prior to transfer to behavioral health, the internal medicine team started quetiapine 25 mg twice daily due to anxiety.

The patient was transferred to inpatient psychiatry on Day 6 of admission with a psychiatric diagnosis of major depressive disorder, recurrent, severe. The patient presented to the psychiatric unit on quetiapine 25 mg twice daily, which was increased to 100 mg at night. The patient was also placed on one‐to‐one observation due to continued suicidal ideation. On Day 7 of admission, the patient stated that she wished she did not wake up from her suicide attempt, asked to leave the unit, and began to sob. Nursing staff attempted verbal de‐escalation; however, as the patient became more agitated, she was administered haloperidol 5 mg, diphenhydramine 50 mg, and midazolam 2 mg intramuscularly. The patient responded well to the medication. The pharmacist on the unit discussed potential treatment options for major depressive disorder with the patient. The patient stated that she would like to retry paroxetine, as she was stable on this medication for 20 years. Additionally, the patient reported that she was only taking dextromethorphan‐bupropion 45–105 mg once daily and did not increase to twice daily after 3 days. The recommendation was discussed with the psychiatrist, who agreed to start paroxetine 20 mg daily. Quetiapine was further increased to 200 mg at night. On Day 8, the patient remained depressed and on one‐to‐one observation. On Days 9 and 10, the patient appeared brighter, was tolerating her medications, and denied thoughts of hurting herself. One‐to‐one observation was discontinued. The paroxetine dose was increased to 40 mg daily on Day 11. The medications remained the same on Days 12 and 13, and the patient was discharged to her sister with plans to return to a previous intensive outpatient program and to continue transcranial magnetic stimulation treatments in addition to continuing paroxetine 40 mg daily and quetiapine 200 mg at night (Figure 1).

FIGURE 1.

Psychiatric medication timeline.

3. Discussion

Medications with new and novel mechanisms of action are important to investigate in the treatment of MDD. A significant concern in this patient population is the risk of suicidality and suicide attempts, and it is essential to evaluate the overdose risks of all antidepressants. For instance, medications with higher overdose dangers, such as tricyclic antidepressants, have largely been replaced by alternatives like SSRIs. Similarly, examining the safety of dextromethorphan‐bupropion in overdose situations is also important. One study in adolescent patients found that bupropion overdose was associated with an increased risk of death over those exposed to SSRIs (0.23% vs. 0%; p < 0.001) [10]. Additionally, there were eight reported deaths from bupropion in 2020 [11].

Dextromethorphan can also be fatal in overdose. A 2009 report highlights five teenage males who fatally overdosed on dextromethorphan after ingesting large amounts for recreational purposes [12]. Additional case reports show the potential dangers of dextromethorphan in overdose [13, 14]. The patient was also positive for PCP, which may have been due to the dextromethorphan component of the combination as false positives have been reported [15]. Dextromethorphan and PCP are both NMDA antagonists with some structural similarities highlighting the importance of analyzing the drug screen in toxicology patients.

Additionally, bupropion overdose may present with major adverse reactions such as seizures including status epilepticus, life‐threatening arrhythmias, and cardiogenic shock [16, 17]. Seizures should be managed in accordance with the available guidelines utilizing benzodiazepines and anti‐epileptics. Patients presenting with arrhythmias, if life‐threatening, should be managed according to Advanced Cardiovascular Life Support (ACLS) guidelines. However, in the setting of a widened QRS, while sodium bicarbonate may be indicated in cases of potential co‐ingestion, bupropion‐induced QRS prolongation is not secondary to sodium channel blockade. Rather, QRS prolongation results from action on gap junctions in the myocardium, and thus sodium bicarbonate boluses may not be effective [18, 19].

While individual overdoses of dextromethorphan or bupropion pose significant risks, the combination of these two substances presents a poorly understood danger. Bupropion extending the half‐life of dextromethorphan as a CYP2D6 inhibitor may extend or affect toxicity. Both drugs act on different neurotransmitter systems, and their combined effects on the central nervous system may increase the risks. Clinicians should be cautious and vigilant when prescribing or considering these medications together, particularly in populations at risk of overdose.

4. Conclusion

This case highlights the importance of studying overdoses of antidepressant medications, given the increased risks of suicide among patients with depression. While new medications and combinations hold promise for improving treatment outcomes, their potential risks must be thoroughly assessed. Understanding the risks of dextromethorphan and bupropion in overdose is essential to ensure patient safety and prevent fatal outcomes.

Author Contributions

D.G. treated the patient and wrote the initial draft and revised the manuscript. J.G. wrote the initial draft and revised the manuscript. J.K. revised the manuscript. J.A. wrote the initial draft and revised the manuscript.

Ethics Statement

The authors have nothing to report.

Consent

The patient provided consent for publication.

Conflicts of Interest

The authors declare no conflicts of interest.

Greer D., Girgis J., Kashani J., and Atherton J., “Dextromethorphan Bupropion Combination Tablet Suicide Attempt by Overdose: A Case Report,” Neuropsychopharmacology Reports 45, no. 3 (2025): e70060, 10.1002/npr2.70060.

Data Availability Statement

All data supporting the findings of this case report are included in the main text of the article. No additional datasets were generated or analyzed during the preparation of this report.