†These authors have contributed equally to this work
Alcohol Use Disorder (AUD) is a prevalent condition often co-occurring with affective disorders. Bupropion, a medication used to treat affective disorders, acts by inhibiting dopamine (DA) and norepinephrine (NE) reuptake, potentially helping to alleviate emotional dysregulation. However, the risk of delirium in AUD patients at therapeutic doses is poorly understood, despite reports linking bupropion overdose to delirium. We report here a rare case of a 49-year-old Chinese male with AUD who developed mood disturbances and relapsed following alcohol detoxification surgery. He was diagnosed with 1. Bipolar II Disorder, Current Depressive Episode, Severe Without Psychotic Features; 2. Harmful Pattern of Alcohol Use. During inpatient treatment, the patient received a combination of medications, including bupropion. Delirium and behavioral disturbances appeared after bupropion initiation but resolved upon its discontinuation. These symptoms recurred when bupropion was reintroduced and resolved again after stopping the medication. After discharge, no further bupropion was used, and the patient remained symptom-free at a one-month follow-up. This case suggests that bupropion may trigger delirium in AUD patients with a history of alcohol withdrawal surgery, underscoring the importance of careful medication selection and personalized treatment in complex cases.
AUD is a substance use disorder characterized by compulsive alcohol-seeking behavior, loss of control over intake, and negative emotional and physical withdrawal symptoms (
In managing a depressive episode in a bipolar disorder patient, careful drug selection is critical to avoid worsening depressive symptoms. Bupropion is commonly used due to its favorable efficacy profile (
Delirium is defined as an acute or fluctuating change in mental status (
Although it is unclear whether bupropion increases the risk of delirium in patients during treatment of depressive episodes in bipolar disorder who are treated after alcohol withdrawal surgery, we present the case of a 49-year-old Chinese male patient with bipolar disorder. This patient experienced frequent mood swings after undergoing alcohol detoxification surgery and relapsing multiple times. Following hospital admission due to depressive symptoms, he was diagnosed with 1. Bipolar II Disorder, Current Depressive Episode, Severe Without Psychotic Features; 2. Harmful Pattern of Alcohol Use. Bupropion was initiated for the management of his depressive episode. He subsequently developed delirium, including visual hallucinations, which subsided one day after discontinuation bupropion. Visual hallucinations re-emerged upon bupropion reintroduction. This case highlights a potential risk of delirium associated with bupropion treatment in AUD patients with a history of detoxification surgery.
The patient, a 49-year-old married male, began occasional alcohol use in 1987, which progressed to uncontrolled daily consumption by 2008, amounting to approximately 12 bottles of beer per day. In 2010, his alcohol intake increased to around 500 ml of high-proof spirits daily. He exhibited compulsive drinking behaviors and experienced typical alcohol withdrawal symptoms, including sweating, hand tremors, and anxiety—that were alleviated by resuming alcohol consumption. In 2016, he developed persistent depressive symptoms, including low mood and anhedonia. In July 2021, the patient was diagnosed with Alcohol-induced depressive disorder according to ICD-11 and underwent bilateral amygdala destruction surgery. Post-surgery, his mood improved, and he achieved abstinence from alcohol. However, in October 2021, he was admitted to the hospital for the first time due to depressed mood and behavioral disturbances. He was diagnosed with 1. Bipolar II Disorder, Current Depressive Episode, Severe Without Psychotic Features; 2. Harmful Pattern of Alcohol Use. During hospitalization, his Michigan Alcohol Screening Test (MAST) score was 15, indicating significant alcohol-related issues, and his Self-Rating Depression Scale (SDS) score was 60, suggesting moderate depression. Following treatment, his symptoms improved, and he was discharged. In December 2021, the patient resumed alcohol consumption, drinking 1–2 beers or 150 ml of spirits weekly. By April 2022, he exhibited symptoms of mood instability, irritability, pressured speech, and excessive spending. He was diagnosed with 1. Bipolar I Disorder, Current Episode Manic, Severe, Without Psychotic Features; 2. Harmful Pattern of Alcohol Use, and was hospitalized again. After discharge, the patient adhered to medication and maintained abstinence. However, by April 2023, he once again presented with depressive symptoms, including anhedonia, diminished speech, reduced activity, and a loss of interest, leading to further hospitalization. Notably, he had no history of hallucinations or delusions.
In 2020, he underwent common bile duct surgery for gallstones. In 2021, he received Bilateral Stereotactic Deep Brain Nucleus Lesioning Surgery for the treatment of AUD. The patient was hospitalized three times (in 2021, 2022, and 2023) for mood disorders and was stabilized on each occasion. The patient denies a history of infectious diseases (e.g., hepatitis, tuberculosis, malaria), chronic conditions (e.g., hypertension, heart disease), or significant neurological insults such as poisoning, high fever, coma, seizures, or traumatic brain injury.
Psychiatric abnormalities were reported in his maternal grandfather, paternal aunt, maternal aunt, and maternal cousin. Both his paternal aunt and maternal grandfather died by suicide.
Vital signs, laboratory tests, and neuroimaging were systematically assessed around symptom onset and post-symptom periods. Key abnormalities included neutropenia, elevated lymphocyte percentage, increased mean platelet volume, elevated total bile acids, and elevated homocysteine. Electrolytes, liver and renal function, glycated hemoglobin, and thyroid function remained within normal limits. Neuroimaging (brain MRI including T1WI, T2WI, T2-FLAIR, and DWI) showed only postoperative changes, with no new structural abnormalities. Detailed results at each time point are summarized in
Clinical and laboratory evaluation at admission and around delirium onset.
| Time point | Assessment/test | Key findings | Reference range |
|---|---|---|---|
| Symptom onset | Vital signs | Within normal limits | — |
| Symptom onset | Complete blood count (CBC) | WBC 10.57 ×109/L | WBC 4–10 ×109/L |
| RBC 3.95 ×10¹²/L, | RBC 3.5–5 ×10¹²/L | ||
| HGB 129 g/L | HGB 120–160 g/L | ||
| PLT 94 ×109/L | PLT 100–300 ×109/L | ||
| Symptom onset | Serum electrolytes | Na 143 mmol/L | Na 135–145 mmol/L |
| K 4.03 mmol/L | K 3.5–5 mmol/L | ||
| Cl 108 mmol/L | Cl 95–109 mmol/L | ||
| Ca 2.22 mmol/L | Ca 2.2–2.8 mmol/L | ||
| Mg 0.85 mmol/L | Mg 0.7–1.1 mmol/L | ||
| P 0.79 mmol/L | P 0.96–2.1 mmol/L | ||
| Symptom onset | Neuroimaging (Brain MRI: T1WI, T2WI, T2-FLAIR, and DWI) | MRI showed postoperative changes consistent with prior stereotactic lesioning, with multiple symmetric lesions involving the bilateral basal ganglia, amygdala, and periventricular regions adjacent to the anterior horns of the lateral ventricles. No ventricular enlargement or midline shift was observed. | — |
| Post-symptom | CBC | HGB 119 g/L | HGB 120–160 g/L |
| HCT 33.9% | HCT 37–52% | ||
| MCH 32.7 pg | MCH 26–31 pg | ||
| PLT 86 ×109/L | PLT 100–300 ×109/L | ||
| NEUT% 76.8% | NEUT% 50–70% | ||
| LYM% 11.9% | LYM% 20–40% | ||
| MONO% 10.5% | MONO% 3–10% | ||
| CRP 17.46 mg/L | CRP 0–10 mg/L |
At symptom onset, vital signs were normal, with mild hematologic and electrolyte abnormalities and no acute neuroimaging findings. On the third day after symptom onset (post-symptoms), thrombocytopenia and inflammatory changes persisted without severe metabolic or organ dysfunction.
The patient recently underwent a comprehensive psychiatric assessment. Assessment tools included the Chinese version of the 24-item Hamilton Depression Rating Scale (HAMD), on which the patient scored 35, indicating severe depressive symptoms. The Hamilton Anxiety Rating Scale (HAMA) score was 6, suggesting an absence of anxiety symptoms. The Positive and Negative Syndrome Scale (PANSS) score was 30, reflecting relatively mild psychopathological symptoms.
The patient also completed self-assessment tools: the Beck Depression Inventory (BDI-20) score was 22, indicating moderate depressive symptoms; the Zung Self-Rating Anxiety Scale (SAS) score was 36, showing no anxiety symptoms. Additionally, the Symptom Checklist-90 (SCL-90) yielded a total score of 171, indicating mild psychological distress.
Based on a comprehensive analysis of the patient’s mood fluctuations, episode patterns, and functional status, a differential diagnosis of schizophrenia is warranted. Schizophrenia is characterized by primary thought disorders and affective blunting, where mood disturbances are typically secondary. It often presents with pronounced disorganization of mental functions, either in an episodic or progressive course, with residual psychotic features persisting during remission.
In contrast, this patient’s depressive mood appears as a primary symptom, with relatively normal functioning during inter-episode periods, and lacks prominent and persistent psychotic features such as hallucinations or delusions. Additionally, the patient has a long-term or frequent history of alcohol use, with significant impairments in physical, psychological, and social functioning following consumption.
Considering the patient’s history of alcohol use and mood symptoms, and following the criteria outlined in the International Classification of Diseases, 11th Revision (ICD-11) (
On the first day of admission, based on the patient’s clinical presentation and diagnostic findings, the following pharmacological treatment plan was established: sodium valproate (0.4 g, three times daily), paliperidone extended-release (3 mg, once daily), escitalopram (5 mg, twice daily), and quetiapine (25 mg, once daily at bedtime for clarity). On the second day, bupropion (75 mg, twice daily) was added to further improve mood, and escitalopram was discontinued. By the eighth day, paliperidone was stopped, and olanzapine (2.5 mg, once daily at bedtime for clarity) was introduced. On the tenth day, the dose of bupropion was increased to 150 mg twice daily. Subsequently, on the eleventh day, olanzapine was increased to 5 mg once daily at bedtime for clarity.
However, on the seventeenth day, the patient exhibited unusual behaviors, such as pulling at doors, pacing in the hall, and reporting visual hallucinations, such as seeing bugs on the floor and cockroach eggs on a glass. The psychiatric evaluation revealed a delayed response in social interactions, intact person orientation but impaired time and place orientation, disorganized associative thinking, repetitive finger movements, pathological volition, and a lack of self-awareness, with hallucinations persisting through the night. The patient’s acute symptoms—including impaired attention, altered level of consciousness, disorientation to time and place, and intra-day symptom fluctuation—were consistent with a diagnosis of Delirium according to ICD-11 criteria, with a clear temporal association with recent drug exposure. Given the potential link between treatment adjustments and delirium onset, olanzapine and bupropion were promptly discontinued. The patient received intravenous citicoline sodium (0.50 g in 250 ml of 0.9% sodium chloride solution) as part of the standard clinical management. Laboratory analyses, including blood counts and biochemical levels, revealed no significant electrolyte imbalances. By the eighteenth day, the hallucinations had resolved.
On the twentieth day, escitalopram was reintroduced at 5 mg once daily. To further investigate the cause of delirium, bupropion was re-administered (150 mg, twice daily) on the twenty-fifth day under the supervision of a physician, with informed consent from the patient and family. During the supervised bupropion re-challenge, the patient was closely monitored in an inpatient setting with regular assessments of mental status and vital signs. Predefined stopping criteria were applied, and bupropion was discontinued immediately upon recurrence of acute neuropsychiatric symptoms, including confusion, impaired attention, and behavioral disorganization, to ensure patient safety. Unfortunately, visual hallucinations re-emerged on the twenty-sixth day. Discontinuation of bupropion on the twenty-seventh day led to the cessation of these hallucinations.
Following 30 days of treatment, the patient’s scores on the HAMD and HAMA had dropped to 7 and 2, respectively, indicating resolution of depressive symptoms, with no recurrence of visual hallucinations. At discharge, the patient reported a significant improvement in depressive symptoms. The patient’s score of 5 on the Chinese version of the Naranjo Adverse Drug Reaction Probability Scale (
At the one-month follow-up, the patient demonstrated strong adherence to the medication regimen and maintained regular, prescribed use of medications outside the hospital. The patient reported good tolerance to the prescribed drugs, stable physical and mental health, and no recurrence of delirium or adverse drug reactions. The patient’s score on the HAMD had further decreased to 6, and the HAMA score to 4, indicating improvements in both depressive and anxiety symptoms. The patient resumed normal daily activities and work and actively engaged in preferred hobbies, reflecting an enhanced quality of life. The timeline of treatment and adverse reaction is illustrated in
Detailed medication administration during hospitalization.
| Start date | Medication | Dose | Route | Frequency | Stop date |
|---|---|---|---|---|---|
| 2023/06/06 | Valproate | 0.4 g | Oral | Three times daily | 2023/07/02 |
| 2023/06/06 | Paliperidone ER | 3 mg | Oral | Once daily | 2023/06/13 |
| 2023/06/06 | Buspirone | 5 mg | Oral | Three times daily | 2023/06/13 |
| 2023/06/06 | Escitalopram | 5 mg | Oral | Twice daily | 2023/06/25 |
| 2023/06/06 | Quetiapine | 25 mg | Oral | Once daily at bedtime | 2023/06/08 |
| 2023/06/07 | Bupropion | 75 mg | Oral | Twice daily | 2023/06/15 |
| 2023/06/08 | Quetiapine | 100 mg | Oral | Once daily at bedtime | 2023/06/12 |
| 2023/06/12 | Quetiapine | 0.2 g | Oral | Once daily at bedtime | 2023/06/19 |
| 2023/06/13 | Buspirone | 10 mg | Oral | Three times daily | 2023/06/21 |
| 2023/06/13 | Olanzapine | 2.5 mg | Oral | Once daily at bedtime | 2023/06/16 |
| 2023/06/15 | Quetiapine | 0.1 g | Oral | Once daily | 2023/06/19 |
| 2023/06/15 | Bupropion ER | 0.15 g | Oral | Twice daily | 2023/06/22 |
| 2023/06/16 | Olanzapine | 5 mg | Oral | Once daily at bedtime | 2023/06/22 |
| 2023/06/19 | Quetiapine | 0.2 g | Oral | Twice daily | 2023/06/21 |
| 2023/06/22 | Lorazepam | 1 mg | Oral | Once daily at bedtime | 2023/06/30 |
| 2023/06/23 | Citicoline sodium | 0.5 g | Intravenous | Once daily | 2023/07/02 |
| 2023/06/23 | 0.9% Sodium Chloride | 250 ml | Intravenous | Once daily | 2023/07/02 |
| 2023/06/25 | Escitalopram | 5 mg | Oral | Once daily | 2023/07/02 |
| 2023/06/26 | Lorazepam | 0.5 mg | Oral | Once daily at bedtime | 2023/07/02 |
| 2023/06/30 | Paliperidone ER | 3 mg | Oral | Once daily | 2023/07/02 |
| 2023/06/30 | Mirtazapine | 7.5 mg | Oral | Once daily at bedtime | 2023/07/02 |
ER, extended-release; IV, intravenous; QHS, once daily at bedtime. The patient was hospitalized from June 6 to July 2, 2023. Clinical changes occurred after evening medications on June 21. Start/stop dates indicate the first and last day of each drug; frequency indicates daily doses. Only generic names are listed; brand names and indications are omitted.
Delirium is an acute and typically fluctuating mental state characterized by reduced attention and additional cognitive deficits or altered levels of awareness (
After confirming the diagnosis, we implemented a combination therapy regimen, including antidepressants, benzodiazepines, and second-generation antipsychotics (
Several factors support the hypothesis that bupropion triggered the delirium. First, bupropion’s pharmacological profile, as it inhibits dopamine and norepinephrine reuptake, increases the concentration of these neurotransmitters in the brain (
Activation of reward pathways suppresses the anti-reward system, and vice versa (
Additional factors may have contributed to the patient’s presentation. Although blood ethanol levels were negative upon admission and during the hallucination episodes, long-term alcohol use is known to induce neuroadaptation (
Furthermore, the patient had undergone Bilateral Stereotactic Deep Brain Nucleus Lesioning Surgery, a neurosurgical intervention used for emotional regulation (
Nevertheless, limitations remain in this case report. The severity of long-term alcohol use was assessed using the Michigan Alcohol Screening Test (MAST, score = 15), which evaluates chronic alcohol-related problems rather than acute withdrawal. Clinical observations during hospitalization and at delirium onset revealed no typical withdrawal features, such as tremor, diaphoresis, autonomic instability, agitation, or seizures. Based on this assessment, the patient met ICD-11 criteria for harmful alcohol use, rather than alcohol dependence or acute withdrawal syndrome. Given the use of multiple medications in situations where single antidepressant efficacy is limited, complex drug interactions may arise (
Personalized treatment planning is essential, as patients exhibit individual differences regarding disease manifestation, drug metabolism, and comorbidities. Standardized treatment approaches may not adequately address these individual needs. Through tailored therapeutic strategies, it is possible to select appropriate drugs, adjust doses, and avoid potential adverse effects, thereby enhancing therapeutic efficacy and patient adherence.
This report underscores the importance of individualized pharmacological treatment and patient management in individuals with a history of chronic alcohol use, potential liver impairment, and prior brain surgery. Specifically, for such patients, when treating depressive episodes in bipolar disorder, bupropion may be associated with an increased risk of hallucinations. Consequently, if hallucinations occur, clinicians should promptly assess the likelihood of adverse drug reactions and consider discontinuing bupropion to ensure patient safety and optimize treatment outcomes of the treatment plan.
The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.
The studies involving humans were approved by Shandong Mental Health Center, Shandong University, Shandong Jinan, PR China, 250014. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article. Written informed consent was obtained from the participant/patient(s) for the publication of this case report.
XK: Data curation, Investigation, Writing – original draft. LC: Conceptualization, Data curation, Supervision, Writing – review & editing. XH: Formal Analysis, Funding acquisition, Project administration, Software, Writing – review & editing. PD: Methodology, Project administration, Resources, Writing – original draft. XC: Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Writing – review & editing.
We sincerely thank all individuals and organizations who have supported this project.
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The author(s) declared that generative AI was not used in the creation of this manuscript.
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