Bupropion
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
- Bupropion
- Pharmacist Assessment Report
- Bupropion: norepinephrine–dopamine reuptake inhibitor → attention deficit-hyperactivity disorder
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Australia Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Bupropion: norepinephrine–dopamine reuptake inhibitor → attention deficit-hyperactivity disorder
One-Sentence Summary
Bupropion is an oral sustained-release tablet marketed in Australia as Zyban. It is predicted by the TxGNN model to be useful for attention deficit-hyperactivity disorder. The prediction is supported by 6 clinical trials (including one completed Phase 3 randomised placebo-controlled trial) and 19 publications, including a Cochrane review of bupropion in adult ADHD.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | attention deficit-hyperactivity disorder |
| TxGNN Prediction Score | 0.9999 |
| Evidence Level | L2 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. From general pharmacology, bupropion inhibits the reuptake of norepinephrine and dopamine (an NDRI) and has no serotonergic activity.
These are the same catecholaminergic pathways targeted by established ADHD medicines. Stimulants such as methylphenidate and amphetamines act by increasing dopamine and norepinephrine, and atomoxetine acts on noradrenaline. Bupropion is therefore mechanistically plausible as a non-stimulant option, and published reviews list it among antidepressant-class medicines used in ADHD, particularly where stimulants are not tolerated or are unsuitable.
This link rests on general pharmacology, not on a mechanism record supplied with the data.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00048360 | Phase 3 | Completed | 162 | 8-week randomised, double-blind, placebo-controlled flexible-dose study of extended-release bupropion (300–450 mg/day) in adults with ADHD; results not summarised in the data |
| NCT00936299 | Phase 4 | Completed | 105 | Bupropion for ADHD in adolescents with substance use disorder |
| NCT00061087 | Phase 2/3 | Completed | 115 | Treatment of adult ADHD in methadone-maintained patients (drug not stated in title) |
| NCT01270555 | NA | Completed | 32 | Open study of bupropion SR in adults with ADHD and recent or current substance use disorders |
| NCT00000268 | NA | Completed | 32 | Cocaine abuse and attention deficit disorder; supportive only |
| NCT04553263 | Early Phase 1 | Withdrawn | 0 | Bupropion and relapse in stimulant use disorder with and without ADHD; no participants enrolled |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 28965364 | 2017 | Systematic review (Cochrane) | Cochrane Database Syst Rev | Bupropion for ADHD in adults, as an alternative where stimulants are not optimal or tolerated |
| 33085721 | 2020 | Systematic review / network meta-analysis | PLoS One | Comparative effects of pharmacologic treatments for adults with ADHD |
| 30097390 | 2018 | Systematic review / network meta-analysis | Lancet Psychiatry | Comparative efficacy and tolerability of ADHD medicines across children, adolescents and adults |
| 40203844 | 2025 | Network meta-analysis | Lancet Psychiatry | Comparative cardiovascular safety of ADHD medicines |
| 37405312 | 2023 | Review | Health Psychol Res | Bupropion pharmacology and its use in depression, ADHD and smoking cessation |
| 38915262 | 2024 | Review | Expert Rev Neurother | Non-stimulant medicines for adults with ADHD |
| 26601963 | 2016 | Review | Curr Pharm Des | Effects and side effects of ADHD drugs, including bupropion |
| 39172673 | 2024 | Review | Am Fam Physician | Overview of ADHD in adults |
| 24259638 | 2014 | Review | Ann Pharmacother | Pathophysiology, aetiology and treatment of ADHD |
| 17136226 | 2006 | Review | Drugs Today (Barc) | Bupropion profile; main action via dopamine and noradrenaline reuptake inhibition |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 8465M | Zyban | Tablet containing bupropion hydrochloride 150 mg (sustained release) | Not recorded in the local data |
Safety Considerations
- Contraindications flagged for review: The data compiled for this report list conditions with a recorded contraindication relationship to bupropion, which are not label text. These include epilepsy, hypertension, liver failure and cirrhosis, kidney disease, bipolar mania, psychotic disorders, anorexia nervosa and bulimia nervosa, substance and opiate dependence, recent myocardial infarction, and central nervous system tumours. They should be confirmed against the TGA-approved Product Information.
- Drug Interactions: 100 interactions were identified. Major-level interactions in the data include fentanyl, lidocaine, dihydrocodeine, codeine, tramadol, methylphenidate, hydrocortisone, aldesleukin, alfentanil and amantadine. Moderate-level interactions include ethanol, alprazolam, nifedipine, hydrochlorothiazide, cetirizine, chlorpheniramine, acebutolol and alfuzosin.
Please refer to the TGA-approved Product Information (PI) for the full warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: A completed Phase 3 randomised placebo-controlled trial, several further completed trials in ADHD populations, and a Cochrane review of bupropion in adult ADHD directly address the predicted disease. The evidence is limited to one Phase 3 trial, with small comorbid-population studies, so it is not yet at the strength of two Phase 3 trials. Seizure-threshold and cardiovascular considerations also require careful patient selection.
To proceed, the following is needed:
- Full results and comparator details of NCT00048360, and review of the Cochrane findings on efficacy and tolerability
- Mechanism of action data from a primary source
- Review of the TGA Product Information for warnings and contraindications, including the seizure risk and blood pressure effects
- A screening and monitoring plan for patients with comorbid substance use, bipolar disorder, eating disorders or epilepsy
- A check of interaction risks with opioids and other concurrent medicines
- Confirmation of whether the single registered product (Zyban) can be used for this purpose, or whether a separate regulatory pathway is needed
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.