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
- Canada Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Bupropion: norepinephrine-dopamine reuptake inhibitor → attention deficit-hyperactivity disorder
One-Sentence Summary
Bupropion is a norepinephrine and dopamine reuptake inhibitor that is marketed in Canada in several single-ingredient products. The TxGNN model predicts it may be effective for attention deficit-hyperactivity disorder, with a score of 0.9999. The data compiled for this report include 6 clinical trials (2 rated as highly relevant, including one completed Phase 3 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 |
| Canada Market Status | Marketed (marketed DINs: 10 of 10) |
| Number of DINs | 10 (marketed: 10) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data are not available in the data compiled for this report. Based on general pharmacological knowledge, bupropion inhibits the reuptake of norepinephrine and dopamine. It has no meaningful serotonergic activity.
These are the same catecholamine pathways targeted by established ADHD treatments such as methylphenidate, amphetamines and atomoxetine. Enhancing noradrenergic and dopaminergic signalling is thought to improve attention and executive function. This gives a plausible mechanistic link between bupropion and ADHD. Reviews in the evidence set also list bupropion among the non-stimulant options for adults who do not respond to, or cannot tolerate, stimulants.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00048360 | Phase 3 | Completed | 162 | 8-week randomized, double-blind, placebo-controlled flexible-dose trial of extended-release bupropion (300–450 mg/day) in adults with ADHD; no results summary in the data |
| NCT00061087 | Phase 2/3 | Completed | 115 | Treatment of adult ADHD in methadone-maintained patients |
| NCT00936299 | Phase 4 | Completed | 105 | Bupropion for ADHD in adolescents with substance use disorder |
| 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 with comorbid attention deficit disorder; mainly a substance-use trial |
| NCT04553263 | Early Phase 1 | Withdrawn | 0 | Relapse prevention in stimulant use disorder; withdrawn with no participants, so no usable ADHD evidence |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 28965364 | 2017 | Cochrane systematic review | Cochrane Database Syst Rev | Bupropion for ADHD in adults |
| 33085721 | 2020 | Systematic review / network meta-analysis | PLoS One | Comparative benefits and harms of drug treatments for adult ADHD |
| 30097390 | 2018 | Systematic review / network meta-analysis | Lancet Psychiatry | Comparative efficacy and tolerability of ADHD medications across children, adolescents and adults |
| 37405312 | 2023 | Review | Health Psychol Res | Bupropion’s pharmacology and its effects in depression, ADHD and smoking cessation |
| 38915262 | 2024 | Review | Expert Rev Neurother | Non-stimulant medications for adults with ADHD |
| 26601963 | 2016 | Review | Curr Pharm Des | Effects and side effects of ADHD drugs, with bupropion listed among common medications |
| 39172673 | 2024 | Review | Am Fam Physician | Overview of ADHD in adults |
| 40203844 | 2025 | Systematic review / network meta-analysis | Lancet Psychiatry | Comparative cardiovascular safety of ADHD medications |
| 24259638 | 2014 | Review | Ann Pharmacother | Pathophysiology, etiology and treatment of ADHD |
| 17136226 | 2006 | Review | Drugs Today (Barc) | Overview of bupropion; mechanism via dopamine and noradrenaline reuptake inhibition |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02275090 | WELLBUTRIN XL | – | – |
| 02439662 | TEVA-BUPROPION XL | – | – |
| 02475812 | TARO-BUPROPION XL | – | – |
| 02275074 | ODAN BUPROPION SR | – | – |
| 02238441 | ZYBAN | – | – |
All 10 licences in the data are valid. Dosage form and indication text are not recorded in the local data.
Safety Considerations
- Contraindication-type relations in the data: Relations compiled for this report suggest caution in epilepsy, hypertension, liver disease and cirrhosis, kidney disease, myocardial infarction, psychotic and manic bipolar disorders, anorexia nervosa and bulimia nervosa, opiate and substance dependence, and central nervous system neoplasm. These are not taken from label text and should be checked against the package insert.
- Drug Interactions: 100 interactions were found. Major-level examples include fentanyl, lidocaine, codeine, dihydrocodeine, tramadol, methylphenidate, hydrocortisone, aldesleukin, alfentanil and amantadine. Moderate-level examples include ethanol, nifedipine, alprazolam, cetirizine and hydrochlorothiazide.
Warnings and contraindications from the package insert have not been compiled. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: One completed Phase 3 placebo-controlled trial in adults with ADHD (NCT00048360) and a Phase 2/3 trial (NCT00061087) directly address the predicted disease. A Cochrane review and network meta-analyses add supporting context, and the NDRI mechanism is plausible. Only one Phase 3 trial is completed, so the evidence level is L2 rather than L1. The trials’ results are not summarised in the data, and the populations are often limited to substance-use comorbidity.
To proceed, the following is needed:
- Results of NCT00048360 and the Cochrane review’s efficacy and safety conclusions
- Package insert warnings and contraindications, in particular seizure risk, blood pressure effects and the interactions listed above
- Confirmed mechanism-of-action data
- Local indication, dosage form and manufacturer details for the Canadian licences
- A patient-selection and monitoring plan that excludes people with seizure disorders, eating disorders or uncontrolled hypertension
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.