Bupropion
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Bupropion
- Bupropion: From Depression and Smoking Cessation to Attention Deficit-Hyperactivity Disorder
Bupropion: From Depression and Smoking Cessation to Attention Deficit-Hyperactivity Disorder
One-Sentence Summary
Bupropion was originally used for depressive disorders (such as major depressive disorder), anxiety-related conditions and nicotine dependence. The TxGNN model predicts it may be effective for attention deficit-hyperactivity disorder (ADHD), with 6 clinical trials (including 1 completed Phase 3 randomised controlled trial) and 20 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Depressive disorders (major depressive disorder, dysthymic disorder), anxiety disorder, nicotine dependence, obesity (from the knowledge graph; the Singapore licence records contain no indication text) |
| Predicted New Indication | Attention deficit-hyperactivity disorder |
| TxGNN Prediction Score | 99.99% |
| Evidence Level | L2 (see note below) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Proceed with Guardrails |
Note on evidence level: The data compiled for this report assigns L1. By the stated rules, L1 requires at least two completed Phase 3 RCTs. Only one clearly qualifying trial (NCT00048360) is identified, plus one Phase 2/3 trial (NCT00061087) whose intervention arm is not confirmed as bupropion. A conservative reading is therefore L2. Supporting evidence also comes from a Cochrane review of bupropion in adult ADHD.
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. From the published literature, bupropion inhibits the reuptake of norepinephrine and dopamine and has no serotonergic activity. It is an antidepressant that also supports smoking cessation.
ADHD is linked to dysfunction of the noradrenergic and dopaminergic systems. Established ADHD treatments, such as stimulants (methylphenidate, amphetamines) and atomoxetine, act on these same pathways. Bupropion's catecholaminergic action therefore gives a plausible mechanism for improving attention and impulsivity. Reviews already list it among the non-stimulant options for adults who do not respond to, or cannot tolerate, stimulants.
The original indications (depression, nicotine dependence) and ADHD often occur together, and several trials test bupropion in people with ADHD and substance use disorders. This fits the very high TxGNN score.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | 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 |
| NCT00061087 | Phase 2/3 | Completed | 115 | Treatment of adult ADHD in methadone-maintained patients (bupropion arm to be confirmed) |
| NCT00936299 | Phase 4 | Completed | 105 | Bupropion for ADHD in adolescents with substance use disorder |
| NCT01270555 | Not applicable | Completed | 32 | Open study of bupropion SR for adult ADHD with recent or current substance use disorders |
| NCT00000268 | Not applicable | Completed | 32 | Cocaine abuse with comorbid attention deficit disorder |
| NCT04553263 | Early Phase 1 | Withdrawn | 0 | Relapse prevention in stimulant use disorder; withdrawn, so provides no usable evidence |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 28965364 | 2017 | Systematic review (Cochrane) | Cochrane Database Syst Rev | Bupropion for adult ADHD, as an alternative when stimulants are not tolerated or ineffective |
| 30097390 | 2018 | Network meta-analysis | Lancet Psychiatry | Comparative efficacy and tolerability of ADHD medications across children, adolescents and adults |
| 33085721 | 2020 | Network meta-analysis | PLoS One | Relative effects of pharmacologic treatments for adult ADHD |
| 27738872 | 2017 | Multiple-treatment comparison | Mol Neurobiol | Efficacy and safety of ADHD treatments in children and adolescents |
| 40203844 | 2025 | Network meta-analysis (safety) | Lancet Psychiatry | Comparative cardiovascular safety (haemodynamics, ECG) of ADHD medications |
| 37405312 | 2023 | Review | Health Psychol Res | Bupropion pharmacology and its effects in depression, ADHD and smoking cessation |
| 38915262 | 2024 | Review | Expert Rev Neurother | Non-stimulant medications for adult ADHD |
| 39172673 | 2024 | Review | Am Fam Physician | Overview of ADHD diagnosis and management in adults |
| 26601963 | 2016 | Review | Curr Pharm Des | Effects and side effects of ADHD drugs, including bupropion |
| 17136226 | 2006 | Review | Drugs Today (Barc) | Bupropion overview: dopamine and noradrenaline reuptake inhibition |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN10983P | WELLBUTRIN SR TABLETS 150 mg | Film-coated tablet | Not stated in the compiled data |
| SIN16411P | CONTRAVE PROLONGED RELEASE TABLET 8MG/90MG | Film-coated extended-release tablet | Not stated in the compiled data |
Both licences are valid single-ingredient registrations. Contrave is the bupropion/naltrexone product.
Safety Considerations
- Contraindications flagged in the knowledge graph (not taken from the package insert): hypertension, epilepsy, liver failure or liver disease (including cirrhosis), kidney disease, manic bipolar disorder, psychotic disorders (schizophreniform, schizoaffective), anorexia nervosa, bulimia nervosa, opiate dependence, substance abuse/dependence, myocardial infarction, central nervous system neoplasm, and others.
- Drug Interactions: 100 interactions were found. Major-level ones among those retrieved include fentanyl, lidocaine, codeine, dihydrocodeine, tramadol, methylphenidate, hydrocortisone, aldesleukin, alfentanil and amantadine. Moderate-level ones include ethanol, alprazolam, nifedipine, hydrochlorothiazide, cetirizine and chlorpheniramine.
- Guardrails for ADHD use: dose-dependent seizure risk, blood pressure monitoring, and caution in patients with comorbid substance use or eating disorders.
Package insert warnings and contraindications were not available and should be checked.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: A completed Phase 3 placebo-controlled trial, several further ADHD trials and a Cochrane review support the use of bupropion in adult ADHD, and its mechanism is plausible. Seizure risk, blood pressure effects and the many knowledge-graph contraindications call for a controlled approach.
To proceed, the following is needed:
- Singapore package insert warnings and contraindications (a blocking gap for safety screening)
- Confirmation of bupropion as the intervention in NCT00061087, and review of the full results of NCT00048360
- Detailed mechanism of action data from DrugBank
- A patient-selection and monitoring plan covering seizure risk, blood pressure, and comorbid substance use or eating disorders
- Singapore approved-indication text for the two licences, and a check of whether an ADHD indication would need a regulatory variation
Other predicted indications: ADHD, inattentive type (L3) lacks subtype-specific trials and is a research question only. The remaining predictions (for example faciodigitogenital syndrome, chondromyxoid fibroma, hypervitaminosis) have no supporting evidence or plausible mechanism and should be held.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.