Baclofen
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
- Baclofen
- Baclofen: From Spasticity (Original Indication Not Listed in Local Records) to Attention Deficit-Hyperactivity Disorder
Baclofen: From Spasticity (Original Indication Not Listed in Local Records) to Attention Deficit-Hyperactivity Disorder
One-Sentence Summary
Baclofen is a GABA-B receptor agonist, and the Singapore licence records compiled for this report do not list an approved indication text. The TxGNN model's top-ranked prediction is attention deficit-hyperactivity disorder (ADHD), but there are 0 clinical trials and 9 publications (mostly Tourette syndrome reviews and rodent studies, none testing baclofen in ADHD patients). The evidence is weak for this top-ranked indication. The better-supported alternative is nicotine dependence (3 Phase 2 trials, 20 publications).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available (all 4 Singapore licences have an empty approved indication text) |
| Predicted New Indication | Attention deficit-hyperactivity disorder |
| TxGNN Prediction Score | 99.32% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 4 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the compiled data. From known pharmacology, baclofen is a GABA-B receptor agonist. GABAergic modulation of cortico-striatal circuits, and of dopaminergic and noradrenergic tone, could plausibly influence impulsivity and hyperactivity.
The link is indirect and extrapolated. The retrieved literature mainly covers Tourette syndrome and tic treatment, which often co-occurs with ADHD, plus rodent studies of impulsivity, hippocampal EEG and social play. None of it tests baclofen in people with ADHD.
The second-ranked prediction, nicotine dependence (score 99.19%), has a clearer rationale. Baclofen dampens mesolimbic dopamine release, and animal studies show it reduces nicotine reward and withdrawal signs. It is covered in more detail below as the more promising lead.
Clinical Trial Evidence
Currently no related clinical trials registered for ADHD.
For reference, the trials found for the better-supported alternative, nicotine dependence:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01821560 | Phase 2 | Completed | 44 | Baclofen effects on brain (fMRI) and behavior in smokers responding to smoking cues |
| NCT00257894 | Phase 2 | Terminated | 41 | Baclofen effect on smoking urge, withdrawal and reinforcement; early termination limits conclusions |
| NCT01228994 | Phase 2 | Terminated | 6 | Placebo-controlled test of baclofen for smoking abstinence; too small to inform efficacy |
Literature Evidence
Publications retrieved for ADHD (none test baclofen in ADHD patients):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 35345730 | 2022 | Review | Cureus | Behavioural, antipsychotic and alpha-agonist treatments for tics in Tourette syndrome, which often co-occurs with ADHD |
| 24295630 | 2013 | Review | International Review of Neurobiology | Emerging treatment strategies in Tourette syndrome |
| 11393328 | 2001 | Review | Paediatric Drugs | Clinical features and management of Tourette syndrome |
| 10342599 | 1999 | Review | Journal of Child Neurology | 450 patients with tics/Tourette syndrome treated with baclofen/botulinum toxin A |
| 21300040 | 2011 | Preclinical (animal) | Brain Research | EEG responses to neurotransmitter agonists in a rat model of ADHD and epilepsy |
| 24062084 | 2014 | Preclinical (animal) | Psychopharmacology | α2A-adrenergic stimulation in the ventral hippocampus reduces impulsive decision-making (guanfacine) |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN10026P | PMS-BACLOFEN TABLET 10 mg | Tablet | Not listed |
| SIN06831P | COLMIFEN 10 TABLET 10 mg | Tablet | Not listed |
| SIN05330P | LIORESAL 10 TABLET 10 mg | Tablet | Not listed |
| SIN09087P | APO-BACLOFEN TABLET 10 mg | Tablet | Not listed |
Safety Considerations
- Disease associations flagged in the TxGNN knowledge graph (not label text): epilepsy, kidney disease, psychotic and related disorders (schizophrenia, schizoaffective disorder, schizophreniform disorder, mental disorder), stroke and cerebrovascular disorders (including cerebral infarction), autonomic nervous system disease (including autonomic dysreflexia and Horner syndrome), pyoureter, and disease of the neck of the urinary bladder. These should be verified against the official package insert.
- Drug Interactions: The interaction query returned 100 records. The main Major interactions are with morphine (including liposomal morphine). Moderate interactions include dronabinol, nabilone, metoclopramide, opium, sibutramine, difenoxin and diphenoxylate. Most of the CNS-depressant combinations call for caution.
Please refer to the package insert for label warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The ADHD prediction rests on a high model score only. There are no clinical trials, and the literature does not test baclofen in ADHD. The mechanistic link is speculative. Several nervous system and psychiatric conditions also appear in the knowledge-graph contraindication list, which calls for caution in a population that often has psychiatric comorbidity.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA, to complete safety screening
- Approved indication text for the Singapore licences
- Mechanism of action data
- Preclinical or early clinical evidence of baclofen in ADHD
- A decision on whether to prioritise nicotine dependence (L2, three Phase 2 trials, two terminated) or myofascial pain syndrome (an oral baclofen vs botulinum toxin A study, n=52, no results) as better-supported candidates
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.