Baclofen
| Evidence Level: L5 | Predicted Indications: 2 |
Table of Contents
Baclofen: From Spasticity to Attention Deficit-Hyperactivity Disorder
One-Sentence Summary
Baclofen is a GABA-B receptor agonist that is marketed in Canada as oral and intrathecal products. The data compiled for this report did not include approved indication text. The TxGNN model predicts it may be effective for attention deficit-hyperactivity disorder (ADHD), but there are 0 clinical trials and only 9 publications (none testing baclofen in ADHD) supporting this direction. A second prediction, nicotine dependence, has 3 Phase 2 trials and is noted in the sections below as the better-supported alternative.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available in the data compiled for this report (the Canadian license records contain no indication text) |
| Predicted New Indication | Attention deficit-hyperactivity disorder |
| TxGNN Prediction Score | 0.9932 |
| Evidence Level | L5 |
| Canada Market Status | Marketed (marketed DINs on record: at least 20) |
| Number of DINs | at least 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Baclofen is a GABA-B receptor agonist. A plausible link to ADHD is that it modulates GABAergic inhibitory tone, which may influence impulsivity and prefrontal-striatal circuits.
However, this link is hypothetical. The supplied literature does not test baclofen in ADHD. The papers cover off-label methylphenidate use in adults, Tourette syndrome and tic treatment, and rodent studies of noradrenergic and neural-circuit mechanisms in impulsivity and social behaviour. The very high TxGNN score (0.9932) is a computational prediction only. No clinical or direct preclinical evidence for baclofen in ADHD is supported by the data compiled.
Alternative candidate: nicotine dependence (TxGNN score 0.9919). Baclofen activates GABA-B receptors, which inhibit mesolimbic dopamine release and may reduce nicotine reward, craving and withdrawal. Rodent studies (PMID 24553576, 18682277) report that baclofen attenuates nicotine’s rewarding effects and withdrawal signs. This indication has Phase 2 trial evidence (evidence level L2, stage S1, “Research Question”), although the evidence is limited, as described below.
Clinical Trial Evidence
ADHD: Currently no related clinical trials registered.
Nicotine dependence (alternative candidate):
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00257894 | Phase 2 | Terminated | 41 | Baclofen effects on smoking urge, withdrawal and reinforcement in moderate to heavy smokers; terminated early, limiting power |
| NCT01821560 | Phase 2 | Completed | 44 | fMRI and candidate-gene study of baclofen’s effects on brain and behavioural responses to smoking cues; small sample, mechanistic and behavioural data |
| NCT01228994 | Phase 2 | Terminated | 6 | Randomized trial of baclofen vs placebo for smoking abstinence; only 6 participants enrolled, cannot support efficacy conclusions |
Literature Evidence
ADHD:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 30122296 | 2019 | Review | L’Encephale | Supervised off-label methylphenidate prescribing in adult ADHD; does not test baclofen |
| 24295630 | 2013 | Review | Int Rev Neurobiol | Emerging treatment strategies in Tourette syndrome, with ADHD as a common comorbidity |
| 11393328 | 2001 | Review | Paediatr Drugs | Clinical characteristics and management of Tourette syndrome |
| 35345730 | 2022 | Review | Cureus | Behavioural intervention, antipsychotics and alpha agonists for tics in Tourette’s syndrome |
| 10342599 | 1999 | Review | J Child Neurol | 450 patients with tics/Tourette’s treated with baclofen/botulinum toxin A; relevant to tics rather than ADHD |
| 21300040 | 2011 | Preclinical (animal) | Brain Res | EEG responses to neurotransmitter agonists in ADHD-model vs kainate-treated rats |
| 24062084 | 2014 | Preclinical (animal) | Psychopharmacology | Guanfacine (α2A agonist) in the ventral hippocampus reduces impulsive decision-making in rats |
| 24496320 | 2014 | Preclinical (animal) | Neuropsychopharmacology | Roles of anterior cingulate cortex and basolateral amygdala in effort-based decision-making in rodents |
| 24103016 | 2013 | Preclinical (animal) | Eur J Neurosci | Habenula integrity is necessary for social play behaviour in rats |
Nicotine dependence (alternative candidate, selected):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 25868070 | 2015 | RCT (conference abstract) | Neuropsychopharmacology | Double-blind, placebo-controlled trial of baclofen for concurrent alcohol and nicotine dependence |
| 29250815 | 2018 | Review | Pharmacotherapy | Current and emerging pharmacotherapies for smoking cessation |
| 24654737 | 2014 | Review | Expert Opin Emerg Drugs | Emerging drugs for tobacco dependence |
| 11841892 | 2002 | Review | Drug Alcohol Depend | GABA-B agonists such as baclofen reduce reinforcing effects of abused drugs, including nicotine, in animal models |
| 24553576 | 2014 | Preclinical (animal) | Psychopharmacology | Baclofen attenuates nicotine reward and withdrawal in rodents |
| 18682277 | 2008 | Preclinical (animal) | Neurosci Lett | Baclofen effects on nicotine conditioned place preference and discrimination in rats |
| 19250803 | 2009 | Preclinical (animal) | Eur Neuropsychopharmacol | Baclofen prevents reinstatement of nicotine seeking in rodents |
| 24971600 | 2015 | Review | Neuropharmacology | GABA-B receptors, including positive allosteric modulators, as a strategy in substance use disorders |
Much of the other nicotine-related literature concerns alcohol use disorder, which is indirect evidence for nicotine.
Canada Market Information
Baclofen has 20 valid single-ingredient licenses in Canada (no cancelled licenses). The data compiled contain product names only, with no dosage form or approved indication text. The main authorizations are:
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02242151 | RIVA-BACLOFEN | Not listed | Not listed |
| 02544490 | JAMP BACLOFEN | Not listed | Not listed |
| 02413639 | BACLOFEN INJECTION | Not listed | Not listed |
| 02485508 | BACLOFEN INTRATHECAL | Not listed | Not listed |
| 02063743 | PMS-BACLOFEN | Not listed | Not listed |
The product names indicate oral, injectable and intrathecal presentations.
Safety Considerations
Knowledge-graph contraindication signals (from drug-disease edges in the TxGNN knowledge graph, not from label text): epilepsy, kidney disease, psychotic and related disorders (psychotic disorder, schizophrenia, schizophreniform disorder, schizoaffective disorder, mental disorder), stroke and cerebrovascular disorders (stroke disorder, cerebrovascular disorder, cerebral infarction, susceptibility to ischemic stroke), autonomic nervous system disorders (autonomic nervous system disease, Horner syndrome, autonomic dysreflexia), and urinary conditions (pyoureter, disease of the neck of the urinary bladder).
The psychiatric signals deserve attention for a possible ADHD use, since patients may have psychiatric comorbidity.
Drug interactions: 100 interactions were found in total. Notable ones:
- Major: Morphine, liposomal morphine
- Moderate: Dronabinol, Metoclopramide, Nabilone, Opium, Sibutramine, Difenoxin, Diphenoxylate
Most of the remaining listed interactions have an unclassified severity level. The Major and Moderate interactions mainly involve other central nervous system depressants and opioids.
Please refer to the package insert for label warnings and contraindications.
Conclusion and Next Steps
Decision: Hold (for ADHD)
Rationale: The ADHD prediction rests on a model score alone (L5). There are no clinical trials, and none of the supplied publications tests baclofen in ADHD. In contrast, nicotine dependence has three Phase 2 trials, but two were terminated early (one with only 6 participants) and efficacy for smoking cessation has not been established. It is better treated as a research question than as a Go.
To proceed, the following is needed:
- Package insert warnings and contraindications from Health Canada, and the approved indication text for each DIN
- Detailed mechanism of action data
- For ADHD: direct preclinical or clinical studies of baclofen in ADHD before further investment
- For nicotine dependence: adequately powered randomized trials, plus review of the psychiatric and other knowledge-graph contraindication signals in target populations
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.