Pregabalin
| Evidence Level: L5 | Predicted Indications: 6 |
Table of Contents
Pregabalin: Tendinitis
One-Sentence Summary
Pregabalin is a gabapentinoid originally used for neuropathic and chronic pain conditions, including postherpetic neuralgia, fibromyalgia, myofascial pain syndrome and anxiety disorder. The TxGNN model predicts it may be effective for Migraine Disorder, the best-supported of its top predictions. Currently 2 clinical trials (one withdrawn Phase 3, one completed Phase 4 that is only indirectly relevant) and 20 publications, including several pediatric randomized trials, support this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Tendinitis |
| TxGNN Prediction Score | 0.9971 |
| Evidence Level | L5 (provisional; see note below) |
| Canada Market Status | Marketed (marketed DINs on record: at least 20) |
| Number of DINs | at least 20 |
| Recommended Decision | Hold |
Note on the prediction list: Six indications were predicted. Tendinitis (0.9971), idiopathic granulomatous myositis (0.9971) and myositis fibrosa (0.9971) score highest, but the data compiled for this report show little or no supporting evidence for them (evidence levels L4 and L5). Inclusion body myositis (0.9952) is also L5. Migraine disorder (0.9947) has the strongest clinical evidence, so this report focuses on it. Migraine with brainstem aura (0.9943) is supported only by preclinical work (L4).
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not currently available in the compiled data. Based on known pharmacology, pregabalin binds the alpha-2-delta subunit of voltage-gated calcium channels and reduces release of excitatory neurotransmitters such as glutamate. This is the basis of its use in neuropathic pain and fibromyalgia.
Migraine shares several features with these conditions, notably central sensitization and excess excitatory neurotransmission. Preclinical studies report that pregabalin raises the threshold for cortical spreading depression, the phenomenon behind migraine aura, and that chronic treatment protects against spreading depolarization in a familial hemiplegic migraine model. These findings provide a plausible mechanistic link.
The evidence is still indirect. The L1 grade is provisional and should be verified by reading the trials in full.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00447369 | Phase 3 | Withdrawn | 70 (planned) | Randomized blinded crossover comparison of pregabalin and sodium valproate for migraine prevention; withdrawn, so no efficacy data |
| NCT02747940 | Phase 4 | Completed | 200 | Brain imaging signatures of chronic pain disorders (chronic migraine and fibromyalgia); not a migraine efficacy trial of pregabalin |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37637787 | 2023 | RCT | Iran J Child Neurol | Pregabalin vs sodium valproate for pediatric migraine prophylaxis |
| 26024701 | 2015 | RCT | Acta Med Iran | Propranolol vs pregabalin for childhood migraine prophylaxis (99 children) |
| 39388181 | 2024 | Network meta-analysis | JAMA Netw Open | Efficacy and safety of preventive medications in pediatric migraine |
| 23797675 | 2013 | Systematic review | Cochrane Database Syst Rev | Gabapentin or pregabalin for prophylaxis of episodic migraine in adults |
| 21479703 | 2011 | Follow-up study | J Headache Pain | Efficacy and tolerability of pregabalin as migraine preventive over 3 months |
| 25669613 | 2015 | Clinical study | Int J Clin Pharmacol Ther | Effects of pregabalin on central sensitization and allodynia in migraine |
| 37924146 | 2023 | Preclinical | Mol Brain | Chronic pregabalin protects against spreading depolarization in a familial hemiplegic migraine model |
| 28223480 | 2017 | Preclinical | PNAS | In vivo imaging shows pregabalin inhibits cortical spreading depression |
| 30880369 | 2019 | Review | Curr Treat Options Neurol | Antiepileptic drugs as preventive migraine therapy |
| 30001248 | 2018 | Review/Safety | Clin Neuropharmacol | Sexual dysfunction reported as an adverse effect of pregabalin |
Canada Market Information
Twenty single-ingredient licences are currently valid. Dosage form and approved-indication text are not available in the compiled data. Five main authorizations:
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02268418 | LYRICA | Not available | Not available |
| 02361183 | TEVA-PREGABALIN | Not available | Not available |
| 02435977 | JAMP-PREGABALIN | Not available | Not available |
| 02449838 | ACH-PREGABALIN | Not available | Not available |
| 02479133 | NRA-PREGABALIN | Not available | Not available |
Safety Considerations
- Knowledge-graph contraindication signals (from the TxGNN knowledge graph, not label text): thrombocytopenia, angioedema (including hereditary and ACE/RAAS-blocker-induced forms), myopathy and rhabdomyolysis, impaired renal function, atrioventricular block, and some psychiatric entries (anxiety, neurotic and dysthymic disorders).
- Drug interactions: 100 interactions were found. Major ones include morphine (including liposomal morphine), which carries a risk of additive central nervous system and respiratory depression. Moderate ones include opioid-type agents (opium, diphenoxylate, difenoxin), cannabinoids (dronabinol, nabilone), metoclopramide, sibutramine and the thiazolidinediones (pioglitazone, rosiglitazone, troglitazone).
- Reported adverse effects: the literature notes sexual dysfunction, mainly at high doses.
Please refer to the package insert for the full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The package insert warnings are also missing, which blocks safety screening.
- The three highest-scoring predictions (tendinitis, granulomatous myositis, myositis fibrosa) rest mainly on the computational score and have no direct clinical support.
To proceed, the following is needed:
- Obtain the Health Canada package insert warnings and contraindications to complete safety screening
- Obtain detailed mechanism-of-action data from DrugBank
- Review the full text of the pediatric RCTs and the Cochrane review (PMID 23797675) to confirm the evidence grade and adult applicability
- Define the target population (adult vs pediatric) and whether a new adult trial is needed
- Assess the interaction risks with opioids and other central nervous system depressants
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.