Pregabalin

Evidence Level: L5

Predicted Indications: 6

Pregabalin

Pharmacist Assessment Report

Pregabalin: Tendinitis (top-ranked); osteoarthritis has the strongest supporting evidence (tendinitis)

One-Sentence Summary

Pregabalin is a gabapentinoid originally used for anxiety disorder, fibromyalgia, myofascial pain syndrome and postherpetic neuralgia. The TxGNN model’s top-ranked prediction is tendinitis, but it has no registered clinical trials and only indirect literature. Better-supported predicted directions are osteoarthritis (9 relevant trials, 1 meta-analysis), headache disorder and migraine disorder.

Quick Overview

Item	Content
Original Indication	Not recorded in the local data
Predicted New Indication	Tendinitis (top-ranked); osteoarthritis has the strongest supporting evidence (tendinitis)
TxGNN Prediction Score	0.9971
Evidence Level	L5 for tendinitis (L1 for osteoarthritis and headache disorder; L2 for migraine disorder)
Australia Market Status	Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data
Number of PBS Items	1 (valid: 1)
Recommended Decision	Hold for tendinitis; Proceed with Guardrails is worth considering for osteoarthritis pain

Why is This Prediction Reasonable?

Detailed mechanism of action data are not available in the data compiled for this report. Pregabalin is generally understood to bind the alpha2-delta subunit of voltage-gated calcium channels. This reduces excitatory neurotransmitter release and dampens neuropathic and central-sensitisation pain signalling. This is consistent with its established use in postherpetic neuralgia and fibromyalgia.

For tendinitis, the link is indirect. Tendinitis is mainly inflammatory and mechanical, so pregabalin could plausibly help only with neuropathic pain components, such as nerve impingement. The very high TxGNN score is not supported by direct clinical data. The retrieved literature consists of a fluoroquinolone-associated disability report, an editorial on piriformis syndrome, a case report of nerve impingement after a marathon and two perioperative rotator cuff repair studies (one RCT, one retrospective cohort). None test pregabalin as a treatment for tendinitis itself.

The other predictions are more plausible:

This would be symptom control, not disease modification.
Migraine and headache disorders: Preclinical work shows pregabalin raises the threshold for cortical spreading depression, a plausible basis for migraine prophylaxis.
Myositis fibrosa, idiopathic granulomatous myositis, inclusion body myositis, osteoarthritis susceptibility and atrophoderma vermiculata: These are prediction-only, with no supportive evidence. Any role would be limited to symptomatic pain relief at most.

Clinical Trial Evidence

There are no registered clinical trials for tendinitis. Findings are summarised from registry descriptions only, and results have not been verified.

Trial Number	Phase	Status	Enrolment	Key Findings
NCT00442546	Phase 3	Completed	307	Multicentre, double-blind, placebo-controlled study of pregabalin for post-operative pain after total knee arthroplasty
NCT04532684	Phase 4	Completed	66	Duloxetine vs pregabalin in knee osteoarthritis with mixed-type pain
NCT00581685	Phase 3	Completed	31	Pregabalin plus celecoxib around total hip arthroplasty; small perioperative study
NCT05447364	Phase 4	Completed	82	75 mg vs 150 mg pregabalin for pain after total knee arthroplasty
NCT03604354	Phase 4	Completed	95	Tapentadol vs pregabalin for post-operative pain after knee arthroplasty
NCT05322681	NA	Unknown	90	Pregabalin for neuropathic pain after knee arthroplasty in patients without central sensitisation
NCT05254652	NA	Unknown	90	Pregabalin in centrally sensitised patients treated with duloxetine after knee arthroplasty
NCT06328062	NA	Recruiting	80	Mirogabalin vs pregabalin after knee arthroplasty
NCT07598474	NA	Recruiting	35	Pregabalin hydrogel phonophoresis with calf muscle technique in Grade III knee OA

Other predicted indications with trials:

NCT06271486: Phase 3, completed, n=75. Pregabalin as an alternative to epidural blood patch for postdural puncture headache.
NCT03910088: Phase 4, completed, n=30. Pregabalin vs hydrocortisone for postdural puncture headache.
Migraine disorder: NCT00447369 (Phase 3, n=70, pregabalin vs sodium valproate) was withdrawn, so it yields no efficacy data.

Literature Evidence

No literature directly addresses pregabalin for tendinitis. The most relevant publications for the better-supported indications are listed below.

PMID	Year	Type	Journal	Key Findings
42481863	2026	Systematic review/Meta-analysis	Inflammopharmacology	Effect of pregabalin on pain and function in knee osteoarthritis (RCT meta-analysis)
23918578	2013	RCT	Yonsei Med J	Meloxicam plus pregabalin for knee osteoarthritis pain
35442367	2022	Comparative clinical study	Rev Assoc Med Bras	Duloxetine vs pregabalin on pain and function in knee osteoarthritis
29066930	2017	Randomised clinical study	J Pain Res	Pregabalin or duloxetine vs placebo for hand osteoarthritis pain
39388181	2024	Network meta-analysis	JAMA Netw Open	Preventive medications in paediatric migraine
37637787	2023	RCT	Iran J Child Neurol	Pregabalin vs sodium valproate in paediatric migraine prophylaxis
26024701	2015	RCT	Acta Med Iran	Propranolol vs pregabalin for childhood migraine prophylaxis
28223480	2017	Preclinical	PNAS	Pregabalin inhibits cortical spreading depression in vivo
34052386	2022	RCT	Arthroscopy	Perioperative pregabalin vs interscalene block after rotator cuff repair (tendon-related, postoperative pain)
39688824	2024	Clinical study	Pain Physician	Prednisolone vs pregabalin for post-dural puncture headache

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
ARTG 2335X	Lyzalon	Capsule 75 mg	Not available in the data compiled for this report

Safety Considerations

Contraindications from the knowledge graph: The TxGNN knowledge graph lists drug-disease contraindication links, which are not drawn from label text. They include thrombocytopenia, several forms of angioedema, myopathy and other muscle diseases (including rhabdomyolysis), impaired renal function and atrioventricular block. Some of these may reflect warnings and precautions, so they should be checked against the PI.
Drug interactions: The interaction screen returned 100 records. The Major interactions identified are with morphine (including liposomal morphine), which is consistent with additive central nervous system and respiratory depression. Moderate interactions include diphenoxylate, difenoxin, dronabinol, nabilone, opium, metoclopramide, sibutramine and the thiazolidinediones (pioglitazone, rosiglitazone, troglitazone).
Sexual dysfunction and abuse potential have also been described.

For label warnings and contraindications, please refer to the TGA-approved Product Information (PI).

Conclusion and Next Steps

Decision: Hold (tendinitis)

Rationale:

The tendinitis prediction has the highest TxGNN score (0.9971) but no registered trials and only indirect literature. The mechanistic link is limited to possible neuropathic pain components.
Their evidence concerns symptom control in specific settings, so they would need cautious, guarded evaluation.

To proceed, the following is needed:

Mechanism of action data and the TGA Product Information (including approved indications, warnings and contraindications), both currently missing
For tendinitis, a focused literature review or a pilot trial in tendinopathy with neuropathic features
A plan for managing opioid co-prescribing and renal impairment
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.