Clonidine

Evidence Level: L5

Predicted Indications: 10

Clonidine

Pharmacist Assessment Report

Clonidine: From Hypertension to Tourette Syndrome

One-Sentence Summary

Clonidine is a centrally acting alpha-2 adrenergic agonist, originally used to treat hypertension, open-angle glaucoma and attention deficit hyperactivity disorder (ADHD). The TxGNN model’s top-ranked prediction is faciodigitogenital syndrome, but that prediction has no supporting evidence. The best-supported prediction in the data compiled for this report is Tourette syndrome, with 2 clinical trials and 18 publications, including European guidelines and a network meta-analysis. This report therefore focuses on Tourette syndrome, and the other predicted indications are summarised briefly below.

Quick Overview

Item	Content
Original Indication	Hypertension, open-angle glaucoma, ADHD (the Australian ARTG entry lists no approved indication text)
Predicted New Indication	Tourette syndrome (the highest-ranked prediction, faciodigitogenital syndrome, has no supporting evidence, so the best-supported prediction is evaluated instead)
TxGNN Prediction Score	0.9998 (Tourette syndrome); 0.9999 for the top-ranked faciodigitogenital syndrome
Evidence Level	L5
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	Proceed with Guardrails

Why is This Prediction Reasonable?

Detailed mechanism of action data are not available in the data compiled for this report. Clonidine is a well-known alpha-2 adrenergic agonist. By stimulating alpha-2 receptors in the brain, it reduces noradrenergic activity, and this is thought to dampen tics, impulsivity and hyperactivity.

Tourette syndrome is a neurodevelopmental disorder that commonly occurs together with ADHD, one of clonidine’s original indications. This overlap is the main reason the prediction is plausible. Clonidine has been used for tics since the late 1970s, and European clinical guidelines and a recent network meta-analysis include it as a treatment option, particularly when tics occur with ADHD.

The evidence level is capped at L3 because the supplied trials are small Phase 4 studies, not confirmatory Phase 3 RCTs. Guideline support is strong, and the level could be upgraded after review of the primary RCT literature.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrolment	Key Findings
NCT00152750	Phase 4	Unknown	32	Tests whether treating night-time sleep with clonidine improves day-time aggression in children with Tourette syndrome and ADHD
NCT00370838	Phase 4	Completed	12	Double-blind crossover comparison of levetiracetam (Keppra) and clonidine for tics in children with Tourette syndrome

No ANZCTR identifiers were included in the data compiled for this report.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
34757514	2022	Guideline	Eur Child Adolesc Psychiatry	European (ESSTS) guideline update on pharmacological treatment of Tourette syndrome and tic disorders
36528030	2023	Network meta-analysis	Lancet Child Adolesc Health	Compares efficacy, tolerability and acceptability of drug treatments in children, adolescents and young adults with Tourette syndrome
38695046	2024	Clinical study	Psychiatry Investigation	Efficacy and safety of the clonidine patch in Tourette syndrome with comorbid ADHD
27132945	2016	Systematic review	J Child Psychol Psychiatry	Systematic review of treatments for Tourette syndrome in children and young people
34286606	2021	Systematic review	J Psychopharmacol	Assesses the quality of evidence for drug treatment of Tourette syndrome
23473832	2013	Review	Eur J Paediatr Neurol	Pharmacological options for Tourette syndrome with comorbid ADHD
89558	1979	Clinical study	Lancet	Early report that small doses of clonidine improved some children unresponsive to haloperidol
6109915	1981	Clinical study	Lancet	Early report of clonidine in Tourette syndrome

Other Predicted Indications

The data compiled for this report also cover nine other predictions. None has stronger evidence than Tourette syndrome.

Predicted Indication	Evidence Level	Summary
Faciodigitogenital syndrome	L5	Highest TxGNN rank, but no trials, no literature and no plausible mechanistic link
Specific developmental disorder	L5	Indirect support from narrative reviews and one animal study; the category is broad and no trials are listed
Chondromyxoid fibroma	L5	No evidence or mechanistic link
Trichotillomania	L5	Only a mouse study suggesting a noradrenergic link; no human evidence
Obesity disorder	L3	Two small mechanistic trials (one terminated Phase 2, one recruiting Phase 1) in obesity-related hypertension and inflammation; not weight-loss trials
Hypervitaminosis	L5	No evidence or mechanistic link
Proximal 16p11.2 microdeletion syndrome	L5	No direct evidence; the link to neurodevelopmental features is speculative
Migraine disorder	L4	Historical studies from the 1970s and 1980s with inconsistent results; current guidelines do not generally favour clonidine
Manic bipolar affective disorder	L3	A 2023 systematic review and a 2022 double-blind placebo-controlled trial of adjuvant clonidine offer limited support; the one listed trial (NCT03065933) was terminated with 5 participants

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
ARTG 13548C	Catapres	Tablet containing clonidine hydrochloride 150 micrograms	Not stated in the data compiled for this report

Safety Considerations

Contraindication signals from the knowledge graph (these come from drug-disease contraindication links in the TxGNN knowledge graph, not from approved label text). They include:

Cardiovascular: hypotensive disorder, myocardial infarction, myocardial ischaemia, coronary thrombosis, sudden cardiac arrest, heart conduction disease
Metabolic: type 1 and type 2 diabetes mellitus, diabetic ketoacidosis, gout, potassium deficiency, hypercalcaemia
Other: liver failure, anuria, pancreatitis, systemic lupus erythematosus, respiratory failure, anxiety and neurotic disorders

Drug interactions: 100 interactions were recorded, and the 20 reviewed here were all rated Moderate. They include:

Corticosteroids (hydrocortisone, dexamethasone, betamethasone, budesonide, triamcinolone)
Antidiabetic agents (insulins, sulfonylureas such as glimepiride, glipizide and glyburide, and SGLT2 inhibitors such as canagliflozin, dapagliflozin and empagliflozin)
Bupropion, morphine and dronabinol

Please refer to the TGA-approved Product Information (PI) for official warnings and contraindications.

Conclusion and Next Steps

Decision: Proceed with Guardrails (Tourette syndrome only)

Rationale:

Clonidine has a plausible mechanism, two small Phase 4 trials, and guideline and network meta-analysis support for Tourette syndrome, especially with comorbid ADHD. The trials are small and not confirmatory.
The other predictions are not ready to progress. Faciodigitogenital syndrome, chondromyxoid fibroma, hypervitaminosis and 16p11.2 microdeletion syndrome should be held. Obesity, migraine, mania and specific developmental disorder remain research questions.

To proceed, the following is needed:

Review of the primary RCT literature to confirm whether the evidence level can be upgraded
Mechanism of action data from DrugBank
Warnings and contraindications from the TGA Product Information, since this safety data was missing from the data compiled for this report
The approved indication text for the Catapres ARTG entry
A safety monitoring plan for paediatric use, covering low blood pressure, sedation and cardiovascular risk
Disclaimer

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