Pramipexole
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
- Pramipexole
- Pramipexole: From Parkinson’s Disease and Restless Legs Syndrome to Attention Deficit-Hyperactivity Disorder
Pramipexole: From Parkinson’s Disease and Restless Legs Syndrome to Attention Deficit-Hyperactivity Disorder
One-Sentence Summary
Pramipexole is a dopamine agonist. The SAHPRA registration data supplied contain no indication text, but the literature describes its established use in Parkinson’s disease and restless legs syndrome. The TxGNN model predicts it may be useful for attention deficit-hyperactivity disorder (ADHD). Support is weak: 1 unrelated clinical trial and 9 publications, with no ADHD-specific trial.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the SAHPRA data supplied (literature describes Parkinson’s disease and restless legs syndrome) |
| Predicted New Indication | Attention deficit-hyperactivity disorder |
| TxGNN Prediction Score | 99.998% |
| Evidence Level | L4 |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data are not available in the Evidence Pack. From the literature, pramipexole is a non-ergot dopamine agonist that prefers D3 receptors (with D2 activity). Dopaminergic dysregulation is implicated in ADHD, and studies link ADHD gene variants to the dopamine D4 receptor and the α2A adrenoceptor.
The link to the original uses is indirect. Restless legs syndrome and periodic limb movements often co-occur with ADHD, and pramipexole treats those conditions. Animal work (spontaneously hypertensive rats) has been proposed as a model of this overlap. This makes the prediction plausible, but it is a hypothesis, not evidence of efficacy.
The only direct clinical report is a single case in which pramipexole plus atomoxetine was used in a patient with ADHD and chronic pain. A randomised trial in Tourette’s syndrome, a neighbouring neurodevelopmental condition, exists, but its results were not provided. No ADHD-specific trial was found.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00558766 | N/A | Completed | 35 | Transcranial magnetic stimulation study of reward signalling in Parkinson’s disease patients on dopaminergic drugs. Does not test ADHD (relevance grade C). |
No SANCTR or PACTR registrations were identified.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22407510 | 2012 | RCT | Movement Disorders | Multicentre placebo-controlled trial of pramipexole in Tourette’s syndrome. Results were not included in the data supplied. |
| 37342213 | 2023 | Case report | Front Pain Res | Remission of chronic low back pain and oral dysesthesia with atomoxetine plus pramipexole in a patient with ADHD. |
| 19412489 | 2006 | Review | Neuropsychiatr Dis Treat | Dopamine agonist pramipexole for restless legs syndrome. |
| 18656214 | 2008 | Review | Rev Neurol | Review of restless legs syndrome. |
| 15540638 | 2004 | Cohort | Dev Med Child Neurol | Periodic leg movements in 252 children with sleep disturbance, including response to pramipexole. |
| 24992083 | 2014 | Clinical study | Clin Neuropharmacol | Piribedil vs pramipexole and ropinirole on vigilance in Parkinson’s disease. Not ADHD. |
| 24079375 | 2013 | Animal study | J Motor Behav | Spontaneously hypertensive rats as a possible model of sleep-related movement disorders that overlap with ADHD. |
| 34182128 | 2021 | Preclinical | Pharmacol Res | Dopamine D4 receptor variants and α2A adrenoceptor heteromers, relevant to ADHD and impulse control. |
| 38649244 | 2024 | Case report | BMJ Case Rep | Hypokalaemia from excess cola intake in a patient with ADHD taking pramipexole among other drugs. Incidental. |
South Africa Market Information
| Registration Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Reg. No. 42/5.4.1/1024 | Pexasp 1Mg | Tablet | Not stated in data supplied |
| Reg. No. 42/5.4.1/1023 | Pexasp | Tablet | Not stated in data supplied |
| Reg. No. 43/5.4.1/0623 | Prames 0.25 | Tablet | Not stated in data supplied |
All three products are oral tablets. Essential Medicines List status was not provided.
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA. No drug interaction records were found in the query.
The literature in the Evidence Pack also points to two signals to weigh in any psychiatric use:
- Impulse-control problems: A Swedish nationwide register study (PMID 34061895) found an increased risk of gambling disorder with pramipexole.
- Psychosis: A case report (PMID 31877244) describes schizophrenia decompensation on clozapine plus pramipexole.
Conclusion and Next Steps
Decision: Hold
Rationale: The ADHD prediction rests on an indirect dopaminergic and comorbidity argument. The only evidence is one case report, a Tourette’s trial and preclinical work, with no ADHD-specific trial. The SAHPRA safety information is also missing, so the candidate cannot yet move to safety screening.
Other predicted indications (all Hold, except schizophrenia):
| Predicted Indication | Evidence Level | Note |
|---|---|---|
| Schizophrenia | L2 | Strongest signal, flagged as a research question. Add-on pramipexole RCT (PMID 35921506, n=200), a Phase 3 add-on trial (NCT01320982, n=400, status unknown, no results provided) and a meta-analysis of prodopaminergic drugs for negative symptoms. |
| ADHD, inattentive type | L5 | ADHD subtype. Evaluate together with ADHD. |
| Specific developmental disorder | L5 | Linked trial is probably a Parkinson’s disease study and target population is unconfirmed. |
| Faciodigitogenital syndrome, chondromyxoid fibroma, perisylvian polymicrogyria syndrome, glycosylation-defect disorder, atypical glycine encephalopathy | L5 | Model prediction only, no mechanistic rationale. |
| Retinal dystrophy with or without extraocular anomalies | L5 | The 14 retrieved papers are generic ocular-anomaly results, none mentioning pramipexole. |
To proceed, the following is needed:
- Download and review the SAHPRA package insert for warnings, contraindications and approved indications (blocking gap).
- Obtain the mechanism of action from DrugBank.
- Obtain the results of the Tourette’s syndrome RCT (PMID 22407510) and search for ADHD-specific pramipexole trials.
- If schizophrenia is pursued, review the Phase 3 trial NCT01320982 for results and prioritise it as a separate research question.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.