Imipramine
| Evidence Level: L3 | Predicted Indications: 7 |
Table of Contents
- Imipramine
Imipramine: Attention deficit-hyperactivity disorder
One-Sentence Summary
Imipramine is a tricyclic antidepressant, originally used for anxiety disorder, neurotic disorder, dysthymic disorder and nocturnal enuresis. The TxGNN model predicts it may be effective for attention deficit-hyperactivity disorder (ADHD), with no registered clinical trials and 19 publications (mostly dated reviews and small clinical reports) currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Attention deficit-hyperactivity disorder |
| TxGNN Prediction Score | 0.9990 |
| Evidence Level | L3 |
| 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 (research question only) |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, imipramine is a tricyclic antidepressant that inhibits the reuptake of noradrenaline and serotonin.
Noradrenergic enhancement in prefrontal circuits is also the mechanism of non-stimulant ADHD drugs such as atomoxetine, so the link is plausible. Imipramine and its metabolite desipramine are described in the literature as non-selective noradrenaline reuptake inhibitors that can be effective when stimulants fail. Older clinical reports support this, including “Imipramine for attention deficit disorder” (1983) and a study of children with ADHD who did not respond to stimulants.
There are limits. The evidence is mostly dated reviews, cardiac and anticholinergic safety concerns apply in children, and approved alternatives exist (stimulants first line, atomoxetine second line).
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Of the 19 publications retrieved, the most relevant are listed below. Most are reviews or small studies; no randomised controlled trials were identified.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 32982805 | 2020 | Meta-review | Front Psychiatry | Efficacy, tolerability and suicidality of antidepressants in children and adolescents, including ADHD and enuresis |
| 15794722 | 2005 | Review | Expert Opin Drug Saf | Safety of non-stimulant ADHD agents; tricyclics such as imipramine and desipramine may be effective but atomoxetine is preferred second line |
| 31776871 | 2019 | Review | CNS Drugs | Pharmacokinetic drug interactions of ADHD agents |
| 17078784 | 2006 | Cohort | Expert Rev Neurother | P300 topography to choose treatment; imipramine noted as a non-selective noradrenaline reuptake inhibitor option |
| 18304665 | 2008 | Clinical study | Int J Psychophysiol | EEG effects of imipramine in children with ADHD who did not respond to stimulants |
| 9465283 | 1996 | Clinical study | Clin EEG | Prolonged P300 latency predicted poor response to imipramine in stimulant non-responders (17 children) |
| 6849467 | 1983 | Clinical report | Am J Psychiatry | Clinical report of imipramine for attention deficit disorder |
| 2258453 | 1990 | Retrospective study | J Clin Psychopharmacol | Carbamazepine may affect plasma imipramine concentrations in 36 children with ADHD |
| 14501767 | 2003 | Clinical study | J Urol | Management of urinary incontinence and nocturnal enuresis in children with ADHD |
| 1974836 | 1990 | Review | Clin Pharm | Overview of ADHD and its pharmacotherapy |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 12113M | Imipramine (Leading) | Tablet containing imipramine hydrochloride 25 mg (s19A) | Not available in the compiled data |
The product is an oral tablet supplied under Section 19A (import of an unregistered product during a shortage). Because approved indication text is not available, check the current Product Information for the exact approved uses.
Cytotoxicity
Not applicable (imipramine is not an antineoplastic drug), so this section is omitted.
Safety Considerations
Product Information warnings and contraindications were not available in the data compiled for this report. Please refer to the TGA-approved Product Information (PI) for label safety information.
The knowledge graph lists the following conditions as contraindication-related, which supports the clinical concerns above (not label text):
- Cardiovascular: coronary artery disease, heart conduction disease, heart disease, sudden cardiac arrest, stroke and cerebrovascular disorders
- Neurological and psychiatric: epilepsy, bipolar disorder, major affective disorder, substance abuse/dependence
- Anticholinergic-related: angle-closure glaucoma, ocular hypertension, benign prostatic hyperplasia, ileus and intestinal obstruction
- Haematological: neutropenia, agranulocytosis, thrombocytopenia
- Other: kidney, liver and gallbladder disease, hyperthyroidism and Graves disease
Drug interactions: 100 interactions were recorded. Examples of Major interactions include epinephrine, bupropion, lorcaserin, dolasetron and potassium citrate. Examples of Moderate interactions include cimetidine, famotidine, clarithromycin, morphine, aspirin, atropine, hyoscyamine, glycopyrronium, loperamide and dicyclomine.
In children, cardiac conduction effects, anticholinergic effects and overdose toxicity are the main concerns.
Conclusion and Next Steps
Decision: Hold (research question only)
Rationale: The mechanistic link is plausible and older reports describe use in stimulant non-responders. However, there are no registered trials and no randomised controlled evidence in the data compiled, and approved alternatives are available. Paediatric cardiac and anticholinergic safety concerns further limit the benefit-risk balance. The high prediction score (0.9990) should not be read as clinical evidence.
To proceed, the following is needed:
- A systematic review of controlled trials of imipramine and desipramine in ADHD, including comparison with atomoxetine and stimulants
- Detailed mechanism of action data
- TGA Product Information safety data (warnings and contraindications) for the Australian product
- A paediatric safety plan covering ECG monitoring, anticholinergic effects and overdose risk
- Clarification of the approved indications of the Section 19A product
Note on other predicted indications
The same analysis ranked other candidates. Most have no supporting evidence and look like model artefacts, including faciodigitogenital syndrome, chondromyxoid fibroma, benign paroxysmal torticollis of infancy, and paranoid and schizoid personality disorders (all Hold). Two stand out:
- Guardrails are ECG and anticholinergic monitoring, overdose toxicity, drug interactions, and comparison with first-line SSRIs and CBT. It partly overlaps with the existing anxiety-related uses.
- Obsessive-compulsive disorder (L3, Research Question). Older comparative studies suggest imipramine is less effective than clomipramine, and approved SSRIs and clomipramine are preferred.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.