Imipramine
| Evidence Level: L3 | Predicted Indications: 7 |
Table of Contents
- Imipramine
- Pharmacist Assessment Report
- Imipramine: From Anxiety Disorder to Attention Deficit-Hyperactivity Disorder
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- India Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Imipramine: From Anxiety Disorder to 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), but there are no registered clinical trials. The direction is supported by 20 publications, mostly older reviews and small studies judged from titles and abstracts only.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Anxiety disorder, neurotic disorder, dysthymic disorder, nocturnal enuresis |
| Predicted New Indication | Attention deficit-hyperactivity disorder |
| TxGNN Prediction Score | 0.9990 |
| Evidence Level | L3 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, imipramine inhibits reuptake of norepinephrine and, to a lesser degree, serotonin. Its active metabolite, desipramine, is mainly noradrenergic.
Enhancing noradrenergic signalling in prefrontal circuits is a recognized way to control ADHD symptoms. It is shared with atomoxetine and desipramine. The literature includes reviews that list imipramine among non-stimulant options when stimulants fail, and a 1983 report titled “Imipramine for attention deficit disorder.”
The original indications (anxiety, dysthymia, enuresis) are related to ADHD by shared monoaminergic mechanisms and frequent co-occurrence in children. The supporting evidence is old, and no trial records exist. The claim therefore rests on older literature and should be treated as a research question rather than a proven use.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 6849467 | 1983 | Clinical study (design not verifiable) | Am J Psychiatry | Report on imipramine for attention deficit disorder; no abstract available |
| 18304665 | 2008 | Clinical study | Int J Psychophysiol | Effects of imipramine on EEG in children with ADHD who did not respond to stimulants |
| 9465283 | 1996 | Clinical study | Clin EEG | In 17 ADHD children who responded poorly to pemoline, prolonged P300 latency predicted poor response to imipramine |
| 32982805 | 2020 | Meta-review | Front Psychiatry | Efficacy, tolerability and suicidality of antidepressants in children, including ADHD and enuresis |
| 15794722 | 2005 | Review | Expert Opin Drug Saf | Safety of non-stimulant ADHD agents; tricyclics such as imipramine may be effective when stimulants are not suitable |
| 31776871 | 2019 | Review | CNS Drugs | Pharmacokinetic drug interactions of ADHD agents |
| 17078784 | 2006 | Review | Expert Rev Neurother | Imipramine and desipramine named as non-selective norepinephrine reuptake inhibitors; P300 topography for choosing treatment |
| 10790990 | 1999 | Review | Evid Rep Technol Assess | Effectiveness and safety of drug and non-drug ADHD interventions |
| 14501767 | 2003 | Clinical study | J Urol | Management of urinary incontinence and nocturnal enuresis in ADHD |
| 6487858 | 1984 | Clinical study | Br J Clin Psychol | 32 hyperactive children on imipramine or methylphenidate, examined for state-dependent learning |
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 110322 | Imipra 25mg Tablet (Cyril Pharmaceuticals) | Strip of 10 tablets | Not stated |
| 6211 | Antipres 25mg Tablet (Psycormedies) | Strip of 10 tablets | Not stated |
| 111868 | Impranit 25mg Tablet (Signit Laboratories) | Strip of 10 tablets | Not stated |
| 58325 | Depsonil 25mg Tablet (Abbott) | Strip of 10 tablets | Not stated |
| 512 | Antidep 25mg Tablet (Torrent Pharmaceuticals) | Strip of 10 tablets | Not stated |
There are 20 valid single-ingredient oral registrations in total, all as tablets.
Safety Considerations
- Contraindications (from knowledge-graph drug-disease links, not label text): epilepsy; kidney, liver and gallbladder disease; bipolar and major affective disorder; blood disorders (thrombocytopenia, neutropenia, agranulocytosis); benign prostatic hyperplasia; cardiovascular conditions (coronary artery disease, heart conduction disease, sudden cardiac arrest, stroke and cerebrovascular disorders); ileus and intestinal obstruction; angle-closure glaucoma and ocular hypertension; hyperthyroidism and Graves disease; substance abuse or dependence.
- Drug Interactions: 290 interactions were recorded. Major ones include epinephrine, bupropion, lorcaserin, potassium citrate and dolasetron. Moderate ones include anticholinergics (atropine, hyoscyamine, glycopyrronium, dicyclomine), cimetidine, famotidine, clarithromycin, morphine, loperamide and acetylsalicylic acid.
- Paediatric concern: Cardiac conduction effects and the high interaction burden, including with stimulants and other ADHD agents, are particular concerns in children.
Please also refer to the package insert, which was not available for this review.
Conclusion and Next Steps
Decision: Hold
Rationale: The ADHD prediction has a plausible noradrenergic mechanism and some older literature, but there are no registered trials. The evidence is mostly reviews and small studies judged from titles and abstracts. Cardiac risk and the heavy interaction burden are significant in children, and established stimulant and non-stimulant options exist. The other predicted indications (ADHD inattentive type, faciodigitogenital syndrome, specific developmental disorder, chondromyxoid fibroma, benign paroxysmal torticollis of infancy) have little or no supporting evidence. Obsessive-compulsive disorder has older literature but is better served by clomipramine and SSRIs. These are also not recommended for advancement.
To proceed, the following is needed:
- Package insert warnings and contraindications for the India-marketed products
- Detailed mechanism of action data
- A systematic review of randomized evidence for imipramine in ADHD, including comparison with atomoxetine and desipramine
- A cardiac safety assessment (ECG monitoring) and a paediatric dosing and interaction plan
- Confirmation of whether the ADHD indication is approved in India, since the registered indication text is blank
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.