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
- Canada 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), with no registered clinical trials but 20 publications (mostly reviews, with a small number of clinical reports) currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Anxiety disorder, neurotic disorder, dysthymic disorder, nocturnal enuresis (Health Canada indication text is not available in the data compiled for this report) |
| Predicted New Indication | Attention deficit-hyperactivity disorder |
| TxGNN Prediction Score | 0.9990 |
| Evidence Level | L3 (provisional; study designs could not be verified from titles alone) |
| Canada Market Status | Marketed (marketed DINs: 8 of 8) |
| Number of DINs | 8 (marketed: 8) |
| Recommended Decision | Proceed with Guardrails |
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 inhibits presynaptic reuptake of norepinephrine and, to a lesser extent, serotonin. Enhanced noradrenergic signaling in prefrontal circuits is the same mechanism targeted by approved non-stimulant ADHD drugs such as atomoxetine, which makes the link biologically plausible.
Imipramine is already used for nocturnal enuresis, a condition that frequently co-occurs with ADHD in children, and for anxiety and dysthymic disorders, which are common comorbidities. Several retrieved reviews describe imipramine and desipramine as non-stimulant options when stimulants fail or are not tolerated, and one study examined imipramine in children with ADHD who did not respond to stimulants.
Overall, imipramine would be a second- or third-line option after approved agents, not a replacement for them.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 6849467 | 1983 | Clinical study (design unverified) | Am J Psychiatry | “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 stimulant-poor-responder children treated with imipramine, prolonged P300 latency predicted poor response |
| 10790990 | 1999 | Review | Evid Rep Technol Assess | Evidence report on effectiveness and safety of drug and non-drug ADHD treatments |
| 15794722 | 2005 | Review | Expert Opin Drug Saf | Safety of non-stimulant ADHD agents; tricyclics such as imipramine may be effective when stimulants are unsuitable |
| 17078784 | 2006 | Clinical study | Expert Rev Neurother | P300 topography to choose treatment; imipramine and desipramine listed as effective noradrenergic options |
| 32982805 | 2020 | Meta-review | Front Psychiatry | Efficacy, tolerability and suicidality of antidepressants in children and adolescents, including ADHD and enuresis |
| 31776871 | 2019 | Review | CNS Drugs | Pharmacokinetic drug interactions of ADHD agents |
| 14501767 | 2003 | Clinical study | J Urol | Management of urinary incontinence and nocturnal enuresis in children with ADHD |
| 6355189 | 1983 | Review | J Dev Behav Pediatr | Overview of pediatric psychopharmacology, including imipramine for attention deficit disorder |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02546345 | JAMP IMIPRAMINE | Not specified | Not specified |
| 00326852 | APO-IMIPRAMINE TABLETS | Tablet | Not specified |
| 00644579 | APO-IMIPRAMINE TABLETS | Tablet | Not specified |
| 00360201 | APO-IMIPRAMINE TABLETS | Tablet | Not specified |
| 02546353 | JAMP IMIPRAMINE | Not specified | Not specified |
Eight single-ingredient licences are currently valid in Canada (the five above are shown).
Safety Considerations
- Contraindication-related conditions (from the knowledge graph, not label text): epilepsy, bipolar disorder, kidney and liver disease, gallbladder disease, blood disorders (thrombocytopenia, neutropenia, agranulocytosis), benign prostatic hyperplasia, substance abuse/dependence, angle-closure glaucoma and ocular hypertension, ileus and intestinal obstruction, hyperthyroidism, and cardiovascular, cerebrovascular and heart conduction disease (including sudden cardiac arrest, coronary artery disease and stroke).
- Drug Interactions: 100 interactions are listed. Major-level examples include epinephrine, bupropion, lorcaserin, potassium citrate and dolasetron. Moderate-level examples include famotidine, cimetidine, clarithromycin, morphine, acetylsalicylic acid and several anticholinergics (atropine, hyoscyamine, glycopyrronium, dicyclomine).
- Key concerns for ADHD use: cardiac conduction effects, anticholinergic burden and overdose toxicity are significant, especially in children.
Please refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The noradrenergic mechanism is plausible and a few published clinical reports, including work in stimulant non-responders, support the idea. However, no trials are registered, study designs are unverified, and cardiac and anticholinergic risks and numerous interactions limit use, so imipramine remains a later-line option behind approved ADHD agents.
To proceed, the following is needed:
- Verification of the study designs of the key publications (for example the 1983 report and the 2008 EEG study) to confirm the evidence level
- Health Canada package insert warnings and contraindications (a blocking gap for safety screening)
- Detailed mechanism of action data
- A safety plan covering ECG monitoring, interaction review and overdose risk, particularly in paediatric patients
- Health Canada indication text and dosage forms for each licence
Other Predicted Indications (Brief Note)
- ADHD, inattentive type: Hold. No trials or subtype-specific literature; the high score likely reflects proximity to the parent ADHD term and should be evaluated under the parent indication.
- Obsessive-compulsive disorder: Research question. A 1985 comparison suggests imipramine is less effective than clomipramine, and SSRIs and clomipramine are already established.
- Faciodigitogenital syndrome, specific developmental disorder, chondromyxoid fibroma, benign paroxysmal torticollis of infancy: Hold. No plausible mechanistic link or direct evidence.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.