Imipramine
| Evidence Level: L3 | Predicted Indications: 7 |
Table of Contents
- Imipramine
- Imipramine: From Unspecified Original Indication to Attention-Deficit/Hyperactivity Disorder (ADHD)
Imipramine: From Unspecified Original Indication to Attention-Deficit/Hyperactivity Disorder (ADHD)
One-Sentence Summary
Imipramine is a long-established tricyclic antidepressant (TCA); the specific original licensed indication is not recorded in this evidence pack, as no UK marketing authorisation data is currently on file for this product. The TxGNN model predicts it may be effective for Attention-Deficit/Hyperactivity Disorder (ADHD), with 1 clinical trial and 20 pieces of literature currently associated with this direction — though most of the literature consists of small, dated studies rather than modern randomised controlled trials, and the single registered trial does not test imipramine directly.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available — no marketing authorisation or licensed indication text on record in this evidence pack |
| Predicted New Indication | Attention-Deficit/Hyperactivity Disorder (ADHD) |
| TxGNN Prediction Score | 99.90% |
| Evidence Level | L3 |
| UK Market Status | Not marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in this evidence pack (flagged as a High-severity data gap). Based on general pharmacological classification, Imipramine is a tricyclic antidepressant (TCA) that inhibits reuptake of noradrenaline and, to a lesser extent, serotonin. Its efficacy in depressive illness is well established historically, and this noradrenergic mechanism is mechanistically similar to atomoxetine, a non-stimulant agent with an established role in ADHD treatment.
The repurposing rationale for ADHD rests on the hypothesis that ADHD involves under-regulation of prefrontal catecholamine (particularly noradrenaline) signalling. Imipramine’s noradrenaline reuptake inhibition is consistent with this hypothesis, and it was in fact used as a second-line agent for ADHD (alongside desipramine) in the 1970s–1980s, before largely being superseded by stimulants and atomoxetine due to concerns about cardiac toxicity and anticholinergic side effects, particularly in paediatric populations.
Because the original licensed indication is not recorded in this evidence pack, the mechanistic link above should be treated as supportive context rather than a confirmed regulatory or clinical basis for extrapolation.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT03220308 | NA | Completed | 103 | Trial of an 8-week mindfulness training programme for children (8–16) with ADHD, combined with parallel mindful parenting training for parents, versus care-as-usual. Note: does not evaluate imipramine directly — relevance graded C (disease-population overlap only, no drug-specific data). |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 6849467 | 1983 | Not classified | Am J Psychiatry | Early clinical report on the use of imipramine specifically for attention deficit disorder. |
| 2830919 | 1988 | Not classified | Biol Psychiatry | Platelet [³H]imipramine binding studied in boys with ADHD before/after methylphenidate; binding parameters did not differ from controls and were unaffected by methylphenidate response. |
| 18304665 | 2008 | Not classified | Int J Psychophysiol | Investigated EEG effects of imipramine in children with ADHD who were non-responders to stimulant medication (dexamphetamine/methylphenidate). |
| 9465283 | 1996 | Not classified | Clin EEG | P300 latency testing used to predict treatment response to imipramine in stimulant-poor-responder ADHD patients. |
| 2258453 | 1990 | Not classified | J Clin Psychopharmacol | Retrospective study of carbamazepine’s effect on plasma imipramine/desipramine concentrations in children with ADHD. |
| 17078784 | 2006 | Cohort/Biomarker | Expert Rev Neurother | Discusses noradrenaline reuptake inhibitors (desipramine, imipramine) and selective agents (atomoxetine) as effective ADHD treatments; uses P300 topography to guide treatment choice. |
| 15794722 | 2005 | Review | Expert Opin Drug Saf | Reviews safety of non-stimulant ADHD agents, including tricyclics such as desipramine and imipramine as options when stimulants are unsuitable. |
| 32982805 | 2020 | Meta-review | Front Psychiatry | Meta-review of antidepressant efficacy, tolerability and suicidality across paediatric psychiatric disorders including ADHD. |
| 1974836 | 1990 | Review | Clin Pharm | General review of ADHD epidemiology, diagnosis and pharmacotherapy. |
| 31776871 | 2019 | Review (DDI) | CNS Drugs | Systematic review of clinically significant drug-drug interactions for ADHD pharmacological agents. |
UK Market Information
No marketing authorisation records are available in this evidence pack. The product is currently recorded as not marketed, with 0 licenses on file. Please consult the current BNF/electronic Medicines Compendium (eMC) or MHRA product database directly for up-to-date licensing status of imipramine-containing products in the UK.
Safety Considerations
Please refer to the SmPC and BNF for safety information. Report suspected adverse reactions via the Yellow Card Scheme.
Note: A Blocking-severity data gap has been identified — product label warnings and contraindications are not currently available in this evidence pack, which prevents a full preliminary safety assessment (S1) from being completed.
Conclusion and Next Steps
Decision: Hold
Rationale: A Blocking-severity data gap (missing label warnings/contraindications) currently prevents even a preliminary safety assessment from being completed, and mechanism-of-action data is also absent (High-severity gap). While the ADHD signal has more supporting literature than other predicted indications in this pack, the evidence is dominated by small, dated observational/pharmacokinetic studies from the 1980s–1990s rather than modern RCTs, and the one registered trial does not test imipramine directly.
To proceed, the following is needed:
- Product label warnings, contraindications and precautions (from MHRA/eMC SmPC)
- Confirmed mechanism of action and original licensed indication(s)
- Assessment of whether any modern, adequately powered RCT evidence exists for imipramine in ADHD (current evidence predates contemporary trial standards)
- Paediatric safety review, given imipramine’s known cardiac and anticholinergic risk profile and historical use in children for this indication
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.