Clomipramine
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Clomipramine: From Obsessive-Compulsive Disorder to Anxiety Disorder
One-Sentence Summary
Clomipramine is a tricyclic antidepressant (TCA) whose classic, long-established clinical role — as documented throughout the literature evidence gathered for this report — is in obsessive-compulsive disorder and depression, with well-recognised extensions into panic disorder and agoraphobia. The TxGNN model predicts it may also be effective for the broader diagnostic category of Anxiety Disorder, with 19 clinical trials and 20 publications currently identified in support of this direction — though most of this evidence concerns specific anxiety-spectrum subtypes (OCD, panic disorder, trichotillomania) rather than “anxiety disorder” as a standalone umbrella diagnosis.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | No UK marketing authorisation is on record in the data reviewed (drug not currently marketed); literature evidence in this pack documents long-standing historical use in obsessive-compulsive disorder and depression |
| Predicted New Indication | Anxiety Disorder |
| TxGNN Prediction Score | 99.93% |
| Evidence Level | L1 |
| UK Market Status | Not Marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not currently available from DrugBank for this evidence pack (data gap DG002, severity: High). Based on the published pharmacological literature retrieved above, Clomipramine is a tricyclic antidepressant (TCA) and is widely recognised as the most serotonin-selective agent within the TCA class, acting primarily through inhibition of serotonin reuptake (with weaker noradrenaline reuptake inhibition). Its efficacy in obsessive-compulsive disorder and depression has been established since the 1970s–1980s and is repeatedly described in the retrieved literature as making it a “reference drug” for these conditions.
Obsessive-compulsive disorder, panic disorder and agoraphobia are all classified within the broader anxiety-disorder spectrum, and clomipramine already has a substantial historical evidence base specifically in panic disorder/agoraphobia (see the agoraphobia-specific evidence identified elsewhere in this evidence pack, rank 7). Predicting efficacy for the general “anxiety disorder” category is therefore best understood as a consolidation of already-documented efficacy across several anxiety-spectrum subtypes, rather than an entirely novel biological hypothesis.
As the TxGNN model’s rationale notes, clomipramine’s strong serotonin reuptake inhibition has long made it a pharmacological reference standard for OCD and anxiety-spectrum disorders more broadly. Although most of the retrieved evidence centres on specific subtypes — OCD, panic disorder, and trichotillomania — rather than “anxiety disorder” as a single diagnosis, the underlying mechanism supporting an anxiolytic/anti-obsessional effect is consistent across these subtypes.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00004310 | Phase 2 | Unknown | 76 | Compared intravenous vs oral pulse-loading of clomipramine followed by 12-week maintenance therapy in OCD — a direct clomipramine dosing/route study |
| NCT00564564 | Phase 4 | Completed | 21 | Open trial comparing clomipramine augmentation vs quetiapine augmentation of SSRIs in SSRI-refractory OCD |
| NCT01404871 | N/A | Completed | 26 | Randomised patients to clomipramine or escitalopram to identify predictors of medication response in OCD |
| NCT00466609 | Phase 4 | Completed | 54 | Double-blind, double-dummy trial comparing fluoxetine alone, fluoxetine + quetiapine, and fluoxetine + clomipramine augmentation in treatment-resistant OCD |
| NCT00254735 | Phase 3 | Completed | 44 | Quetiapine vs placebo added to baseline SSRI/clomipramine therapy in severe OCD |
| NCT01148316 | N/A | Completed | 144 | Adaptive treatment strategy study in paediatric/adolescent psychiatric disorders; notes clomipramine and SSRIs as approved pharmacotherapy for paediatric OCD |
| NCT04436952 | N/A | Withdrawn | 0 | Planned comparison of TMS with/without exposure-response prevention (ERP) vs ERP alone, citing SSRI/clomipramine + ERP as the treatment gold standard — trial withdrawn, limited evidentiary value |
| NCT02374567 | Phase 3 | Terminated | 407 | Multicentre pharmacovigilance study of psychopharmacological treatment safety in gerontopsychiatric inpatients — relevant TCA-class safety context |
| NCT00074815 | Phase 3 | Completed | 124 | Evaluated whether cognitive behavioural therapy augments SRI-class (including clomipramine) treatment response in paediatric OCD partial responders |
| NCT03299166 | Phase 2/3 | Completed | 426 | Troriluzole vs placebo as adjunctive therapy in OCD patients with inadequate response to SSRI, clomipramine, venlafaxine or desvenlafaxine |
No ISRCTN or EU Clinical Trials Register (EU CTR) identifiers were present in the evidence pack for this candidate.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 7795952 | 1995 | RCT | J Child Adolesc Psychiatr Nurs | Clomipramine was the first effective TCA agent for OCD; serotonin reuptake blockade appears essential to its anti-obsessional effect |
| 3887445 | 1985 | RCT | Psychiatry Research | 12-week double-blind trial of clomipramine vs imipramine in 23 OCD outpatients; both produced modest symptom reduction |
| 1474179 | 1992 | RCT | J Clin Psychopharmacol | Compared clomipramine, clonazepam and clonidine against a diphenhydramine control in OCD; serotonergic/adrenergic agents reduced obsessive-compulsive symptoms |
| 1933762 | 1991 | RCT | Can J Psychiatry | Intravenous clomipramine controlled OCD symptoms refractory to oral therapy, with 3-year follow-up |
| 38014714 | 2023 | Network Meta-analysis | Cochrane Database Syst Rev | Network meta-analysis of pharmacological treatments, including clomipramine, for panic disorder in adults |
| 34582562 | 2021 | Review (Cochrane) | Cochrane Database Syst Rev | Updated Cochrane review of medication, including clomipramine, for trichotillomania (an anxiety-spectrum condition) |
| 24214100 | 2013 | Review (Cochrane) | Cochrane Database Syst Rev | Earlier Cochrane review of medication, including clomipramine, for trichotillomania |
| 11450830 | 2001 | Review | J Am Anim Hosp Assoc | Overview of clomipramine use in separation-anxiety-related conditions, providing mechanistic context |
| 3887336 | 1985 | Review | Psychiatr Clin North Am | Classic review establishing clomipramine’s efficacy in OCD, an anxiety-spectrum disorder |
| 12063477 | 2002 | Review | J Am Acad Dermatol | Review of trichotillomania discussing shared anxiety/OCD-spectrum mechanisms relevant to serotonergic treatment |
UK Market Information
Clomipramine does not currently hold a marketing authorisation in the UK according to the regulatory data reviewed for this evidence pack — no product licences are on record (0 of 0). This should be treated as a data gap requiring confirmation against the current MHRA products register rather than as a definitive statement of UK availability, since it directly affects whether this candidate can be prescribed without further regulatory action.
Safety Considerations
Please refer to the SmPC and BNF for safety information. Report suspected adverse reactions via the Yellow Card Scheme.
Note: No structured safety data (key warnings, contraindications, or drug-drug interactions) were available for Clomipramine in this evidence pack (data gap DG001, severity: Blocking — this blocks progression through the S1 safety screening stage). Separately, several of the literature items identified above and elsewhere in this evidence pack describe TCA-class adverse-effect signals in case reports and pharmacovigilance studies (e.g. clomipramine-induced pancytopenia, clomipramine-induced tourettism, orthostatic hypotension, and seizure risk with antidepressants generally). These are incidental literature findings, not confirmed structured safety data, and must not be relied upon in place of the SmPC.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The predicted indication (Anxiety Disorder) is supported by L1-level evidence (multiple completed Phase 2–4 studies and RCTs) and a mechanistically coherent rationale — clomipramine’s strong serotonin reuptake inhibition has a long, well-documented history in closely related anxiety-spectrum subtypes (OCD, panic disorder, trichotillomania). However, this candidate currently sits at decision stage S3 with a Blocking data gap on UK safety/prescribing information (DG001) and no confirmed UK marketing authorisation, so guardrails are essential before any further action.
To proceed, the following is needed:
- Formal SmPC/BNF safety data — key warnings, contraindications, and drug interaction profile (resolves blocking gap DG001)
- Detailed mechanism of action data from DrugBank (resolves data gap DG002)
- Confirmation of current UK marketing authorisation status, since the evidence pack records 0 licences and “Not Marketed”
- Clarification of the original licensed indication(s) in the UK, to properly assess similarity/overlap with the predicted anxiety-disorder indication
- A safety monitoring plan reflecting known TCA-class risks (cardiac conduction effects, anticholinergic burden, overdose toxicity) given the age and vulnerability of populations studied in the trials above (e.g. paediatric and gerontopsychiatric cohorts)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.