Trazodone
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Trazodone: From Depression to Obsessive-Compulsive Disorder
One-Sentence Summary
Trazodone is an antidepressant marketed in South Africa as oral capsules. The TxGNN model predicts it may be useful for Obsessive-Compulsive Disorder (OCD). Support is limited to 1 small double-blind placebo-controlled study, several open-label series and case reports from 1984-1993, and no registered clinical trials.
Quick Overview
| Item | Content |
|---|---|
| Predicted New Indication | Obsessive-compulsive disorder |
| TxGNN Prediction Score | 99.95% |
| Evidence Level | L2 (one published small double-blind RCT, no registered trial; no Phase 3 evidence) |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the Evidence Pack. The following comes from general pharmacology and the retrieved literature. Trazodone is described as a 5-HT2A/2C receptor antagonist with weak serotonin reuptake inhibition. OCD responds mainly to serotonin reuptake inhibitors such as clomipramine, fluoxetine, fluvoxamine and paroxetine. Serotonergic modulation is therefore a plausible bridge between the two conditions.
The SAHPRA registration data provided does not state an approved indication. The literature describes trazodone as an antidepressant approved for depression. OCD often co-occurs with depression, and some early reports describe patients whose obsessive-compulsive symptoms improved alongside their mood. A 1990 series in clomipramine-resistant patients also suggests a possible role as an add-on treatment.
The high TxGNN score is a model prediction, not clinical proof. The clinical signal is old, small, and mostly uncontrolled.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 1629380 | 1992 | RCT | J Clin Psychopharmacol | Double-blind, placebo-controlled study of trazodone in OCD. Outcome and sample size are not visible in the excerpt provided. |
| 2119885 | 1990 | Case series | Clin Neuropharmacol | 9 clomipramine-resistant patients: mild overall improvement, 3 marked responders whose symptoms returned on withdrawal. |
| 3501130 | 1987 | Case series | Psychopathology | Trazodone response in OCD, with or without an MAO inhibitor, correlated with changes in caudate glucose metabolism on PET. |
| 8434675 | 1993 | Case series | Am J Psychiatry | Trazodone in OCD and trichotillomania. |
| 3571943 | 1986 | Open pilot trial | Int Clin Psychopharmacol | Trazodone plus tryptophan in 11 patients: marginal benefit, and several patients tolerated the combination poorly. |
| 8331098 | 1993 | Review | J Clin Psychiatry | Biological approaches to treatment-resistant OCD, mainly augmentation of a potent serotonin reuptake inhibitor. |
| 26088119 | 2015 | Review | Curr Pharm Des | Off-label trazodone use, including OCD, with benefits and risks. |
| 27744763 | 2017 | Review | Postgrad Med | Trazodone’s mechanism, dosing, adverse effects, and use in psychiatric and medical conditions. |
| 4009160 | 1985 | Case report | J Nerv Ment Dis | Two patients with severe OCD and depression, unresponsive to other antidepressants, improved rapidly on trazodone. |
| 18200402 | 2007 | Case report | Rev Bras Psiquiatr | Adding trazodone to sertraline in one OCD patient, described as a probable synergistic action. |
Ten further publications were retrieved but are not listed here. They are mostly case reports and brief reports.
South Africa Market Information
| Registration Number | Product Name | Dosage Form |
|---|---|---|
| Reg. No. 54/1.2/0145 | Sariprev 50 | Capsule (oral) |
| Reg. No. E/1.2/9 | Molipaxin | Capsule (oral) |
| Reg. No. 43/1.2/0698 | Biotech trazodone | Capsule (oral) |
The registration data provided does not include approved indication text. Only oral capsules are registered, so any OCD use would be off-label.
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
Conclusion and Next Steps
Decision: Hold
Rationale: The evidence is one small double-blind study with an unconfirmed outcome and uncontrolled reports from the 1980s and early 1990s. There are no registered trials and no Phase 3 evidence. In addition, the SAHPRA safety information is missing, which blocks the safety screening step.
To proceed, the following is needed:
- The SAHPRA package insert (warnings, contraindications, interactions), which is the blocking gap
- Full-text review of the 1992 placebo-controlled study (PMID 1629380) to confirm its sample size and outcome
- Mechanism of action data from DrugBank
- A modern controlled trial, or a systematic review, of trazodone as monotherapy or as an add-on to a serotonin reuptake inhibitor in OCD, including tolerability data
The other nine predicted indications are weaker. Agoraphobia and phobic disorder have hypothesis-level panic disorder data from the 1980s. The remaining seven are either indirect or model-only signals.
These results are for research reference only and do not constitute medical advice. Repurposing candidates require clinical validation before use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.