Trazodone

Evidence Level: L3

Predicted Indications: 9

Trazodone

Pharmacist Assessment Report

Trazodone: Obsessive-compulsive disorder

One-Sentence Summary

Trazodone was originally used to treat depressive disorders (unipolar depression, major depressive disorder) and anxiety disorder. The TxGNN model predicts it may be effective for obsessive-compulsive disorder (OCD), but no clinical trials are registered, and support comes from 20 publications, mostly small, older studies (one small double-blind placebo-controlled study from 1992, with mixed results).

Quick Overview

Item	Content
Original Indication	Not recorded in the local data
Predicted New Indication	Obsessive-compulsive disorder
TxGNN Prediction Score	0.9995
Evidence Level	L3
Canada Market Status	Marketed (marketed DINs on record: at least 20)
Number of DINs	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 information, trazodone acts on serotonergic pathways (5-HT2A antagonism, weak serotonin reuptake inhibition, and its active metabolite m-CPP). Its efficacy in depression is established, and mechanistically it may be applicable to OCD.

OCD responds mainly to serotonin reuptake inhibitors, which is why a serotonergic antidepressant is a plausible candidate. Published reports include a small double-blind placebo-controlled study, plus open-label and case-based reports of trazodone as an add-on in clomipramine-resistant OCD.

The results are mixed and the studies are small. m-CPP has been reported to worsen OCD symptoms in some studies, which creates mechanistic uncertainty.

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, testing its anti-obsessive efficacy in a controlled setting
2119885	1990	Case series/Open-label	Clin Neuropharmacol	Nine clomipramine-resistant OCD patients: mild overall improvement; 3 responded well, with symptoms returning on withdrawal and improving on re-administration
3501130	1987	Cohort/Open-label	Psychopathology	Response to trazodone in OCD correlated with changes in caudate glucose metabolism on PET
26088119	2015	Review	Curr Pharm Des	Review of off-label trazodone use, including OCD, with benefits and risks
27744763	2017	Review	Postgrad Med	Review of trazodone mechanism, dosing, adverse effects, and use in psychiatric and medical conditions
8993077	1996	Review	Psychopharmacol Bull	Issues in mono- and polypharmacotherapy of OCD; OCD responds mainly to potent serotonin reuptake inhibitors
3571943	1986	Pilot (open-label)	Int Clin Psychopharmacol	Trazodone plus tryptophan in 11 OCD patients: marginal benefit and poor tolerability in several
4009160	1985	Case report	J Nerv Ment Dis	Two severe OCD patients with depression, previously treatment-resistant, improved rapidly on trazodone
8434675	1993	Case series	Am J Psychiatry	Trazodone in OCD and trichotillomania
29343875	2017	Case report	Riv Psichiatr	Prolonged-release trazodone in a patient with bipolar II disorder and OCD comorbidity

Canada Market Information

Trazodone has 20 valid single-ingredient authorizations in Canada. Dosage form and approved indication text are not available in the data compiled for this report.

DIN	Product Name	Dosage Form	Approved Indication
02164388	TRAZODONE-150 D	Not available	Not available
02442825	JAMP TRAZODONE	Not available	Not available
01937235	PMS TRAZODONE HCL TAB 100MG	Not available	Not available
02442817	JAMP TRAZODONE	Not available	Not available
02537915	AG-TRAZODONE	Not available	Not available

Safety Considerations

Knowledge-graph contraindications (from the TxGNN knowledge graph, not label text):

Cardiac rhythm and cardiovascular: long QT syndrome (including familial), torsades de pointes, heart disease, cardiovascular disease
Blood pressure and autonomic: orthostatic hypotension, postural orthostatic tachycardia syndrome, multiple system atrophy
Other: priapism, benign prostatic hyperplasia, blood coagulation disease, potassium deficiency disease, inappropriate ADH syndrome, nephrogenic syndrome of inappropriate antidiuresis

Drug Interactions: 100 interactions were identified. The ones listed in the data compiled for this report include the following.

Major: bupropion, lorcaserin, dolasetron, palonosetron, cisapride, dexfenfluramine, fenfluramine
Moderate: famotidine, loperamide, aprepitant, morphine, clarithromycin, bisacodyl, dronabinol, eliglustat, and others

Several Major interactions (cisapride, dolasetron, palonosetron) are consistent with QT-prolongation concerns, and others (lorcaserin, fenfluramines) with serotonergic effects.

Please refer to the package insert for label warnings and contraindications.

Conclusion and Next Steps

Decision: Hold

Rationale: The evidence for OCD is limited to one small double-blind study and several small open-label studies and case reports, mostly from the 1980s and 1990s, with mixed results. No registered clinical trials exist, and the m-CPP metabolite adds mechanistic uncertainty. Safety data from the package insert is also missing, so safety screening cannot proceed.

To proceed, the following is needed:

Health Canada package insert warnings and contraindications (a blocking gap)
Mechanism of action data from DrugBank
Full review of the 1992 double-blind study and a systematic assessment of trazodone in OCD, including the m-CPP concern
A well-designed randomized trial, for example as augmentation in serotonin reuptake inhibitor-resistant OCD
A safety plan covering QT prolongation, cardiovascular risk, and serotonergic drug interactions
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.