Case Report

Similar Effects of Tramadol and Venlafaxine in Major Depressive Disorder

Authors: Roy R. Reeves, DO, PhD, Sera K. Cox, MD


he analgesic tramadol has many characteristics in common with the antidepressant venlafaxine. The drugs are structurally similar, share both serotonergic and noradrenergic properties, and undergo a similar metabolic fate. In this study, a patient, who developed significant depression following cessation of tramadol after several years of therapy, is described. Her depression was then treated with venlafaxine with excellent response. It appears that tramadol may have provided a prophylactic antidepressant effect in this patient. Because of its similarities to venlafaxine, tramadol may possibly exert a degree of antidepressant effect in certain patients, particularly those with chronic pain.

Key Points

* Tramadol is a centrally acting μm-opioid receptor agonist analgesic, which also enhances the action of serotonin and norepinephrine.

* Tramadol and venlafaxine are structurally similar and undergo a similar metabolic fate.

* Tramadol may exert a degree of antidepressant effect in some patients.

* Venlafaxine may be beneficial for the treatment of pain in certain individuals.

This content is limited to qualifying members.

Existing members, please login first.

If you have an existing account please login now to access this article or view your purchase options.

Purchase only this article ($15)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.


1. Manocha A, Sharma KK, Mediratta PK. On the mechanism of anticonvulsant effect in mice. Pharmacol Biochem Behav 2005;82:74–81.
2. Raffa RB, Friderichs E, Reimann W, et al. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an “atypical” opioid analgesic. J Pharmacol Exp Ther 1992;260:275–285.
3. Rojas-Corrales MO, Gilbert-Rahola J, Mico JA. Role of atypical opiates in OCD: experimental approach through the study of 5-HT2A/C receptor mediated behavior. Psychopharmacology 2007;190:221–231.
4. Goldsmith TD, Shapira NA, Keck PE. Rapid remission of OCD with tramadol hydrochloride (letter). Am J Psychiatry 1999;156:660–661.
5. Lange-Asschenfeldt C, Weigman H, Hiemke C, et al. Serotonin syndrome as a result of fluoxetine in a patient with tramadol abuse: plasma level-correlated symptomatology (letter). J Clin Psychopharmacol 2002;22:440–441.
6. Lantz MS, Buchalter EN, Giambanco V. Serotonin syndrome following the administration of tramadol and paroxetine (letter). Int J Geriatric Psychiatry 1998;13:343–345.
7. Houlihan DJ. Serotonin syndrome resulting from coadministration of tramadol, venlafaxine, and mirtazepine. Ann Pharmacother 2004;38:411–413.
8. Rojas-Corrales MO, Gilbert-Rahola J, Mico JA. Tramadol induces antidepressant-type effects in mice. Life Sci 1998;63:PL175–PL180.
9. Fanelli J, Montgomery C. Use of the analgesic tramadol in antidepressant potentiation (abstract). Psychopharmacol Bull 1996;32:442.
10. Shapira NA, Verduin ML, DeGraw JD. Treatment of refractory major depression with tramadol monotherapy (letter). J Clin Psychiatry 2001;62:205–206.
11. Rojas-Corrales MO, Berrocoso E, Gilbert-Rahola J, et al. Antidepressant-like effects of tramadol and its enantiomers in reserpinized mice: comparative study with desipramine, fluvoxamine, venlafaxine, and opiates. J Psychopharmacol 2004;18:404–411.
12. Stoll A, Reuter S. Treatment augmentation with opiates in severe and refractory major depression. Am J Psychiatry 1999;156:2017.
13. Bodkin JA, Zornberg GL, Lukas SE, et al. Buprenorphrine treatment of refractory depression. J Clin Psychopharmacol 1994;15:49–57.
14. Gross-Isserhoff R, Dillon KA, Israeli M, et al. Regionally selected increases in opioid receptor density in the brains of suicide victims. Brain Res 1990;530:312–316.
15. Dwight M, Arnold L, O’Brien H, et al. Venlafaxine treatment of fibromyalgia. Psychopharmacol Bull 1996;32:435.
16. Songer DA, Schulte H. Venlafaxine for the treatment of chronic pain. Am J Psychiatry 1996;153:737.
17. Galer BS. Neuropathic pain of peripheral origin: advances in pharmacological treatment. Neurology 1995;12:S17–S25.
18. Wang CP, Howell SR, Scantia J, et al. The disposition of venlafaxine enantiomers in dogs, rats, and humans receiving venlafaxine. Chirality 1992;4:84–90.
19. McNeil Phamaceuticals. Ultram product information. 1996.
20. Markowitz JS, Patrick KS. Venlafaxine-tramadol similarities. Med Hypotheses 1998;51:167–168.
21. Yardley JP, Morris Husbands GE, Slack G, et al. 2-phenyl-2-(1- hydroxycycloalkyl) ethylamine derivatives: synthesis and antidepressant activity. J Med Chem 1990;33:2899–2905.