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• W4244369782 abstract "Back to table of contents Previous article Next article Letter to the EditorFull AccessMania and Tramadol-Fluoxetine CombinationANA GONZALEZ-PINTO, M.D., HARKAITZ IMAZ, M.D., JOSE LUIS PÉREZ DE HEREDIA, M.D., MIGUEL GUTIERREZ, M.D., and JUAN ANTONIO MICÓ, M.D., ANA GONZALEZ-PINTOSearch for more papers by this author, M.D., HARKAITZ IMAZSearch for more papers by this author, M.D., JOSE LUIS PÉREZ DE HEREDIASearch for more papers by this author, M.D., MIGUEL GUTIERREZSearch for more papers by this author, M.D., and JUAN ANTONIO MICÓSearch for more papers by this author, M.D., Vitoria, SpainPublished Online:1 Jun 2001https://doi.org/10.1176/appi.ajp.158.6.964-aAboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Tramadol is a centrally acting analgesic that actives the mu opioid receptor and enhances the action of serotonin and noradrenaline by interference with their uptake and release mechanisms. It has been suggested (1) that tramadol could be useful in the treatment of obsessive-compulsive disorder associated with the use of selective serotonin reuptake inhibitors (SSRIs). Discussion has included possible pharmacological interaction, leading to side effects such as serotonin syndrome. Also, tramadol-induced mania in a patient with bipolar disorder has been reported (2), but to our knowledge, there are no reports of tramadol-induced mania in patients with unipolar disorder. We present a report of a patient with serotonin syndrome and mania who had no previous history of manic episodes and was being treated with fluoxetine and tramadol.Ms. A was a 72-year-old woman who had been treated with fluoxetine, 20 mg/day, for the last 10 years. She had had no cognitive deficits, had never been hospitalized, and had had only one previous major depressive episode, occurring 10 years before. She had been taking acetaminophen for the last year for articular pain. She was planning to take a trip, so her doctor prescribed tramadol to relieve the pain. After 18 days of taking tramadol, 150 mg/day, and fluoxetine, 20 mg/day, Ms. A began to feel nervous, had a temperature of 37.2°C, piloerection, and muscular contractions.She stopped taking tramadol, and her physical symptoms disappeared by day 21. Nevertheless, she was agitated, euphoric, and hyperactive, slept less than 3 hours a day, and demonstrated rapid speech and paranoid ideation. She was conscious and oriented at all times. Ms. A was hospitalized for 3 days and stopped taking fluoxetine; haloperidol treatment was initiated at 5 mg/day. The results of a physical examination were normal. After discharge, her symptoms continued, so by day 31 she was hospitalized again. She then began treatment with olanzapine, 10 mg/day. Two weeks later she was euthymic and was discharged from the hospital while taking olanzapine, 10 mg/day.This case of serotonin syndrome and mania in the same patient could be due to the fluoxetine-tramadol treatment combination. Tramadol contains a mono-O-desmethyl metabolite that has less serotonergic activity than tramadol. The rate of production of this metabolite is influenced by the CYP2D6 system. Fluoxetine could previously have inhibited CYP2D6 production, and, consequently, tramadol would have accumulated in serum, conveying a greater risk of adverse effects.Also, preclinical reports have suggested an antidepressant effect with tramadol therapy (3). If this is the case, tramadol could induce mania itself in a manner similar to that of antidepressants, although the present episode probably was precipitated by coadministration of two compounds with similar mechanisms of action. In conclusion, it is important to consider the potential risk of inducing mania and serotonergic syndrome when using tramadol combined with SSRIs.References1. Goldsmith TB, Shapira NA, Keck PE Jr: Rapid remission of OCD with tramadol hydrochloride (letter). Am J Psychiatry 1999; 156:660–661Medline, Google Scholar2. Watts BV, Grady TA: Tramadol-induced mania (letter). Am J Psychiatry 1997; 154:1624Link, Google Scholar3. Rojas-Corrales MO, Gibert-Rahola J, Mico JA: Tramadol induces antidepressant-type effects in mice. Life Sci 1998; 63:175–180Crossref, Google Scholar FiguresReferencesCited byDetailsCited byMania after codeine self-medication in a case of panic disorderMinerva Psychiatry, Vol. 63, No. 3Archives of Toxicology, Vol. 92, No. 8European Journal of Hospital Pharmacy, Vol. 24, No. 2Heroin-induced chronic hypomania: a case report21 August 2014 | Journal of Substance Use, Vol. 21, No. 1Selective serotonin re-uptake inhibitors (SSRIs)Tramadol-induced mania in a patient with depression17 March 2015 | The Brown University Psychopharmacology Update, Vol. 26, No. 4Severe Manic Episode Associated With Tramadol in a Patient With Recurrent Depressive DisorderJournal of Clinical Psychopharmacology, Vol. 35, No. 2Manic Episodes Associated With TramadolJournal of Clinical Psychopharmacology, Vol. 35, No. 1Clinical Toxicology, Vol. 53, No. 6Serotonin Syndrome23 October 2013 | Journal of Pharmacy Practice, Vol. 27, No. 1BMC Psychiatry, Vol. 13, No. 1Réanimation, Vol. 20, No. 5The Truth behind Tramadol and Antidepressants: An Interaction of Concern?1 March 2009 | Canadian Pharmacists Journal / Revue des Pharmaciens du Canada, Vol. 142, No. 2ANTIDEPRESSANTSDrug and Alcohol Dependence, Vol. 103, No. 1-2Expert Opinion on Pharmacotherapy, Vol. 9, No. 5Postmortem Urine Immunoassay Showing False-Positive Phencyclidine Reactivity in a Case of Fatal Tramadol OverdoseAmerican Journal of Forensic Medicine & Pathology, Vol. 27, No. 4Serotonin Syndrome Resulting from Coadministration of Tramadol, Venlafaxine, and Mirtazapine12 January 2004 | Annals of Pharmacotherapy, Vol. 38, No. 3Psychiatry and Clinical Neurosciences, Vol. 58, No. 4, Vol. 26Reactions Weekly, Vol. &NA;, No. 863 Volume 158Issue 6 June 2001Pages 964-a-965 Metrics History Published online 1 June 2001 Published in print 1 June 2001" @default.
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• W4244369782 title "Mania and Tramadol-Fluoxetine Combination" @default.
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