Background: Tramadol is a central analgesic with a unique pharmacological profile in that it is an opioid agonist and an inhibitor of serotonin and norepinephrine reuptake. We describe a case of abuse of tramadol in a binge pattern in a young woman who had initially received the prescription of tramadol as an analgesic as needed. Case Description: The patient had no history of drug or alcohol abuse, but suffered from depression. Over time, she had increased the doses up to 30 ml of tramadol 100 mg/ml oral solution a week. She took the drug in consecutive ‘pinches', from afternoon to evening. Tramadol improved her mood, gave her euphoria, but also caused constipation and urinary retention. Detoxification was carried out by partial replacement with tramadol 100 mg extended release and gradual reduction of the number of pinches. The patient found it hard to follow the program because of withdrawal symptoms of an opioid type and especially because of the worsening of depression. Conclusion: The action of tramadol on the monoaminergic system is believed to be a factor that limits abuse liability and gives advantageous antidepressant-like properties, but it also involves the risk of inducing abuse of the analgesic to improve mood as if it were a stimulant.

Barkin RL: Extended-release tramadol (Ultram ER): a pharmacotherapeutic, pharmacokinetic, and pharmacodynamic focus on effectiveness and safety in patients with chronic/persistent pain. Am J Ther 2008;15:157-166.
Desmeules JA: A risk-benefit assessment of tramadol in the management of pain. Eur J Pain 2000;4(suppl A):15-21.
Epstein DH, Preston KL, Jasinski DR: Abuse liability, behavioral pharmacology, and physical-dependence potential of opioids in humans and laboratory animals: lessons from tramadol. Biol Psychol 2006;73:90-99.
Raffa RB: Basic pharmacology relevant to drug abuse assessment: tramadol as example. J Clin Pharm Ther 2008;33:101-108.
Ward AS, Haney M, Fischman MW, Foltin RW: Binge cocaine self-administration in humans: intravenous cocaine. Psychopharmacology (Berl) 1997;132:375-381.
Cho AK, Melega WP: Patterns of methamphetamine abuse and their consequences. J Addict Dis 2002;21:21-34.
Zung WWK: A rating instrument for anxiety disorders. Psychosomatics 1971;12:371-379.
Zung WWK: A self-rating depression scale. Arch Gen Psychiatry 1965;12:63-70.
Grond S, Sablotzki A: Clinical pharmacology of tramadol. Clin Pharmacokinet 2004;43:879-923.
Driessen B, Reimann W: Interaction of the central analgesic, tramadol, with the uptake and release of 5-hydroxytryptamine in the rat brain in vitro. Br J Pharmacol 1992;105:147-151.
Desmeules JA, Piguet V, Collart L, Dayer P: Contribution of monoaminergic modulation to the analgesic effect of tramadol. Br J Clin Pharmacol 1996;41:7-12.
Valle M, Garrido MJ, Pavon JM, Calvo R, Troconiz IF: Pharmacokinetic-pharmacodynamic modeling of the antinociceptive effects of main active metabolites of tramadol, (+)-O-desmethyltramadol and (-)-O-desmethyltramadol, in rats. J Pharmacol Exp Ther 2000;293:646-653.
Gillen C, Haurand M, Kobelt DJ, Wnendt S: Affinity, potency and efficacy of tramadol and its metabolites at the cloned human mu-opioid receptor. Naunyn Schmiedebergs Arch Pharmacol 2000;362:116-121.
Frink MC, Hennies HH, Englberger W, Haurand M, Wilffert B: Influence of tramadol on neurotransmitter systems of the rat brain. Arzneimittelforschung 1996;46:1029-1036.
Rojas-Corrales MO, Berrocoso E, Gibert-Rahola J, Micó JA: Antidepressant-like effects of tramadol and other central analgesics with activity on monoamines reuptake, in helpless rats. Life Sci 2002;72:143-152.
Yalcin I, Aksu F, Bodard S, Chalon S, Belzung C: Antidepressant-like effect of tramadol in the unpredictable chronic mild stress procedure: possible involvement of the noradrenergic system. Behav Pharmacol 2007;18:623-631.
Barber J: Examining the use of tramadol hydrochloride as an antidepressant. Exp Clin Psychopharmacol 2011;19:123-130.
Lofwall MR, Walsh SL, Bigelow GE, Strain EC: Modest opioid withdrawal suppression efficacy of oral tramadol in humans. Psychopharmacology (Berl) 2007;194:381-393.
Duke AN, Bigelow GE, Lanier RK, Strain EC: Discriminative stimulus effects of tramadol in humans. J Pharmacol Exp Ther 2011;338:255-262.
Stoops WW, Lofwall MR, Nuzzo PA, Craig LB, Siegel AJ, Walsh SL: Pharmacodynamic profile of tramadol in humans: influence of naltrexone pretreatment. Psychopharmacology (Berl) 2012;223:427-438.
Senay EC, Adams EH, Geller A, Inciardi JA, Muñoz A, Schnoll SH, Woody GE, Cicero TJ: Physical dependence on Ultram (tramadol hydrochloride): both opioid-like and atypical withdrawal symptoms occur. Drug Alcohol Depend 2003;69:233-241.
Taghaddosinejad F, Mehrpour O, Afshari R, Seghatoleslami A, Abdollahi M, Dart RC: Factors related to seizure in tramadol poisoning and its blood concentration. J Med Toxicol 2011;7:183-188.
Nelson EM, Philbrick AM: Avoiding serotonin syndrome: the nature of the interaction between tramadol and selective serotonin reuptake inhibitors. Ann Pharmacother 2012;46:1712-1716.
Jeppesen U, Gram LF, Vistisen K, Loft S, Poulsen HE, Brøsen K: Dose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram, fluoxetine, fluvoxamine and paroxetine. Eur J Clin Pharmacol 1996;51:73-78.
Paar WD, Poche S, Gerloff J, Dengler HJ: Polymorphic CYP2D6 mediates O-demethylation of the opioid analgesic tramadol. Eur J Clin Pharmacol 1997;53:235-239.
Rouini MR, Ardakani YH, Soltani F, Aboul-Enein HY, Foroumadi A: Development and validation of a rapid HPLC method for simultaneous determination of tramadol, and its two main metabolites in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci 2006;830:207-211.
Ehrenreich H, Poser W: Dependence on tramadol. Clin Investig 1993;72:76.
Rodriguez Villamañan JC, Albaladejo Blanco C, Sanchez Sanchez A, Carvajal A, Martin Arias L, Garcia del Pozo J: Withdrawal syndrome after long-term treatment with tramadol. Br J Gen Pract 2000;50:406.
Freye E, Levy J: Acute abstinence syndrome following abrupt cessation of long-term use of tramadol (Ultram): a case study. Eur J Pain 2000;4:307-311.
Thomas AN, Suresh M: Opiate withdrawal after tramadol and patient-controlled analgesia. Anaesthesia 2000;55:826-827.
Yates WR, Nguyen MH, Warnock JK: Tramadol dependence with no history of substance abuse. Am J Psychiatry 2001;158:964.
Barsotti CE, Mycyk MB, Reyes J: Withdrawal syndrome from tramadol hydrochloride. Am J Emerg Med 2003;21:87-88.
Soyka M, Backmund M, Hasemann S: Tramadol use and dependence in chronic noncancer pain patients. Pharmacopsychiatry 2004;37:191-192.
Pollice R, Casacchia M, Bianchini V, Mazza M, Conti CM, Roncone R: Severe tramadol addiction in a 61 year-old woman without a history of substance abuse. Int J Immunopathol Pharmacol 2008;21:475-476.
Stoehr JD, Essary AC, Ou C, Ashby R, Sucher M: The risk of tramadol abuse and dependence: findings in two patients. JAAPA 2009;22:31-32, 34-35.
Tjäderborn M, Jönsson AK, Ahlner J, Hägg S: Tramadol dependence: a survey of spontaneously reported cases in Sweden. Pharmacoepidemiol Drug Saf 2009;18:1192-1198.
Reeves RR, Cox SK: Similar effects of tramadol and venlafaxine in major depressive disorder. South Med J 2008;101:193-195.
Tao Q, Stone DJ, Borenstein MR, Codd EE, Coogan TP, Desai-Krieger D, Liao S, Raffa RB: Differential tramadol and O-desmethyl metabolite levels in brain vs plasma of mice and rats administered tramadol hydrochloride orally. J Clin Pharm Ther 2002;27:99-106.
Means-Christensen AJ, Roy-Byrne PP, Sherbourne CD, Craske MG, Stein MB: Relationships among pain, anxiety, and depression in primary care. Depress Anxiety 2008;25:593-600.
Babalonis S, Lofwall MR, Nuzzo PA, Siegel AJ, Walsh SL: Abuse liability and reinforcing efficacy of oral tramadol in humans. Drug Alcohol Depend 2013;129:116-122.
Raffa RB, Buschmann H, Christoph T, Eichenbaum G, Englberger W, Flores CM, Hertrampf T, Kögel B, Schiene K, Strassburger W, Terlinden R, Tzschentke TM: Mechanistic and functional differentiation of tapentadol and tramadol. Expert Opin Pharmacother 2012;13:1437-1449.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.