Cognitive Impairment and Tramadol Dependence Medhat M. Bassiony, MD, MSc, MBBCh, Usama M. Youssef, MD, MSc, MBBCh, Mervat S. Hassan, MD, MSc, MBBCh, Ghada M. Salah El-Deen, MD, MSc, MBBCh, Hayam El-gohari, MD, MSc, MBBCh, Mohamed Abdelghani, MD, MSc, MBBCh, Ahmed Abdalla, MD, MSc, MBBCh, and Dalia H. Ibrahim, MD, MSc, MBBCh Abstract: Background and Objective: Cognitive impairment is one of the con- sequences of substance abuse. Tramadol abuse is a public health problem in Egypt. The objective of this study was to estimate the prevalence and correlates of cognitive impairment among tramadol-abuse patients and control subjects. Methods: This study included 100 patients with tramadol abuse and 100 control subjects (matched for age, sex, and education) who were recruited from Zagazig University Hospital, Egypt. Patients were divided into 2 groups: patients who used tramadol only (tramadol-alone group) and pa- tients who used tramadol and other substances (polysubstance group). The participants were interviewed using Montreal Cognitive Assessment test and had urine screening for drugs. Results: Twenty-four percent of the cases used tramadol alone, whereas the remaining used tramadol and other substances, mainly cannabis (66%) and benzodiazepines (27%). Tramadol-abuse patients were about 3 times more likely to have cognitive impairment than control subjects (81% vs 28%). Tramadol-alone patients were more than 2 times more likely to have cog- nitive impairment than control subjects (67% vs 28%). Cognitive impairment was significantly associated with polysubstance abuse. There was no association between cognitive impairment and sociodemographic or clinical factors. Conclusions: Cognitive impairment occurs commonly among tramadol- abuse patients. Memory impairment is the most common cognitive domain to be affected. There is a significant association between cognitive impair- ment and polysubstance abuse. Key Words: cognitive impairment, Egypt, tramadol abuse (J Clin Psychopharmacol 2017;37: 61–66) T he lifetime prevalence of substance use disorders (SUDs) in Egypt was 9.6% according to a recent national survey. 1 Twenty percent to 40% of adults with SUD have used tramadol in Egypt. 2–4 Eighty-three percent of Egyptian school students with SUD have used tramadol at least once in their lifetime. 5 The main source of the nonmedical use of tramadol is the black market through illegal transaction mainly from China that made it easily accessible and cheap. 6,7 Almost half of the tramadol-abuse pa- tients had psychiatric comorbidity, and more than three-fourths had cluster B personality disorders. 8 Depending on these reports, the Egyptian Ministry of Health moved tramadol from Schedule III to Schedule I (highly addictive). 9 Continued drug use causes cognitive deficits that aggravate the difficulty of establishing sustained abstinence. 10 In fact, drug addiction has been characterized as a disease of “pathological learning” by several investigators. 10,11 Estimates regarding the prevalence of cognitive impairment (CI) in SUD patients vary widely and range from approximately 30% to 80%. 12 These defi- cits may range from the relatively subtle temporary effects of can- nabis use 13 to the moderate executive control deficits observed in chronic cocaine users even following several months of absti- nence. 14 Although these estimates do not include alcoholics who develop permanent cognitive deficits such as Wernicke-Korsakoff syndrome, they do include the enduring visuospatial information processing deficits observed in nondemented persons with alcohol use disorders. 15 Fishbain et al 16 reviewed 22 studies and reported that patients on stable opioid doses had some impairment of psychomotor abilities in 30% of the studies. Opioid-dependent patients also experience cognitive function problems during opi- oid substitution therapy. 17 Full opioid agonists (eg, morphine) have been shown to im- pair some aspects of psychomotor and cognitive performance in some studies. 18 Few studies have examined the effects of tramadol on performance. Zacny 19 reported that neither tramadol (50 and 100 mg orally) nor morphine (25 mg orally) impaired psychomo- tor performance relative to placebo in sporadic drug users. Two studies 20,21 revealed that acute tramadol administration (50–400 mg orally administered) did not impair performance in opioid- dependent volunteers; however, interpretation is complicated because participants were tested while in opioid withdrawal in those studies. In addition, 2 studies evaluated the relationship be- tween short-term (2–7 days) tramadol use and cognitive functions. The first study 22 found worse cognitive performance in the mor- phine group than in the tramadol group. The second study 23 reported comparable CI for the tramadol and fentanyl groups. Although there are several reports in the literature on the ef- fects of neurotransmitters agonist and antagonist in learning and memory, the effect of tramadol as a drug with mechanism of ac- tion affecting both mu receptor and serotonin, norepinephrine and dopamine reuptake has not been well studied. All the previous studies have investigated the acute effects of tramadol or other opi- oids, but no studies looked at the relationship between long-term tramadol use, abuse, or dependence and CI. Therefore, this study was designed to evaluate and compare the effect of chronic use of high doses of tramadol on cognitive functions. The objectives of this study were: 1. to assess the prevalence and sociodemographic and clinical cor- relates of CI in patients with tramadol abuse who seek treatment; 2. to compare CI between tramadol-abuse patients and control subjects; and 3. to compare CI between those who use tramadol alone and control subjects. METHODS Subjects One hundred consecutive patients with a diagnosis of opi- oid use disorder attributed to tramadol (OUD-T) according to From the Psychiatry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt. Received May 29, 2016; accepted after revision October 18, 2016. Reprints: Medhat M. Bassiony, MD, MSc, MBBCh, Psychiatry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt (e‐mail: mbassiony@hotmail.com). Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0271-0749 DOI: 10.1097/JCP.0000000000000617 ORIGINAL CONTRIBUTION Journal of Clinical Psychopharmacology • Volume 37, Number 1, February 2017 www.psychopharmacology.com 61 Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.