Harm related to recreational ketamine use and its relevance for the clinical use of ketamine. A systematic review and comparison study

References

• Taylor P, Ingwersen W. Importance of ketamine. Vet Rec. 2016;178(11):271.
   PubMed Web of Science ®Google Scholar
• WHO. Ketamine (INN). Update Review Report. Expert Committee on Drug Dependence. Thirty-seventh Meeting. Geneva, Switzerland 2015. Available from: https://www.who.int/medicines/access/controlled-substances/6_1_Ketamine_Update_Review.pdf
   Google Scholar
• Pribish A, Wood N, Kalava A. A review of nonanesthetic uses of ketamine. Anesthesiol Res Pract. 2020;2020:5798285.
   PubMed Web of Science ®Google Scholar
• Alqaysum ZA, Hakami AH, Qussadi AM, et al. Ketamine versus standard opioid treatment for acute pain in the emergency department: systematic review and meta-analysis. Ann Med Health Sci Res. 2021;11:1.
   Web of Science ®Google Scholar
• Bell RF, Eccleston C, Kalso EA. Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database Syst Rev. 2017;6(6):Cd003351.
   PubMedGoogle Scholar
• Corriger A, Pickering G. Ketamine and depression: a narrative review. Drug Des Devel Ther. 2019;13:3051–3067.
   PubMed Web of Science ®Google Scholar
• Kryst J, Kawalec P, Mitoraj AM, et al. Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials. Pharmacol Rep. 2020;72(3):543–562.
   PubMed Web of Science ®Google Scholar
• Fava M, Freeman MP, Flynn M, et al. Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD). Mol Psychiatry. 2020;25(7):1592–1603.
   PubMed Web of Science ®Google Scholar
• Feder A, Rutter SB, Schiller D, et al. The emergence of ketamine as a novel treatment for posttraumatic stress disorder. Adv Pharmacol. 2020;89:261–286.
   PubMedGoogle Scholar
• Wilkinson ST, Ballard ED, Bloch MH, et al. The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis. Am J Psychiatry. 2018;175(2):150–158.
   PubMed Web of Science ®Google Scholar
• Daly EJ, Singh JB, Fedgchin M, et al. Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2018;75(2):139–148.
   PubMed Web of Science ®Google Scholar
• Jones JL, Mateus CF, Malcolm RJ, et al. Efficacy of ketamine in the treatment of substance use disorders: a systematic review. Front Psychiatry. 2018;9:277.
   PubMed Web of Science ®Google Scholar
• McIntyre RS, Carvalho IP, Lui LMW, et al. The effect of intravenous, intranasal, and oral ketamine in mood disorders: a meta-analysis. J Affect Disord. 2020;276:576–584.
   PubMed Web of Science ®Google Scholar
• Siegel AN, Di Vincenzo JD, Brietzke E, et al. Antisuicidal and antidepressant effects of ketamine and esketamine in patients with baseline suicidality: a systematic review. J Psychiatr Res. 2021;137:426–436.
   PubMed Web of Science ®Google Scholar
• Di Vincenzo JD, Siegel A, Lipsitz O, et al. The effectiveness, safety and tolerability of ketamine for depression in adolescents and older adults: a systematic review. J Psychiatr Res. 2021;137:232–241.
   PubMed Web of Science ®Google Scholar
• FDA (Food and Drug Administration). FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor’s office or clinic 2019. [cited 2021 Mar 31]. Available form:https://www.fda.gov/news-events/press-announcements/fda-approves-new-nasal-spray-medication-treatment-resistant-depression-available-only-certified
   Google Scholar
• EMA. European Medicines Agency (EMA). Spravato 2020. Retrieved from https://www.ema.europa.eu/en/medicines/human/EPAR/spravato
   Google Scholar
• EMCDDA. European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). European Drug Report 2019: trends and Developments, Publications Office of the European Union, Luxembourg 2019. Available form:https://www.emcdda.europa.eu/system/files/publications/11364/20191724_TDAT19001ENN_PDF.pdf
   Google Scholar
• Johnston LD, Miech RA, O’Malley PM, et al. Monitoring the future. National survey results on drug use, 1975–2019. 2019 Overview. Key findings on adolescent drug use 2020. Available form: https://cdn.ymaws.com/www.fadaa.org/resource/resmgr/files/resource_center/mtf-overview2019.pdf
   Google Scholar
• Li JH, Vicknasingam B, Cheung YW, et al. To use or not to use: an update on licit and illicit ketamine use. Subst Abuse Rehabil. 2011;2:11–20.
   PubMedGoogle Scholar
• Ho RC, Zhang MW. Ketamine as a rapid antidepressant: the debate and implications. BJPsych Advances. 2016;22(4):222–233.
   Google Scholar
• Palamar JJ, Salomone A, Rutherford C, et al. Extensive underreported exposure to ketamine among electronic dance music party attendees. J Gen Intern Med. 2021;36(1):235–237.
   PubMed Web of Science ®Google Scholar
• Singh I, Morgan C, Curran V, et al. Ketamine treatment for depression: opportunities for clinical innovation and ethical foresight. Lancet Psychiatry. 2017;4(5):419–426.
   PubMed Web of Science ®Google Scholar
• Short B, Fong J, Galvez V, et al. Side-effects associated with ketamine use in depression: a systematic review. Lancet Psychiatry. 2018;5(1):65–78.
   PubMed Web of Science ®Google Scholar
• Morgan CJ, Curran HV. Ketamine use: a review. Addiction. 2012;107(1):27–38.
   PubMed Web of Science ®Google Scholar
• Orhurhu VJ, Vashisht R, Claus LE, et al. Ketamine Toxicity. StatPearls. Treasure Island (FL): StatPearls Publishing. Copyright © 2021, StatPearls Publishing LLC; 2021.
   Google Scholar
• Wei YB, Yang JR, Yin Z, et al. Genitourinary toxicity of ketamine. Hong Kong Med J. 2013;19(4):341–348.
   PubMed Web of Science ®Google Scholar
• Sassano-Higgins S, Baron D, Juarez G, et al. A review of ketamine abuse and diversion. Depress Anxiety. 2016;33(8):718–727.
   PubMed Web of Science ®Google Scholar
• Ng J, Lui LMW, Rosenblat JD, et al. Ketamine-induced urological toxicity. potential mechanisms and translation for adults with mood disorders receiving ketamine treatment. Psychopharmacology (Berl); 2021 Apr; 238(4):917–926.
   Google Scholar
• Bokor G, Anderson PD. Ketamine: an update on its abuse. J Pharm Pract. 2014;27(6):582–586.
   PubMedGoogle Scholar
• Morgan CJ, Rees H, Curran HV. Attentional bias to incentive stimuli in frequent ketamine users. Psychol Med. 2008;38(9):1331–1340.
   PubMed Web of Science ®Google Scholar
• Winstock AR, Mitcheson L, Gillatt DA, et al. The prevalence and natural history of urinary symptoms among recreational ketamine users. BJU Int. 2012;110(11):1762–1766.
   PubMed Web of Science ®Google Scholar
• Morgan CJ, Muetzelfeldt L, Curran HV. Consequences of chronic ketamine self-administration upon neurocognitive function and psychological wellbeing: a 1-year longitudinal study. Addiction. 2010;105(1):121–133.
   PubMed Web of Science ®Google Scholar
• Zhu W, Ding Z, Zhang Y, et al. Risks associated with misuse of ketamine as a rapid-acting antidepressant. Neurosci Bull. 2016;32(6):557–564.
   PubMed Web of Science ®Google Scholar
• Liu Y, Lin D, Wu B, et al. Ketamine abuse potential and use disorder. Brain Res Bull. 2016;126(Pt 1):68–73.
   PubMedGoogle Scholar
• Pérez-Esparza R, Kobayashi-Romero LF, García-Mendoza AM, et al. Promises and concerns regarding the use of ketamine and esketamine in the treatment of depression. Acta Psychiatr Scand. 2019;140(2):182–183.
   PubMed Web of Science ®Google Scholar
• Rasmussen KG. Has psychiatry tamed the “ketamine tiger?” Considerations on its use for depression and anxiety. Prog Neuro Psychopharmacol Biol Psychiatry. 2016;64:218–224.
   PubMed Web of Science ®Google Scholar
• Zhang MW, Harris KM, Ho RC. Is off-label repeat prescription of ketamine as a rapid antidepressant safe? Controversies, ethical concerns, and legal implications. BMC Med Ethics. 2016;17(1):4.
   PubMedGoogle Scholar
• Zhang MW, Ho R. Critical appraisal of existing ketamine trials: existing limitations and limited applicability for treatment. Am J Psychiatry. 2016;173(4):431.
   PubMed Web of Science ®Google Scholar
• Zhang MW, Ho RC. Controversies of the Effect of Ketamine on Cognition. Front Psychiatry. 2016;7:47.
   PubMed Web of Science ®Google Scholar
• McIntyre RS, Rosenblat JD, Nemeroff CB, et al. Synthesizing the evidence for ketamine and esketamine in treatment-resistant depression: an international expert opinion on the available evidence and implementation. Am J Psychiatry. 2021;178(5):383–399.
   PubMed Web of Science ®Google Scholar
• Na KS, Kim YK. Increased use of ketamine for the treatment of depression: benefits and concerns. Prog Neuropsychopharmacol Biol Psychiatry. 2021;104:110060.
   PubMed Web of Science ®Google Scholar
• Rosenblat JD, Carvalho AF, Li M, et al. Oral ketamine for depression: a systematic review. J Clin Psychiatry. 2019;80(3):3.
   Web of Science ®Google Scholar
• Wang LJ, Chen CK, Lin SK, et al. Cognitive profile of ketamine-dependent patients compared with methamphetamine-dependent patients and healthy controls. Psychopharmacology (Berl). 2018;235(7):2113–2121.
   PubMed Web of Science ®Google Scholar
• Ke X, Ding Y, Xu K, et al. The profile of cognitive impairments in chronic ketamine users. Psychiatry Res. 2018;266:124–131.
   PubMed Web of Science ®Google Scholar
• Zeng H, Su D, Jiang X, et al. The similarities and differences in impulsivity and cognitive ability among ketamine, methadone, and non-drug users. Psychiatry Res. 2016;243:109–114.
   PubMed Web of Science ®Google Scholar
• Zhang C, Tang WK, Liang HJ, et al. Other drug use does not impact cognitive impairments in chronic ketamine users. Drug Alcohol Depend. 2018;186:1–8.
   PubMed Web of Science ®Google Scholar
• Zhang C, Xu Y, Zhang B, et al. Cognitive impairment in chronic ketamine abusers. Psychiatry Res. 2020;291:113206.
   PubMed Web of Science ®Google Scholar
• Liao Y, Tang J, Corlett PR, et al. Reduced dorsal prefrontal gray matter after chronic ketamine use. Biol Psychiatry. 2011;69(1):42–48.
   PubMed Web of Science ®Google Scholar
• Liang HJ, Lau CG, Tang A, et al. Cognitive impairments in poly-drug ketamine users. Addict Behav. 2013;38(11):2661–2666.
   PubMed Web of Science ®Google Scholar
• Liang HJ, Lau CG, Tang KL, et al. Are sexes affected differently by ketamine? An exploratory study in ketamine users. Subst Use Misuse. 2014;49(4):395–404.
   PubMed Web of Science ®Google Scholar
• Tang WK, Liang HJ, Lau CG, et al. Relationship between cognitive impairment and depressive symptoms in current ketamine users. J Stud Alcohol Drugs. 2013;74(3):460–468.
   PubMed Web of Science ®Google Scholar
• Tang WK, Lau CG, Ungvari GS, et al. Recovery of cognitive functioning following abstinence from ketamine. Addict Behav. 2019;99:106081.
   PubMed Web of Science ®Google Scholar
• Morgan CJ, Muetzelfeldt L, Curran HV. Ketamine use, cognition and psychological wellbeing: a comparison of frequent, infrequent and ex-users with polydrug and non-using controls. Addiction. 2009;104(1):77–87.
   PubMed Web of Science ®Google Scholar
• Tang J, Liao Y, He H, et al. Sleeping problems in Chinese illicit drug dependent subjects. BMC Psychiatry. 2015;15(1):28.
   PubMedGoogle Scholar
• Morgan CJ, Duffin S, Hunt S, et al. Neurocognitive function and schizophrenia-proneness in individuals dependent on ketamine, on high potency cannabis (‘skunk’) or on cocaine. Pharmacopsychiatry. 2012;45(7):269–274.
   PubMed Web of Science ®Google Scholar
• González-Sáiz F, Domingo-Salvany A, Barrio G, et al. Severity of dependence scale as a diagnostic tool for heroin and cocaine dependence. Eur Addict Res. 2009;15(2):87–93.
   PubMed Web of Science ®Google Scholar
• Morgan CJ, Huddy V, Lipton M, et al. Is persistent ketamine use a valid model of the cognitive and oculomotor deficits in schizophrenia? Biol Psychiatry. 2009;65(12):1099–1102.
   PubMed Web of Science ®Google Scholar
• Liao Y, Tang J, Ma M, et al. Frontal white matter abnormalities following chronic ketamine use: a diffusion tensor imaging study. Brain. 2010;133(Pt 7):2115–2122.
   PubMedGoogle Scholar
• Liao Y, Tang J, Fornito A, et al. Alterations in regional homogeneity of resting-state brain activity in ketamine addicts. Neurosci Lett. 2012;522(1):36–40.
   PubMed Web of Science ®Google Scholar
• Liao Y, Tang J, Liu J, et al. Decreased thalamocortical connectivity in chronic ketamine users. PLoS One. 2016;11(12):e0167381.
   PubMed Web of Science ®Google Scholar
• Hung CC, Zhang S, Chen CM, et al. Striatal functional connectivity in chronic ketamine users: a pilot study. Am J Drug Alcohol Abuse. 2020;46(1):31–43.
   PubMed Web of Science ®Google Scholar
• Hung CC, Liu YH, Huang CC, et al. Effects of early ketamine exposure on cerebral gray matter volume and functional connectivity. Sci Rep. 2020;10(1):15488.
   PubMed Web of Science ®Google Scholar
• Li CR, Zhang S, Hung CC, et al. Depression in chronic ketamine users: sex differences and neural bases. Psychiatry Res Neuroimaging. 2017;269:1–8.
   PubMed Web of Science ®Google Scholar
• Narendran R, Frankle WG, Keefe R, et al. Altered prefrontal dopaminergic function in chronic recreational ketamine users. Am J Psychiatry. 2005;162(12):2352–2359.
   PubMed Web of Science ®Google Scholar
• Liu SYW, Ng SKK, Tam YH, et al. Clinical pattern and prevalence of upper gastrointestinal toxicity in patients abusing ketamine. J Dig Dis. 2017;18(9):504–510.
   PubMed Web of Science ®Google Scholar
• Liu W, Wu W, Wei Y, et al. Epidemiologic characteristics and risk factors in patients with ketamine-associated lower urinary tract symptoms accompanied by urinary tract infection: a cross-sectional study. Medicine (Baltimore). 2019;98(23):e15943.
   PubMed Web of Science ®Google Scholar
• Rodrigues NB, Siegel A, Lipsitz O, et al. Effectiveness of intravenous ketamine in mood disorder patients with a history of neurostimulation. CNS Spectr 2020 1–7. doi:https://doi.org/10.1017/S1092852920002187
   Google Scholar
• McIntyre RS, Lipsitz O, Rodrigues NB, et al. The effectiveness of ketamine on anxiety, irritability, and agitation: implications for treating mixed features in adults with major depressive or bipolar disorder. Bipolar Disord. 2020;22(8):831–840.
   PubMed Web of Science ®Google Scholar
• Reich DL, Silvay G. Ketamine: an update on the first twenty-five years of clinical experience. Can J Anaesthesia. 1989;36(2):186–197.
   PubMed Web of Science ®Google Scholar
• Andrade C. Ketamine for depression, 4: in what dose, at what rate, by what route, for how long, and at what frequency? J Clin Psychiatry. 2017;78(7):e852–e7.
   PubMed Web of Science ®Google Scholar
• Balzer N, McLeod SL, Walsh C, et al. Low-dose ketamine for acute pain control in the emergency department: a systematic review and meta-analysis. Acad Emerg Med. 2021 Apr;28(4):444–454.
   PubMed Web of Science ®Google Scholar
• Green SM, Hummel CB, Wittlake WA, et al. What is the optimal dose of intramuscular ketamine for pediatric sedation? Acad Emerg Med. 1999;6(1):21–26.
   PubMed Web of Science ®Google Scholar
• Schoevers RA, Chaves TV, Balukova SM, et al. Oral ketamine for the treatment of pain and treatment-resistant depression†. Br J Psychiatry. 2016;208(2):108–113.
   PubMed Web of Science ®Google Scholar
• Craven R.Ketamine. Anaesthesia. 2007;62(Suppl 1):48–53.
   Google Scholar
• Michelet D, Brasher C, Horlin AL, et al. Ketamine for chronic non-cancer pain: a meta-analysis and trial sequential analysis of randomized controlled trials. Eur J Pain. 2018;22(4):632–646.
   PubMed Web of Science ®Google Scholar
• Jafarinia M, Afarideh M, Tafakhori A, et al. Efficacy and safety of oral ketamine versus diclofenac to alleviate mild to moderate depression in chronic pain patients: a double-blind, randomized, controlled trial. J Affect Disord. 2016;204:1–8.
   PubMed Web of Science ®Google Scholar
• Arabzadeh S, Hakkikazazi E, Shahmansouri N, et al. Does oral administration of ketamine accelerate response to treatment in major depressive disorder? Results of a double-blind controlled trial. J Affect Disord. 2018;235:236–241.
   PubMed Web of Science ®Google Scholar
• Fedgchin M, Trivedi M, Daly EJ, et al. Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression: results of a randomized, double-blind, active-controlled study (TRANSFORM-1). Int J Neuropsychopharmacol. 2019;22(10):616–630.
   PubMed Web of Science ®Google Scholar
• Popova V, Daly EJ, Trivedi M, et al. Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: a randomized double-blind active-controlled study. Am J Psychiatry. 2019;176(6):428–438.
   PubMed Web of Science ®Google Scholar
• McGirr A, Berlim MT, Bond DJ, et al. A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychol Med. 2015;45(4):693–704.
   PubMed Web of Science ®Google Scholar
• Canuso CM, Singh JB, Fedgchin M, et al. Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: results of a double-blind, randomized, placebo-controlled study. Am J Psychiatry. 2018;175(7):620–630.
   PubMed Web of Science ®Google Scholar
• Acevedo-Diaz EE, Cavanaugh GW, Greenstein D, et al. Comprehensive assessment of side effects associated with a single dose of ketamine in treatment-resistant depression. J Affect Disord. 2020;263:568–575.
   PubMed Web of Science ®Google Scholar
• Feifel D, Dadiomov D, Cl K. Safety of repeated administration of parenteral ketamine for depression. Pharmaceuticals (Basel. 2020;13(7):7.
   Google Scholar
• Li CC, Wu ST, Cha TL, et al. A survey for ketamine abuse and its relation to the lower urinary tract symptoms in Taiwan. Sci Rep. 2019;9(1):7240.
   PubMedGoogle Scholar
• Skeldon SC, Goldenberg SL. Urological complications of illicit drug use. Nat Rev Urol. 2014;11(3):169–177.
   PubMed Web of Science ®Google Scholar
• Bergman SA. Ketamine: review of its pharmacology and its use in pediatric anesthesia. Anesth Prog. 1999;46(1):10–20.
   PubMedGoogle Scholar
• Abdallah CG, Adams TG, Kelmendi B, et al. Ketamine’s mechanism of action: a path to rapid-acting antidepressants. Depress Anxiety. 2016;33(8):689–697.
   PubMed Web of Science ®Google Scholar
• Kim M, Cho S, Lee JH. The effects of long-term ketamine treatment on cognitive function in complex regional pain syndrome: a preliminary study. Pain Med. 2016;17(8):1447–1451.
   PubMed Web of Science ®Google Scholar
• Chen LY, Chen CK, Chen CH, et al. Association of craving and depressive symptoms in ketamine-dependent patients undergoing withdrawal treatment. Am J Addict. 2020;29(1):43–50.
   PubMed Web of Science ®Google Scholar
• Gossop M, Darke S, Griffiths P, et al. The Severity of Dependence Scale (SDS): psychometric properties of the SDS in English and Australian samples of heroin, cocaine and amphetamine users. Addiction. 1995;90(5):607–614.
   PubMed Web of Science ®Google Scholar
• Uosukainen H, Tacke U, Winstock AR. Self-reported prevalence of dependence of MDMA compared to cocaine, mephedrone and ketamine among a sample of recreational poly-drug users. Int J Drug Policy. 2015;26(1):78–83.
   PubMed Web of Science ®Google Scholar
• De Luca MT, Meringolo M, Spagnolo PA, et al. The role of setting for ketamine abuse: clinical and preclinical evidence. Rev Neurosci. 2012;23(5–6):769–780.
   PubMed Web of Science ®Google Scholar
• Van Amsterdam J, Pierce M, Van Den Brink W. van den Brink W. Is Europe facing an emerging opioid crisis comparable to the US? Ther Drug Monit. 2021;43(1):42–51.
   PubMed Web of Science ®Google Scholar
• Pavarin RM, Marani S, Turino E. Ketamine abusers referring to emergency departments in northern Italy: a cross- sectional study. Ann Ist Super Sanita. 2019;55(4):338–344.
   PubMed Web of Science ®Google Scholar
• Palamar JJ, Acosta P, Le A, et al. Adverse drug-related effects among electronic dance music party attendees. Int J Drug Policy. 2019;73:81–87.
   PubMed Web of Science ®Google Scholar
• Fan N, Xu K, Ning Y, et al. Profiling the psychotic, depressive and anxiety symptoms in chronic ketamine users. Psychiatry Res. 2016;237:311–315.
   PubMed Web of Science ®Google Scholar
• Glue P, Medlicott NJ, Neehoff S, et al. Safety and efficacy of extended release ketamine tablets in patients with treatment-resistant depression and anxiety: open label pilot study. Ther Adv Psychopharmacol. 2020;10:2045125320922474.
   Web of Science ®Google Scholar
• Glue P, Russell B, Medlicott NJ. Influence of formulation and route of administration on ketamine’s safety and tolerability: systematic review. Eur J Clin Pharmacol. 2021;77(5):671–676.
   PubMed Web of Science ®Google Scholar
• Gao M, Rejaei D, Liu H. Ketamine use in current clinical practice. Acta Pharmacol Sin. 2016;37(7):865–872.
   PubMed Web of Science ®Google Scholar
• Villanueva-Perez VL, Cerdá-Olmedo G, Samper JM, et al. Oral ketamine for the treatment of type I complex regional pain syndrome. Pain Pract. 2007;7(1):39–43.
   PubMedGoogle Scholar