No Evidence for Development of Tolerance after Repeated Use of Propofol for Electroconvulsive Therapy

Abstract

Introduction: The short-acting narcotic propofol is used for sedation during electroconvulsive therapy (ECT). It remains unclear whether patients develop tolerance to propofol after repeated administration. Therefore, we studied whether propofol dosage had to be increased during a course of ECT.

Methods: This retrospective study evaluated records of 39 in- and outpatients at a Swiss psychiatric hospital who underwent 10–21 ECT sessions for affective disorder over 4–28 weeks in 2011–2013. We examined the dose of propofol required to achieve deep sedation at the first and last ECT sessions.

Results: 13/39 patients (33.3%) needed a slightly higher propofol dose at the last ECT session than at the first (Group 1), 12 patients (30.8%) needed the same dose at the first and last sessions (Group 2) and 14 patients (35.9%) needed a lower final dose (Group 3).

Conclusions: In our study patients did not appear to develop tolerance to propofol after repeated administration. Although the lack of a systematic dosing scheme in our study limits the conclusions that can be drawn, recent studies in animal models indicate that tolerance development is rather unlikely with propofol. Further studies are required to clarify the question of whether repeated use of propofol leads to tolerance.

Key words

propofol - misuse - dependence - addiction - toxicity

• References

• 1 Langley MS, Heel RC. Propofol. A review of its pharmacodynamic and pharmacokinetic properties and use as an intravenous anaesthetic. Drugs 1988; 35: 334-372
• 2 Soyka M. Missbrauchspotential von Propofol – Was ist gesichert?. Suchtmed 2012; 14: 47-52
• 3 Boyle WA, Shear JM, White PF et al. Long-term sedative infusion in the intensive care unit: Propofol vs. midazolam. J Drug Dev 1991; 4 (Suppl. 03) 43-45
• 4 Yang B, Wang BF, Lai MJ et al. Differential involvement of GABAA and GABAB receptors in propofol self-administration in rats. Acta Pharmacol Sin 2011; 32: 1460-1465
• 5 Weerts EM, Ator NA, Griffiths RR. Comparison of the intravenous reinforcing effects of propofol and methohexital in baboons. Drug Alcohol Depend 1999; 57: 51-60
• 6 Li KY, Xiao C, Xiong M et al. Nanomolar propofol stimulates glutamate transmission to dopamine neurons: a possible mechanism of abuse potential?. J Pharmacol Exp Ther 2008; 325: 165-174
• 7 Pain L, Oberling P, Sandner G et al. Effect of midazolam on propofol-induced positive affective state assessed by place conditioning in rats. Anesthesiology 1997; 87: 935-943
• 8 Soyka M. Suchtpotential von Propofol. Deutscher Anästhesiecongress. Leipzig 2012;
• 9 Bonnet U, Harkener J, Scherbaum N. A case report of propofol dependence in a physician. J Psychoactive Drugs 2008; 40: 215-217
• 10 Follette JW, Farley WJ. Anesthesiologist addicted to propofol. Anesthesiology 1992; 77: 817-818
• 11 Fritz GA, Niemczyk WE. Propofol dependency in a lay person. Anesthesiology 2002; 96: 505-506
• 12 Koopmann A, von der Goltz C, Hermann D et al. Propofol addiction initiated by anesthetic use. Am J Psychiatry 2011; 168: 211-212
• 13 Monroe T, Hamza H, Stocks G et al. The misuse and abuse of propofol. Subst Use Misuse 2011; 46: 1199-1205
• 14 Roh S, Park JM, Kim DJ. A case of propofol dependence after repeated use for endoscopy. Endoscopy 2011; 43 (Suppl. 02) UCTN: E362
• 15 Schneider U, Rada D, Rollnik JD et al. Propofol dependency after treatment of tension headache. Addict Biol 2001; 6: 263-265
• 16 LeSage MG, Stafford D, Glowa JR. Abuse liability of the anesthetic propofol: self-administration of propofol in rats under fixed-ratio schedules of drug delivery. Psychopharmacology (Berl) 2000; 153: 148-154
• 17 Roussin A, Montastruc JL, Lapeyre-Mestre M. Pharmacological and clinical evidences on the potential for abuse and dependence of propofol: a review of the literature. Fundam Clin Pharmacol 2007; 21: 459-466
• 18 Zacny JP, Lichtor JL, Coalson DW et al. Subjective and psychomotor effects of subanesthetic doses of propofol in healthy volunteers. Anesthesiology 1992; 76: 696-702
• 19 Zacny JP, Lichtor JL, Zaragoza JG et al. Assessing the behavioral effects and abuse potential of propofol bolus injections in healthy volunteers. Drug Alcohol Depend 1993; 32: 45-57
• 20 Brandner B, Blagrove M, McCallum G et al. Dreams, images and emotions associated with propofol anaesthesia. Anaesthesia 1997; 52: 750-755
• 21 Weetman DB, Mascardo LA, Ross MB et al. Propofol as a drug of diversion. Am J Health Syst Pharm 2004; 61: 1185-1186
• 22 Bonnet U. Assessment of the addictive risk of propofol. Fortschr Neurol Psychiatr 2011; 79: 442-452
• 23 Drummer OH. A fatality due to propofol poisoning. J Forensic Sci 1992; 37: 1186-1189
• 24 Iwersen-Bergmann S, Rosner P, Kuhnau HC et al. Death after excessive propofol abuse. Int J Legal Med 2001; 114: 248-251
• 25 Kirby RR, Colaw JM, Douglas MM. Death from propofol: accident, suicide, or murder?. Anesth Analg 2009; 108: 1182-1184
• 26 Klausz G, Rona K, Kristof I et al. Evaluation of a fatal propofol intoxication due to self administration. J Forensic Leg Med 2009; 16: 287-289
• 27 Kranioti EF, Mavroforou A, Mylonakis P et al. Lethal self administration of propofol (Diprivan). A case report and review of the literature. Forensic Sci Int 2007; 167: 56-58
• 28 Roussin A, Mirepoix M, Lassabe G et al. Death related to a recreational abuse of propofol at therapeutic dose range. Br J Anaesth 2006; 97: 268
• 29 Deer TR, Rich GF. Propofol tolerance in a pediatric patient. Anesthesiology 1992; 77: 828-829
• 30 Fassoulaki A, Farinotti R, Mantz J et al. Does tolerance develop to the anaesthetic effects of propofol in rats?. Br J Anaesth 1994; 72: 127-128
• 31 Au J, Walker WS, Scott DH. Withdrawal syndrome after propofol infusion. Anaesthesia 1990; 45: 741-742
• 32 Au J, Walker WS, Scott DH. Withdrawal syndrome after propofol infusion. Anaesthesia 1991; 46: 238
• 33 Cawley MJ, Guse TM, Laroia A et al. Propofol withdrawal syndrome in an adult patient with thermal injury. Pharmacotherapy 2003; 23: 933-939
• 34 Grant IS, Worsley M. Withdrawal syndrome after propofol. Anaesthesia 1991; 46: 238
• 35 Imray JM, Hay A. Withdrawal syndrome after propofol. Anaesthesia 1991; 46: 704
• 36 Cohen Y, Feldinger E, Ogorek D et al. Increased propofol requirement during succeeding administrations for electroconvulsive therapy. J Clin Anesth 2004; 16: 282-285
• 37 Setlock MA, Palmisano BW, Berens RJ et al. Tolerance to propofol generally does not develop in pediatric patients undergoing radiation therapy. Anesthesiology 1996; 85: 207-209
• 38 Earley PH, Finver T. Addiction to propofol: a study of 22 treatment cases. J Addict Med 2013; 7: 169-176
• 39 Bonnet U, Scherbaum N. Craving dominates propofol addiction of an affected physician. J Psychoactive Drugs 2012; 44: 186-190
• 40 Cha HJ, Cha JH, Cho HY et al. Dependence potential of propofol: behavioral pharmacology in rodents. Biomol Ther (Seoul) 2012; 20: 234-238
• 41 Ihmsen H, Schywalsky M, Tzabazis A et al. Development of acute tolerance to the EEG effect of propofol in rats. Br J Anaesth 2005; 95: 367-371
• 42 Keidan I, Perel A, Shabtai EL et al. Children undergoing repeated exposures for radiation therapy do not develop tolerance to propofol: clinical and bispectral index data. Anesthesiology 2004; 100: 251-254