Digitalis intoxication induced by paroxetine co-administration

Abstract

We write to express our considerable reservations about the conclusions of the Case Report by Norio Yasui-Furukori and Sunao Kaneko (March 4, p 788).1Yasui-Furukori N Kaneko S Digitalis intoxication induced by paroxetine co-administration.Lancet. 2006; 367: 788Summary Full Text Full Text PDF PubMed Scopus (22) Google Scholar In a woman of 68 years, the most likely explanation of digoxin toxicity is hospital-induced improved concordance, with the expected rise in plasma concentration with a daily dose of 250 μg. The patient was not followed-up long enough after restart of digoxin to exclude this possibility.It is biologically implausible that enzyme inhibition by paroxetine would cause digoxin concentrations to more than double: 80% of digoxin is excreted unchanged in man.2Dollery C Therapeutic drugs. Churchill Livingstone, London1991Google Scholar Although paroxetine interferes with the efflux pump transporter P-glycoprotein in vitro, inhibition of intestinal P-glycoprotein alone will not double digoxin concentrations because oral bioavailability of digoxin is high. Inhibition of renal P-glycoprotein causing decreased digoxin elimination is biologically plausible, but a 15% decrease in the area under the serum concentration time profile (AUC) has been seen for digoxin when paroxetine was administered at steady state.3GlaxoSmithKline PAXIL (paroxetine hydrochloride) prescribing information. GlaxoSmithKline, Research Triangle Park2005http://www.fda.gov/medwatch/safety/2005/Paxil_PI%20_9-27-05.pdfGoogle Scholar An epidemiological study revealed no evidence of an increased risk of digoxin toxicity with paroxetine compared with tricyclic antidepressants or benzodiazepines.4Juurlink DN Mamdani MM Kopp A Herrmann N Laupacis A A population-based assessment of the potential interaction between serotonin-specific reuptake inhibitors and digoxin.Br J Clin Pharmacol. 2005; 59: 102-107Crossref PubMed Scopus (25) Google ScholarOf greater concern is the advice proffered by Yasui-Furukori and Kaneko at the end of their report. Venlafaxine and citalopram in overdose are both far more toxic to the cardiovascular system than other drugs in this category.5Kelly CA Dhaun N Laing WJ Strachan FE Good AM Bateman DN Comparative toxicity of citalopram and the newer antidepressants after overdose.J Toxicol Clin Toxicol. 2004; 42: 67-71Crossref PubMed Scopus (111) Google Scholar Advice to substitute these drugs is, in our view, unsupported by any evidence in the paper, and goes against standard prescribing advice. Heart disease is a contraindication to venlafaxine prescription, and tachycardia is an acknowledged adverse effect of citalopram. To our mind this is a case of digitalis-induced psychosis due to excess therapeutic dosing in a susceptible patient.We declare that we have no conflict of interest. We write to express our considerable reservations about the conclusions of the Case Report by Norio Yasui-Furukori and Sunao Kaneko (March 4, p 788).1Yasui-Furukori N Kaneko S Digitalis intoxication induced by paroxetine co-administration.Lancet. 2006; 367: 788Summary Full Text Full Text PDF PubMed Scopus (22) Google Scholar In a woman of 68 years, the most likely explanation of digoxin toxicity is hospital-induced improved concordance, with the expected rise in plasma concentration with a daily dose of 250 μg. The patient was not followed-up long enough after restart of digoxin to exclude this possibility. It is biologically implausible that enzyme inhibition by paroxetine would cause digoxin concentrations to more than double: 80% of digoxin is excreted unchanged in man.2Dollery C Therapeutic drugs. Churchill Livingstone, London1991Google Scholar Although paroxetine interferes with the efflux pump transporter P-glycoprotein in vitro, inhibition of intestinal P-glycoprotein alone will not double digoxin concentrations because oral bioavailability of digoxin is high. Inhibition of renal P-glycoprotein causing decreased digoxin elimination is biologically plausible, but a 15% decrease in the area under the serum concentration time profile (AUC) has been seen for digoxin when paroxetine was administered at steady state.3GlaxoSmithKline PAXIL (paroxetine hydrochloride) prescribing information. GlaxoSmithKline, Research Triangle Park2005http://www.fda.gov/medwatch/safety/2005/Paxil_PI%20_9-27-05.pdfGoogle Scholar An epidemiological study revealed no evidence of an increased risk of digoxin toxicity with paroxetine compared with tricyclic antidepressants or benzodiazepines.4Juurlink DN Mamdani MM Kopp A Herrmann N Laupacis A A population-based assessment of the potential interaction between serotonin-specific reuptake inhibitors and digoxin.Br J Clin Pharmacol. 2005; 59: 102-107Crossref PubMed Scopus (25) Google Scholar Of greater concern is the advice proffered by Yasui-Furukori and Kaneko at the end of their report. Venlafaxine and citalopram in overdose are both far more toxic to the cardiovascular system than other drugs in this category.5Kelly CA Dhaun N Laing WJ Strachan FE Good AM Bateman DN Comparative toxicity of citalopram and the newer antidepressants after overdose.J Toxicol Clin Toxicol. 2004; 42: 67-71Crossref PubMed Scopus (111) Google Scholar Advice to substitute these drugs is, in our view, unsupported by any evidence in the paper, and goes against standard prescribing advice. Heart disease is a contraindication to venlafaxine prescription, and tachycardia is an acknowledged adverse effect of citalopram. To our mind this is a case of digitalis-induced psychosis due to excess therapeutic dosing in a susceptible patient. We declare that we have no conflict of interest.