Gallbladder Emptying in Patients with Major Depression: A Case Series

Abstract

Introduction: Although several adverse effects of antidepressants on the gastrointestinal tract have been described (bleeding, constipation, dolichocolon), their influence on gallbladder motility was not investigated.The aim of our study was to investigate the effects of selected antidepressants on gallbladder emptying in patients with major depression.

Methods: The study was set up as an open clinical trial, with the same intervention (ingestion of test meal provoking gallbladder emptying) undertaken in 112 patients with major depression. There were 30 patients not taking antidepressants (the control group), 25 patients taking amitriptyline, 30 patients taking maprotiline, and 27 patients taking fluoxetine. The volume of gallbladder in the study patients was measured by ultrasonography before the test meal, and 15, 30, 45 and 60 min after the meal.

Results: 1 h after ingestion of the study meal, the amitriptyline group showed incomplete gallbladder emptying (F=10.829, df=3, p=0.000; mean residual volume 11.0±6.1 mL), while in the control, maprotiline and fluoxetine groups emptying of gallbladder was complete (mean residual volumes 5.0±3.3 mL, 5.6±3.7 mL and 5.7±2.3 mL, respectively).

Discussion: In patients with cholecystitis, it would be wise to use antidepressants which do not impair gallbladder emptying, like maprotiline or fluoxetine, and to avoid amitriptyline.

gallbladder - antidepressants - major depression

References

• 1 Olfson M, Marcus SC. National patterns in antidepressant medication treatment.  Arch Gen Psychiatry. 2009;  66 848-856
• 2 Gelenberg AJ. A review of the current guidelines for depression treatment.  J Clin Psychiatry. 2010;  71 e15
• 3 Jankovic SM, Prostran M, Todorovic Z. Pharmacology and Toxicology. 2nd ed., Medical Faculty, Kragujevac, Serbia, 2007; 
• 4 de Abajo FJ, García-Rodríguez LA. Risk of upper gastrointestinal tract bleeding associated with selective serotonin reuptake inhibitors and venlafaxine therapy: interaction with nonsteroidal anti-inflammatory drugs and effect of acid-suppressing agents.  Arch Gen Psychiatry. 2008;  65 795-803
• 5 Yamamoto T, Abe K, Hattori K. et al . High prevalence of gastroduodenal mucosal injury in patients taking selective serotonin reuptake inhibitors.  Dig Endosc. 2010;  22 77
• 6 de Abajo FJ, Montero D, Rodríguez LA. et al . Antidepressants and risk of upper gastrointestinal bleeding.  Basic Clin Pharmacol Toxicol. 2006;  98 304-310
• 7 Zeino Z, Sisson G, Bjarnason I. Adverse effects of drugs on small intestine and colon.  Best Pract Res Clin Gastroenterol. 2010;  24 133-141
• 8 van Soest EM, Dieleman JP, Siersema PD. et al . Tricyclic antidepressants and the risk of reflux esophagitis.  Am J Gastroenterol. 2007;  102 1870-1877
• 9 Alda Díez M, Espuelas Monge M, García-Campayo J. Dolichocolon as unwanted effect of treatment with the anti-depressant mirtazapine.  Aten Primaria. 2004;  33 106-107
• 10 Basse P, Rørdam P. Ischemic colitis complicating imipramine overdose and alcohol ingestion.  Case report. Eur J Surg. 1992;  158 187-188
• 11 Gorard DA, Healy JC, O’Donnell LJ. et al . Inhibition of 5-hydroxytryptamine re-uptake impairs human gall-bladder emptying.  Aliment Pharmacol Ther. 1994;  8 461-464
• 12 Janković SM, Jokovićæ V, Mirčić G. et al . Effects of cisapride on human gallbladder: an ultrasonographic study.  Hellenic Journal of Gastroenterology. 1996;  9 35-37
• 13 Faul F, Erdfelder E, Buchner A. et al . Statistical power analyses using G*Power 3.1: Tests for correlation and regression analyses.  Behavior Research Methods. 2009;  41 1149-1160
• 14 Faul F, Erdfelder E, Lang AG. et al . G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences.  Behavior Research Methods. 2007;  39 175-191
• 15 Machin D, Campbell MJ, Walters SJ. Medical statistics: a textbook for the health sciences. 4th edition John Wiley & Sons, Chichester, UK; 2007
• 16 Balemba OB, Salter MJ, Mawe GM. Innervation of the extrahepatic biliary tract.  The anatomical record part A. 2004;  280A 836-847
• 17 Jankovićæ S, Beleslin DB. Effects of nicardipine, nifedipine and verapamil on acetylcholine-induced contractions of diseased human gallbladder: antiacetylcholine action of dihydropyridine calcium antagonists.  Iugoslav Physiol Pharmacol Acta. 1989;  25 279-283
• 18 Grider JR. Role of cholecystokinin in the regulation of gastrointestinal motility.  J Nutr. 1994;  124 1334S-1339S
• 19 Varga G, Balint A, Burghardt B. et al . Involvement of endogenous CCK1 and CCK2 receptors in colonic motor function.  Br J Pharmacol. 2004;  141 1275-1284
• 20 Kwok YH, Mitchelson F. Comparison of the antimuscarinic activity of mianserin and amitriptyline in the cat superior cervical ganglion.  Naunyn Schmiedebergs Arch Pharmacol. 1981;  316 161-164
• 21 Richardson JS, Mattio TG, Giacobini E. Amitriptyline and imipramine inhibit the release of acetylcholine from parasympathetic nerve terminals in the rat iris.  Can J Physiol Pharmacol. 1984;  62 857-859
• 22 Knorring L, Mörnstad H, Forsgren L. et al . Acute effects of different antidepressant drugs on saliva secretion and accommodation range.  Pharmacopsychiatry. 1986;  19 106-110
• 23 Möller HJ, Riehl T, Dietzfelbinger T. et al . A controlled study of the efficacy and safety of mianserin and maprotiline in outpatients with major depression.  Int Clin Psychopharmacol. 1991;  6 179-192
• 24 Chew ML, Mulsant BH, Pollock BG. et al . Anticholinergic activity of 107 medications commonly used by older adults.  J Am Geriatr Soc. 2008;  56 1333-1341
• 25 To CT, Bagdy G. Anxiogenic effect of central CCK administration is attenuated by chronic fluoxetine or ipsapirone treatment.  Neuropharmacology. 1999;  38 279-282
• 26 Hamon M, Gozlan H, Bourgoin S. et al . Opioid receptors and neuropeptides in the CNS in rats treated chronically with amoxapine or amitriptyline.  Neuropharmacology. 1987;  26 531-539
• 27 Mihajlović G, Djukić-Dejanovićæ S, Jovanović-Mihajlovićæ N. et al . Comparison of safety between individualized and empiric dose regimen of amitriptyline in the treatment of major depressive episode.  Psychiatr Danub. 2010;  22 354-357

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