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Synergistic Effects of Citalopram and Morphine in the Renal Colic Pain Relief; a Randomized Clinical Trial

Mehrdad Esmailian, Mehdi Keshavarz



Introduction: Although the synergistic effects of opioids and other analgesic drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) have been established in relieving acute pain due to renal calculi, no studies today have evaluated the concomitant administration of opiates and other drugs with analgesic effects, such as serotonin re-uptake inhibitors. Considering the high prevalence of renal colic, the present study was carried out to compare the effect of concomitant prescription of morphine and a placebo with that of morphine and citalopram on the management of acute pain due to renal calculi. Methods: The present double-blind randomized clinical trial was carried out from October 2012 to March 2013 in the Al-Zahra educational Hospital in Isfahan, Iran. A total of 90 patients with acute renal colic pain were randomly divided into two groups of 45 subjects. The subjects in one group received morphine/ placebo and another one morphine/citalopram. The patients’ pain severity was determined by visual analogue scale (VAS) before and 20 minutes after administration of medications. In case of persistent pain the second or even third dose was administered and the pain severity was once again determined. Data were analyzed with STATA 11.0 using chi-squared, two-way ANOVA, Bonferroni post hoc test, and log rank test. Results: The decrease in pain severity in the morphine/citalopram group was significantly compared to the morphine/placebo group and the time before administration of the medications (p<0.001). In contrast, administration of morphine/placebo did not have a significant effect on pain severity at this interval (p=0.32). Kaplan-Meier curve showed that the first injection was successful in relieving pain in 15 (33.3%) and 26 (57.8%) subjects in the morphine/placebo and morphine/citalopram groups, respectively. The second injection of these medications resulted in therapeutic success in 35 (87.8%) and 42 (95.6%) subjects in the above groups, respectively. Log rank test showed a significant difference in the treatment success between the two groups (p=0.001). Conclusion: It seems that the combination of citalopram and morphine sulfate causes increased efficacy and higher success rate in pain control of patients presented to the emergency department with a complaint of renal colic.


Pain management; renal colic; morphine; citalopram; emergencies


Curhan GC, Willett WC, Rimm EB, Stampfer MJ. Family history and risk of kidney stones. J Am Soc Nephrol. 1997;8(10):1568-73.

Safdar B, Degutis LC, Landry K, Vedere SR, Moscovitz HC, D’Onofrio G. Intravenous morphine plus ketorolac is superior to either drug alone for treatment of acute renal colic. Ann Emerg Med. 2006;48(2):173-81.

Labrecque M, Dostaler L-P, Rousselle R, Nguyen T, Poirier S. Efficacy of nonsteroidal anti-inflammatory drugs in the treatment of acute renal colic: a meta-analysis. Arch Intern Med. 1994;154(12):1381-7.

Segura JW, Preminger GM, Assimos DG, et al. Ureteral stones clinical guidelines panel summary report on the management of ureteral calculi. J Urol. 1997;158(5):1915-21.

Holdgate A, Pollock T. Nonsteroidal anti-inflammatory drugs (NSAIDs) versus opioids for acute renal colic. Cochrane Database Syst Rev. 2004;1:CD004137.

Teichman JM. Acute renal colic from ureteral calculus. N Engl J Med. 2004;350(7):684-93.

Tramŕr DM, Williams J, Carroll D, Wiffen P, Moore R, McQuay H. Comparing analgesic efficacy of non‐steroidal anti‐inflammatory drugs given by different routes in acute and chronic pain: a qualitative systematic review. Acta Anaesthesiol Scand. 1998;42(1):71-9.

Cevik E, Cinar O, Salman N, et al. Comparing the efficacy of intravenous tenoxicam, lornoxicam, and dexketoprofen trometamol for the treatment of renal colic. Am J Emerg Med. 2012;30(8):1486-90.

Hemrika D, Bossuyt P. Ketorolac versus morphine for severe pain. Trial. 1997;350:774-9.

Schröder W, Vry J, Tzschentke TM, Jahnel U, Christoph T. Differential contribution of opioid and noradrenergic mechanisms of tapentadol in rat models of nociceptive and neuropathic pain. Eur J Pain. 2010;14(8):814-21.

Bomholt SF, Mikkelsen JD, Blackburn-Munro G. Antinociceptive effects of the antidepressants amitriptyline, duloxetine, mirtazapine and citalopram in animal models of acute, persistent and neuropathic pain. Neuropharmacology. 2005;48(2):252-63.

O'Connor A, Schug SA, Cardwell H. A comparison of the efficacy and safety of morphine and pethidine as analgesia for suspected renal colic in the emergency setting. J Accid Emerg Med. 2000;17(4):261-4.

Tartau L. The effects of citalopram and escitalopram in visceral pain and behavioral models in mice: experimental researches. Eur J Pain. 2009;13:S56.

Reinhart DJ. Minimising the adverse effects of ketorolac. Drug Saf. 2000;22(6):487-97.

Rafieian-Kopaei M, Gray AM, Spencer PS, Sewell RD. Contrasting actions of acute or chronic paroxetine and fluvoxamine on morphine withdrawal-induced place conditioning. Eur J Pharmacol. 1995;275(2):185-9.

Sacerdote P, Brini A, Mantegazza P, Panerai AE. A role for serotonin and beta-endorphin in the analgesia induced by some tricyclic antidepressant drugs. Pharmacol Biochem Behav. 1987;26(1):153-8.

Campo JV, Perel J, Lucas A, et al. Citalopram treatment of pediatric recurrent abdominal pain and comorbid internalizing disorders: an exploratory study. J Am Acad Child Adolesc Psychiatry. 2004;43(10):1234-42.

Aragona M, Bancheri L, Perinelli D, et al. Randomized double‐blind comparison of serotonergic (Citalopram) versus noradrenergic (Reboxetine) reuptake inhibitors in outpatients with somatoform, DSM‐IV‐TR pain disorder. European Journal of Pain. 2005;9(1):33-8.

Brown CS, Franks AS, Wan J, Ling FW. Citalopram in the treatment of women with chronic pelvic pain: an open-label trial. J Reprod Med. 2008;53(3):191-5.

Qinying C, Zhixiong T, Jinwei W. Therapeutic effects of citalopram on alleviating pain of peripheral neuropathy in type 2 diabetic patients. Med J Chin PLA. 2008;3:32-8.

Jensen MP, Smith DG, Ehde DM, Robinsin LR. Pain site and the effects of amputation pain: further clarification of the meaning of mild, moderate, and severe pain. Pain. 2001;91(3):317-22.

Farrar JT, Portenoy RK, Berlin JA, Kinman JL, Strom BL. Defining the clinically important difference in pain outcome measures. Pain. 2000;88(3):287-94

DOI: https://doi.org/10.22037/emergency.v2i1.5591


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