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