Evaluation of antidepressant and analgesic activity of tapentadol with mirtazapine: an experimental study

Pankaj K. Chaudhary, Atul Jain, Asha Pathak, Neha Sharma, Atul K. Mishra, Arvind K. Maurya, Vikas Gaur


Background: Data comparing tapentadol with an antidepressant is limited. A comparison of tapentadol with mirtazapine at different dose has not been performed, the other antidepressant in the same therapeutic class with a significant market share, has been undertaken. In the absence of relevant data to assess the place that tapentadol should occupy in the therapeutic arsenal, indirect comparisons are the most rigorous way to go. We conducted a study evaluate antidepressant and analgesic activity of tapentadol with mirtazapine at different doses in Swiss albino mice.

Methods: Tapentadol was administered at 10, 20 and 40 mg/kg (i.p) once daily for 14 days to swiss albino mice of either sex. The immobility period for antidepressant activity of mice were recorded in forced swim test and reaction time for analgesic activity of mice were recorded in tail flick test of the control and drug treated group. The antidepressant and analgesic activity of tapentadol (10, 20, 40 mg/kg i.p) was compared with that of mirtazapine (3, 5, 7 mg/kg i.p), administered for 14 days.

Results: Tapentadol produced better antidepressant at (20, 40 mg/kg), but less at 10 mg/kg and significant analgesic activity at all the three doses, as indicated by reduction in immobility times and increase in reaction time as compared to control. Mirtazapine produced no antinociceptive activity at 3 mg/kg, but significant at 5, 7 mg/kg and showed better antidepressant activity at all the three doses in mice. The result of this study indicates the better analgesic activity of tapentadol at all the doses and least antidepressant activity at 10 mg/kg, as compared to mirtazapine which has shown better antidepressant activity at all the three doses but no analgesic activity at 3 mg/kg.

Conclusion: It can be concluded that tapentadol is a better drug in case of depression associated with pain compared to mirtazapine in mice.


Antidepressant, Analgesic, Tail flick test, Forced swim test, Tapentadol, Mirtazapine

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Hyman S, Chisholm D, Kessler R, Patel V, Ford WH. Mental disorders. In: Jamison DT, Breman JG, Measham AR, Alleyne G, Claeson M, Evans DB, et al, editors. Disease Control Priorities in Developing Countries. 2nd Edition. New York: Oxford University Press for the World Bank; 2006: 605-25.

World Health Organization. Mental and behavioural disorders, Department of Mental Health, 2000. Available at Accessed 10 February 2015.

Aaron R, Joseph A, Abraham S, Muliyil J, George K, Prasad J, et al. Suicides in young people in rural southern India. Lancet. 2004;363:1117-8.

Narrow US. One year prevalence of depressive disorders among adults 18 and over in the U.S.: NIMH ECA prospective data. Population Estimates Based on U.S. Census Estimated Residential Population age 18 and Over on Unpublished Table, July 1; 1981.

WHO Report on Mental Illness Released October 4, 2001. Available at: Accessed 7 Aug 2012.

Sathoskar RS, Bhandarkar SD, Rege NN. Pharmacology and Pharmacotherapeutics. Revised 19th edition., Mumbai: Popular Prakashan Pvt. Ltd.; 2005: 202-12.

Rafieian-Kopaei M, Sewell RD. Newer antidepressants: Analgesic and relative mono amine reuptake inhibitor potency. Pham Pharmacol. 1994;46:1088.

Jung AC, Staiger T, Sullivan M. The efficacy of selective serotonin reuptake inhibitors for the management of chronic pain. J Gen Intern Med. 1997;12:384-9.

Lin LL, Lin AY, Knopf JL. Cytosolic phospholipase A2 is coupled to hormonally regulated release of arachidonic acid. Proc Natl Acad Sci U S A. 1992;89:6147-51.

D’Armour FE, Smith DL. A method for determining loss of pain sensation. J Pharmacol Exp Ther. 1941;72:74-9.

Ramabadran K, Bansinath M. A critical analysis of the experimental evaluation of nociceptive reactions in animals. Pharm Res. 1986;3(5):263-70.

Rojas-Corrales MO, Gibert-Rahola J, Micó JA. Tramadol induces antidepressant-type effects in mice. Life Sci. 1998;63(12):PL175-80.

Tayal V, Kalra BS, Chawla S. Evaluation of antidepressant activity of tramadol in mice. Indian J Pharmacol. 2008;40(3):129-30.

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.

Muth-Selbach U, Hermanns H, Driehsen C, Lipfert P, Freynhagen R. Racemic intrathecal mirtazapine but not its enantiomers acts anti-neuropathic after chronic constriction injury in rats. Brain Res Bull. 2009;79(1):63-8.

Brannon GE, Stone KD. The use of mirtazapine in a patient with chronic pain. J Pain Symptom Manage. 1999;18(5):382 5.

Singh VP, Jain NK, Kulkarni SK. On the antinociceptive effect of fluoxetine, a selective serotonin reuptake inhibitor. Brain Res. 2001;915(2):218-26.

Anjaneyulu M, Chopra K. Possible involvement of cholinergic and opioid receptor mechanisms in fluoxetine mediated antinociception response in streptozotocin-induced diabetic mice. Eur J Pharmacol. 2006;538(1-3):80-4.