Main Article Content



To assess the antinociceptive activity of some selective serotonin reuptake inhibitors (SSRI- fluoxetine, escitalopram) and atypical antidepressant (mirtazapine).

Materials and methods

Adult wistar albino rats were grouped to receive control (normal saline), SSRI (fluoxetine, escitalopram), atypical antidepressant (mirtazapine) and standard (morphine). Different doses of fluoxetine, escitalopram, mirtazapine & morphine were administered intraperitoneally in order to assess their antinociceptive activity using tail flick analgesiometer method to pretested sensitive rats. Tail flick latencies (TFL) were assessed at 0, 30, 60, 90 and 120 min after drug administration.


Fluoxetine in doses of 5mg/kg and 10 mg/kg produced significant increase in TFL at all times of observation while 2 mg/kg dose did not show any change. Escitalopram failed to produce any change to tail flick latency with all doses at all time of observation. Mirtazapine in both the higher doses (5mg/kg and 7mg/kg) increased tail flick latency at all time of observation while lower dose (3mg/kg) produced no effect.


The SSRI fluoxetine and antidepressant mirtazapine possesses significant antinociceptive activity whereas the SSRI escitalopram does not. However these need to be further proved in other animal models and in clinical studies.


Antidepressant Analgesia Chronic pain SSRI

Article Details

How to Cite
R Agrawal, K Saha, & S Mohapatra. (2021). Comparative evaluation of analgesic activity of SSRI and atypical antidepressant: an experimental study. International Journal of Research in Pharmacology & Pharmacotherapeutics, 5(3), 251-255. Retrieved from


  1. [1]. Brannon GE, Stone KD. The use of mirtazapine in a patient with chronic pain. J Pain Symptom Manage 18, 1999, 382-5.
  2. [2]. Kosten TR, George TP. The Neurobiology of Opioid Dependence: Implications for Treatment. Science & Practice Perspectives.1 (1), 2002, 13-20.
  3. [3]. Bradley RH, Barkin RL, Jerome J, DeYoung K, Dodge CW. Efficacy of venlafaxine for the long term treatment of chronic pain with associated major depressive disorder. Am J Ther 10, 2003, 318-23.
  4. [4]. Rafieian-Kopaei M, Sewell RDE. Newer antidepressants: Analgesia and relative monoamine reuptake inhibitory potency. J Pharm Pharmacol 46, 1994, 1088-92
  5. [5]. Schreiber S, Rigai T, Katz Y, Pick CG. The antinociceptive effect of mirtazapine in mice is mediated through serotonergic, noradrenergic and opioid mechanisms. Brain Research Bulletin 58(6), 2002, 601-5.
  6. [6]. Gulecha V, Sivakumar T, Upaganlawer A, Khandare R, Upasani C. Tephrosia purpurea Linn leaves attenuate pain and inflammation in experimental animals. Int j Nutr Pharmacol Neurol Dis 1, 2011, 146-5.
  7. [7]. Max MB, Lynch SA, Muir J, Shoaf SE, Smoller B, Dubner R. Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy. N Engl J Med 326, 1992, 1250-6.
  8. [8]. Goldenberg D, Mayskiy M, Mossey C, Ruthazer R, Schmid C. A randomized, double-blind crossover trial of fluoxetine and amitriptyline in the treatment of fibromyalgia. Arthritis Rheum 39, 1996, 1852-9.
  9. [9]. Rani PU, Naidu MU, Prasad VB, Rao TR, Shobha JC. An evaluation of antidepressants in rheumatic pain conditions. Anesth Analg 83, 1996, 371-5.
  10. [10]. Gray AM, Pache DM, Sewell RD. Do alpha2-adrenoceptors play an integral role in the antinociceptive mechanism of action of antidepressant compounds? Eur J Pharmacol. 378(2), 1999, 161–168.
  11. [11]. Rang HP, Dale MM, Ritter JM, Flower RJ. Rang and Dale’s Pharmacology. Edinburgh: Churchill Livingstone; 6, 2007.
  12. [12]. Prajapati R, Umbarkar R, Parmar S, Sheth N. Antidepressant like activity of Lagenaria siceraria (Molina) Standley fruits by evaluation of the forced swim behavior in rats. Int J Nutr Pharmacol Neurol Dis 1, 2011, 152-6.
  13. [13]. Guyton AC, Hall JE. Medical physiology. Philadelphia: WB Saunders Co. 9, 1996.
  14. [14]. 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 48, 2005, 252-63.
  15. [15]. Muth-Selbach U, Hermanns H, Driehsen C, Lipfert P, Freynhagen R. Racemic intrathecal mirtazapine but not its enantiomers acts antineuropathic after chronic constriction injury in rats. Brain Res Bull 79, 2009, 63-8.
  16. [16]. 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 538, 2006, 80-4.
  17. [17]. Hyttel J. Pharmacological characterization of selective serotonin reuptake inhibitors (SSRIs). Int Clin Psychopharmacol 9, 1994, 19-26.
  18. [18]. Richelson E, Synaptic effects of antidepressants. J Clin Psycho pharmacol. 16(3- 2), 1996, 1S-7S; discussion 7S-9S.