Antidepressant effect of atypical antipsychotic ziprasidone in albino rats

Rajiv Kumar, Hansraj Kumar, U. S. P. Keshri, Manju Gari


Background: Depression is a common psychiatric illness but conventional antidepressants are often shows unpredictable response. Pharmacological profiles of many atypical antipsychotics have potential antidepressant effect. Ziprasidone is an atypical antidepressant with 5HT1A agonistic activity and 5HT1D, 5HT2A and D2 receptors antagonistic activity. It’s a potential candidate for evaluating possible antidepressant activity.

Methods: Behavioural despair test are widely used for evaluation of potential antidepressant molecule. Tail suspension test is a variant of behavioural despair test. Healthy male Wistar albino rat 18 in number and weighing between of 150-200 grams were divided in 3 groups with 6 rats in each group. Group A was treated with 0.9% Normal Saline, Group B with Fluoxetine and Group C with Ziprasidone for 28 days. Tail suspension test was done on day 0, 7, 14, 21 and 28 days.

Results: In comparison to Normal saline both the drugs shows significant antidepressant activity after 28 days of treatment. While antidepressant activity of fluoxetine started to appear from day 7; that of ziprasidone started to appear from 14th day.

Conclusions: Ziprasidone can be suitable candidate for clinical trials of Major Depressive Disorders not responding to conventional antidepressant. 


Antidepressant, Atypical antipsychotics, Depression, Tail suspension test, Ziprasidone

Full Text:



Diagnostic and Statistical Manual of Mental Disorders. 4th ed, Text Revision ed. Washington, DC American Psychiatric Association; 2000.

Christian J. Teter, Judith C. Kando, and Barbara G. Wells; Major Depressive Disorder; Basicmedical Key; 2016.

Pompili M, Serafini G, Innamorati M. Suicidal Behavior and Alcohol Abuse. International Journal of Environmental Research and Public Health. 2010;7(4):1392-431.

Susan J. Rogers, Jose E. Cavazos, Epilepsy: In pharmacotherapy pathophyl approach Joseph. T. 7 ed, Mc Graw Hill, New York; 2010:927.

Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry. 2000;157(10):1552-62.

Brigitta B. Pathophysiology of depression and mechanisms of treatment. Dialogues in Clinical Neuroscience. 2002;4(1):7-20.

Salleh MR. Life Event, Stress and Illness. The Malaysian Journal of Medical Sciences: MJMS. 2008;15(4):9-18.

Xue R, Jin ZL, Chen HX, Yuan L, He XH, Zhang YP, et al. Antidepressant-like effects of 071031B, a novel serotonin and norepinephrine reuptake inhibitor. Eur Neuropsychopharmacol. 2012;23:728-41.

Ruhe HG, Huyser J, Swinkels JA, Schene AH. Switching antidepressants after a first selective serotonin reuptake inhibitor in major depressive disorder: a systematic review. J Clin Psychiatry. 2006;67:1836-55.

Sprouse JS. Comparison of the novel antipsychotic ziprasidone with clozapine and olanzapine: inhibition of dorsal raphe cell firing and the role of 5-HT1A receptor activation. Neuropsychopharmacology. 1999;21(5):622-31.

Glen L. Stimmel (Clinical Therapeutics) Ziprasidone: An atypical antipsychotic drug for the treatment of schizophrenia. 2002;24(1):21-37.

Ghosh MN. Toxicity studies, In: Ghosh MN, editor, Fundamentals of Experimental Pharmacology 5th ed, Kolkata: Hilton and Company; 2011:167.

Bikash medhi Practical manual of experimental and clinical pharmacology 1st edition; 2010:24.

Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl). 1985;85(3):367-70.

Chermat R, Thierry B, Mico JA, Stéru L, Simon P. Adaptation of the tail suspension test to the rat. J Pharmacol (Paris). 1986;17:348-50.

Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N. Engl J Med. 2008;358(3):252-60.

Detke MJ, Rickels M, Lucki I. Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacology (Berl). 1995;121(1):66-72.

Elhwuegia AS. Central monoamines and their role in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28:435-51.

Prozac Pharmacology, Pharmacokinetics, Studies, Metabolism. Available at: 2007.

Chen J, Gao K, Kemp DE. Second-generation Antipsychotics in Major Depressive Disorder: Update and Clinical Perspective. Curr Opin Psychiatry. 2011;24:10-7.

Konstantinidis A, Papageorgiou K, Grohmann R, Horvath A, Engel R, Kasper S. Increase of antipsychotic medication in depressive inpatients from 2000 to 2007: results from the AMSP International Pharmacovigilance Program. Int J Neuropsychopharmacol. 2011;1-9.

Stahl SM. Antipsychotic agents, Stahl’s Essential Psychopharmacology Neuroscientific Basis and Practical Application 4th Edition, Cambridge university press; 2000:159.

Sprouse JS, Reynolds LS, Braselton JP, Rollema H, Zorn SH. Comparison of the Novel Antipsychotic Ziprasidone with Clozapine and Olanzapine: Inhibition of Dorsal Raphe Cell Firing and the Role of 5-HT1A Receptor Activation; Neuropsychopharmacology. 1999:21(5):622-31.

Konstantinidis A, Papageorgiou K, Grohmann R, Horvath A, Engel R, Kasper S. Increase of antipsychotic medication in depressive inpatients from 2000 to 2007: results from the AMSP International Pharmacovigilance Program. Int J Neuropsychopharmacol. 2011;1-9.

Rajkumar R, Pandey DK Mahesh R. 1-(m-Chlorophenyl)piperazine induced depressogenic –like behaviour in rodents by stimulating the neuronal 5-HT(2A) receptors: Proposal of a modified rodent antidepressant assay. Eur J Pharmacol. 2009;608 (1-3):32-41.

Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STARD report. Am J Psychiatry. 2006;163:1905-17.

El-Khalil N, Joyce M, Atkinson S. Extended-release quetiapine fumerate (quetiapine XR) as adjunctive therapy in major depressive disorder (MDD) in patients with an inadequate response to ongoing antidepressant treatment: a multicentre, randomized, double-blind, placebo-controlled study. Int J Neuropsychopharmacol. 2010;13(7):917-32.

Berman RM, Fava M, Thase ME. Aripiprazole augmentation in major depressive disorder : a double blind, placebo-controlled study in patients with inadequate response to antidepressant. CNS Spectr. 2009;14(4):197-206.