Evaluation Of Antidepressant Activity Of Statins Alone And In Combination With Fluoxetine In Acute And Chronic Behavioural Models Of Depression.

CONTEXT

To study the role of statins (Atorvastatin, Simvastatin, and Pravastatin) as novel pharmacological option in treatment of depression.

AIM

To evaluate antidepressant activity of statins (HMG-CoA reductase inhibitor) in combination with Fluoxetine in acute and chronic forced swim test in rats.

DESIGN

An experimental animal study.

MATERIALS AND METHODS

Male albino wistar rats of either sex with weight range 150-250 grams were used. Part 1 is Dose finding study in acute forced swim test with three doses of Atorvastatin (2.5 mg/kg, 5 mg/kg, 10 mg/kg), Simvastatin (2.5 mg/kg, 5 mg/kg, 10 mg/kg), and Pravastatin (10 mg/kg, 20 mg/kg, 40 mg/kg) each were done. Part 2 was conducted to study the effects of statins (Atorvastatin, Simvastatin, and Pravastatin) and Fluoxetine (10 mg/kg) per se and in combination, on immobility of rats in acute forced swim test were compared. In part 3 effects of statins (Atorvastatin, Simvastatin, and Pravastatin) and Fluoxetine per se and in combination on immobility of rats in chronic forced swim test were compared. Open field test was performed to discriminate between the general behavioural stimulation (false positives) and antidepressant effect of study drugs. All study drugs were given orally. In Part 2 & 3 maximum effective dose of statin from part 1 was utilised.

STATISTICS

ANOVA with post-hoc Tukeys test, significant effects were analyzed further using post hoc Newman-Keuls tests.

RESULTS

In part 1 of dose finding study most effective doses for Atorvastatin, Simvastatin and Pravastatin were 10 mg/kg, 10 mg/kg and 40 mg/kg respectively. In this part acute forced swim test showed, no statistically significant reduction in duration of immobility by any of the statins (Atorvastatin, Simvastatin, and Pravastatin) as compared to control. In Part 2 acute forced swim test, When combined with Fluoxetine, Atorvastatin (157.83 ± 10.51) and Simvastatin (167.66 ± 7.71) showed significant reduction in duration of immobility when compared with control (183.66 ± 9.52) but not against Fluoxetine (161.33 ± 8.68) alone. In part 3 chronic forced swim test, Atorvastatin (132.16 ± 7.19 sec) and Simvastatin (130.50 ± 5.68 sec) significantly potentiated action of Fluoxetine. However Pravastatin did not significantly potentiated the action of Fluoxetine. In open field test done before acute and chronic forced swim test (Part 2 & 3 respectively), there was no statistically significant difference between test groups for line crossing, rearing, and defecation suggesting that there was no general behavioural stimulation of rats and reduction in duration of immobility with test drugs was due to antidepressant effect.

CONCLUSION

Present study shows that Atorvastatin, Simvastatin, and Pravastatin do not exhibit independent antidepressant activity, but they can have synergistic effect with SSRI like Fluoxetine. Atorvastatin and Simvastatin may help to reduce the dose of Fluoxetine thereby minimizing adverse effects of Fluoxetine.