PMC:3767251 / 10162-13850 JSONTXT

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are prescribed worldwide and chronic treatment often lasts several months. The observation that these classes of drugs have anti-inflammatory potential might led to important clinical implication. Moreover, it has been observed that patients with chronic inflammatory disorders have high prevalence of depression121314. Earlier studies have demonstrated analgesic activity of antidepressants but there is scanty information on anti-inflammatory activity of various groups of antidepressants.\nIn our study, a significant anti-inflammatory activity of fluoxetine and venlafaxine 40 mg/kg was observed in rat paw oedema model but this activity was blunted, when prazosin was added to venlafaxine and fluoxetine. Addition of prazosin resulting in loss of anti-inflammatory activity of fluoxetine and venlafaxine is indicative of probable role of noradrenergic/serotonergic pathway in inflammation.\nFluoxetine dose-dependently inhibited the release of tumour necrosis factor-α (TNF-α) from lipopolysaccharide (LPS)-treated monocytes and anti-oedema effect of fluoxetine was partially suppressed by the opioid antagonist naloxone1516. Other hypothesis was brought up that serotonin/noradrenaline transporters are expressed in peripheral leucocytes and amines released from these cells have immunomodulatory role on interacting with receptors present on immune cells171819. In our study, a significant anti-inflammatory activity of venlafaxine at a dose of 40 mg/kg and fluoxetine was observed but amitryptline did not show significant anti-inflammatory potential which is in contrast to earlier published studies202122. This could be due to low dose of amitryptline used in our study.\nIn our study, we observed significant increase in blood pressure with venlafaxine 40mg/kg and fluoxetine when administered for 14 days, which is in concordance with earlier published studies45. Increase in blood pressure with venlafaxine is documented but data for association of fluoxetine with increase in BP are lacking. In a meta-analysis with 3744 patients, dose-dependent increase in supine diastolic blood pressure with venlafaxine was observed5. One study documents increase in blood pressure with intracerebral administration of fluoxetine mainly attributed to increase in sympathetic tone and vasopressin release23. In two studies, low rate of sustained hypertension with fluoxetine was observed2425. Whether hypertension is a class effect of antidepressants or is associated with all classes of antidepressants is still not clear.\nWe did not observe increased risk of gastric ulceration with any of the test drugs used in our study whereas literature shows increased propensity of gastric ulcerations with selective serotonin reuptake inhibitors as these block the uptake of serotonin into platelets, leading to an impairment in the platelet haemostatic response26. Also, concurrent use of NSAIDs, anticoagulants, and antiplatelet agents with SSRIs leads to increase risk of GI bleeding6. In a nested case control study, risk of gastric bleeding with venlafaxine was found to be significantly higher than matched controls27. These findings were in contrast to our observations; which could be attributed to short duration (14 days) of drug administration.\nIn conclusion, venlafaxine in high dose and fluoxetine showed potent anti-inflammatory activity in rats. This effect was associated with an increase in blood pressure on chronic therapy but did not have adverse gastric tolerability when administered as monotherapy. Limitations of our study were that ED50 was not elucidated of various test drugs and gastric tolerability was not studied in combination with NSAIDs."}

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The observation that these classes of drugs have anti-inflammatory potential might led to important clinical implication. Moreover, it has been observed that patients with chronic inflammatory disorders have high prevalence of depression121314. Earlier studies have demonstrated analgesic activity of antidepressants but there is scanty information on anti-inflammatory activity of various groups of antidepressants.\nIn our study, a significant anti-inflammatory activity of fluoxetine and venlafaxine 40 mg/kg was observed in rat paw oedema model but this activity was blunted, when prazosin was added to venlafaxine and fluoxetine. Addition of prazosin resulting in loss of anti-inflammatory activity of fluoxetine and venlafaxine is indicative of probable role of noradrenergic/serotonergic pathway in inflammation.\nFluoxetine dose-dependently inhibited the release of tumour necrosis factor-α (TNF-α) from lipopolysaccharide (LPS)-treated monocytes and anti-oedema effect of fluoxetine was partially suppressed by the opioid antagonist naloxone1516. Other hypothesis was brought up that serotonin/noradrenaline transporters are expressed in peripheral leucocytes and amines released from these cells have immunomodulatory role on interacting with receptors present on immune cells171819. In our study, a significant anti-inflammatory activity of venlafaxine at a dose of 40 mg/kg and fluoxetine was observed but amitryptline did not show significant anti-inflammatory potential which is in contrast to earlier published studies202122. This could be due to low dose of amitryptline used in our study.\nIn our study, we observed significant increase in blood pressure with venlafaxine 40mg/kg and fluoxetine when administered for 14 days, which is in concordance with earlier published studies45. Increase in blood pressure with venlafaxine is documented but data for association of fluoxetine with increase in BP are lacking. In a meta-analysis with 3744 patients, dose-dependent increase in supine diastolic blood pressure with venlafaxine was observed5. One study documents increase in blood pressure with intracerebral administration of fluoxetine mainly attributed to increase in sympathetic tone and vasopressin release23. In two studies, low rate of sustained hypertension with fluoxetine was observed2425. Whether hypertension is a class effect of antidepressants or is associated with all classes of antidepressants is still not clear.\nWe did not observe increased risk of gastric ulceration with any of the test drugs used in our study whereas literature shows increased propensity of gastric ulcerations with selective serotonin reuptake inhibitors as these block the uptake of serotonin into platelets, leading to an impairment in the platelet haemostatic response26. Also, concurrent use of NSAIDs, anticoagulants, and antiplatelet agents with SSRIs leads to increase risk of GI bleeding6. In a nested case control study, risk of gastric bleeding with venlafaxine was found to be significantly higher than matched controls27. These findings were in contrast to our observations; which could be attributed to short duration (14 days) of drug administration.\nIn conclusion, venlafaxine in high dose and fluoxetine showed potent anti-inflammatory activity in rats. This effect was associated with an increase in blood pressure on chronic therapy but did not have adverse gastric tolerability when administered as monotherapy. Limitations of our study were that ED50 was not elucidated of various test drugs and gastric tolerability was not studied in combination with NSAIDs."}