Evaluation of anti-inflammatory activity, effect on blood pressure & gastric tolerability of antidepressants.
ABSTRACT Background & objectives: Antidepressants are being used as analgesics for various pain related disorders like neuropathic and non neuropathic pain. Although their analgesic activity is well recognized but anti-inflammatory potential of antidepressants is still inconclusive. Since the antidepressants are used for longer duration, it becomes important to elucidate effect of anti-depressants on blood pressure and gastric mucosa. This study was undertaken to evaluate the anti-inflammatory potential of various antidepressant drugs as well as their effect on blood pressure and gastric tolerability on chronic administration in rats. Methods: Rat paw oedema model was used for studying anti-inflammatory activity, single dose of test drug (venlafaxine 20 and 40 mg/kg, amitryptline 25 mg/kg, fluoxetine 20 mg/kg) was administered intraperitoneally 45 min prior to administration of 0.1 ml of 1 per cent carrageenan in sub-planter region. Oedema induced in test group was compared with normal saline treated control group. For studying effect on blood pressure and gastric tolerability, test drugs were administered for 14 days. Blood pressure was recorded on days 0, 7 and 14 using tail cuff method. On day 14, 4 h after drug administration, rats were sacrificed and stomach mucosa was examined for ulcerations. Results: Pretreatment of rats with venlafaxine (40 mg/kg) resulted in a significant decrease in paw oedema as compared to control (2.4 ± 0.15 to 1.1 ± 0.16 ml, P<0.01). Similarly, in the group pretreated with fluoxetine, significant decrease in paw oedema was observed in comparison to control (P<0.05). Significant change in mean blood pressure was seen in rats pretreated with venlafaxine 40 mg/kg (126.7 ± 4.2 to 155.2 ± 9.7, P<0.05) and fluoxetine (143.5 ± 2.6 to 158.3 ± 1.2, P<0.05) on day 7. No significant difference with regard to gastric tolerability was observed among groups. Interpretation & conclusions: Our findings showed significant anti-inflammatory activity of venlafaxine (40 mg/kg) and fluoxetine but these drugs were also associated with an increase in blood pressure. No significant change in mean ulcer index was observed among groups.
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ABSTRACT: The present study compared blood pressure levels between subjects with clinical anxiety and depressive disorders with healthy controls. Cross-sectional data were obtained in a large cohort study, the Netherlands Study of Depression and Anxiety (N=2981). Participants were classified as controls (N=590) or currently or remittedly depressed or anxious subjects (N=2028), of which 1384 were not and 644 were using antidepressants. Regression analyses calculated the contributions of anxiety and depressive disorders and antidepressant use to diastolic and systolic blood pressures, after controlling for multiple covariates. Heart rate and heart rate variability measures were subsequently added to test whether effects of anxiety/depression or medication were mediated by vagal control over the heart. Higher mean diastolic blood pressure was found among the current anxious subjects (beta=0.932; P=0.03), although anxiety was not significantly related to hypertension risk. Remitted and current depressed subjects had a lower mean systolic blood pressure (beta=-1.74, P=0.04 and beta=-2.35, P=0.004, respectively) and were significantly less likely to have isolated systolic hypertension than controls. Users of tricyclic antidepressants had higher mean systolic and diastolic blood pressures and were more likely to have hypertension stage 1 (odds ratio: 1.90; 95% CI: 0.94 to 3.84; P=0.07) and stage 2 (odds ratio: 3.19; 95% CI: 1.35 to 7.59; P=0.008). Users of noradrenergic and serotonergic working antidepressants were more likely to have hypertension stage 1. This study shows that depressive disorder is associated with low systolic blood pressure and less hypertension, whereas the use of certain antidepressants is associated with both high diastolic and systolic blood pressures and hypertension.Hypertension 03/2009; 53(4):631-8. · 7.63 Impact Factor
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ABSTRACT: Venlafaxine hydrochloride, a structurally novel antidepressant, is also the first nontricyclic serotonin/norepinephrine reuptake inhibitor. Although venlafaxine has an overall side effect and safety profile that is comparable to other newer antidepressants, it can cause both transient and sustained elevations of supine diastolic blood pressure (SDBP), probably the result of noradrenergic potentiation. Presented here is a meta-analysis of original data on blood pressure, using both random effects and a multivariate survival analyses. The sample consisted of 3744 patients with major depression who were studied in controlled clinical trials comparing venlafaxine with imipramine and/or placebo. Patients were treated for 6 weeks of acute phase therapy; some responders received up to 1 year of continuation phase therapy. Venlafaxine and imipramine were associated with small, but statistically significant, increases in SDBP during acute phase therapy. When compared with imipramine and placebo, venlafaxine was also associated with a greater proportion of persistent elevations of SDBP during continuation therapy. The effect of venlafaxine was highly dose dependent, and the incidence of elevated SDBP was statistically and clinically significant only at dosages above 300 mg/day. Venlafaxine did not adversely affect the control of blood pressure for patients with preexisting high blood pressure or elevated baseline values. Venlafaxine has a dose-dependent effect on SDBP that is clinically significant at high dosages. Concern about blood pressure effects should not deter first-line use of this effective antidepressant, although more extensive studies of patients with cardiovascular diseases are still necessary.The Journal of Clinical Psychiatry 11/1998; 59(10):502-8. · 5.14 Impact Factor
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ABSTRACT: To examine the association between selective serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding. Population based case-control study. General practices included in the UK general practice research database. Subjects: 1651 incident cases of upper gastrointestinal bleeding and 248 cases of ulcer perforation among patients aged 40 to 79 years between April 1993 and September 1997, and 10 000 controls matched for age, sex, and year that the case was identified. Review of computer profiles for all potential cases, and an internal validation study to confirm the accuracy of the diagnosis on the basis of the computerised information. Current use of selective serotonin reuptake inhibitors or other antidepressants within 30 days before the index date. Current exposure to selective serotonin reuptake inhibitors was identified in 3.1% (52 of 1651) of patients with upper gastrointestinal bleeding but only 1.0% (95 of 10 000) of controls, giving an adjusted rate ratio of 3.0 (95% confidence interval 2.1 to 4.4). This effect measure was not modified by sex, age, dose, or treatment duration. A crude incidence of 1 case per 8000 prescriptions was estimated. A small association was found with non-selective serotonin reuptake inhibitors (relative risk 1.4, 1.1 to 1.9) but not with antidepressants lacking this inhibitory effect. None of the groups of antidepressants was associated with ulcer perforation. The concurrent use of selective serotonin reuptake inhibitors with non-steroidal anti-inflammatory drugs increased the risk of upper gastrointestinal bleeding beyond the sum of their independent effects (15.6, 6.6 to 36.6). A smaller interaction was also found between selective serotonin reuptake inhibitors and low dose aspirin (7.2, 3.1 to 17.1). Selective serotonin reuptake inhibitors increase the risk of upper gastrointestinal bleeding. The absolute effect is, however, moderate and about equivalent to low dose ibuprofen. The concurrent use of non-steroidal anti-inflammatory drugs or aspirin with selective serotonin reuptake inhibitors greatly increases the risk of upper gastrointestinal bleeding.BMJ Clinical Research 11/1999; 319(7217):1106-9. · 14.09 Impact Factor