Vandana Tayal

Efficacy of Antidepressants as Analgesics: A Review

Persistent pain disorders are usually not adequately alleviated by nonsteroidal anti‐inflammatory drugs or other simple analgesics. Use of antidepressants as adjuvant therapy for the control of persistent pain is currently being practiced in disorders such as fibromyalgia, neuropathic pain, rheumatoid conditions, low back pain, and headache. This review describes the various mechanisms of analgesic activity of antidepressants along with their efficacy and tolerability profiles. Meta‐analyses and clinical studies of these agents were retrieved through the use of MEDLINE, Google scholar, and Cochrane databases. Antidepressants are effective in both neuropathic and non‐neuropathic pain and have diverse mechanisms independent of their antidepressant effects. Tricyclic antidepressants (amitryptiline, nortryptiline, desipramine) are effective compounds in the treatment of neuropathic pain, fibromyalgia, low back pain, and headaches. Studies are ongoing for the dual serotonin norepinephrine reuptake inhibitors (duloxetine, venlafaxine) in several persistent pain conditions and these may be recommended in neuropathic pain, migraines, and fibromyalgia. Evidence suggests that although the analgesic effects of selective serotonin reuptake inhibitors (fluoxetine, paroxetine, citalopram) are limited and inconsistent, yet they have a superior tolerability profile compared with tricyclic antidepressants.

Antidepressant-Like Activity of Tramadol in Mice

Objective: To evaluate antidepressant-like effect of tramadol in mice. Materials and Methods: Tramadol was administered at three different doses (10, 20, and 40 mg/kg, i.p.) once daily for 7 days to Swiss albino mice of either sex. The immobility period of control and drug-treated mice was recorded in forced swim test (FST). The antidepressant effect of tramadol was compared to that of fluoxetine (20 mg/kg, i.p.), administered for seven successive days. Results: Tramadol produced significant antidepressant effect at all the three (10, 20, and 40 mg/kg) doses, as indicated by reduction in immobility times of drug-treated mice compared to control mice. The efficacy of tramadol at doses of 10 and 20 mg/kg was comparable to that of fluoxetine, but antidepressant activity in animals administered with tramadol 40 mg/kg was significantly less as compared to fluoxetine-pretreated mice. Conclusion: The results of the present study indicate antidepressant-like activity of tramadol.

Evaluation of antidepressant activity of tramadol in mice

Objective: To evaluate antidepressant like effect of tramadol in mice. Materials and Methods: Tramadol was administered at three different doses (10,20 and 40 mg/kg, i.p) once daily for 7 days to Swiss albino mice of either sex. The immobility period of control and drug treated mice were recorded in tail suspension test (TST).The antidepressant effect of tramadol was compared to that of fluoxetine (20 mg/kg, i.p), administered for seven days. Results: Tramadol produced significant antidepressant effect at all the doses, as indicated by reduction in immobility times as compared to control. The efficacy of tramadol at doses of 20 and 40 mg/kg was comparable with that of fluoxetine. Tramadol at 10 mg/kg dose showed significantly less antidepressant activity compared to fluoxetine. Conclusion: The results of the present study indicate antidepressant like activity of tramadol.

Evaluation of gastric tolerability, antinociceptive and antiinflammatory activity of combination NSAIDs in rats

BACKGROUND Non-steroidal antiinflammatory drugs (NSAIDs) are one of the most commonly prescribed drugs in clinical practice. Presently, several varieties of fixed dose combinations (FDCs) of NSAIDs are available over the counter and are being prescribed too. There is paucity of literature regarding comparative efficacy of these combinations against their individual component. Various clinical studies have documented increased incidence of gastric ulcerations with usage of more than one NSAID simultaneously. OBJECTIVES To study gastric tolerability, antinociceptive and antiinflammatory activity of combination NSAIDs in rats. MATERIALS AND METHODS Gastric tolerability of different NSAIDs was observed after administration of drugs for 7 days orally. On 7 th day, 4 h after drug administration, rats were sacrificed and stomach mucosa was examined for ulcerations. Analgesic or antinociceptive activity of single and combination NSAIDs was evaluated using Writhing test model. For induction of writhing, 4% normal saline (hypertonic saline) was injected (0.1 ml/10 gm) intraperitoneally. Evaluation of antiinflammatory activity for FDCs of NSAIDs was done by using rat paw edema model with the aid of plethysmometer. Paw edema was induced by injecting 0.1 ml of 1% formalin in sub-planter region of hind paw. RESULTS Analgesic activity was found to be enhanced or significant only in the group pretreated with combination of nimesulide with ibuprofen as compared to ibuprofen-alone group (P = 0.01). Decrease in mean paw edema (antiinflammatory activity) was not significant in rats pretreated with combination NSAIDs as compared to NSAID-alone group. Mean gastric ulcer index was significant in groups pretreated with diclofenac alone (P = 0.03) and in combination groups of nimesulide with diclofenac and ibuprofen with paracetamol as compared to control (P = 0.03, P = 0.007). CONCLUSION Addition of ibuprofen to paracetamol and combining diclofenac to nimesulide, significantly increased severity of gastric ulcerations. Fixed dose combination does not possess additional analgesic activity over their individual components, only exception being combination of nimesulide with ibuprofen, which has additional analgesic activity over ibuprofen alone, and this combination was not found to be ulcerogenic. Antiinflammatory activity of ibuprofen, paracetamol and nimesulide was significantly enhanced after addition of diclofenac.

Effect of Celecoxib on Anticonvulsant Activity of Carbamazepine against Maximal Electroshock-Induced Convulsions in Mice

This study investigates the effect of celecoxib alone and in combination with carbamazepine (CBZ) on maximal electroshock-induced convulsions in mice. Celecoxib (30, 45, 60, 75 and 90 mg/kg) and CBZ (2, 4, 6 and 8 mg/kg) were each given alone in increasing doses, and CBZ was given in combination with a single dose of celecoxib (30 mg/kg) 40 min prior to electroshock-induced convulsions. The percentage protection and duration of hind limb extension were determined using an electroconvulsiometer. The ED50 value (dose at which there is protection in 50% of animals) of CBZ alone and in combination with celecoxib was determined. When administered alone, CBZ showed an increase in percentage protection at increasing doses, with 100% protection occurring at a dose of 8 mg/kg. However, treatment with celecoxib alone demonstrated maximum protection of 50% occurring at the 60 mg/kg dose. Moreover, celecoxib given at 30 mg/kg did not show any protection. Nevertheless, coadministration of celecoxib (30 mg/kg) enhanced the effect of the subprotective dose of CBZ and was more effective than CBZ given alone. Combined treatment with celecoxib enhanced the potency of CBZ and significantly reduced its ED50 value. This study suggests that celecoxib has an anticonvulsant effect of its own and it also potentiates the anticonvulsant efficacy of CBZ against maximal electroshock-induced convulsions in mice.

Fixed-dose combinations for cough and common cold in India: an assessment of availability and rationality.

This study was conducted to determine the number and composition of the various cough and cold formulations available in the Indian market and to study their pharmacological rationale over a period of 7 years. Data for the study was collected from an annual Drug Compendium entitled ‘THE DRUG TODAY’ of the years 2001, 2004, and 2007. Medications were assessed for total number, different formulations, and number of constituents present in each formulation, their pharmacological group and amount of each constituent per dose. Rationality of available preparations was assessed on a seven‐point scoring criteria. There are over thirteen hundred drug products for cough and cold in the Indian market, which is an increase of 71.2% from the year 2001. More than 90% of the preparations were fixed‐dose combinations (FDCs). Majority of the cough and cold preparations had 3–4 constituents. Many preparations contained more than one constituent of the same pharmacological group. Some preparations had constituents with opposing action. A wide variation in the amount of each constituent present per dose in different formulations was observed. The number of banned drug combinations for cough and cold showed an increase from 9 in 2001 to 27 in 2007. Rationality assessment of the FDC preparations revealed that most of the preparations were irrational and had no documented benefit in the treatment of common cold. Availability of such a large number of irrational FDCs for cough and cold requires serious review of the legal provisions in India for drug manufacturing and marketing.