Single Ascending Dose Safety and Pharmacokinetics of CDRI-97/78: First-in-Human Study of a Novel Antimalarial Drug.

Background. CDRI 97/78 has shown efficacy in animal models of falciparum malaria. The present study is the first in-human phase I trial in healthy volunteers. Methods. The study was conducted in 50 healthy volunteers in a single, ascending dose, randomized, placebo-controlled, double blind design. The dose ranges evaluated were from 80 mg to 700 mg. Volunteers were assessed for clinical, biochemical, haematological, radiographic, and electrocardiographic parameters for any adverse events in an in-house facility. After evaluation of safety study results, another cohort of 16 participants were administered a single oral dose of 200 mg of the drug and a detailed pharmacokinetic analysis was undertaken. Results. The compound was found to be well tolerated. MTD was not reached. The few adverse events noted were of grade 2 severity, not requiring intervention and not showing any dose response relationship. The laboratory and electrocardiographic parameters showed statistically significant differences, but all were within the predefined normal range. These parameters were not associated with symptoms/signs and hence regarded as clinically irrelevant. Mean values of T 1/2, MRT, and AUC0-∞ of the active metabolite 97/63 were 11.85 ± 1.94 h, 13.77 ± 2.05 h, and 878.74 ± 133.15 ng·h/mL, respectively Conclusion. The novel 1,2,4 trioxane CDRI 97/78 is safe and will be an asset in malarial therapy if results are replicated in multiple dose studies and benefit is shown in confirmatory trials.

Comparison between acetylator phenotype and genotype polymorphism of n-acetyltransferase-2 in tuberculosis patients.

BACKGROUND: Isoniazid (INH) is one of the most important drugs of antitubercular treatment regime, and in some cases it causes hepatotoxicity. It is metabolized by hepatic N-acetyltransferase-2 (NAT2). AIM: To compare whether both methods, i.e., genotype NAT2 and phenotype test of measuring serum INH levels, are useful to identify acetylator status of patients on antitubercular treatment (ATT). METHODS: A total of 251 tuberculosis (TB) patients on standard treatment were followed up to 6 months for this study. NAT2 genotype was assessed by PCR with restriction fragment length polymorphism (RFLP) whereas serum INH levels were measured by fluorometry. RESULTS: Of the 251 patients, 50 (19.9%) developed ATT-induced hepatotoxicity. By phenotypic estimation, in the hepatotoxicity group, 17/50 (34%) were slow acetylators whereas 33/50 (66%) were fast acetylators. Genotypically, 19/50 (38%) were slow acetylators and 31/50 (62%) fast acetylators. By phenotypic analysis, in non-hepatotoxicity group, 46/201 (22.9%) were slow acetylators and 155/201 (77.1%) fast acetylators. By genotypic analysis, 30/201 (14.9%) were slow acetylators and 171/201 (85%) fast acetylators. Overall, slow acetylators (25.1%) measured phenotypically were not significantly different from slow acetylators (19.5%) measured genotypically. CONCLUSION: This study suggests that the acetylator status of TB patients can be detected by phenotypic method as efficaciously as by genotypic method. Therefore, phenotypic method can replace genotypic method to determine acetylating status as phenotypic method is simple and inexpensive.

Effect of combination of thalidomide and sulfasalazine in experimentally induced inflammatory bowel disease in rats.

Thalidomide provided significant protection against tri nitro benzene sulfonic acid induced colitis. Combination therapy also reduced colonic inflammation and all the biochemical parameters (myeloperoxidase assay, malondialdehyde assay and tumor necrosis factor-alpha, estimation) were significant as compared to control as well as thalidomide alone treated group. Combination therapy showed additive effect of thalidomide which restored lipid peroxidation as well as reduced myeloperoxidase and TNF-a towards the normal levels. Morphological and histological scores were significantly reduced in combination groups. In experimental model of colitis, oral administration of thalidomide (150 mg/kg) alone as well as its combination with sulfasalazine (360 mg/kg) significantly reduced the colonic inflammation. The results indicate the additive effect of thalidomide with sulfasalazine in rat colitis model which requires further confirmation in human studies.

Development of tool for the assessment of comprehension of informed consent form in healthy volunteers participating in first-in-human studies.

Informed consent is a process that involves providing all pertinent study information to the potential study participant. The information imparted in the form gives all such information as would enable a potential participant to come to a decision regarding his/her participation in the study. Various study related aspects are outlined in the participant information leaflet including the background of the study, the benefits and risks, treatment alternatives; the methodology of the study, follow up schedules, confidentiality of the data, compensations and remunerations and right to not participate or withdraw from the study. We have continued a similar exercise for a phase I, first-in-human study, conducted by our center. Here, the volunteers were asked certain questions pertaining to the trial background, design, patients' rights and miscellaneous categories. They were then assessed and the scores compared to come up with certain conclusions. The median (range) for the entire comprehension score was calculated and statistically analyzed on various aspects. Readability of the ease of reading of the consent form was also analyzed on a Flesch-Kinkaid reading scale. A total of 69 volunteers were screened out of which 50 were enrolled in the study. The median (range) score was 27 (19 to 33) and the mean (S.D.) score was 28.9 (3.1). The maximum correct responses were observed for the questions falling under the volunteers' rights category. The Flesch reading ease score was 54 and the Flesch-Kincaid Grade level score was 9.8. Investigators may be encouraged to incorporate such tools in their informed consent process.

Effect of cilostazol on platelet aggregation in patients with non-ST elevation acute coronary syndrome.

AIMS: The optimal antithrombotic regimen for non-ST elevation acute coronary syndrome(NSTEACS) has not yet been defined and the risk of ischemic events remains high in these patients. We aimed to evaluate the effect of cilostazol on agonist induced platelet aggregation and serum plasminogen activator inhibitor-1(PAI-1) in the patients with NSTEACS administered along with the standard antiplatelet regimen. PATIENTS AND METHODS: 40 patients of NSTEACS presenting within 72 h of onset of symptoms were randomized to cilostazol or placebo in 1 : 1 ratio, in whom a conservative treatment strategy was adopted. Cilostazol 100 mg b.i.d was administered within 12 h of hospital admission for 7 days along with standard doses of aspirin and clopidogrel. The primary end points were effect on agonist-induced platelet aggregation and serum PAI-1 levels after 7 days of treatment. Safety and clinical outcome assessment were also done at 7 and 30 days. RESULTS: Patients in the triple therapy group showed significant decrease in the ADP (25.5 +/- 27.4 vs. 5.6 +/- 8.4; p = 0.003) and collagen (24.9 +/- 25.5 vs. 11.7 +/- 11; p = 0.04) induced percentage platelet aggregation after 7 days of treatment compared to the dual therapy group. There was no significant change in levels of serum PAI-1 (50.30 +/- 10.17 ng/ml vs. 53.47 +/- 14.08 ng/ml; p = 0.42). The composite of recurrent ischemia, myocardial infarction, need for intervention and death occurred in 4 patients in the cilostazol group compared to 7 in the placebo group at the end of 30 days of follow-up (p = 0.48). CONCLUSION: Cilostazol has additional platelet aggregation inhibition action in patients with NSTEACS along with aspirin and clopidogrel.

A drug utilization study to provide background data for bringing amendments in the drug dispensing policy of a pediatric referral center.

OBJECTIVES: The purpose of this study was to generate data regarding the drug utilization pattern in pediatric population of our tertiary care hospital so that we could generate an essential medicine list (EML). BACKGROUND: Drug therapy accounts for a major portion of expenditure toward health care. Reduction in health care cost for an individual can be achieved by lowering the cost of drug treatment. METHODS: This was an observational study conducted in the Advanced Pediatric Centre of our hospital, during which prescriptions and case records were reviewed. RESULTS: During the study a total of 891 prescriptions were reviewed. Antibiotics and nutritional supplements were the major drugs prescribed. A large percentage of drugs were prescribed as trade names. Eighty three per cent of the drugs were prescribed from the National List Of Essential Medicine 2003 (India). Antibiotics accounted for the major bulk of cost of drugs, most of which were purchased by the patients. CONCLUSIONS: Restricted use of newer antibiotics, branded drugs and prescribing from the EML could be considered as targets for reduction of cost of therapy.

Evaluation of the ability of clinical research participants to comprehend informed consent form.

BACKGROUND: The comprehension of informed consent is an integral part of clinical trials. Though India is rapidly becoming a hub of clinical trials very few studies have dealt with the issue of comprehension of informed consent by the patients participating in these trials. METHODS: Patients who were invited to participate in a phase 3 multicentric trial of a novel lipid lowering agent were evaluated for comprehension score. The participants were explained about the structured consent form which included the question on background details for the study, design of the study, rights of the patients and miscellaneous aspects pertinent to the clinical trial. The questionnaire comprised of 24 items and each correct answer was assigned a score of 1. Total comprehension score (CS) was obtained by summing all the scores. RESULTS: Participants were from diverse socio economic and educational backgrounds. The mean +/- SD CS achieved by the participants was 13.4 +/- 2.9; median 14(6 to 20). The highest correct responses were obtained for questions on background details (38%). For most of the categories the mean CS was more than 50%. Aspects related to design were mostly difficult to comprehend. No significant difference in the CS was noted between participants from different educational and socioeconomic groups. 8 patients refused to give consent, fear of adverse drug reactions (n = 3) and inability to follow up (n = 5) were the reasons cited by the patients. CONCLUSION: In conclusion, CS of patients in trials conducted in developing countries can be reasonably good if the investigators explain the consent form in simple language to the participants and CS is not related to the educational status of the participants. Moreover, though a larger majority of patients agree to participate after knowing study details, some patients exercise their right to refuse.

Efficacy of biologicals in the treatment of rheumatoid arthritis. a meta-analysis.

Rheumatoid arthritis (RA) is a chronic multisystem disease. A characteristic feature of RA is persistent inflammatory synovitis, usually involving the peripheral joints in a symmetric distribution. The prevalence of RA is approximately 0.8% of the population (range: 0.3-2.1%); women are affected approximately 3 times more often than men. The current therapeutic approach is to start a disease-modifying agent early in the illness to prevent eventual joint damage. Older disease-modifying anti-rheumatic drugs include methotrexate, sulphasalazine and hydroxychloroquine. Newer ones such as leflunomide and cyclosporin are also used. A recent advance in the management of rheumatoid arthritis is the use of biological agents, which block certain key molecules involved in the pathogenesis of the illness. They include tumour-necrosis-factor-alpha-blocking agents such as infliximab, etanercept and adalimumab, the anti-CD-20 agent, rituximab, and CTLA-4 Ig abatacept. The present study was planned with the aim of evaluating the efficacy of such newer biological therapies in refractory RA at various time points. Databases including Medline, Embase and the Cochrane Library were searched for all relevant studies up to January 2007. A total of 26 studies were included in present meta-analysis. The method of DerSimonian and Laird [Control Clin Trials 1986;7:177-188] was used to calculated a pooled odds ratio (OR) for the American College of Rheumatology (ACR) criteria 20, 50 and 70, at 24, 54 and 96 weeks. The overall pooled OR were found to be significantly more than the placebo at all 3 time points for all 3 criteria (ACR 20, 50 70). In conclusion, biologicals as a group are highly effective in the treatment of RA. Biologicals were efficacious both in treatment naïve and methotrexate-refractory patients.

Sildenafil for pulmonary hypertension: need for evidence generation.

BACKGROUND: The present meta-analysis was conducted with the aim of comparing the usefulness of sildenafil for the management of pulmonary hypertension (PH). METHODS: A systematic electronic and manual search was conducted to retrieve all published and unpublished randomized clinical trials of sildenafil in PH. Pertinent data related to various outcomes were extracted. Sildenafil was planned for comparison with placebo, prostacyclin analogs and endothelin receptor antagonists. For continuous data weighted mean difference was used while fixed or random effects models were used for dichotomous data. Revman (Version 4.2) was used for all calculations. RESULTS: Five studies with a total of 190 patients were included in the final analysis. As compared to placebo sildenafil showed a significant improvement in 6-min walk test (68.90 (95% CI 31.14 - 106.65), p = 0.0003), mean pulmonary artery pressure (-13.04 (95% CI - 25.94 to -0.15), p = 0.05), mean cardiac index (0.39 (95% CI 0.24 - 0.54), p < 0.00001), mean Borg dyspnea score (-1.23 (95% CI -1.36 to -1.10), p < 0.00001), mean pulmonary vascular resistance (-171 (95% CI -300 to -30.90), p = 0.02), improvement in functional class (6.48 (95% CI 2.74 - 15.33), p < 0.001) and a nonsignificant change in mean right atrial pressure and clinical worsening. No study satisfied inclusion criteria for comparison with prostacyclin analogs. In comparison with bosentan, sildenafil did not show a significant difference for any of the clinical outcomes of concern. CONCLUSION: In conclusion, sildenafil was shown to produce a significant improvement in functional and clinical outcomes as compared to placebo. There was no significant difference between sildenafil and bosentan for the study outcomes. There is a definite need for conducting adequately powered randomized controlled trials of sildenafil comparing it to placebo and also to other treatments approved for use in PH.

Seasonal variation in plasma levels of lithium in the Indian population: is there a need to modify the dose?

INTRODUCTION: Lithium still remains an important choice in the therapy of manic-depressive psychosis (MDP), and though there are reports of seasonal variation in lithium levels from a few countries, such studies have not been conducted in India. Variability in the lithium level can lead to lack of efficacy or toxicity, making seasonal variation clinically relevant. METHODS: A retrospective case sheet audit was performed for 101 MDP patients for recording plasma lithium level, oral lithium dose, age and gender for one year. The overall average oral lithium dose and level were recorded; the monthly average to which it most closely matched was noted as the control month, and values of other months were compared with this control month by Friedman's test followed by Dunn's test. RESULTS: The mean age of patients was 38.22 (standard deviation 12.07) years, and 72 out of 101 patients were male. The mean lithium dose in November (938.61 +/- 243.40 mg/day), which was the closest to the overall mean dose (938.24 +/- 241.78 mg/day) was taken as the control month, which when compared with other monthly values, did not show any significant difference. The June (0.54 +/- 0.23 meq/L), July (0.55 +/- 0.24 meq/L) and August (0.55 +/- 0.24 meq/L) mean plasma lithium values were significantly high when compared to the October value (0.45 +/- 0.22 meq/L) as control. High-low variability between the plasma lithium values of different months was found to be 25 percent. CONCLUSION: The present study showed a significant high variability of lithium levels in different months of the year, therefore frequent plasma level monitoring and oral lithium dose adjustment to prevent situations of toxicity and lack of efficacy in MDP.

Effect of Manuka honey and sulfasalazine in combination to promote antioxidant defense system in experimentally induced ulcerative colitis model in rats.

Manuka honey (MH, 5g/kg) provided protection against trinitro-benzo-sulphonic acid induced colonic damage. Combination therapy (MH+sulfasalazine) also reduced colonic inflammation and all the biochemical parameters were significant compared to control and MH alone treated group. Combination therapy showed additive effect of the MH which restored lipid peroxidation and improvement of antioxidant parameters. Morphological and histological scores were significantly reduced in combination groups. In inflammatory model of colitis, oral administration of MH (5g/kg) and combination with sulfasalazine (360 mg/kg) with MH (5g/kg) significantly reduced the colonic inflammation. The results indicate the additive effect of Manuka honey with sulfasalazine in colitis.

Experimentally induced various inflammatory models and seizure: understanding the role of cytokine in rat.

BACKGROUND: The mechanism of epileptogenesis is not well established. There is higher incidence of seizures among patients with chronic inflammatory disease. Cytokines are rapidly induced in the brain after a variety of stimuli including inflammation. Aim of this study was to produce various inflammatory models and seizure to understand the role of TNFalpha in above mentioned models. MATERIALS AND METHODS: A total of 54 male rats were included in the study. Animals were divided into 3 groups of colitis, arthritis, and cotton wool granuloma. Each group had 3 subgroups of control, model and treatment. At the end of 3 days in colitis, 17 days in arthritis and 7 days in cotton wool granuloma groups a subconvulsive dose of PTZ (40 mg/kg i.p) was injected to note seizure onset and seizure score. Brain samples were subjected to DNA fragmentation testing. Presence of inflammation was confirmed by morphology and histology. Plasma and brain TNFalpha levels were measured. RESULTS: The models of colitis, arthritis and CWG were effectively produced as evidenced by morphology and histology scores (p<0.001). Seizure onset was reduced and grade was increased (p<0.001). Thalidomide reduced the morphological, histological (p<0.002), DNA fragmentation and seizure grade (p<0.001) while increased seizure onset (p<0.001) in the arthritis group. TNFalpha levels in both plasma and brain were reduced following thalidomide treatment (p<0.002) in arthritis group. There were no significant findings in colitis or cotton wool granuloma groups. CONCLUSION: Inflammation was associated with decreased threshold to PTZ induced seizure. Thalidomide is effective in reducing the extent of arthritis as well as reducing the seizure scoring and increasing seizure onset in the adjuvant arthritis group. Thalidomide was also effective in reducing TNFalpha levels thus contributing to its antiepileptic activity.

Effect of different doses of Manuka honey in experimentally induced inflammatory bowel disease in rats.

To evaluate the effect of different doses of Manuka honey in experimentally induced inflammatory bowel disease in rats. Adult Wistar rats of either sex were used (n = 30). Colitis was induced by a single intracolonic administration of TNBS dissolved in 35% ethanol. The rats (n = 30) were divided into five groups (n = 6) and were treated with vehicle (ethanol), TNBS, Manuka honey (5 g/kg, p.o.), Manuka honey (10 g/kg, p.o.) or sulfasalazine (360 mg/kg, p.o.) body weight for 14 days. After completion of treatment, the animals were killed and the following parameters were assessed: morphological score, histological score and different antioxidant parameters.Manuka honey at different doses provided protection against TNBS-induced colonic damage. There was significant protection with Manuka honey 5 g/kg as well as with 10 g/kg body weight compared with the control (p < 0.001). All the treated groups showed reduced colonic inflammation and all the biochemical parameters were significantly reduced compared with the control in the Manuka honey treated groups (p < 0.001). Manuka honey at different doses restored lipid peroxidation as well as improved antioxidant parameters. Morphological and histological scores were significantly reduced in the low dose Manuka honey treated group (p < 0.001). In the inflammatory model of colitis, oral administration of Manuka honey 5 g/kg and Manuka honey 10 g/kg body weight significantly reduced the colonic inflammation. The present study indicates that Manuka honey is efficacious in the TNBS-induced rat colitis model, but these results require further confirmation in human studies.

Bacopa monniera ameliorates amnesic effects of diazepam qualifying behavioral-molecular partitioning.

Benzodiazepines are known to produce amnesia by involvement of GABAergic system and by interference of long term potentiation (LTP). In this study, we examined effect of Bacopa monniera on downstream molecules of LTP after diazepam-induced amnesia in mice. We used a Morris water maze scale for evaluating the effect of Bacopa monniera after screening for muscle coordination by rota rod. The index of acquisition and retrieval was recorded as escape latency time (ELT). Behavioral results showed that Bacopa monniera (120 mg kg(-1) oral) significantly reversed diazepam- (1.75 mg kg(-1) i.p.) induced amnesia in Morris water maze task. The molecular studies revealed that diazepam upregulated mitogen activated protein kinase (MAP kinase), phosphorylated CREB (pCREB) and inducible nitric oxide synthase (iNOS), while it downregulated nitrite, nitrate, total nitrite, cAMP response element binding protein (CREB) expression, phosphodiesterase, cyclic adenosine monophosphate (cAMP) without affecting calmodulin levels. Bacopa monniera suppressed the diazepam induced upregulation of MAP kinase, pCREB and iNOS and attenuated the downregulation of nitrite. It did not affect the cAMP, PDE, nitrate, total nitrite, total CREB level. These behavioral findings displayed the reversal of diazepam-induced amnesia by Bacopa monniera without qualifying the molecular details although some downstream molecules of LTP may be involved.

Association of anticardiolipin antibodies levels with instent restenosis in patients with coronary artery disease.

Present study was conducted to evaluate the association of IgG anticardiolipin antibodies with instent restenosis in patients having undergone percutaneous intervention with bare metal or drug eluting stents. Coronary artery disease patients with stent placement at least 6 months prior were screened for eligibility. 26 satisfied the inclusion/exclusion criteria. 10 patients with symptoms of restenosis, confirmed on check angiography served as cases and 16 without symptoms of restenosis served as control. Unpaired t- test was applied to ascertain the significance of any difference between control and study groups. Antibody levels were estimated on ELISA reader. The mean (+/- SD) anticardiolipin antibodies levels in cases and controls were 11.8 +/- 5.1 GPL/U/ml and 14.3 +/- 10.2 GPL/U/ml, respectively. The difference was not statistically significant (P > 0.05). In conclusion, we did not observe any significant correlation between the level of IgG aCL and instent restenosis.

Effects of green tea extract on learning, memory, behavior and acetylcholinesterase activity in young and old male rats.

OBJECTIVE: To study the effects of green tea extract administration on age-related cognition in young and old male Wistar rats. METHODS: Young and old rats were orally administered 0.5% green tea extract for a period of eight weeks and were evaluated by passive avoidance, elevated maze plus paradigm and changes in acetylcholinesterase activity. RESULTS: Treatment of young and old rats with the extract resulted in no significant difference in performance on the rota rod treadmill test/righting reflex time. Green tea extract significantly improved learning and memory in older rats, with increased retention latency to enter difference in passive avoidance test. In the elevated maze test, green tea treatment resulted in significantly more number of entries in the enclosed arm by the young and old rats. Decline in acetylcholinesterase activity was observed in the cerebrum of green tea treated old rats in comparison to the green tea treated young rats. CONCLUSION: Green tea extract administration is effective in enhancing learning and memory in aged rats, and hence, may serve useful in reversing age-related deficits.

A meta-analysis to evaluate the efficacy of statins in children with familial hypercholesterolemia.

This meta-analysis was conducted to evaluate the effect of statins on the lipid profile in pediatric and adolescent patients with familial hypercholesterolemia (FH). Randomized, double-blind, controlled trials comparing statins with placebo were identified through electronic and manual search; percent reductions from baseline were calculated for various lipid parameters. Standardized mean differences (effect size) with 95% confidence interval (CI) were calculated for each study and pooled effect size was calculated. A total of 6 studies were included in the meta-analysis. As compared to placebo, statins caused a significant decrease in total cholesterol (TC) [-3.11% (95% CI -3.46 to -2.99)], low-density lipoprotein (LDL) [-4.01% (95% CI -4.27 to -3.81)], triglyceride (TG) [-1.41 (95% CI -1.66 to -1.26)] and a significant increase in high-density lipoprotein (HDL) [1.12 (95% CI 0.73 1.13)]. In conclusion, statins were shown to have good efficacy for the treatment of FH in children.

Study of association between use of complementary and alternative medicine and non-compliance with modern medicine in patients presenting to the emergency department.

CONTEXT: Complementary and alternative medicines (CAMs) are extensively used by the public. Noncompliance is an important cause of therapy failure. AIM: This study was done to determine prevalence of emergency admission due to noncompliance with modern medicine following switching over to CAM and to identify any significant association for CAM use among noncompliers. SETTING AND DESIGN: This cross-sectional study was conducted in the emergency unit of a tertiary healthcare institute. MATERIALS AND METHODS: Demographic factors and system affected were compared between compliers and noncompliers. Prevalence, reasons and nature of noncompliance were determined. Age, gender, outcome, relation strength and potential preventability of noncompliance, precipitating and previous disease and noncompliant drugs were compared for significant association between CAM using and other noncompliers. STATISTICAL ANALYSIS: Student's 't' test, Chi square test and odds ratio were used. RESULTS: Of the 506 patients interviewed 168 (33%) were noncompliant. In 160 (95%) patients noncompliance was due to under-dosing. Lack of knowledge and CAM use constituted 144 (86%) noncompliance-related admissions. Thirty-three (7%) admissions were strongly related to noncompliance and CAM use. Age, gender, outcome, drug use and diseases except chronic obstructive pulmonary disease (COPD) and asthma showed no association while relation strength and potential preventability of emergency admission was less with CAM-using noncompliers. Noncompliance was observed for hypertension, diabetes, COPD and asthma, seizure disorder, tuberculosis and hemophilia besides hepatic and renal failure. The CAM noncompliers used CAM more for modern medicine incurable or unaffordable than curable diseases. CONCLUSION: Advice for regular treatment and frequent monitoring can decrease CAM use-related noncompliance admissions.

Randomized double-blind study comparing the efficacy and safety of lamotrigine and amitriptyline in painful diabetic neuropathy.

AIMS: To compare the efficacy and safety of lamotrigine and amitriptyline in controlling chronic painful peripheral neuropathy in diabetic patients. METHODS: A randomized, double-blind, crossover, active-control, clinical trial with variable dose titration was carried out (n = 53). Amitriptyline orally, at doses of 10, 25 and 50 mg at night-time, each dose for 2 weeks, and lamotrigine orally, at doses of 25, 50 and 100 mg twice daily, each dose for 2 weeks, by optional titration were used. There was a placebo washout period for 2 weeks between the two drugs. Assessment for pain relief, overall improvement and adverse events were carried out. RESULTS: Good, moderate and mild pain relief were noted in 19 (41%), six (13%) and seven (15%) patients on lamotrigine and 13 (28%), five (11%) and 15 (33%) patients on amitriptyline, respectively, by patient's global assessment of efficacy and safety. Patient and physicians global assessment, McGill pain questionnaire and Likert pain scale showed no significant difference between the treatments, although improvement with both treatments was seen from 2 weeks. Of the 44 adverse events reported, 33 (75%) were with amitriptyline, sedation being the commonest [in 19 (43%) patients]. Lamotrigine caused adverse events in 11 (25%), of which rash in three (7%) and elevations of creatinine in four (9%) were the most common. The preferred lamotrigine dose was 25 mg twice daily. CONCLUSIONS: As there are few differences between the two treatments in efficacy, lamotrigine 25 mg twice daily might be the first choice as it is associated with fewer adverse effects in our population.