| 2018 | Role of glutamate and its receptors in migraine with reference to amitriptyline and transcranial magnetic stimulation therapy. | Brain Res | Glutamate plays an important role in migraine pathogenesis but there is paucity of studies on glutamate in migraine subtypes, effect of treatment on glutamate levels and the changes in glutamate receptors. In this study we report the glutamate levels and changes in glutamate receptors following amitriptyline (AMT) or repetitive Transcranial Magnetic Stimulation (rTMS) therapy. One hundred and fifty migraine patients having more than 4 migraine attacks per month were included. Thirty patients were treated with AMT and 120 with rTMS; 24 patients received 3 sessions, 36 received single session of rTMS and 60 patients received sham stimulation. The severity of headache was assessed by VAS score, Migraine Index (MI) and frequency of headache. Good outcome was defined by 50% improvement in headache frequency; severity and MI. Plasma glutamate level were measured by enzyme linked immunosorbant assay and relative expression of NR2B and mGluR3 receptors by real time polymerase chain reaction. The changes in these parameters before and after treatment were measured and correlated with the clinical parameters. Glutamate levels (P = 0.006) and NR2B receptor expressions (P < 0.001) were significantly higher in migraine patients compared to the controls. Chronic migraine patients had higher glutamate level (P = 0.05). Glutamate and NR2B receptor declined after treatment (P < 0.001). There was a decline in glutamate levels following rTMS (P = 0.03), sham stimulation (P = 0.05) and AMT treatment (P = 0.003). NR2B receptors also declined after rTMS (P = 0.005) and AMT treatment (P = 0.01). It can be concluded that migraine is associated with high plasma glutamate and NR2B receptor which decline following AMT or rTMS therapy. |
| 2018 | A study of oxidative stress in migraine with special reference to prophylactic therapy. | Int J Neurosci | The role of oxidative stress markers in migraine and effect of treatment on these has been reported.One hundred and fifty patients having > four attacks of migraine headache/month were included. Headache severity, Migraine Index (MI) and frequency of headache were noted. 120 patients received repetitive transcranial magnetic stimulation (rTMS) therapy and 30 patients received Amitriptyline (AMT). Recovery was defined by 50% improvement in frequency, severity or reduction in MI. Oxidative stress and antioxidant markers have been estimated in patients before and after treatment and correlate the clinical and outcome parameters.Glutathione (GSH) (P < 0.001), glutathione-S-transferase (GST) (P = 0.049) and total antioxidant activity (TAC) (P < 0.001) level were significantly reduced in migraine patients. GSH (P = 0.02), GST (P = 0.05) and TAC (P < 0.001) were reduced in ictal migraineurs compared to controls. GSH (P < 0.001) and TAC (P = 0.003) levels increased after treatment compared to the base line. There is an increase in GSH levels in the patients who had improved following rTMS (P = 0.003); placebo (P = 0.001) and AMT (P = 0.013). TAC levels were also increased following rTMS (P = 0.009) and AMT (P = 0.020).There is evidence of oxidative stress in migraine pathophysiology. Following treatment, oxidative stress declined following both pharmacological and rTMS. |
| 2013 | Amitriptyline vs divalproate in migraine prophylaxis: a randomized controlled trial. | Acta Neurol Scand | This study compares efficacy and safety of divalproate extended release (DVA-ER) and amitriptyline (AMT) in migraine.Three hundred migraineurs having >4 attacks monthly were randomized into DVA-ER or AMT. The primary end points were >50% reduction in frequency, ≥1 grade improvement in the severity, and >50% improvement in a visual analogue scale (VAS). Secondary end points were functional disability, rescue medication, and adverse events.The median age was 32 years, and 241 were women. 150 patients each received DVA-ER and AMT. At 3 months, 74.7% in DVA-ER and 62% patients in AMT group improved in headache frequency (P = 0.02) and at 6 months, 65.3% and 54%, respectively (P = 0.90). At 3 months, the VAS score improved by >50% in 80.7% in DVA-ER and 64% in AMT (P = 0.005). At 6 months, there was no significant difference between the two groups in VAS score (69.3% vs 56%; P = 0.47) and other outcome parameters. The composite side effects were also not different between the two groups (68% vs 81%); however, hair fall, menstrual irregularity, polycystic ovary, and weight gain were commoner in DVA-ER group.Divalproate extended release is more effective at 3 months than AMT; however, at 6 months, both are equally effective in migraine prophylaxis. |
| 2012 | Hypnotic relaxation vs amitriptyline for tension-type headache: let the patient choose. | Headache | Although both pharmacological and behavioral interventions may relieve tension-type headache, data are lacking regarding treatment preference, long-term patient compliance, and feasibility of behavioral intervention in a standard neurological outpatient clinic setting.To describe patient choice, long-term compliance, and clinical outcome in a neurological clinic setting where patients are given the choice of the approach they wish to pursue.Patients presenting to the headache clinic with a diagnosis of tension-type headache that justified prophylactic therapy (frequent episodic tension-type headache or chronic tension-type headache) were given the choice of amitriptyline (AMT) treatment or hypnotic relaxation (HR), and were treated accordingly. Patients were given the option to cross-over to the other treatment group at each visit. HR was performed during standard length neurology clinic appointments by a neurologist trained to perform hypnosis (Y.E.). Follow-up interviews were performed between 6 and 12 months following treatment initiation to evaluate patient compliance, changes in headache frequency or severity, and quality-of-life parameters.Ninety-eight patients were enrolled, 92 agreed to receive prophylactic therapy of some kind. Fifty-three (57.6%) patients chose HR of which 36 (67.9%) actually initiated this treatment, while 39 (42.4%) chose pharmacological therapy with AMT of which 25 (64.1%) patients actually initiated therapy. Patients with greater analgesic use were more likely to opt for AMT (P= .0002). Eleven of the patients initially choosing AMT and 2 of the patients initially choosing HR crossed over to the other group. Seventy-four percent of the patients in the HR group and 58% of patients in the AMT group had a 50% reduction in the frequency of headaches (P= .16). Long-term adherence to treatment with HR exceeded that of AMT. At the end of the study period, 26 of 47 patients who tried HR compared with 10 of 27 who tried AMT continued receiving their initial treatment.HR treatment was a more popular choice among patients. Patients choosing HR reported greater symptom relief than those choosing AMT and were found to have greater treatment compliance. Patients receiving HR were less likely to change treatments. HR practiced by a neurologist is feasible in a standard neurological outpatient clinic setting; HR training should be considered for neurologists involved in headache treatment. |
| 2009 | Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain. | BMC Neurol | Few direct head-to-head comparisons have been conducted between drugs for the treatment of diabetic peripheral neuropathic pain (DPNP). Approved or recommended drugs in this indication include duloxetine (DLX), pregabalin (PGB), gabapentin (GBP) and amitriptyline (AMT). We conducted an indirect meta-analysis to compare the efficacy and tolerability of DLX with PGB and GBP in DPNP, using placebo as a common comparator.We searched PubMed, EMBASE, CENTRAL databases and regulatory websites for randomized, double-blind, placebo-controlled, parallel group or crossover clinical trials (RCTs) assessing DLX, PGB, GBP and AMT in DPNP. Study arms using approved dosages with assessments after 5-13 weeks were eligible. Efficacy criteria were: reduction in 24-hour pain severity (24 h PS) for all three drugs, and response rate (>or= 50% pain reduction) and Patient Global Impression of Improvement/Change (PGI-I/C) for DLX and PGB only. Tolerability criteria included: discontinuation, diarrhoea, dizziness, headache, nausea and somnolence. Direct comparisons versus placebo were conducted with pooled fixed - and random-effects analyses on endpoints reported in at least two studies of each drug. Indirect comparisons were performed between DLX and each of PGB and GBP using Bayesian simulation.Three studies of DLX, six of PGB, two of GBP and none of AMT met the inclusion criteria. In random-effects and fixed-effects analyses of DLX, PGB and GBP, all were superior to placebo for all efficacy parameters, with some tolerability trade-offs. Indirect comparison of DLX with PGB found no differences in 24 h PS, but significant differences in PGI-I/C, favouring PGB, and in dizziness, favouring DLX were apparent. Comparing DLX and GBP, there were no statistically significant differences.From the few available studies suitable for indirect comparison, DLX shows comparable efficacy and tolerability to GBP and PGB in DPNP. Duloxetine provides an important treatment option for this disabling condition. |
| 2008 | Degradation of endocannabinoids in chronic migraine and medication overuse headache. | Neurobiol Dis | Chronic migraine (CM) is frequently associated with medication overuse headache (MOH). The endocannabinoid system plays a role in modulating pain including headache and is involved in the common neurobiological mechanism underlying drug addiction and reward system. Anandamide (AEA) and 2-arachidonoylglycerol are the most biologically active endocannabinoids, which bind to both central and peripheral cannabinoid receptors. The level of AEA in the extracellular space is controlled by cellular uptake via a specific AEA membrane transporter (AMT), followed by intracellular degradation by the enzyme AEA hydrolase (fatty acid amide hydrolase, FAAH). AMT and FAAH have also been characterized in human platelets. We assayed the activity of AMT and of FAAH in platelets isolated from four groups of subjects: MOH, CM without MOH, episodic migraine and controls. AMT and FAAH were significantly reduced in CM and MOH, compared to either controls or episodic migraine group. This latter finding was observed in both males and females with CM and MOH. Changes observed in the biochemical mechanisms degrading endogenous cannabinoids may reflect an adaptative behaviour induced by chronic headache and/or drug overuse. |