Oral Amitriptyline Research Articles

A Rare Case of Self-biting Behavior in Chiari Malformation 1

Abstract Chiari malformation (CM) 1 is the most common of all types and is often found incidentally. Neurological symptoms occur due to compression of the cerebellum or medulla at the foramen magnum and/or development of syrinx. Psychiatric symptoms have also been reported. We report a case of CM who underwent decompression surgery but developed self-biting of fingers first on the left hand, which resolved and then on the right hand with extensive mutilation and tissue damage. He improved with oral amitriptyline, but the cause of his self-biting remains unexplained. It is not uncommon to find psychiatric disorders in patients with neurological disorders; therefore, a detailed history and a holistic approach are warranted.

Oral proniosomal amitriptyline and liraglutide for management of diabetic neuropathy: Exceptional control over hyperglycemia and neuropathic pain

Exploitation of nanocarriers provides a compartment for enclosing drugs to protect them from degradation and potentiate their therapeutic efficiency. In the current study, amitriptyline- and liraglutide-loaded proniosomes were constructed for management of diabetic neuropathy, a serious complication associated with diabetes, that triggers spontaneous pain in patients and results in impaired quality of life. The developed therapeutic proniosomes were extensively characterized via dynamic light scattering, scanning electron microscopy, transmission electron microscopy, and Fourier transform-infrared spectroscopy. High entrapment efficiency could be attained for both drugs in the proniosomes, and the reconstituted amitriptyline- and liraglutide-loaded niosomes possessed spherical morphology and particle sizes of 585.3 nm and 864.4 nm, respectively. In a diabetic neuropathy rat model, oral administration of the developed amitriptyline- and liraglutide-loaded proniosomes significantly controlled blood glucose levels, reduced neuropathic pain, oxidative stress and inflammatory markers, and improved histological structure of the sciatic nerve as compared to the oral and subcutaneous administration of amitriptyline and liraglutide, respectively. Loading of the tricyclic antidepressant amitriptyline and the antidiabetic peptide liraglutide into proniosomes resulted in exceptional control over hyperglycemia and neuropathic pain, and thus could provide an auspicious delivery system for management of neuropathic pain and control of blood glucose levels.

Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial

Most patients with irritable bowel syndrome (IBS) are managed in primary care. When first-line therapies for IBS are ineffective, the UK National Institute for Health and Care Excellence guideline suggests considering low- dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown, and they are infrequently prescribed in this setting. This randomised, double-blind, placebo-controlled trial (Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment [ATLANTIS]) was conducted at 55 general practices in England. Eligible participants were aged 18 years or older, with Rome IV IBS of any subtype, and ongoing symptoms (IBS Severity Scoring System [IBS-SSS] score ≥75 points) despite dietary changes and first-line therapies, a normal full blood count and C-reactive protein, negative coeliac serology, and no evidence of suicidal ideation. Participants were randomly assigned (1:1) to low-dose oral amitriptyline (10 mg once daily) or placebo for 6 months, with dose titration over 3 weeks (up to 30 mg once daily), according to symptoms and tolerability. Participants, their general practitioners, investigators, and the analysis team were all masked to allocation throughout the trial. The primary outcome was the IBS-SSS score at 6 months. Effectiveness analyses were according to intention-to-treat; safety analyses were on all participants who took at least one dose of the trial medication. This trial is registered with the ISRCTN Registry (ISRCTN48075063) and is closed to new participants. Between Oct 18, 2019, and April 11, 2022, 463 participants (mean age 48·5 years [SD 16·1], 315 [68%] female to 148 [32%] male) were randomly allocated to receive low-dose amitriptyline (232) or placebo (231). Intention-to-treat analysis of the primary outcome showed a significant difference in favour of low-dose amitriptyline in IBS-SSS score between groups at 6 months (-27·0, 95% CI -46·9 to -7·10; p=0·0079). 46 (20%) participants discontinued low-dose amitriptyline (30 [13%] due to adverse events), and 59 (26%) discontinued placebo (20 [9%] due to adverse events) before 6 months. There were five serious adverse reactions (two in the amitriptyline group and three in the placebo group), and five serious adverse events unrelated to trial medication. To our knowledge, this is the largest trial of a tricyclic antidepressant in IBS ever conducted. Titrated low-dose amitriptyline was superior to placebo as a second-line treatment for IBS in primary care across multiple outcomes, and was safe and well tolerated. General practitioners should offer low-dose amitriptyline to patients with IBS whose symptoms do not improve with first-line therapies, with appropriate support to guide patient-led dose titration, such as the self-titration document developed for this trial. National Institute for Health and Care Research Health Technology Assessment Programme (grant reference 16/162/01).

A systematic chart review of pharmacological interventions in patients with clozapine-induced hypersalivation

ObjectivesTo investigate the efficacy and tolerability of medications, such as mouthwash use of 1 % atropine sulfate and tropicamide drops, oral amitriptyline and amisulpride used for clozapine-induced hypersalivation (CIH). MethodsThe medical charts of inpatients with psychotic disorders between 2010 and 2022 were reviewed retrospectively. We detected 161 patients with eligible data who received or commenced clozapine. Primary outcome was defined as the percentage change in the diameter of a wet patch on the pillow (DWP) for improvements in CIH. ResultsThe frequency of CIH was 42 % (n = 68). The first step medications for CIH were tropicamide drops (49 %), atropine drops (43 %) and amitriptyline (3 %). After the first step, the median DWP significantly decreased by −33 %. During the index hospitalization, in 18 patients with persistent CIH, the median DWP significantly decreased by −42 % with the second step medications which also included amisulpride. There were no reported serious adverse events. The change in DWP was significantly correlated with the duration of clozapine treatment (r = 306) and clozapine serum level at discharge (r = 0.294). A linear regression model showed a link between the change in DWP and reduced Positive and Negative Syndrome Scale scores. ConclusionsOur findings emphasize that mouthwash use of atropine or tropicamide drops has a satisfying and tolerable effect in treating CIH. Switching medications for CIH seems to be effective when CIH persists despite a first step agent. Controlled follow-up studies are needed to understand the relationship between CIH, clozapine serum levels, illness severity, and functioning.

Intravenous methylcobalamin effectively ameliorated painful diabetic neuropathy: A randomized double-blind placebo controlled trial

Objective. Painful diabetic neuropathy (PDN) is a prevalent debilitating consequence of diabetes mellitus with lack of satisfactory therapeutic options. Methylcobalamin (MeCbl) is one of vitamin B12 analogs with known neurotrophic effects. We aimed to determine if MeCbl can relieve PDN. Materials and methods. This was a randomized (1:1) double-blind placebo-controlled trial involving PDN patients. Treatment and control group received daily 12.5 mg oral amitriptyline bid with either 500 µg of intravenous MeCbl or saline injection given on alternating days, respectively, for a 9-consecutive day period. PDN was assessed with douleur neuropathique 4 (DN4) questionnaire. Numeric pain rating scale (NPRS) was used to monitor pain intensity and treatment response. All investigators and patients were kept blinded throughout the study period. Outcomes. 42 patients, 21 on each arm had completed the study. The NPRS reduction can already be observed as early as day 2 post-intervention. Both the treatment and control group demonstrated sustained reduction of NPRS by almost one point per each time point of evaluation in the first three days (p<0.001). NPRS reduction remained until the end of the study period. The treatment group had a significantly lower NPRS score by 1.29 than that of the control group during the entire study period (95% CI -1.84 – -0.75; p < 0.001). Treatment group experienced significantly higher NPRS reduction when compared with control (4.19±1.54 vs. 2.1± 0.83; 95% CI 1.32-2.87; p < 0.001), i.e. 62.6% from baseline. Conclusions. MeCbl significantly and safely relieved PDN in a relatively rapid onset.

Efficacy of pharmacologic treatment in tinnitus patients without specific or treatable origin: A network meta-analysis of randomised controlled trials.

BackgroundAlthough tinnitus has a prevalence between 20 and 42.8%, the currently recommended management for tinnitus, such as tinnitus support and psychologic therapies, are relatively time-consuming and expensive. Several new pharmacologic treatments designed for tinnitus patients without specific origin had been developed but their efficacy remains unclear.MethodsThe current Network Meta-Analysis (NMA) of randomised controlled trials (RCTs) was conducted to evaluate the efficacy of different pharmacologic treatments for tinnitus management in tinnitus patients without specific or treatable origin (i.e. primary tinnitus). Databases were searched from inception to April 5th, 2021. All network meta-analytic procedures were conducted under the frequentist model. We calculated the effect size of outcomes with different rating scales with standardized mean difference. PROSPERO registration: CRD42020177742.FindingsOverall, 36 RCTs were included with 2,761 participants. The main results revealed that pharmacologic interventions with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) and those with anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) were associated with superior improvement in tinnitus severity and response rate compared to placebo/control. Oral amitriptyline were associated with the highest improvement in tinnitus severity and the fourth highest response rate. None of the investigated interventions was associated with different changes in quality of life compared to placebo/control. All the investigated treatments were associated with similar drop-out rate to placebo/control.InterpretationThe current NMA suggests a potential role for treatments with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) or anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) as the preferable effective treatments for tinnitus without specific or treatable origin.Fundingnone.

Comparison between Two Low Doses of Amitriptyline in the Management of Chronic Neck Pain: A Randomized, Double-Blind, Comparative Study.

Chronic neck pain (CNP) is a major concern for pain therapists. Many drugs including antidepressants such as amitriptyline have been used in the management of CNP. This study compared the efficacy and safety of 2 different doses of amitriptyline (5 mg and 10 mg at bedtime) in patients with CNP. A total of 80 patients of both sexes with idiopathic CNP, ranging in age from 18 to 75 years, were divided into 2 groups that received 5 or 10 mg oral amitriptyline at bedtime for 120 days. The primary outcome measure was neck pain disability index (NPDI). Neck pain intensity, Athens Insomnia Scale score, Hospital Anxiety and Depression Scale (HADS), side effects of the drug, and patient satisfaction were secondary outcome measures. NPDI decreased by 71.9% ± 13.4% in the 10 mg group compared to 47.3% ± 17.3% in the 5 mg group, representing a statistically significant difference (95% confidence interval: 27.3–12.6). Additionally, the 10 mg group showed greater mean reductions in pain score and HADS scores (both the anxiety and depression subscales), as well as improvement in sleep disturbance compared to the 5 mg group. A higher dose (10 mg) of amitriptyline at bedtime significantly reduced neck pain intensity, sleep disturbance, and anxiety and depression compared to a lower dose (5 mg) in patients with idiopathic and nontraumatic CNP after 120 days of treatment, with no significant difference between groups in the rate of side effects.

Current standard of care in treatment of bladder pain syndrome/interstitial cystitis.

Bladder pain syndrome/interstitial cystitis (BPS/IC) is a debilitating, systemic pain syndrome with a cardinal symptom of bladder related pain with associated systemic symptoms. It is characterized by an inflammation that partially or completely destroys the mucus membrane and can extend into the muscle layer; however, the etiology and pathogenesis is still enigmatic. It has been suggested that mast cell activation, defects in the glycosaminoglycan layer, non-functional proliferation of bladder epithelial cells, neurogenic inflammation, microvascular abnormalities in the submucosal layer, autoimmunity and infectious causes may cause BPS/IC. Available treatment options include general relaxation techniques, patient education, behavioral treatments, physical therapy, multimodal pain therapy, oral (amitriptyline, cimetidine, hydroxyzine) and intravesical treatments (heparin, lidocaine, hyaluronic acid and chondroitin sulfate), hydrodistension and other more invasive treatments. Available treatments are mostly not based on a high level of evidence. Lack of understanding of disease mechanisms has resulted in lack of targeted therapies on this area and a wealth of empirical approaches with usually inadequate efficacy. The aim of this article is to review the available evidence on the pathophysiological mechanisms of BPS/IC as they relate to available treatment options.

Oral flunarizine versus oral amitriptyline in migraine prophylaxis – A prospective open label study

Objectives: To compare the effectiveness and tolerability of flunarizine and amitriptyline in migraine prophylaxis. Also to assess the disability associated with migraine using Migraine Disability Assessment Test (MIDAS) and Headache Impact Test-6 (HIT-6) questionnaires. Materials and Methods: The study was a prospective observational, open-label, comparative study, conducted for six months among migraine patients attending Tertiary Care Hospital, Mandya. Patients were prescribed either Amitriptyline 25 mg or flunarizine 10 mg OD for three months. Effectiveness was assessed by the number of episodes of migraine attacks, pain severity score on Visual Analogue Scale (VAS), tolerability of adverse reactions reported and disability assessed using MIDAS and HIT-6 questionnaires. Results: Out of 103 patients, 55 were prescribed Amitriptyline and 48 patients flunarizine. 49.5% of patients were between 18 to 30 years of age. At the end of three months of treatment, the frequency and severity of headaches decreased from baseline in both the groups. The overall percentage of responders with >50% reduction from baseline in number of migraine episodes and pain severity together were 67.3% and 50% in amitriptyline and flunarizine groups respectively. There was reduction in MIDAS and HIT-6 scores in both groups, without significant difference between the groups. Both the drugs were well tolerated, with most common adverse effects being dry mouth, somnolence, and constipation. Conclusion: Both amitriptyline and flunarizine are effective in prophylaxis of migraine, with significant reduction in number of episodes and severity of headache from baseline to end of treatment. However, Amitriptyline had a higher overall responder rate when compared to Flunarizine, with similar tolerability profile. Keywords: Migraine prophylaxis, Amitriptyline, Flunarizine, MIDAS, HIT-6.

Analgesic Effects of Topical Amitriptyline in Patients With Chemotherapy-Induced Peripheral Neuropathy: Mechanistic Insights From Studies in Mice

Oral amitriptyline hydrochloride (amitriptyline) is ineffective against some forms of chronic pain and is often associated with dose-limiting adverse events. We evaluated the potential effectiveness of high-dose topical amitriptyline in a preliminary case series of chemotherapy-induced peripheral neuropathy patients and investigated whether local or systemic adverse events associated with the use of amitriptyline were present in these patients. We also investigated the mechanism of action of topically administered amitriptyline in mice. Our case series suggested that topical 10% amitriptyline treatment was associated with pain relief in chemotherapy-induced peripheral neuropathy patients, without the side effects associated with systemic absorption. Topical amitriptyline significantly increased mechanical withdrawal thresholds when applied to the hind paw of mice, and inhibited the firing responses of C-, Aβ- and Aδ-type peripheral nerve fibers in ex vivo skin-saphenous nerve preparations. Whole-cell patch-clamp recordings on cultured sensory neurons revealed that amitriptyline was a potent inhibitor of the main voltage-gated sodium channels (Nav1.7, Nav1.8, and Nav1.9) found in nociceptors. Calcium imaging showed that amitriptyline activated the transient receptor potential cation channel, TRPA1. Our case series indicated that high-dose 10% topical amitriptyline could alleviate neuropathic pain without adverse local or systemic effects. This analgesic action appeared to be mediated through local inhibition of voltage-gated sodium channels. PerspectiveOur preliminary case series suggested that topical amitriptyline could provide effective pain relief for chemotherapy-induced peripheral neuropathy patients without any systemic or local adverse events. Investigation of the mechanism of this analgesic action in mice revealed that this activity was mediated through local inhibition of nociceptor Nav channels.

Pharmacokinetic study of oral amitriptyline in horses.

The purpose of this study was to evaluate the pharmacokinetics of oral amitriptyline in horses. Oral amitriptyline (1mg/kg) was administered to six horses. Blood samples were collected from jugular and lateral thoracic vein at predetermined times from 0 to 24hr after administration. Plasma concentrations were determined by high-performance liquid chromatography and analyzed using noncompartmental methods. Pharmacodynamic parameters including heart rate, respiration rate, and intestinal motility were evaluated, and electrocardiographic examinations were performed in all subjects. The mean maximum plasma concentration (Cmax ) of amitriptyline was 30.7ng/ml, time to maximum plasma concentration (Tmax ) 1-2hr, elimination half-life (t1/2 ) 17.2hr, area under plasma concentration-time curve (AUC) 487.4ngml-1 hr-1 , apparent clearance (Cl/F) 2.6Lhr-1 kg-1 , and apparent volume of distribution (Vd/F) 60.1L/kg. Jugular vein sampling overestimated the amount of amitriptyline absorbed and should not be used to study uptake following oral administration. Heart rate and intestinal motility showed significant variation (p<.05). Electrocardiography did not provide conclusive results. Further studies are required to discern if multiple dose treatment would take the drug to steady state as expected, consequently increasing plasma concentrations.

Discontinuation of oral amitriptyline and nortriptyline due to adverse effects in outpatients with neuropathic pain: a retrospective study

Discontinuation of oral amitriptyline and nortriptyline due to adverse effects in outpatients with neuropathic pain: a retrospective study

Comparison of Carbamazipine and Amitryptyline for the Reduction of Diabetic Neuropathic Pain: A Randomized Clinical Trial

Background: Diabetic neuropathy is very difficult to treat. Objective: The purpose of the present study was to compare the efficacy and safety of carbamazepine and amitryptyline for reduction of diabetic neuropathic pain. Methodology: This was a randomized controlled trial conducted in the department of Neurology including Neuropathy Clinic of BSMMU and in collaboration with department of Endocrinology, BSMMU, Dhaka from January 2012 to December 2013 for a period of two (2) years. Adult diabetic patients presented with neuropathic pain with symmetrical involvement of distal limbs from indoor and outpatient department of Neurology including Neuropathy clinic as well as indoor and outpatient department of Endocrinology, BSMMU were enrolled in the study population. The study population was divided into two groups named as group A and group B. The group A was experimental group. In this group, patients were treated with oral carbamazepine 400mg/day in two divided doses for initial 2 weeks, then 600mg/ day in three divided doses for further 4 weeks. The group B was control group. In this group, patients were treated with oral amitriptyline 25mg/ day at night for initial 2 weeks, then 50mg/day taking at night for further 4 weeks. During trial, three follow ups were taken at 2 weeks interval and encountered the clinical response by pain score (VAS) and the side effects. The first follow up after 2 weeks of treatment; the second follow up was after 4 weeks of treatment and the third follow up was after 6 weeks of treatment. Result: A total number of 110 cases clinically diagnosed as painful diabetic polyneuropathy, then 56 cases randomly selected for Group A and 54 cases randomly selected for Group B. During follow up of 6 weeks, 2 case of Group A developed skin rash for which they discontinued drug. From rest of cases, 2 from Group A and 4 from Group B were dropped out. Because they did not come for follow up. So finally 52 cases for Group A group and 50 cases for Group B group were studied. A total of 102 patients were included in the study. They were divided into four Groups according to their age. The mean age was found 52.17(±10.02) years in Group A and 53.41(±8.82) years in Group B. The mean (±SD) of percent improvement in Group A and Group B were 41.11(±11.29) vs. 31.76(±19.14) (P&lt;0.05). Dizziness and Drowsiness were found in Group A as 33.3% and 37.0%. But in Group B dryness of mouth and constipation were found as 46.3% and 7.4%. Conclusion: In conclusion carbamazepine produced greater improvements than amitriptyline in relieving pain and paresthesia associated with diabetic neuropathy. Bangladesh Journal of Neuroscience 2017; Vol. 33 (1): 6-12

Management of Bladder Pain Syndrome: Green-top Guideline No. 70.

Management of Bladder Pain Syndrome: Green-top Guideline No. 70.

The beneficial effects of oral amitriptyline in anxiety-induced hyperventilation syndrome; a case series

The beneficial effects of oral amitriptyline in anxiety-induced hyperventilation syndrome; a case series

Pharmacokinetics of intravenous and oral amitriptyline and its active metabolite nortriptyline in Greyhound dogs

ObjectiveTo evaluate the pharmacokinetics of amitriptyline and its active metabolite nortriptyline after intravenous (IV) and oral amitriptyline administration in healthy dogs. Study designProspective randomized experiment. AnimalsFive healthy Greyhound dogs (three males and two females) aged 2–4 years and weighing 32.5–39.7 kg. MethodsAfter jugular vein catheterization, dogs were administered a single oral or IV dose of amitriptyline (4 mg kg−1). Blood samples were collected at predetermined time points from baseline (0 hours) to 32 hours after administration and plasma concentrations of amitriptyline and nortriptyline were measured by liquid chromatography triple quadrupole mass spectrometry. Non-compartmental pharmacokinetic analyses were performed. ResultsOrally administered amitriptyline was well tolerated, but adverse effects were noted after IV administration. The mean maximum plasma concentration (CMAX) of amitriptyline was 27.4 ng mL−1 at 1 hour and its mean terminal half-life was 4.33 hours following oral amitriptyline. Bioavailability of oral amitriptyline was 6%. The mean CMAX of nortriptyline was 14.4 ng mL−1 at 2.05 hours and its mean terminal half-life was 6.20 hours following oral amitriptyline. Conclusions and clinical relevanceAmitriptyline at 4 mg kg−1 administered orally produced low amitriptyline and nortriptyline plasma concentrations. This brings into question whether the currently recommended oral dose of amitriptyline (1–4 mg kg−1) is appropriate in dogs.

Evaluation of the pharmacokinetics of oral amitriptyline and its active metabolite nortriptyline in fed and fasted Greyhound dogs.

This study reports the pharmacokinetics of oral amitriptyline and its active metabolite nortriptyline in Greyhound dogs. Five healthy Greyhound dogs were enrolled in a randomized crossover design. A single oral dose of amitriptyline hydrochloride (actual mean dose 8.1 per kg) was administered to fasted or fed dogs. Blood samples were collected at predetermined times from 0 to 24h after administration, and plasma drug concentrations were measured by liquid chromatography with mass spectrometry. Noncompartmental pharmacokinetic analyses were performed. Two dogs in the fasted group vomited following amitriptyline administration and were excluded from analysis. The range of amitriptyline CMAX for the remaining fasted dogs (n=3) was 22.8-64.5ng/mL compared to 30.6-127ng/mL for the fed dogs (n=5). The range of the amitriptyline AUCINF for the three fasted dogs was 167-720h·ng/mL compared to 287-1146h·ng/mL for fed dogs. The relative bioavailability of amitriptyline in fasted dogs compared to fed dogs was 69-91% (n=3). The exposure of the active metabolite nortriptyline was correlated to amitriptyline exposure (R(2) =0.84). Due to pharmacokinetic variability and the small number of dogs completing this study, further studies are needed assessing the impact of feeding on oral amitriptyline pharmacokinetics. Amitriptyline may be more likely to cause vomiting in fasted dogs.

Parsonage-Turner Syndrome Initially Suspected of Being Orthopedic Diseases in a Primary Care Setting: A Case Report

Parsonage-Turner syndrome (PTS), also known as neuralgic amyotrophy or brachial neuritis, consists of a complex set of symptoms including sudden onset shoulder pain, usually unilaterally, followed by progressive neurologic deficits such as motor weakness, dysesthesia and numbness. We report a case of a 45-year-old Japanese man with PTS, who was initially suspected of having orthopedic diseases, such as cervical spondylosis and suprascapular nerve entrapment syndrome. The patient presented with acute-onset severe pain in his right arm and neck, followed by muscle weakness. We diagnosed PTS by taking a detailed medical history, ruling out other differential diagnoses, and by considering the characteristic clinical symptoms and the denervation pattern identified by needle electromyography. High-dose corticosteroid therapy prednisolone (PSL) relieved the initial sharp pain and oral amitriptyline successfully relieved the residual nighttime pain. Doses of PSL and amitriptyline were tapered, pain was alleviated, and the patient returned to full-time work after discharge in one-and-a-half years. For prompt diagnosis, physicians should consider the possibility of PTS in patients with acute onset of severe arm pain or subsequent muscle weakness and muscle atrophy in the arm or shoulder girdle. J Med Cases. 2014;5(4):197-201 doi: http://dx.doi.org/10.14740/jmc1696w

An assessment of the in vivo effects of intravenous lipid emulsion on blood drug concentration and haemodynamics following oro-gastric amitriptyline overdose

Background. Overdose with lipophilic drugs, such as amitriptyline, may cause cardiotoxicity in overdose. Severe poisoning can be resistant to traditional treatments. Intravenous lipid emulsion (ILE) has been recommended as a novel therapy for the treatment of such overdoses; however, a little is known about the effects of ILE-infusion on drug concentration and haemodynamics in the early/absorptive phase after oral poisoning. Method. Thirty minutes after oro-gastric administration of amitriptyline (70 mg/kg), either 20% intravenous lipid emulsion (ILE), 8.4% sodium bicarbonate or Hartmann's solution was infused to anaesthetized and ventilated rodents (n = 10 per group). Heart rate, blood pressure, cutaneous ECG – QRS interval duration (QRS-d), and survival were serially recorded over 120 min. Blood drug concentrations were also collected during this period. Continuous variables were compared using one-way ANOVA. Results. ILE infusion significantly decreased the survival compared to other treatments (10% ILE vs 70% bicarbonate vs 70% Hartmann's solution, p = 0.005). There was a gradual prolongation of QRS-d and fall in blood pressure over time compared to baseline (T0) measurement for both ILE and Hartmann's solution treatments. This was associated with significantly increased blood AMI concentration with ILE treatment at T60, T90 and T120 min to the other treatments (p < 0.02). Conclusion. Administration of ILE early after oral amitriptyline overdose resulted in worse survival and no improvement in haemodynamics. In addition, blood amitriptyline concentrations were higher in the ILE-treated group. This suggests that either drug absorption from the gastrointestinal-tract was facilitated or drug redistribution was retarded when ILE was given early after oral poisoning.

A comparative study of efficacy and safety of gabapentin versus amitriptyline as coanalgesics in patients receiving opioid analgesics for neuropathic pain in malignancy

Objective:To assess the efficacy and safety of gabapentin and amitriptyline along with opioids in patients suffering from neuropathic pain in malignancy.Materials and Methods:Eighty-eight adult patients between 18 and 70 years of age with neuropathic pain in stage III malignant disease, matched for baseline charactistics, were randomly assigned to two groups. Group A received oral tramadol and gabapentin and group B received oral tramadol and amitriptyline. The treatment duration of each patient was 6 months. Visual analog scale (VAS) was the primary efficacy parameter. Verbal rating scale (VRS) score, percentage of pain relief (PPR), and global pain score (GPS) were the secondary efficacy parameters. Oral morphine tablets or fentanyl transdermal patch were used as rescue medication. Data analysis was carried out in Graph Pad instat.Results:There was decline in VAS pain score from baseline in both the groups in the early phase of the study though there was no statistically detectable difference between them at any study point. Similar changes were seen in the secondary efficacy parameters too. Thus both the drugs were effective in providing relief to cancer patients with neuropathic pain though there was no statistically detectable difference in efficacy between them. Six patients in group A and eight patients in group B required rescue medication. A total of 12 subjects in the gabapentin group and 15 subjects in the amitriptyline group experienced adverse events which were of mild to moderate grades.Conclusions:Amitriptyline may be a suitable alternative for management of neuropathic pain in cancer patients although gabapentin is widely used for this purpose. The lower cost of amitriptyline may favor patient compliance with lesser number of drop-outs.