Low-dose Amitriptyline Research Articles

Low-dose titrated amitriptyline as second-line treatment for adults with irritable bowel syndrome in primary care: the ATLANTIS RCT.

Irritable bowel syndrome, characterised by abdominal pain and a change in stool form or frequency, is most often managed in primary care. When first-line therapies are ineffective, National Institute for Health and Care Excellence guidelines suggest considering low-dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown and they are infrequently prescribed by general practitioners. To evaluate the clinical and cost-effectiveness of low-dose titrated amitriptyline as a second-line treatment for irritable bowel syndrome in primary care. A pragmatic, randomised, multicentre, two-arm, double-blind, placebo-controlled trial. A nested, qualitative study explored participant and general practitioner experiences of treatments and trial participation, and implications for wider use of amitriptyline for irritable bowel syndrome in primary care. Participants, clinicians, investigators and analysts were masked to allocation. Fifty-five general practices in three regions in England (Wessex, West of England, West Yorkshire). Patients aged ≥ 18 years meeting Rome IV criteria for irritable bowel syndrome with ongoing symptoms after trying first-line treatments and no contraindications to TCAs. Amitriptyline 10 mg once-daily, self-titrated by participants to a maximum of 30 mg once-daily or matched placebo for 6 months. Participants randomised 1 : 1 with most having the option to continue blinded treatment for a further 6 months. The primary participant-reported outcome was the effect of amitriptyline on global irritable bowel syndrome symptoms at 6 months, measured using the irritable bowel syndrome Severity Scoring System, with a 35-point between-group difference defined as the minimum clinically important difference. The key secondary outcome was the proportion of participants reporting subjective global assessment of relief at 6 months, defined as somewhat, considerable, or complete relief of symptoms. Other secondary outcomes included: effect on global symptoms, via the irritable bowel syndrome Severity Scoring System, and subjective global assessment of relief of irritable bowel syndrome symptoms at 3 and 12 months; effect on somatic symptom-reporting at 6 months; anxiety an-d depression scores; ability to work and participate in other activities at 3, 6 and 12 months; acceptability, tolerability and adherence to trial medication. Four hundred and sixty-three participants were randomised to amitriptyline (232) or placebo (231). An intention-to-treat analysis of the primary outcome showed a significant difference in favour of amitriptyline for irritable bowel syndrome Severity Scoring System score between arms at 6 months [-27.0, 95% confidence interval (CI) -46.9 to -7.10; p = 0.008]. For the key secondary outcome of subjective global assessment of relief of irritable bowel syndrome symptoms, amitriptyline was superior to placebo at 6 months (odds ratio 1.78, 95% CI 1.19 to 2.66; p = 0.005). Amitriptyline was superior to placebo across a range of other irritable bowel syndrome symptom measures but had no impact on somatoform symptom-reporting, anxiety, depression, or work and social adjustment scores. Adverse event trial withdrawals were more common with amitriptyline (12.9% vs. 8.7% for placebo) but most adverse events were mild. The qualitative study thematically analysed 77 semistructured interviews with 42 participants and 16 GPs. Most participants found the self-titration process acceptable and empowering. General practitioners should offer low-dose amitriptyline to patients with irritable bowel syndrome whose symptoms do not improve with first-line therapies. Guidance and resources should support GP-patient communication to distinguish amitriptyline for irritable bowel syndrome from use as an antidepressant and to support patients managing their own dose titration. This trial is registered as ISRCTN48075063. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/162/01) and is published in full in Health Technology Assessment Vol. 28, No. 66. See the NIHR Funding and Awards website for further award information.

Low-dose amitriptyline for irritable bowel syndrome

Low-dose amitriptyline for irritable bowel syndrome

Low-dose Naltrexone Improves post–COVID-19 condition Symptoms

Treatments for myalgic encephalomyelitis and chronic fatigue syndrome can be adapted for post-COVID-19 condition. Our aim was to compare treatments in patients from our post-COVID-19 clinic. We conducted a retrospective cohort study and included consecutive patients enrolled in our post-COVID-19 clinic. We included patients who received low-dose naltrexone, amitriptyline, duloxetine, and physical therapy, and evaluated improvements in fatigue, pain, dyspnea, and brain fog recorded in the electronic health record. We calculated the adjusted relative hazard of improvement using Cox proportional models. We adjusted for demographic characteristics, comorbidities, and prior COVID-19 hospitalization. We included the first 108 patients with post-COVID-19 enrolled in the clinic. Most of the patients received amitriptyline. The relative hazard of improvement for those taking low-dose naltrexone was 5.04 (95% CI, 1.22-20.77; P = 0.02) compared with physical therapy alone. Both fatigue and pain were improved in patients taking low-dose naltrexone; only fatigue was improved in patients taking amitriptyline. Post-COVID-19 condition symptoms may improve in patients taking medications adapted from myalgic encephalomyelitis and chronic fatigue syndrome. Randomized controlled trials should evaluate these medications and translational studies should further evaluate their mechanisms of action.

Factors associated with the use of traditional doses of amitriptyline for chronic pain management: A cross-sectional study.

There are studies on the effect of low-dose amitriptyline on pain control, but there is a lack of studies on the use of amitriptyline for chronic pain and the factors associated with the prescription of traditional doses. We used a national sample cohort of patients aged ≥ 18 years who were prescribed amitriptyline along with chronic pain, without psychiatric disorders, between 2002 to 2015. We categorized the prescriptions into 2 groups according to the daily dose: low doses (≤25 mg) and traditional doses (>25 mg). Multivariable logistic regression models were used to identify factors associated with traditional dose prescriptions. Among 177,769 prescriptions for amitriptyline, 15,119 (8.5%) were prescribed for chronic pain. The prevalence of prescriptions and proportion of traditional doses of amitriptyline tended to decrease during the study period. Male sex (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.05-1.13); age 65-80 years (OR 1.12, 95% CI 1.08-1.16), especially ≥ 80 years (OR 1.55, 95% CI 1.45-1.65); headaches (OR 1.18, 95% CI 1.10-1.27), receiving medical aids (OR 2.58, 95% CI 2.46-2.71); and being prescribed benzodiazepines or zolpidem concomitantly (OR 1.10, 95% CI 1.06-1.15) were significantly associated with traditional dose prescriptions of amitriptyline. Although traditional dose prescriptions of amitriptyline have been declining, close monitoring is still required in the presence of the above-mentioned factors.

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).

Low-dose amitriptyline in irritable bowel syndrome: ready for primary care?

Low-dose amitriptyline in irritable bowel syndrome: ready for primary care?

Dental health of patients using antidepressants and methamphetamines

The search was performed in the PubMed database, and the results of own research on the effects of antidepressants on dental health were presented. Literature data on the impact of methamphetamine use on dental health are also provided. Selective serotonin reuptake inhibitors have been shown to cause bru-xism, which can exacerbate temporomandibular joint disorder, and tricyclic antidepressants (especially low-dose amitriptyline) can reduce the risk of bruxism caused by another antidepressant. Antidepressants, mostly tricyclic, cause xerostomia, leading to the salivary hypofunction. Similar effects such as bruxism and xerostomia are also noted when using methamphetamines. Saliva contains a high concentration of calcium and phosphate ions, which serve as raw materials for the remineralization process, it also buffers organic acids formed by dental plaque, thereby preventing periodontitis and caries. Xerostomia due to the use of antidepressants or methamphetamines causes taste disorders, the appearance of bad breath, mouth ulcers, impairs the processes of chewing, swallowing and speech, changes the microbial colonization of the oral cavity, causing the development of dental ca-ries, candidiasis, atrophy of the mucous membrane and a burning sensation, difficulties in keeping dentures, negatively affects the quality of life of patients. Therefore, it is important for dentists to be aware of the oral problems associated with the use of methamphetamines and antidepressants, identify them early, and not only provide topical treatment, but also discuss with patients the risks associated with their lifestyle or treatment.

Off-label low dose amitriptyline for insomnia disorder: Patient-reported outcomes.

Low dose amitriptyline is prescribed off-label to improve sleep maintenance in patients with insomnia disorder. Data on treatment outcomes are limited. We aimed to assess patient-reported treatment effect and side effects of low dose amitriptyline for insomnia in routine care data. Cross-sectional study: Seven hundred fifty-two consecutive patients with insomnia disorder having sleep maintenance problems were treated in an outpatient sleep clinic with low dose amitriptyline (10-20 mg based on self-titration). Treatment was intended to improve sleep maintenance. Before the planned follow-up consultation (approximately 6 weeks after start treatment) patients completed an online treatment evaluation questionnaire. Treatment (dose, adherence), sleep, fatigue, satisfaction and side effects were assessed by multiple-choice questions with room for free-text elaboration. 53.7% of the patients reported to use amitriptyline up to 10mg/day, 42.9% used a self-increased dose of mostly 20 mg/day, while 3.5% had discontinued treatment. 73.9% of the total study population reported improvement of sleep maintenance, 31.3% improved sleep onset, 35.2% improved daytime fatigue, and 45.8% reported to be (very) satisfied with treatment results. 66.1% reported at least one side effect. The reported side effects were generally the already known side effects of amitriptyline. These patient-reported outcomes support the clinical observations that low dose amitriptyline improves sleep maintenance on the short term and that it is generally well tolerated. This further justifies randomized controlled trials in patients with insomnia disorder and sleep maintenance problems to assess the effectiveness and safety of low dose amitriptyline on the short and long term.

Amitriptyline at low-dose and titrated for irritable bowel syndrome as second-line treatment (The ATLANTIS trial): protocol for a randomised double-blind placebo-controlled trial in primary care

BackgroundIrritable bowel syndrome (IBS) is a common functional bowel disorder that has a considerable impact on patient quality of life and substantial societal and health care resource costs. Current treatments are often ineffective. Tricyclic antidepressants have shown promise in secondary care populations but their effectiveness in a primary care setting remains unclear.MethodsATLANTIS is a randomised, multi-centre, parallel-group, two-arm, double-blind, placebo-controlled trial of low-dose amitriptyline as a second-line treatment for IBS in primary care. Participants will be invited by letter, or recruited opportunistically, from general practices in three regions of England (West Yorkshire, Wessex, and West of England) and screened for eligibility. A total of 518 adult patients with IBS, who are symptomatic despite first-line therapies, will be randomised 1:1 to amitriptyline or identical placebo for 6 months. Treatment will commence at a dose of 10 mg (or one placebo tablet) daily at night, with dose titration up to a maximum of 30 mg at night, depending on side effects and response to treatment. Participant-reported assessments will be conducted at baseline and 3, 6, and 12 months post-randomisation. The primary objective is to determine the effectiveness of amitriptyline, compared with placebo, in improving participant-reported global symptoms of IBS at 6 months (using the IBS Severity Scoring System). Secondary outcomes include relief of IBS symptoms, effect on IBS-associated somatic symptoms (Patient Health Questionnaire-12), anxiety and depression (Hospital Anxiety and Depression Scale), ability to work and participate in other activities (Work and Social Adjustment Scale), acceptability and tolerability of treatment, self-reported health care use, health-related quality of life (EQ-5D-3L), and cost-effectiveness. A nested, qualitative study will explore patient and general practitioner experiences of treatments and trial participation, including acceptability, adherence, unanticipated effects, and implications for wider use of amitriptyline for IBS in primary care.DiscussionDetermining the clinical and cost-effectiveness of low-dose amitriptyline as a second-line treatment for IBS in primary care will provide robust evidence to inform management decisions.Trial registrationISRCTN ISRCTN48075063. Registered on 7th June 2019.

A Comparative Study to Analyze the Effect of Gabapentin with Amitriptyline Versus Pregabalin with Amitriptyline in Neuropathic Pain in Cancer Patients Undergoing Palliative Care

Introduction: Antiepileptics and antidepressant medications are known for managing neuropathic pain. We aim to compare the effects of pregabalin with low-dose amitriptyline and gabapentin with low-dose amitriptyline in managing neuropathic pain in cancer patients undergoing palliative care. Materials and Methods: We conducted our study on 160 cancer patients who were having neuropathic pain and were undergoing palliative care treatment in our institute. It was a hospital-based, randomized, tertiary cancer center-based observational study. After taking approval from the institutional ethics committee and taking written informed consent from patients, the patients were divided into two groups and the effect of medicines on incidence of neuropathic pain was observed; the incidence of burning sensation and the incidence of adverse effects of medications were also analyzed. Statistical analysis was done using paired t-test and SPSS version 20 software. Results: The onset of relief in pain was earlier in the pregabalin group as compared to the gabapentin group. There was more reduction in a burning sensation in the pregabalin group as compared to the gabapentin group. The incidence of headaches was the same in both groups. Nausea and vomiting were more in the pregabalin group but the overall difference in adverse effects was not statistically significant (P > 0.05) Conclusions: In the management of neuropathic pain in cancer patients who are undergoing palliative care, a combination of pregabalin with amitriptyline was found to be more effective in pain relief than gabapentin with amitriptyline.

The Effectiveness and Adverse Events of Amitriptyline and Aripiprazole in Very Elderly Patients With BMS.

Burning mouth syndrome (BMS) is defined by chronic oral burning sensations without any corresponding abnormalities. Besides amitriptyline, aripiprazole has been reported as a possible medication to manage BMS. However, especially for elderly patients, the adverse events of these medications would be a problem. The aim of the present study was to investigate the differences in the effectiveness and adverse events of amitriptyline and aripiprazole in very elderly patients with BMS. This is a retrospective comparative study of 80 years old and older patients with BMS who were initially treated with amitriptyline or aripiprazole and who were new outpatients of our department from April 2017 to March 2020. All clinical data, including sex, age, comorbid physical diseases, comorbid psychiatric disorders, the prescribed doses (initial, maximum, and effective dose), prognosis, and adverse events, were collected from their medical charts. Each medication was selected considering their medical history. Amitriptyline was prescribed in 13 patients (11 women, 82.3 ± 2.1 years old) and aripiprazole was prescribed in 27 patients (26 women, 84.2 ± 3.8 years old). There were no significant between-group differences in sex, age, duration of illness, pain intensity, salivation, and psychiatric comorbidity at the first examination. Amitriptyline clinically improved more patients (7 patients, 53.8%) with the effective dose of 10 (7.5, 15.0) mg than aripiprazole (11 patients, 40.7%) of which the effective dose was 1.0 (0.5, 1.5) mg, although there were no significant between-group differences. The adverse events of amitriptyline were found in 9 patients (69.2%) and most patients had constipation (46.2%). For aripiprazole, 7 patients (25.9%) showed adverse events, most of them reported sleep disorder (11.1%). Amitriptyline had significantly longer duration taking medication (p = 0.021) and lower discontinuation (p = 0.043) despite of higher occurrence rate of adverse events (p = 0.015) compared to aripiprazole. These results suggest that both psychopharmacotherapies with a low dose of amitriptyline and aripiprazole are effective for the very elderly patients with BMS. Furthermore, aripiprazole may have some advantages in the adverse events compared to amitriptyline; however, the low dose amitriptyline monotherapy may have more benefit in the effectiveness and tolerability over prudent collaboration with primary physicians.

The effect of intravesical cocktail therapy combined with low-dose amitriptyline on primary bladder pain syndrome

We compared the effectiveness of intravesical combination treatment and intravesical treatment plus low-dose amitriptyline in patients with primary bladder pain syndrome (PBPS). A total of 53 patients were included in the study. Demographic data, voiding frequency, nocturia, visual analog scale (VAS) scores, validated O'Leary-Sant IC Symptom Index (ICSI), and IC Problem Index (ICPI) scores and scores on the Short Form-36 (SF-36) questionnaire were collected from the patients at the beginning of the treatment, and at the 6th week and 6th month of the treatment. The patients were divided into two groups. Group 1 received intravesical treatment for 6 weeks. Group 2 received intravesical treatment plus amitriptyline at a dosage of 10mg/day. The frequencies of voiding and VAS scores were significantly improved in groups 1 and 2 at the 6th week compared with pretreatment (in group 1 p< 0.001, p< 0.001, and in group 2 p< 0.001, p< 0.001 respectively). The median ICSI and ICPI scores also significantly decreased in groups 1 and 2 (in group 1 p< 0.001, p< 0.001, and in group 2 p< 0.001, p< 0.001 respectively). Scores on the dimensions of the SF-36 questionnaire were significantly improved in both groups. There was no significant change in terms of VAS, nocturia, ICSI or ICPI scores when comparing the 6th week and 6th month results in groups 1 and 2 (all p> 0.05). Only role functioning/emotional achieved a significant improvement in group 2 (p =0.007). Intravesical combination therapies are effective in PBPS treatment. Adding low-dose amitriptyline to intravesical therapy in patients with PBPS improves emotional status.

TIMELAPSE study\u2014efficacy of low-dose amitriptyline versus cognitive behavioral therapy for chronic insomnia in patients with medical comorbidity: study protocol of a randomized controlled multicenter non-inferiority trial

BackgroundInsomnia is common in people with long-term medical conditions and is related to increased mortality and morbidity. Cognitive behavioral therapy for insomnia (CBT-I) is first choice treatment and effective for people with insomnia and comorbid long-term medical conditions. However, CBT-I has some limitations as it might not always be available or appeal to patients with medical conditions. Furthermore, a small proportion of patients do not respond to CBT-I. Preliminary evidence and clinical experience suggest that low-dose amitriptyline (AM) might be an effective alternative to treat insomnia in patients with medical comorbidity. In this randomized controlled trial, we will determine whether AM is non-inferior to the first choice treatment for insomnia, CBT-I.Methods/designThis study will test if treatment with low-dose amitriptyline for insomnia in patients with medical comorbidity is non-inferior to CBT-I in a multicenter randomized controlled non-inferiority trial. Participants will be 190 adults with a long-term medical condition and insomnia. Participants will be randomly allocated to one of two intervention arms: 12 weeks AM (starting with 10 mg per day, and if ineffective at 3 weeks, doubling this dose) or 12 weeks of CBT-I consisting of 6 weekly sessions and a follow-up session 6 weeks later. The primary outcome is subjective insomnia severity, measured with the Insomnia Severity Index (ISI). The primary endpoint is at 12 weeks. Secondary outcomes include sleep quality (e.g., sleep efficiency), questionnaires on daytime functioning (physical functioning and impairment of functioning), and symptoms (e.g., fatigue, pain, anxiety) at 12 weeks and 12 months post treatment and relapse of insomnia until 12 months after treatment.DiscussionIrrespective of the outcome, this study will be a much-needed contribution to evidence based clinical guidelines on the treatment of insomnia in patients with medical comorbidity.Trial registrationDutch Trial Register NTR NL7971. Registered on 18 August 2019

Treatment effectiveness for Vocal Cord Dysfunction in adults and adolescents: A systematic review.

To determine whether treatment effectiveness can be established for a range of vocal cord dysfunction (VCD) interventions in adolescents and adults. A systematic review of the literature and risk of bias appraisal was completed using the Joanna Briggs Institute Critical Appraisal Tools. Data were qualitatively synthesized in the broad intervention groups of glottic airway and respiratory retraining, pharmacological therapies, airway device therapies and psychological therapies. Nine electronic databases, two clinical trial registries and the grey literature were searched from inception to September 2021 for articles on VCD interventions or equivalent terms. Studies were included if they were randomized controlled trials, non-randomized controlled trials, quasi-experimental pre- and post-test studies and within-subject repeated measure designs, participants were 13years or older, VCD was diagnosed using laryngoscopy or CT larynx, VCD intervention was provided and outcome measures reported on VCD symptoms. The search yielded no randomized controlled trials. There were 17 quasi-experimental studies that met the eligibility criteria, and these studies reported on glottic airway and respiratory retraining, botulinum toxin injections, inspiratory muscle strength training and amitriptyline; all were associated with VCD symptom reduction. In addition, 2 within-subject repeated measure studies reported inspiratory muscle strength training and respiratory retraining to be effective in reducing symptoms in participants with exertional VCD. The included studies were reported in full-text publications (11) and conference proceedings (8). There was a high risk of bias and low quality of evidence across all intervention areas. Glottic airway and respiratory retraining, botulinum toxin injections, low-dose amitriptyline and inspiratory muscle strength training devices have been associated with symptom reduction in adults and adolescents with vocal cord dysfunction. Limited objective data exist to support the effectiveness of these interventions, and robust controlled trials are needed in this area. Systematic Review Registration: CRD42018092274 (PROSPERO).

Effect of low-dose amitriptyline on reducing pain in clinical knee osteoarthritis compared to benztropine: study protocol of a randomised, double blind, placebo-controlled trial

BackgroundKnee osteoarthritis is a major cause of pain and disability. Pain control is poor, with most patients remaining in moderate to severe pain. This may be because central causes of pain, a common contributor to knee pain, are not affected by current treatment strategies. Antidepressants, such as amitriptyline, have been used to treat chronic pain in other conditions. The aim of this randomised, double blind, controlled trial, is to determine whether low dose amitriptyline reduces pain in people with painful knee osteoarthritis over 3 months compared to benztropine, an active placebo.Methods/designOne hundred and sixty people with painful radiographic knee osteoarthritis will be recruited via clinicians, local and social media advertising. Participants will be randomly allocated in a 1:1 ratio to receive either low dose amitriptyline (25 mg) or active placebo (benztropine mesylate, 1 mg) for 3 months. The primary outcome is change from baseline in knee pain (WOMAC pain subscale) at 12 weeks. Secondary outcomes include change in function (total WOMAC) and the proportion of individuals achieving a substantial response (≥ 50% reduction in pain intensity, measured by Visual Analog Scale, VAS, from no pain to worst pain imaginable, 0-100 mm) and moderate response (≥ 30% reduction in pain intensity, measured by VAS) at 12 weeks. Intention to treat analyses will be performed. Subgroup analyses will be done.DiscussionThis study will provide high level evidence regarding the effectiveness of low dose amitriptyline compared to benztropine in reducing pain and improving function in knee OA. This trial has the potential to provide an effective new therapeutic approach for pain management in knee osteoarthritis, with the potential of ready translation into clinical practice, as it is repurposing an old drug, which is familiar to clinicians and with a well described safety record.Trial registrationAustralian New Zealand Clinical Trials Registry prior to recruitment commencing (ACTRN12615000301561, March 31, 2015, amended 14 December 2018, February 2021). Additional amendment requested 18 July 2021.

Assessment of Short-term Outcomes of 10 mg Daily Amitriptyline Therapy in Globus Pharyngeus Patients

Background: Globus pharyngeus or feeling of a lump in the throat is a very common complaint in patients visiting the otolaryngology outpatient department. Pharmacotherapy with low dose amitriptyline has a significant effect in relieving the symptoms, although success rate varies among patients. Objectives: Aim for this study was to find out the benefits of low dose amitriptyline therapy in the management of Globus pharyngeus on a short term basis. Materials &amp; Methods: This is an observational study conducted from Jan 2019 to Jan 2020. Total 50 patients were included in this study. Inclusion criteria were – subjective feeling of a lump in the throat persisting for more than 2 months, Clinical oral examination and Upper GI endoscopy revealed normal findings, age between 18–60 years of both sexes. All the patients were prescribed with 10mg Amitriptyline per oral at night for 2 months, and patients were followed during the course of treatment to assess relief of symptoms and to evaluate any side effects. Results: In this study male to female ratio was 1:4. Mean age of study group was 42.66 (_ 4.78) years. Symptomatic relief occurred in 37 (74%) patients. Increased somnolence was found in 21 patients (42%) during first 2 weeks of treatment, No improvement occurred in 8 patients (16%), and worsening of symptom occurred in 5 patients (10%). Conclusion: Low dose Amitriptyline is effective in alleviating symptoms of globus pharyngeus in most patients on a short-term basis. Although some minor side effects can occur, these are manageable. KYAMC Journal.2021;12(02): 75-77

Role of serum amitriptyline concentration and CYP2C19 polymorphism in predicting the response to low-dose amitriptyline in irritable bowel syndrome

BackgroundLow-dose amitriptyline (AMT) is an effective treatment for diarrhea-dominant irritable bowel syndrome (IBS-D). Its efficacy depends upon its serum concentration and the patient's CYP2C19 genotype. AimsTo identify the association between serum AMT and nortriptyline (NT) concentration and CYP2C19 polymorphism and the clinical response in IBS-D patients. MethodsNinety IBS-D patients were treated of AMT for 6 weeks. Efficacy was evaluated by the results of the Adequate Relief question each week and an IBS severity scoring system (IBS-SSS) at 0, 3, and 6 weeks. CYP2C19 genotyping was performed by direct sequencing. AMT and NT steady-state serum concentrations were detected by high-performance liquid chromatography. ResultsThe CYP2C19 polymorphism exhibited a significant influence on the NT serum concentration but did not predict the clinical efficacy of AMT for treating IBS-D. The NT steady-state and dose-corrected serum concentrations were significantly correlated with an improvement in the IBS-SSS score after 6 weeks, whereas the AMT serum concentration was not correlated with clinical improvement. The cut-off NT steady-state serum concentration of 2.91 ng/ml may help distinguish responders from non-responders. ConclusionsNT serum concentration but not CYP2C19 polymorphism may be correlated with the clinical efficacy of AMT for treating IBS-D, and such a response may occur at the upper NT threshold of 2.91 ng/ml.

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.

Effect of low-dose amitriptyline on low back pain with a neuropathic component: a post hoc analysis

Low back pain (LBP) is a major, global health problem, with limited effective treatments [ [1] Global Burden of Disease 2019 Diseases and Injuries CollaboratorsGlobal burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020; 396: 1204-1222 Abstract Full Text Full Text PDF PubMed Scopus (492) Google Scholar , [2] Maher C Underwood M Buchbinder R Non-specific low back pain. Lancet. 2017; 389: 736-747 Abstract Full Text Full Text PDF PubMed Scopus (595) Google Scholar ]. We recently conducted a clinical trial to examine the efficacy of a low-dose tricyclic antidepressant (TCA; amitriptyline) in those with chronic, nonspecific LBP [ [3] Urquhart D Wluka A van Tulder M Heritier S Forbes A Fong C et al. Efficacy of low-dose amitriptyline for chronic low back pain: a randomized clinical trial. JAMA Intern Med. 2018; 178: 1474-1481 Crossref PubMed Scopus (21) Google Scholar ]. Although we found no statistically superior effect favoring low-dose amitriptyline for our primary outcome, there was a significant improvement in disability and consistent evidence across multiple outcomes to suggest a beneficial effect. Given LBP is a complex, heterogeneous condition [ [2] Maher C Underwood M Buchbinder R Non-specific low back pain. Lancet. 2017; 389: 736-747 Abstract Full Text Full Text PDF PubMed Scopus (595) Google Scholar ], we hypothesized that a specific patient subgroup may benefit from treatment with a low-dose TCA.

OnabotulinumtoxinA for chronic migraine during pregnancy: a real world experience on 45 patients

ObjectiveTo report the pregnancy outcomes on patients with chronic migraine exposed to onabotulinumtoxinA from Hull Headache Clinic.BackgroundMigraines are common in women of reproductive age and those with chronic migraine have a major impact on their activities of daily living and health-related quality of life. Apart from low dose amitriptyline and beta-blockers all other prophylactic agents have proven teratogenic effects. OnabotulinumtoxinA is approved as preventive treatment for adult patients with chronic migraine, although its impact on pregnancy is unknown.MethodsWe prospectively collected data for efficacy and safety on all patients treated with onabotulinumtoxinA at the Hull Headache Clinic. The toxin is administered as per PREEMPT paradigm. Female patients of reproductive age group receiving onabotulinumtoxinA are given advice on contraception and the unknown impact of the toxin on pregnancy. They are asked to report pregnancy when they are appraised on the risk/benefit of treatment continuation. All patients are consented for access to their medical records and pregnancy outcome and those who wished to continue are asked to sign a disclaimer. Pregnancy outcome data was collected on all patients for the mode of delivery, birth weight and congenital malformation and any other unexpected outcomes.ResultsOver 9 years period 45 patients reported pregnancy while receiving onabotulinumtoxinA. All patients had received onabotulinumtoxinA within 3 months prior to the date of conception. 32 patients wished to continue treatment during pregnancy while the remaining 13 stopped treatment. Apart from 1 miscarriage in the treatment group, all patients had full term healthy babies of normal birth weight and no congenital malformations.ConclusionWe report our experience of 45 patients exposed to onabotulinumtoxinA during pregnancy. Although the numbers are small, there was no impact of the toxin found on the pregnancy outcomes.