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BMJ (Clinical Research Ed.) May 2024The studyFord AC, Wright-Hughes A, Alderson SL, et al. Amitriptyline at low-dose and titrated for irritable bowel syndrome as second-line treatment in primary care...
The studyFord AC, Wright-Hughes A, Alderson SL, et al. 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. 2023;402:1773-85.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/irritable-bowel-syndrome-low-dose-antidepressant-improves-symptoms/.
Topics: Irritable Bowel Syndrome; Humans; Amitriptyline; Double-Blind Method; Antidepressive Agents; Randomized Controlled Trials as Topic; Antidepressive Agents, Tricyclic; Treatment Outcome; Clinical Trials, Phase III as Topic
PubMed: 38692664
DOI: 10.1136/bmj.q871 -
The Journal of Headache and Pain Apr 2024Acupuncture showed better improvement than sham acupuncture in reducing attack frequency of tension-type headache (TTH), but its effectiveness relative to first-line... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
Acupuncture showed better improvement than sham acupuncture in reducing attack frequency of tension-type headache (TTH), but its effectiveness relative to first-line drugs for TTH is unknown, which impedes the recommendation of acupuncture for patients who are intolerant to drugs for TTH. We aimed to estimate the relative effectiveness between acupuncture and tricyclic antidepressants (TCAs) through indirect treatment comparison (ITC) meta-analysis.
METHODS
We searched Ovid Medline, Embase, and Cochrane Library from database inception until April 13, 2023. Randomized controlled trials of TCAs or acupuncture in the prevention of TTH in adults were included. The primary outcome was headache frequency. The secondary outcomes were headache intensity, responder rate, and adverse event rate. Bayesian random-effect models were used to perform ITC meta-analysis, and confidence of evidence was evaluated by using the GRADE approach.
RESULTS
A total of 34 trials involving 4426 participants were included. Acupuncture had similar effect with TCAs in decreasing TTH frequency (amitriptyline: mean difference [MD] -1.29, 95% CI -5.28 to 3.02; amitriptylinoxide: MD -0.05, 95% CI -6.86 to 7.06) and reducing TTH intensity (amitriptyline: MD 2.35, 95% CI -1.20 to 5.78; clomipramine: MD 1.83, 95% CI -4.23 to 8.20). Amitriptyline had a higher rate of adverse events than acupuncture (OR 4.73, 95% CI 1.42 to 14.23).
CONCLUSION
Acupuncture had similar effect as TCAs in reducing headache frequency of TTH, and acupuncture had a lower adverse events rate than amitriptyline, as shown by very low certainty of evidence.
Topics: Humans; Tension-Type Headache; Antidepressive Agents, Tricyclic; Acupuncture Therapy; Randomized Controlled Trials as Topic
PubMed: 38679721
DOI: 10.1186/s10194-024-01776-5 -
Annales de Dermatologie Et de... Jun 2024Vestibulodynia is a highly prevalent chronic pain disorder affecting the vulva having a major impact on women's physical, psychological, and sexual well-being. It...
Vestibulodynia: Clinical characteristics, first-line treatments, and factors associated with escalation of treatment with EMG-guided injections of botulinum toxin in a retrospective french cohort study.
BACKGROUND
Vestibulodynia is a highly prevalent chronic pain disorder affecting the vulva having a major impact on women's physical, psychological, and sexual well-being. It remains an underrecognized disease that responds insufficiently to therapies such as physiotherapy and medication.
AIM
To assess the global efficacy of first-line therapies and factors associated with treatment escalation in women with vestibulodynia.
PATIENTS AND METHODS
This retrospective cohort study was conducted at the dermatology outpatient clinic of the University Hospital in Besancon (France) between 2013 and 2017 and follow-up until 2021.
RESULTS
Among 132 patients, the mean [standard deviation] age at diagnosis was 27.2 [±9.45] years, with an average duration of symptoms of 42.3 [±37.92] months. Most cases comprised provoked (75.0%) or secondary (72.7%) vestibulodynia. At least one comorbid pain or psychologic condition was identified respectively in 63 (47.7%) and 23 patients (54.5%). Vulvar hyperesthesia associated with pelvic floor muscle dysfunction was present in 121 patients (91.6%) and vulvar erethism was noted in 94 patients (71.2%). First-line treatments consisted of pelvic floor physiotherapy with biofeedback in 85% of patients, associated with amitriptyline in 36% of cases, and of additional lidocaine cream in 17%. Fifty-two patients (39%) presented at least a good response to first-line treatment, with only 21 (15%) being in complete remission, irrespective of therapeutic strategy (p = 0.25). Botulinum toxin injections were performed in 54 patients. Patients with either primary vestibulodynia (p = 0.04) or spontaneous vestibulodynia (p = 0.03) were more likely to receive this treatment.
CONCLUSION
Our study highlights the current lack of efficacy of first-line treatments in vestibulodynia. Considering the high prevalence of muscular dysfunction, botulinum toxin injections are of particular interest despite a lack of randomized controlled trials in this indication.
Topics: Humans; Female; Retrospective Studies; Vulvodynia; Adult; France; Botulinum Toxins, Type A; Electromyography; Young Adult; Neuromuscular Agents; Middle Aged; Chronic Pain; Treatment Outcome; Lidocaine; Adolescent
PubMed: 38678773
DOI: 10.1016/j.annder.2024.103277 -
Frontiers in Neurology 2024Vestibular migraine (VM) is a newly defined clinical condition. Several vestibular abnormalities have been reported in patients with VM. However, to date, no specific...
INTRODUCTION
Vestibular migraine (VM) is a newly defined clinical condition. Several vestibular abnormalities have been reported in patients with VM. However, to date, no specific vestibular examinations are used to define VM. Therefore, the utility of vestibular examinations is limited. Currently, the role of vestibular examination has not been clearly defined. We speculated that the results of vestibular examinations could predict the prognosis of VM. We investigated the relationship between the vestibular examination results and clinical outcomes in patients with VM.
METHODS
This study included 25 patients with VM. Vestibular examinations, including the video head impulse test (V-HIT), cervical and ocular vestibular evoked myogenic potential (c-VEMP and o-VEMP), posturography, and several questionnaires, including the Dizziness Handicap Inventory (DHI), were conducted at the initial evaluation. Lifestyle modifications for VM and conventional pharmacological prophylactic treatments, including lomerizine, amitriptyline, and valproic acid, were performed. After 4 weeks of treatment, clinical improvements were evaluated using the Clinical Global Improvement Scale (CGI-s). The relationships among the CGI-S score, several clinical variables, and the results of several vestibular examinations were evaluated. Each patient was further classified into two subgroups according to treatment outcomes concerning vertigo and headache: CGI-S score from 0 to 2 (good response [GR]) and CGI-S score > 3 (poor response [PR]).
RESULTS
Overall, after treatment, most of the patients had improved dizziness and headache, and the CGI-s was 2.7 ± 1.3. There were 12 GRs, and 13 had PRs. Thus, neither V-HIT nor posturography predicted the prognosis. For c-VEMP, patients with GRs had significantly small AR concerning PR (19.2 ± 12.8 and 62.5 ± 42.5, respectively, [ < 0.01]). There were five normal, six unilateral, and 14 bilateral no response in 500hz o-VEMP. CGI-s of normal, unilateral, and bilateral no response was 1.4 ± 0.5, 2.8 ± 1.3, and 3.1 ± 1.2, respectively. There was a statistically significant difference between the normal and bilateral non-response o-VEMP groups ( < 0.05).
CONCLUSION
Patients with VM had improvements in both headache and vertigo through a combination of lifestyle changes and prophylactic medications. Vestibular examinations, especially o- or c-VEMP, are beneficial for predicting the treatment outcomes of VM. The pathophysiology of VM is closely related to vestibular abnormalities, particularly the otolith-related pathways.
PubMed: 38660093
DOI: 10.3389/fneur.2024.1370940 -
Urologiia (Moscow, Russia : 1999) Mar 2024To assess the quality of life of patients with interstitial cystitis (IC) and to study effective options used to control symptoms on outpatient basis.
AIM
To assess the quality of life of patients with interstitial cystitis (IC) and to study effective options used to control symptoms on outpatient basis.
MATERIALS AND METHODS
The results of a descriptive prospective cross-sectional cohort study are presented. The medical charts of patients who were treated in the City Clinical Hospital named after Spasokukotsky from 2021 to 2023 were analyzed. Eighty inpatient medical charts of various patients with a final diagnosis of IC with Hunner's lesion were identified. Only 53 patients were interviewed due to the inclusion/exclusion criteria. Respondents were asked to complete a survey consisting of 15 questions. The survey was carried out online for patients who did not require surgical treatment at the time of the study, and offline for patients admitted for repeated surgical treatment.
RESULTS
The average age of respondents was 59.011.1 years. 58% (31) of patients noted the presence of constant pain in the pelvic area during the day, while 85% (45) of patients reported pain outside the bladder area, in the urethra and perineum. The intensity of pain in the pelvic area was 4.9 (2.3-5.6) points. Higher pain scores 6.24 (5.8-9.0) were observed in 47% (25) of patients admitted for repeat surgical treatment. 62% (33) of patients had a titer of bacteria in a urine test above 104, while 51% (27) of patients experienced relief of symptoms after taking antibacterial drugs. For the treatment and symptomatic relief, the following are most often used: pentosan sodium polysulfate (26%, n=14), antibacterial drugs of the nitrofuran group (25%, n=13), amitriptyline (15%, n=8), non-steroidal anti-inflammatory drugs (11%, n=6) patients. 23% (12) of respondents received intravesical therapy. The time from the onset of symptoms to the final diagnosis was 48 (24-96) months.
CONCLUSIONS
Although infection is a criterion for excluding the diagnosis of IC, more than 62% of patients have positive urine culture. The results obtained indicate the need to improve existing approaches to the diagnosis of IC, as well as to develop treatment algorithms for painful bladder syndrome to control symptoms.
Topics: Humans; Cystitis, Interstitial; Middle Aged; Quality of Life; Cross-Sectional Studies; Female; Male; Aged; Prospective Studies; Adult; Cohort Studies; Ambulatory Care
PubMed: 38650399
DOI: No ID Found -
Biochemistry. Biokhimiia Mar 2024Some tricyclic antidepressants (TCAs), including amitriptyline (ATL), clomipramine (CLO), and desipramine (DES), are known to be effective for management of neuropathic...
Some tricyclic antidepressants (TCAs), including amitriptyline (ATL), clomipramine (CLO), and desipramine (DES), are known to be effective for management of neuropathic pain. It was previously determined that ATL, CLO, and DES are capable of voltage-dependent blocking of NMDA receptors of glutamate (NMDAR), which play a key role in pathogenesis of neuropathic pain. Despite the similar structure of ATL, CLO, and DES, efficacy of their interaction with NMDAR varies significantly. In the study presented here, we applied molecular modeling methods to investigate the mechanism of binding of ATL, CLO, and DES to NMDAR and to identify structural features of the drugs that determine their inhibitory activity against NMDAR. Molecular docking of the studied TCAs into the NMDAR channel was performed. Conformational behavior of the obtained complexes in the lipid bilayer was simulated by the method of molecular dynamics (MD). A single binding site (upper) for the tertiary amines ATL and CLO and two binding sites (upper and lower) for the secondary amine DES were identified inside the NMDAR channel. The upper and lower binding sites are located along the channel axis at different distances from the extracellular side of the plasma membrane. MD simulation revealed that the position of DES in the lower site is stabilized only in the presence of sodium cation inside the NMDAR channel. DES binds more strongly to NMDAR compared to ATL and CLO due to simultaneous interaction of two hydrogen atoms of its cationic group with the asparagine residues of the ion pore of the receptor. This feature may be responsible for the stronger side effects of DES. It has been hypothesized that ATL binds to NMDAR less efficiently compared to DES and CLO due to its lower conformational mobility. The identified features of the structure- and cation-dependent mechanism of interaction between TCAs and NMDAR will help in the further development of effective and safe analgesic therapy.
Topics: Receptors, N-Methyl-D-Aspartate; Antidepressive Agents, Tricyclic; Molecular Docking Simulation; Molecular Dynamics Simulation; Binding Sites; Amitriptyline; Humans; Clomipramine; Cations; Desipramine; Protein Binding
PubMed: 38648769
DOI: 10.1134/S0006297924030106 -
Headache May 2024In this retrospective cross-sectional real-world evidence study from the Danish Headache Center (DHC), a national tertiary headache center in Denmark, we sought to...
OBJECTIVE
In this retrospective cross-sectional real-world evidence study from the Danish Headache Center (DHC), a national tertiary headache center in Denmark, we sought to identify potential pharmacological agents for the treatment of new daily persistent headache (NDPH).
BACKGROUND
NDPH is an enigmatic headache disorder with abrupt onset and chronic duration for which evidence-based treatments are lacking. NDPH is a diagnosis of exclusion, for which secondary headaches must be ruled out and the etiology remains idiopathic. The sparse investigations of this disorder have not yielded a pathophysiological basis and no effective treatment for NDPH has been found.
METHODS
All patients with an NDPH diagnosis at the DHC were enrolled (n = 64). First, we reviewed the records of all patients with an NDPH diagnosis to evaluate whether they fulfilled the diagnostic criteria. Next, we extracted all the trialled acute and prophylactic pharmacological interventions for the included patients. Then, pharmacological interventions that had been tried in ≥ 20 patients were analyzed post hoc with efficacy as the outcome, which was stratified in five effect categories ("no effect," "partial effect," "full effect," "partial effect and cessation due to adverse events," and "full effect and cessation due to adverse events"). Descriptive statistical analysis was performed, and the results were schematically presented (see Table 2).
RESULTS
Fifty-one patients out of 64 were found to fulfill NDPH criteria and were included in the study. The drugs tried by ≥ 20 patients were amitriptyline (n = 34), candesartan (n = 27), and mirtazapine (n = 20). No patients experienced a complete effect with these drugs while 9% (3/34), 26% (7/27), and 15% (3/20) experienced a partial effect with no adverse events that led to treatment discontinuation, respectively. The remaining patients experienced either no effect or a partial effect with adverse events leading to treatment discontinuation.
CONCLUSION
In this study we add real-world evidence to suggest that prophylactic drugs conventionally used for treating chronic migraine and chronic tension-type headache have limited utility for treating NDPH; however, a partial response in 26% of patients using candesartan and 15% of patients using mirtazapine warrants further investigation in randomized double-blinded placebo-controlled trials.
Topics: Humans; Retrospective Studies; Female; Male; Middle Aged; Headache Disorders; Adult; Tertiary Care Centers; Cross-Sectional Studies; Denmark; Aged
PubMed: 38646979
DOI: 10.1111/head.14715 -
BMJ Neurology Open 2024Migraine is the second most common prevalent disorder worldwide and is a top cause of disability with a substantial economic burden. Many preventive migraine medications...
BACKGROUND
Migraine is the second most common prevalent disorder worldwide and is a top cause of disability with a substantial economic burden. Many preventive migraine medications have notable side effects that affect different body organs.
METHOD
We systematically searched for published randomised controlled trials (RCTs) using terms for migraine/headache and preventive medications. Using eligibility criteria, two reviewers independently assessed the articles. Cochrane risk-of-bias tool was applied to assess the quality of the studies. Data were classified by system organ class (SOC).
RESULTS
Thirty-two RCTs with 21 780 participants met the eligibility criteria for the incidence of adverse events (AEs). Additionally, 33 RCTs with 22 615 participants were included to synthesise the incidence of serious AEs (SAEs). The percentage of attributed AEs and SAEs to each SOC for 10 preventive drugs with different dosing regimens was calculated. Amitriptyline and topiramate had a higher incidence of nervous system disorders; Topiramate was also associated with a higher incidence of psychiatric disorders. All drugs showed a certain incidence of infections and infestations, with Onabotulinumtoxin A (BTA) having the lowest rate. BTA had a higher incidence of musculoskeletal disorders than the other drugs. Calcitonin gene-related peptide (CGRP) monoclonal antibodies (MAbs) such as fremanezumab and galcanezumab were linked to more general disorders and administration site conditions than other drugs.
CONCLUSION
Notably, the observed harm to SOCs varies among these preventive drugs. We suggest conducting head-to-head RCTs to evaluate the safety profile of oral medications, BTA, and CGRP MAbs in episodic and/or chronic migraine populations.
PROSPERO REGISTRATION NUMBER
CRD42021265993.
PubMed: 38646505
DOI: 10.1136/bmjno-2023-000616 -
Cephalalgia : An International Journal... Apr 2024Pediatric migraine prophylaxis is indicated when headaches are frequent and/or disabling. We aimed to conduct a study to compare the efficacy of cinnarizine and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Pediatric migraine prophylaxis is indicated when headaches are frequent and/or disabling. We aimed to conduct a study to compare the efficacy of cinnarizine and amitriptyline in pediatric migraine prophylaxis.
METHODS
In a randomized, double-blind trial, patients aged 4-17 years with migraine who were eligible for prophylaxis enrolled. The primary outcome was a reduction response rate of ≥50% with < 0.005 with respect to headache characteristics. The secondary outcome was migraine disability assessment. We evaluated patients every four weeks for three months: T1: week 4, T2: week 8 and T3: week 12. The safety profile was also assessed.
RESULTS
Thirty patients were randomly assigned to each group. However, 43 patients completed the trial. Headache frequency decreased in amitriptyline group more effectively in T1 ( = 0.004). Amitriptyline was more successful in reducing the headache duration in all three periods ( < 0.005). There was no significant difference in severity improvement and reducing disability score between the two groups ( > 0.005). No serious adverse events were observed.
CONCLUSIONS
Both medications are effective in ameliorating migraine headaches and related disabilities. However, amitriptyline appears be a preferable option over cinnarizine, given its faster onset of action, efficacy in reducing headache duration and longer-lasting effects. The study was registered with the Iranian Registry of Clinical Trials (IRCT) under the code IRCT-20191112045413N1.
Topics: Humans; Child; Cinnarizine; Amitriptyline; Iran; Treatment Outcome; Migraine Disorders; Headache; Analgesics; Double-Blind Method
PubMed: 38641932
DOI: 10.1177/03331024241230963 -
Brain, Behavior, and Immunity Jul 2024Vestibulodynia is a complex pain disorder characterized by chronic discomfort in the vulvar region, often accompanied by tactile allodynia and spontaneous pain. In...
Vestibulodynia is a complex pain disorder characterized by chronic discomfort in the vulvar region, often accompanied by tactile allodynia and spontaneous pain. In patients a depressive behaviour is also observed. In this study, we have used a model of vestibulodynia induced by complete Freund's adjuvant (CFA) focusing our investigation on the spinal cord neurons and microglia. We investigated tactile allodynia, spontaneous pain, and depressive-like behavior as key behavioral markers of vestibulodynia. In addition, we conducted in vivo electrophysiological recordings to provide, for the first time to our knowledge, the characterization of the spinal sacral neuronal activity in the L6-S1 dorsal horn of the spinal cord. Furthermore, we examined microglia activation in the L6-S1 dorsal horn using immunofluorescence, unveiling hypertrophic phenotypes indicative of neuroinflammation in the spinal cord. This represents a novel insight into the role of microglia in vestibulodynia pathology. To address the therapeutic aspect, we employed pharmacological interventions using GABApentin, amitriptyline, and PeaPol. Remarkably, all three drugs, also used in clinic, showed efficacy in alleviating tactile allodynia and depressive-like behavior. Concurrently, we also observed a normalization of the altered neuronal firing and a reduction of microglia hypertrophic phenotypes. In conclusion, our study provides a comprehensive understanding of the CFA-induced model of vestibulodynia, encompassing behavioral, neurophysiological and neuroinflammatory aspects. These data pave the way to investigate spinal cord first pain plasticity in vestibulodynia.
Topics: Animals; Disease Models, Animal; Spinal Cord; Freund's Adjuvant; Mice; Hyperalgesia; Vulvodynia; Female; Microglia; Neurons; Neuroinflammatory Diseases; Gabapentin; Amitriptyline; Depression; Mice, Inbred C57BL
PubMed: 38636564
DOI: 10.1016/j.bbi.2024.04.012