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The Journal of Headache and Pain Oct 2022Multiple clinical trials with different exercise protocols have demonstrated efficacy in the management of migraine. However, there is no head-to-head comparison of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple clinical trials with different exercise protocols have demonstrated efficacy in the management of migraine. However, there is no head-to-head comparison of efficacy between the different exercise interventions.
METHODS
A systematic review and network meta-analysis was performed involving all clinical trials which determined the efficacy of exercise interventions in reducing the frequency of monthly migraine. Medical journal search engines included Web of Science, PubMed, and Scopus spanning all previous years up to July 30, 2022. Both aerobic and strength/resistance training protocols were included. The mean difference (MD, 95% confidence interval) in monthly migraine frequency from baseline to end-of-intervention between the active and control arms was used as an outcome measure. Efficacy evidence from direct and indirect comparisons was combined by conducting a random effects model network meta-analysis. The efficacy of the three exercise protocols was compared, i.e., moderate-intensity aerobic exercise, high-intensity aerobic exercise, and strength/resistance training. Studies that compared the efficacy of migraine medications (topiramate, amitriptyline) to exercise were included. Additionally, the risk of bias in all included studies was assessed by using the Cochrane Risk of Bias version 2 (RoB2).
RESULTS
There were 21 published clinical trials that involved a total of 1195 migraine patients with a mean age of 35 years and a female-to-male ratio of 6.7. There were 27 pairwise comparisons and 8 indirect comparisons. The rank of the interventions was as follows: strength training (MD = -3.55 [- 6.15, - 0.95]), high-intensity aerobic exercise (-3.13 [-5.28, -0.97]), moderate-intensity aerobic exercise (-2.18 [-3.25, -1.11]), topiramate (-0.98 [-4.16, 2.20]), placebo, amitriptyline (3.82 [- 1.03, 8.68]). The RoB2 assessment showed that 85% of the included studies demonstrated low risk of bias, while 15% indicated high risk of bias for intention-to-treat analysis. Sources of high risk of bias include randomization process and handling of missing outcome data.
CONCLUSION
Strength training exercise regimens demonstrated the highest efficacy in reducing migraine burden, followed by high-intensity aerobic exercise.
Topics: Adult; Amitriptyline; Exercise; Female; Humans; Male; Migraine Disorders; Network Meta-Analysis; Resistance Training; Topiramate
PubMed: 36229774
DOI: 10.1186/s10194-022-01503-y -
Lancet (London, England) Nov 2023Most 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... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
BACKGROUND
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.
METHODS
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.
FINDINGS
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.
INTERPRETATION
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.
FUNDING
National Institute for Health and Care Research Health Technology Assessment Programme (grant reference 16/162/01).
Topics: Humans; Male; Female; Middle Aged; Irritable Bowel Syndrome; Amitriptyline; England; Double-Blind Method; Primary Health Care; Treatment Outcome
PubMed: 37858323
DOI: 10.1016/S0140-6736(23)01523-4 -
The Journal of Headache and Pain May 2023While there are several trials that support the efficacy of various drugs for migraine prophylaxis against placebo, there is limited evidence addressing the comparative... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
While there are several trials that support the efficacy of various drugs for migraine prophylaxis against placebo, there is limited evidence addressing the comparative safety and efficacy of these drugs. We conducted a systematic review and network meta-analysis to facilitate comparison between drugs for migraine prophylaxis.
METHODS
We searched MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov from inception to August 13, 2022, for randomized trials of pharmacological treatments for migraine prophylaxis in adults. Reviewers worked independently and in duplicate to screen references, extract data, and assess risk of bias. We performed a frequentist random-effects network meta-analysis and rated the certainty (quality) of evidence as either high, moderate, low, or very low using the GRADE approach.
RESULTS
We identified 74 eligible trials, reporting on 32,990 patients. We found high certainty evidence that monoclonal antibodies acting on the calcitonin gene related peptide or its receptor (CGRP(r)mAbs), gepants, and topiramate increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo. We found moderate certainty evidence that beta-blockers, valproate, and amitriptyline increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, and low certainty evidence that gabapentin may not be different from placebo. We found high certainty evidence that, compared to placebo, valproate and amitriptyline lead to substantial adverse events leading to discontinuation, moderate certainty evidence that topiramate, beta-blockers, and gabapentin increase adverse events leading to discontinuation, and moderate to high certainty evidence that (CGRP(r)mAbs) and gepants do not increase adverse events.
CONCLUSIONS
(CGRP(r)mAbs) have the best safety and efficacy profile of all drugs for migraine prophylaxis, followed closely by gepants.
Topics: Adult; Humans; Topiramate; Valproic Acid; Gabapentin; Calcitonin Gene-Related Peptide; Network Meta-Analysis; Amitriptyline; Antibodies, Monoclonal; Migraine Disorders
PubMed: 37208596
DOI: 10.1186/s10194-023-01594-1 -
JAMA Network Open May 2022Amitriptyline is an established medication used off-label for the treatment of fibromyalgia, but pregabalin, duloxetine, and milnacipran are the only pharmacological... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Amitriptyline is an established medication used off-label for the treatment of fibromyalgia, but pregabalin, duloxetine, and milnacipran are the only pharmacological agents approved by the US Food and Drug Administration (FDA) to treat fibromyalgia.
OBJECTIVE
To investigate the comparative effectiveness and acceptability associated with pharmacological treatment options for fibromyalgia.
DATA SOURCES
Searches of PubMed/MEDLINE, Cochrane Library, Embase, and Clinicaltrials.gov were conducted on November 20, 2018, and updated on July 29, 2020.
STUDY SELECTION
Randomized clinical trials (RCTs) comparing amitriptyline or any FDA-approved doses of investigated drugs.
DATA EXTRACTION AND SYNTHESIS
This study follows the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Four independent reviewers extracted data using a standardized data extraction sheet and assessed quality of RCTs. A random-effects bayesian network meta-analysis (NMA) was conducted. Data were analyzed from August 2020 to January 2021.
MAIN OUTCOMES AND MEASURES
Comparative effectiveness and acceptability (defined as discontinuation of treatment owing to adverse drug reactions) associated with amitriptyline (off-label), pregabalin, duloxetine, and milnacipran (on-label) in reducing fibromyalgia symptoms. The following doses were compared: 60-mg and 120-mg duloxetine; 150-mg, 300-mg, 450-mg, and 600-mg pregabalin; 100-mg and 200-mg milnacipran; and amitriptyline. Effect sizes are reported as standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes with 95% credible intervals (95% CrIs). Findings were considered statistically significant when the 95% CrI did not include the null value (0 for SMD and 1 for OR). Relative treatment ranking using the surface under the cumulative ranking curve (SUCRA) was also evaluated.
RESULTS
A total of 36 studies (11 930 patients) were included. The mean (SD) age of patients was 48.4 (10.4) years, and 11 261 patients (94.4%) were women. Compared with placebo, amitriptyline was associated with reduced sleep disturbances (SMD, -0.97; 95% CrI, -1.10 to -0.83), fatigue (SMD, -0.64; 95% CrI, -0.75 to -0.53), and improved quality of life (SMD, -0.80; 95% CrI, -0.94 to -0.65). Duloxetine 120 mg was associated with the highest improvement in pain (SMD, -0.33; 95% CrI, -0.36 to -0.30) and depression (SMD, -0.25; 95% CrI, -0.32 to -0.17) vs placebo. All treatments were associated with inferior acceptability (higher dropout rate) than placebo, except amitriptyline (OR, 0.78; 95% CrI, 0.31 to 1.66). According to the SUCRA-based relative ranking of treatments, duloxetine 120 mg was associated with higher efficacy for treating pain and depression, while amitriptyline was associated with higher efficacy for improving sleep, fatigue, and overall quality of life.
CONCLUSIONS AND RELEVANCE
These findings suggest that clinicians should consider how treatments could be tailored to individual symptoms, weighing the benefits and acceptability, when prescribing medications to patients with fibromyalgia.
Topics: Amitriptyline; Duloxetine Hydrochloride; Fatigue; Female; Fibromyalgia; Humans; Male; Middle Aged; Milnacipran; Network Meta-Analysis; Pain; Pregabalin; United States; United States Food and Drug Administration
PubMed: 35587348
DOI: 10.1001/jamanetworkopen.2022.12939 -
European Journal of Investigation in... Aug 2023This review aimed to investigate the metabolic alterations associated with psychopharmacological treatment of neuropsychiatric disorders, which can significantly impact... (Review)
Review
This review aimed to investigate the metabolic alterations associated with psychopharmacological treatment of neuropsychiatric disorders, which can significantly impact patients' physical health and overall quality of life. The study utilized the PRISMA methodology and included cross-sectional, retrospective studies, and randomized clinical trials from reputable databases like SCOPUS, CLARIVATE, SCIENCE DIRECT, and PUBMED. Out of the 64 selected studies, various psychotropic drug classes were analyzed, including antidepressants, anticonvulsants, and antipsychotics. Among the antidepressants, such as amitriptyline, Imipramine, and clomipramine, weight gain, constipation, and cardiovascular effects were the most commonly reported metabolic adverse effects. SSRI antidepressants like Fluoxetine, Sertraline, Citalopram, Escitalopram, and Paroxetine exhibited a high prevalence of gastrointestinal and cardiac alterations. Regarding anticonvulsants, valproic acid and Fosphenytoin were associated with adverse reactions such as weight gain and disturbances in appetite and sleep patterns. As for antipsychotics, drugs like Clozapine, Olanzapine, and Risperidone were linked to weight gain, diabetes, and deterioration of the lipid profile. The findings of this review emphasize the importance of continuous monitoring for adverse effects, particularly considering that the metabolic changes caused by psychopharmacological medications may vary depending on the age of the patients. Future research should focus on conducting field studies to further expand knowledge on the metabolic effects of other commonly prescribed psychotropic drugs. Overall, the study highlights the significance of understanding and managing metabolic alterations induced by psychopharmacological treatment to enhance patient care and well-being.
PubMed: 37623307
DOI: 10.3390/ejihpe13080110 -
Schmerz (Berlin, Germany) Dec 2021Pregnancy and pain of different origins is an unfavorable combination that presents all practitioners with special challenges. Pain negatively affects the homeostasis of... (Review)
Review
BACKGROUND
Pregnancy and pain of different origins is an unfavorable combination that presents all practitioners with special challenges. Pain negatively affects the homeostasis of humans. Patient compliance and in-depth knowledge of the fetotoxicity and teratogenicity of the substances are necessary to maintain a balance between therapy for the mother and safety of the unborn child.
OBJECTIVES
Experts from various disciplines who are entrusted with the care of pregnant patients with pain have come together to develop drug and nondrug therapy concepts with the aim of providing adequate analgesia for pregnant pain patients.
MATERIALS AND METHODS
Relevant questions were formulated by experts and subjected to a literature search. Combined with further national and international recommendations, treatment concepts were developed and discussed in an interdisciplinary manner. Core statements were then drawn up and given recommendation grades.
RESULTS
Depending on the trimester, paracetamol, ibuprofen, diclofenac, metamizole, and opioids can be administered carefully in the event of pain; special care is required with nonsteroidal anti-inflammatory drugs (NSAIDs ) in the last trimester. COX‑2 inhibitors are not recommended. For neuropathic pain, amitriptyline, duloxetine, and venlafaxine are considered safe. Non-pharmacological treatment concepts are also available, namely transcutaneous electrical nerve stimulation (TENS therapy), kinesio tapes, and acupuncture. Lymphatic drainage is recommended in cases of edema, if not caused by preeclampsia.
CONCLUSIONS
A deliberated concept for pain therapy during pregnancy should be initiated with a non-pharmacological intervention and, if necessary, supplemented with pharmacological agents.
Topics: Acetaminophen; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Child; Consensus; Female; Humans; Neuralgia; Pain Management; Pregnancy
PubMed: 34324048
DOI: 10.1007/s00482-021-00571-4 -
World Journal of Psychiatry Jun 2023Available pharmacotherapies for autism spectrum disorders (ASD) are reviewed based on clinical and research experience, highlighting some older drugs with emerging... (Review)
Review
Available pharmacotherapies for autism spectrum disorders (ASD) are reviewed based on clinical and research experience, highlighting some older drugs with emerging evidence. Several medications show efficacy in ASD, though controlled studies in ASD are largely lacking. Only risperidone and aripiprazole have Federal Drug Administration approval in the United States. Methylphenidate (MPH) studies showed lower efficacy and tolerability for attention deficit hyperactivity disorder (ADHD) than in the typically developing (TD) population; atomoxetine demonstrated lower efficacy but comparable tolerability to TD outcomes. Guanfacine improved hyperactivity in ASD comparably to TD. Dex-troamphetamine promises greater efficacy than MPH in ASD. ADHD medications reduce impulsive aggression in youth, and may also be key for this in adults. Controlled trials of the selective serotonin reuptake inhibitors citalopram and fluoxetine demonstrated poor tolerability and lack of efficacy for repetitive behaviors. Trials of antiseizure medications in ASD remain inconclusive, however clinical trials may be warranted in severely disabled individuals showing bizarre behaviors. No identified drugs treat ASD core symptoms; oxytocin lacked efficacy. Amitriptyline and loxapine however, show promise. Loxapine at 5-10 mg daily resembled an atypical antipsychotic in positron emission tomography studies, but may be weight-sparing. Amitriptyline at approximately 1 mg/ kg/day used cautiously, shows efficacy for sleep, anxiety, impulsivity and ADHD, repetitive behaviors, and enuresis. Both drugs have promising neurotrophic properties.
PubMed: 37383284
DOI: 10.5498/wjp.v13.i6.262 -
The Journal of Pediatric Pharmacology... 2022Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder that can present quite a challenge to clinicians caring for children with this complex disease....
Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder that can present quite a challenge to clinicians caring for children with this complex disease. Different therapeutic interventions are recommended for prophylaxis and acute abortive therapy for a CVS attack. The aim of this review is to summarize therapeutic treatment recommendations from the 2008 North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHN) Consensus Statement on the Diagnosis and Management of Cyclic Vomiting Syndrome and discuss studies contemporary to this expert recommendation. After an extensive search of medical databases, 8 studies that evaluated therapeutic treatments for CVS were identified. Amitriptyline and cyproheptadine remain the standard of care for prophylaxis. Nutritional supplements such as carnitine and coenzyme Q10 have shown efficacy in decreasing episodes and severity in small studies with high tolerability among patients. The combination of ondansetron and sumatriptan are recommended for abortion of an acute vomiting episode, but other agents such as aprepitant and sedative agents can be considered when vomiting is refractory to initial treatments.
PubMed: 35002554
DOI: 10.5863/1551-6776-27.1.12 -
Neurologia Oct 2022Phantom limb pain (PLP) is a type of neuropathic pain that affects the territory of an amputated limb or other surgically removed body parts. Between 60% and 90% of... (Review)
Review
INTRODUCTION
Phantom limb pain (PLP) is a type of neuropathic pain that affects the territory of an amputated limb or other surgically removed body parts. Between 60% and 90% of amputees suffer from PLP during follow-up. There are a range of therapeutic options for PLP, both pharmacological (gabapentin, amitriptyline, tricyclic antidepressants, etc) and non-pharmacological (transcutaneous electrical nerve stimulation, hypnosis, acupuncture, etc). A widely accepted hypothesis considers PLP to be the consequence of postamputation cortical reorganisation. New treatment approaches, such as mirror therapy (MT), have been developed as a result of Ramachandran's groundbreaking research in the 1990s. This review analyses the current evidence on the efficacy of MT for treating PLP.
DEVELOPMENT
We performed a literature review of publications registered from 2012 to 2017 on the CINAHL, Cochrane, Scopus, and PubMed (including Medline) databases Using the descriptors "phantom limb‿ and "mirror therapy.‿ We identified 115 publications addressing MT in PLP. Of these, 17 (15%) contributed useful information for pooled analysis.
CONCLUSIONS
MT seems to be effective in relieving PLP, reducing the intensity and duration of daily pain episodes. It is a valid, simple, and inexpensive treatment for PLP. The methodological quality of most publications in this field is very limited, highlighting the need for additional, high-quality studies to develop clinical protocols that could maximise the benefits of MT for patients with PLP.
Topics: Humans; Phantom Limb; Mirror Movement Therapy; Amputees; Transcutaneous Electric Nerve Stimulation; Pain Management
PubMed: 30447854
DOI: 10.1016/j.nrl.2018.08.003 -
Cureus Jul 2023Chronic pain is a very common problem in patients with spinal cord injury (SCI) as it affects 80% of these patients, which negatively affects their quality of life.... (Review)
Review
Chronic pain is a very common problem in patients with spinal cord injury (SCI) as it affects 80% of these patients, which negatively affects their quality of life. Despite many advantages that exist in the management of any type of pain (neuropathic, nociceptive, mixed) in these patients, there is no cure, and the analgesic effect of some treatments is inadequate. This study aims to conduct an evidence-based systematic review regarding the various interventions used for the management of pain after SCI. The PubMed, Physiotherapy Evidence Database (PEDro), and Cochrane Library databases were searched from 1969 to 2023. The risk of bias was assessed using the PEDro scoring system. A total of 57 studies met the inclusion criteria and were included in this systematic review. Among the different interventions at present, 18 studies examined the role of oral medications, 11 studies examined the role of minimally invasive methods (injection and infusion), 16 studies investigated physiotherapy and alternative treatments, and 12 studies examined the role of repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and cranial electrotherapy stimulation (CES) in the management of pain in patients after SCI. Gabapentin and pregabalin are very effective in managing chronic neuropathic pain after SCI, and pregabalin also seems to reduce anxiety and sleep disturbances in the patients. It is noteworthy that lamotrigine, valproate, and carbamazepine do not have an analgesic effect, but mirogabalin is a novel and promising drug. Antidepressants (selective serotonin reuptake inhibitors and serotonin and noradrenaline reuptake inhibitors) did not reduce the pain of the patients, although some studies showed an efficacy of amitriptyline especially in depressed patients and tramadol should be considered short-term with caution. Also, tDCS and rTMS reduced pain. Moreover, botulinum toxin type A, lidocaine, ketamine, and intrathecal baclofen significantly reduced pain intensity, although the sample of the studies was small. Physiotherapy and alternative treatments seem to relieve pain, and transcutaneous electrical nerve stimulation had the greatest reduction of pain intensity. In conclusion, several pharmaceutical and non-pharmaceutical methods exist, which can reduce pain in patients after SCI. The type of intervention can be considered by the physician depending on the patients' preference, age, medical history, type of pain, and associated symptoms. However, more studies with greater samples and with better methodological quality should be conducted.
PubMed: 37644939
DOI: 10.7759/cureus.42657