-
The Cochrane Database of Systematic... Feb 2018Fibromyalgia is a chronic widespread pain condition affecting millions of people worldwide. Current pharmacotherapies are often ineffective and poorly tolerated.... (Review)
Review
BACKGROUND
Fibromyalgia is a chronic widespread pain condition affecting millions of people worldwide. Current pharmacotherapies are often ineffective and poorly tolerated. Combining different agents could provide superior pain relief and possibly also fewer side effects.
OBJECTIVES
To assess the efficacy, safety, and tolerability of combination pharmacotherapy compared to monotherapy or placebo, or both, for the treatment of fibromyalgia pain in adults.
SEARCH METHODS
We searched CENTRAL, MEDLINE, and Embase to September 2017. We also searched reference lists of other reviews and trials registries.
SELECTION CRITERIA
Double-blind, randomised controlled trials comparing combinations of two or more drugs to placebo or other comparators, or both, for the treatment of fibromyalgia pain.
DATA COLLECTION AND ANALYSIS
From all studies, we extracted data on: participant-reported pain relief of 30% or 50% or greater; patient global impression of clinical change (PGIC) much or very much improved or very much improved; any other pain-related outcome of improvement; withdrawals (lack of efficacy, adverse events), participants experiencing any adverse event, serious adverse events, and specific adverse events (e.g. somnolence and dizziness). The primary comparison was between combination and one or all single-agent comparators. We also assessed the evidence using GRADE and created a 'Summary of findings' table.
MAIN RESULTS
We identified 16 studies with 1474 participants. Three studies combined a non-steroidal anti-inflammatory drug (NSAID) with a benzodiazepine (306 participants); two combined amitriptyline with fluoxetine (89 participants); two combined amitriptyline with a different agent (92 participants); two combined melatonin with an antidepressant (164 participants); one combined carisoprodol, paracetamol (acetaminophen), and caffeine (58 participants); one combined tramadol and paracetamol (acetaminophen) (315 participants); one combined malic acid and magnesium (24 participants); one combined a monoamine oxidase inhibitor with 5-hydroxytryptophan (200 participants); and one combined pregabalin with duloxetine (41 participants). Six studies compared the combination of multiple agents with each component alone and with inactive placebo; three studies compared combination pharmacotherapy with each individual component but did not include an inactive placebo group; two studies compared the combination of two agents with only one of the agents alone; and three studies compared the combination of two or more agents only with inactive placebo.Heterogeneity among studies in terms of class of agents evaluated, specific combinations used, outcomes reported, and doses given prevented any meta-analysis. None of the combinations of drugs found provided sufficient data for analysis compared with placebo or other comparators for our preferred outcomes. We therefore provide a narrative description of results. There was no or inadequate evidence in any comparison for primary and secondary outcomes. Two studies only reported any primary outcomes of interest (patient-reported pain relief of 30%, or 50%, or greater). For each 'Risk of bias' item, only half or fewer of studies had unequivocal low risk of bias. Small size and selective reporting were common as high risk of bias.Our GRADE assessment was therefore very low for primary outcomes of pain relief of 30% or 50% or greater, PGIC much or very much improved or very much improved, any pain-related outcome, participants experiencing any adverse event, any serious adverse event, or withdrawing because of an adverse event.Three studies found some evidence that combination pharmacotherapy reduced pain compared to monotherapy; these trials tested three different combinations: melatonin and amitriptyline, fluoxetine and amitriptyline, and pregabalin and duloxetine. Adverse events experienced by participants were not serious, and where they were reported (in 12 out of 16 studies), all participants experienced them, regardless of treatment. Common adverse events were nausea, dizziness, somnolence, and headache.
AUTHORS' CONCLUSIONS
There are few, large, high-quality trials comparing combination pharmacotherapy with monotherapy for fibromyalgia, consequently limiting evidence to support or refute the use of combination pharmacotherapy for fibromyalgia.
Topics: 5-Hydroxytryptophan; Acetaminophen; Adult; Amitriptyline; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Benzodiazepines; Carisoprodol; Drug Therapy, Combination; Duloxetine Hydrochloride; Fibromyalgia; Fluoxetine; Humans; Magnesium; Malates; Melatonin; Monoamine Oxidase Inhibitors; Muscle Relaxants, Central; Pregabalin; Randomized Controlled Trials as Topic
PubMed: 29457627
DOI: 10.1002/14651858.CD010585.pub2 -
The Clinical Journal of Pain Nov 2016To systematically review the evidence for duloxetine in the management of painful diabetic neuropathy (PDN). (Review)
Review
OBJECTIVE
To systematically review the evidence for duloxetine in the management of painful diabetic neuropathy (PDN).
METHODS
Electronic searches of Medline and PubMed were performed from 2005 till October 2015 using medical subject headings and free-text words. Two independent reviewers extracted the data and assessed the methodological quality of the selected studies.
RESULTS
Twenty-three studies met our inclusion criteria and 8 were considered of high quality and were included to this review. Because of heterogeneity of the studies included in this review, statistical pooling of the data was not possible. We found good evidence for use of duloxetine in PDN over placebo and pregabalin but there was no benefit of duloxetine over amitriptyline.
CONCLUSIONS
Duloxetine has a beneficial effect over placebo. Nevertheless, the evidence of superiority of duloxetine over pregabalin and amitriptyline should be explored further as there was only 1 trial for each category. Provided majority of the PDN patients share cardiovascular complications, use of duloxetine will be a good option for treating pain associated with PDN over amitriptyline. Future randomized controlled trials should be designed keeping this in mind.
Topics: Analgesics; Diabetic Neuropathies; Duloxetine Hydrochloride; Humans; Neuralgia; Randomized Controlled Trials as Topic
PubMed: 26710221
DOI: 10.1097/AJP.0000000000000343 -
Turkish Journal of Anaesthesiology and... Aug 2022Intraoperative shivering is quite common after regional anaesthesia, which not only increases the total body oxygen requirement but also causes discomfort to the...
Pharmacological Interventions for the Treatment and Control of Shivering in Adult Patients Undergoing Elective Surgery Under Regional Anaesthesia: A Systematic Review and Meta-Analysis.
Intraoperative shivering is quite common after regional anaesthesia, which not only increases the total body oxygen requirement but also causes discomfort to the patients. The aim of this systematic review is to determine the effectiveness of pharmacological agents administered intra-operatively for treating shivering in adult patients who are undergoing elective surgery under regional (i.e., central neuraxial) anaesthesia so that an optimal choice of an agent can be recommended for clinical application. A literature search was carried out using PubMed, Cochrane Library, CINAHL databases, and hand searches to identify relevant studies. After literature screening and information extraction, a systematic review was performed. Meta-analysis was performed for the primary outcome. The primary outcome was to evaluate the effectiveness of pharmacological agents used for the treatment and control of intraoperative shivering and the time taken to control shivering. The secondary outcome includes recurrence of shivering after pharmacological intervention and identification of common adverse effects related to them. In total, 10 studies (791 patients) were included. Common interventions were opioids, central α2 receptor agonist, and few other medications like magnesium sulfate, ondansetron, nefopam, and amitriptyline. Tramadol and dexmedetomidine were the most frequently documented drugs compared with other drugs to resolve shivering. The most effective drug with approximately 100% response rate was dexmedetomidine with the dose of 0.5 μg kg-1 intravenously given just after the appearance of shivering. Studies showed that tramadol is also an effective drug used to control shivering in most patients, and its effect is comparable with the pethidine.
PubMed: 35979970
DOI: 10.5152/TJAR.2021.20008 -
Progress in Brain Research 2020Visual snow syndrome is a debilitating disorder characterized by tiny flickering dots (like TV static) in the entire visual field and a set of accompanying visual...
BACKGROUND
Visual snow syndrome is a debilitating disorder characterized by tiny flickering dots (like TV static) in the entire visual field and a set of accompanying visual (palinopsia, enhanced entoptic phenomena, photophobia, nyctalopia), nonvisual (e.g. tinnitus) and nonperceptional (e.g. concentration problems, irritability) symptoms. Its pathophysiology is enigmatic and therapy is often frustrating.
OBJECTIVES
To summarize our current understanding of pathophysiology and treatment of visual snow syndrome.
METHODS
A systematic search of PubMed database was performed using the key word "visual snow" and predefined in- and exclusion criteria. The results were stratified into "treatment" and "pathophysiology." Additionally, we conducted a search with the key words "persistent migraine aura" and "persistent visual aura" and screened for mis-diagnosed patients actually fulfilling the criteria for visual snow syndrome. The reference lists of most publications and any other relevant articles known to the authors were also reviewed and added if applicable.
RESULTS
From the 50 original papers found by searching for "visual snow," 21 were included according to the inclusion and exclusion criteria. Additional four publications came searching for "persistent migraine aura" or "persistent visual aura." Further publications derived from literature references resulting in a total of 20 articles for pathophysiology and 15 for treatment with some overlaps. Regarding pathophysiology, hyperexcitability of the visual cortex and a processing problem of higher order visual function are assumed, but the location is still in discussion. In particular, it is unclear if the primary visual cortex, the visual association cortex or the thalamocortical pathway is involved. Regarding treatment, data is available on a total of 153 VSS patients with medication mentioned for 54 resulting in a total of 136 trials. From the 44 different medications tried, only eight were effective at least once. The best data is available for lamotrigine being effective in 8/36 (22.2%, including one total response and no worsening), followed by topiramate being effective in 2/13 (15.4%, no total response and one worsening). The only other medication resulting in worsening of VSS was amitriptyline according to our literature review. The others reported to be effective at least once were valproate, propranolol, verapamil, baclofen, naproxen and sertraline. The nonpharmacological approach using color filters of the yellow-blue color spectrum might also be helpful in some patients.
CONCLUSIONS
Visual snow syndrome is still far from being fully understood. In respect of pathophysiology, a disorder of visual processing is likely. The best pharmacological evidence exists for lamotrigine, which can be discussed off-label. As nonpharmacological option, patients might benefit from tinted glasses for everyday use.
Topics: Humans; Migraine with Aura; Vision Disorders
PubMed: 33008511
DOI: 10.1016/bs.pbr.2020.05.020 -
BMJ Clinical Evidence Jan 2007Chronic tension-type headache (CTTH) is a disorder that evolves from episodic tension-type headache, with daily or very frequent episodes of headache lasting minutes to... (Review)
Review
INTRODUCTION
Chronic tension-type headache (CTTH) is a disorder that evolves from episodic tension-type headache, with daily or very frequent episodes of headache lasting minutes to days. It affects 4.1% of the general population in the USA, and is more prevalent in women (up to 65% of cases).
METHODS AND OBJECTIVES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for chronic tension-type headache? What are the effects of non-drug treatments for chronic tension-type headache? We searched: Medline, Embase, The Cochrane Library and other important databases up to October 2005 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 38 systematic reviews, RCTs or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, amitriptyline, benzodiazepines, botulinum toxin, cognitive behavioural therapy, Indian head massage, mirtazapine, regular acute pain relief medication, relaxation and electromyographic biofeedback, serotonin reuptake inhibitor antidepressants, and tricyclic antidepressants (other than amitriptyline).
Topics: Gene Library; Headache; Relaxation; United States; United States Food and Drug Administration
PubMed: 19454042
DOI: No ID Found -
The Cochrane Database of Systematic... Jul 2015This is an updated version of the original Cochrane review published in Issue 12, 2012. That review considered both fibromyalgia and neuropathic pain, but the effects of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane review published in Issue 12, 2012. That review considered both fibromyalgia and neuropathic pain, but the effects of amitriptyline for fibromyalgia are now dealt with in a separate review.Amitriptyline is a tricyclic antidepressant that is widely used to treat chronic neuropathic pain (pain due to nerve damage). It is recommended as a first line treatment in many guidelines. Neuropathic pain can be treated with antidepressant drugs in doses below those at which the drugs act as antidepressants.
OBJECTIVES
To assess the analgesic efficacy of amitriptyline for relief of chronic neuropathic pain, and the adverse events associated with its use in clinical trials.
SEARCH METHODS
We searched CENTRAL, MEDLINE, and EMBASE to March 2015, together with two clinical trial registries, and the reference lists of retrieved papers, previous systematic reviews, and other reviews; we also used our own hand searched database for older studies.
SELECTION CRITERIA
We included randomised, double-blind studies of at least four weeks' duration comparing amitriptyline with placebo or another active treatment in chronic neuropathic pain conditions.
DATA COLLECTION AND ANALYSIS
We performed analysis using three tiers of evidence. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison, 8 to 12 weeks' duration, parallel design), second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison, and third tier from data involving small numbers of participants that were considered very likely to be biased or used outcomes of limited clinical utility, or both.
MAIN RESULTS
We included 15 studies from the earlier review and two new studies (17 studies, 1342 participants) in seven neuropathic pain conditions. Eight cross-over studies with 302 participants had a median of 36 participants, and nine parallel group studies with 1040 participants had a median of 84 participants. Study quality was modest, though most studies were at high risk of bias due to small size.There was no first-tier or second-tier evidence for amitriptyline in treating any neuropathic pain condition. Only third-tier evidence was available. For only two of seven studies reporting useful efficacy data was amitriptyline significantly better than placebo (very low quality evidence).More participants experienced at least one adverse event; 55% of participants taking amitriptyline and 36% taking placebo. The risk ratio (RR) was 1.5 (95% confidence interval (CI) 1.3 to 1.8) and the number needed to treat for an additional harmful outcome was 5.2 (3.6 to 9.1) (low quality evidence). Serious adverse events were rare. Adverse event and all-cause withdrawals were not different, but were rarely reported (very low quality evidence).
AUTHORS' CONCLUSIONS
Amitriptyline has been a first-line treatment for neuropathic pain for many years. The fact that there is no supportive unbiased evidence for a beneficial effect is disappointing, but has to be balanced against decades of successful treatment in many people with neuropathic pain. There is no good evidence of a lack of effect; rather our concern should be of overestimation of treatment effect. Amitriptyline should continue to be used as part of the treatment of neuropathic pain, but only a minority of people will achieve satisfactory pain relief. Limited information suggests that failure with one antidepressant does not mean failure with all.
Topics: Adult; Amitriptyline; Analgesics, Non-Narcotic; Antidepressive Agents, Tricyclic; Humans; Neuralgia; Randomized Controlled Trials as Topic
PubMed: 26146793
DOI: 10.1002/14651858.CD008242.pub3 -
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 -
Annals of Internal Medicine Nov 2014Multiple treatments for painful diabetic peripheral neuropathy are available. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple treatments for painful diabetic peripheral neuropathy are available.
PURPOSE
To evaluate the comparative effectiveness of oral and topical analgesics for diabetic neuropathy.
DATA SOURCES
Multiple electronic databases between January 2007 and April 2014, without language restriction.
STUDY SELECTION
Parallel or crossover randomized, controlled trials that evaluated pharmacologic treatments for adults with painful diabetic peripheral neuropathy.
DATA EXTRACTION
Duplicate extraction of study data and assessment of risk of bias.
DATA SYNTHESIS
65 randomized, controlled trials involving 12 632 patients evaluated 27 pharmacologic interventions. Approximately one half of these studies had high or unclear risk of bias. Nine head-to-head trials showed greater pain reduction associated with serotonin-norepinephrine reuptake inhibitors (SNRIs) than anticonvulsants (standardized mean difference [SMD], -0.34 [95% credible interval {CrI}, -0.63 to -0.05]) and with tricyclic antidepressants (TCAs) than topical capsaicin 0.075%. Network meta-analysis showed that SNRIs (SMD, -1.36 [CrI, -1.77 to -0.95]), topical capsaicin (SMD, -0.91 [CrI, -1.18 to -0.08]), TCAs (SMD, -0.78 [CrI, -1.24 to -0.33]), and anticonvulsants (SMD, -0.67 [CrI, -0.97 to -0.37]) were better than placebo for short-term pain control. Specifically, carbamazepine (SMD, -1.57 [CrI, -2.83 to -0.31]), venlafaxine (SMD, -1.53 [CrI, -2.41 to -0.65]), duloxetine (SMD, -1.33 [CrI, -1.82 to -0.86]), and amitriptyline (SMD, -0.72 [CrI, -1.35 to -0.08]) were more effective than placebo. Adverse effects included somnolence and dizziness with TCAs, SNRIs, and anticonvulsants; xerostomia with TCAs; and peripheral edema and burning sensation with pregabalin and capsaicin.
LIMITATION
Confidence in findings was limited because most evidence came from indirect comparisons of trials with short (≤3 months) follow-up and unclear or high risk of bias.
CONCLUSION
Several medications may be effective for short-term management of painful diabetic neuropathy, although their comparative effectiveness is unclear.
PRIMARY FUNDING SOURCE
Mayo Foundation for Medical Education and Research.
Topics: Analgesics, Opioid; Anticonvulsants; Antidepressive Agents, Tricyclic; Bias; Capsaicin; Diabetic Neuropathies; Humans; Pain; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors
PubMed: 25364885
DOI: 10.7326/M14-0511 -
Drugs 2001Despite the widespread use of herbal medicines, documented herb-drug interactions are sparse. We have reviewed the literature to determine the possible interactions... (Review)
Review
Despite the widespread use of herbal medicines, documented herb-drug interactions are sparse. We have reviewed the literature to determine the possible interactions between the seven top-selling herbal medicines (ginkgo, St John's wort, ginseng, garlic, echinacea, saw palmetto and kava) and prescribed drugs. Literature searches were performed using the following databases: Medline (via Pubmed), Cochrane Library, Embase and phytobase (all from their inception to July 2000). All data relating to herb-drug interactions were included regardless of whether they were based on case reports, case series, clinical trials or other types of investigation in humans. In vitro experiments were excluded. Data were extracted by the first author and validated by the second author. 41 case reports or case series and 17 clinical trials were identified. The results indicate that St John's wort (Hypericum perforatum) lowers blood concentrations of cyclosporin, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline; furthermore it causes intermenstrual bleeding, delirium or mild serotonin syndrome, respectively, when used concomitantly with oral contraceptives (ethinylestradiol/desogestrel), loperamide or selective serotonin-reuptake inhibitors (sertaline, paroxetine, nefazodone). Ginkgo (Ginkgo biloba) interactions include bleeding when combined with warfarin, raised blood pressure when combined with a thiazide diuretic and coma when combined with trazodone. Ginseng (Panax ginseng) lowers blood concentrations of alcohol and warfarin, and induces mania if used concomitantly with phenelzine. Garlic (Allium sativum) changes pharmacokinetic variables of paracetamol, decreases blood concentrations of warfarin and produces hypoglycaemia when taken with chlorpropamide. Kava (Piper methysticum) increases 'off' periods in Parkinson patients taking levodopa and can cause a semicomatose state when given concomitantly with alprazolam. No interactions were found for echinacea (Echinacea angustifolia, E. purpurea, E. pallida) and saw palmetto (Serenoa repens). In conclusion, interactions between herbal medicines and synthetic drugs exist and can have serious clinical consequences. Healthcare professionals should ask their patients about the use of herbal products and consider the possibility of herb-drug interactions.
Topics: Drug Interactions; Drug Prescriptions; Echinacea; Garlic; Ginkgo biloba; Herb-Drug Interactions; Humans; Hypericum; Kava; Panax; Phytotherapy; Plant Extracts; Plant Preparations; Serenoa
PubMed: 11772128
DOI: 10.2165/00003495-200161150-00002 -
Frontiers in Neurology 2017Antidepressants are widely used in the treatment of chronic pain. Applied doses are lower than those needed to unfold an antidepressive effect. While efficacy of...
BACKGROUND
Antidepressants are widely used in the treatment of chronic pain. Applied doses are lower than those needed to unfold an antidepressive effect. While efficacy of antidepressants for chronic pain has been reported in large randomized-controlled trials (RCT), there is inconsistent data on adverse effects and tolerability. We aimed at synthesizing data from RCT to explore adverse effect profiles and tolerability of antidepressants for treatment of chronic pain.
METHODS
Systematic literature research and meta-analyses were performed regarding side effects and safety of different antidepressants in the treatment of chronic pain according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The National Center for Biotechnology Information library and MEDLINE were searched. Randomized placebo-controlled trials were included in quantitative data synthesis.
RESULTS
Out of 1,975 screened articles, 33 papers published between 1995 and 2015 were included in our review and 23 studies were included in the meta-analyses. A higher risk for adverse effects compared to placebo was observed in all antidepressants included in our analyses, except nortriptyline. The most prevalent adverse effects were dry mouth, dizziness, nausea, headache, and constipation. Amitriptyline, mirtazapine, desipramine, venlafaxine, fluoxetine, and nortriptyline showed the highest placebo effect-adjusted risk of adverse effects. Risk for withdrawal due to adverse effects was highest in desipramine (risk ratio: 4.09, 95%-confidence interval [1.31; 12.82]) followed by milnacipran, venlafaxine, and duloxetine. The most common adverse effects under treatment with antidepressants were dry mouth, dizziness, nausea, headache, and constipation followed by palpitations, sweating, and drowsiness. However, overall tolerability was high. Each antidepressant showed distinct risk profiles of adverse effects.
CONCLUSION
Our synthesized data analysis confirmed overall tolerability of low-dose antidepressants for the treatment of chronic pain and revealed drug specific risk profiles. This encompassing characterization of adverse effect profiles might be useful in defining multimodal treatment regimens for chronic pain which also consider patients' comorbidities and co-medication.
PubMed: 28769859
DOI: 10.3389/fneur.2017.00307