-
American Family Physician Feb 2023Fibromyalgia is a chronic, centralized pain syndrome characterized by disordered processing of painful stimuli. Fibromyalgia is diagnosed more frequently in women and...
Fibromyalgia is a chronic, centralized pain syndrome characterized by disordered processing of painful stimuli. Fibromyalgia is diagnosed more frequently in women and occurs globally, affecting 2% of people in the United States. Patients with fibromyalgia have diffuse chronic pain, poor sleep, fatigue, cognitive dysfunction, and mood disturbances. Comorbid conditions, such as functional somatic syndromes, psychiatric diagnoses, and rheumatologic conditions may be present. The Fibromyalgia Rapid Screening Tool is a helpful screening method for patients with diffuse chronic pain. The American College of Rheumatology criteria or the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society Pain Taxonomy diagnostic criteria can diagnose fibromyalgia. Establishing the diagnosis and providing education can reassure patients and decrease unnecessary testing. A multidisciplinary approach that incorporates nonpharmacologic therapies and medications to address problematic symptoms is most effective. Patient education, exercise, and cognitive behavior therapy can improve pain and function. Duloxetine, milnacipran, pregabalin, and amitriptyline are potentially effective medications for fibromyalgia. Nonsteroidal anti-inflammatory drugs and opioids have not demonstrated benefits for fibromyalgia and have significant limitations.
Topics: Humans; Female; Fibromyalgia; Chronic Pain; Pregabalin; Analgesics; Duloxetine Hydrochloride
PubMed: 36791450
DOI: No ID Found -
Metabolism: Clinical and Experimental Oct 2021Diabetic neuropathy is a neurodegenerative disorder that may alter both the somatic and autonomic peripheral nervous systems in the context of diabetes mellitus (DM). It... (Review)
Review
Diabetic neuropathy is a neurodegenerative disorder that may alter both the somatic and autonomic peripheral nervous systems in the context of diabetes mellitus (DM). It is a prevalent and burdensome chronic complication of DM, that requires timely management. Optimized glycemic control (mainly for type 1 DM), multifactorial intervention (mainly for type 2 DM), with lifestyle intervention/physical exercise, and weight loss represent the basis of management for diabetic distal symmetrical polyneuropathy, and should be implemented early in the disease course. Despite better understanding of the pathogenetic mechanisms of diabetic peripheral neuropathy, there is still a stringent need for more pathogenetic-based agents that would significantly modify the natural history of the disease. The paper reviews the available drugs and current recommendations for the management of distal symmetrical polyneuropathy, including pain management, and for diabetic autonomic neuropathy. Evaluation of drug combinations that would perhaps be more efficient in slowing the progression of the disease or even reversing it, and that would provide a better pain management is still needed.
Topics: Diabetic Neuropathies; Duloxetine Hydrochloride; Gabapentin; Humans; Life Style; Pain Management; Pregabalin; Risk Factors; Weight Loss
PubMed: 34411554
DOI: 10.1016/j.metabol.2021.154867 -
Diabetes & Metabolism Journal Nov 2023Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. The lifetime prevalence of DPN is thought to be >50%, and 15%-25% of... (Review)
Review
Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. The lifetime prevalence of DPN is thought to be >50%, and 15%-25% of patients with diabetes experience neuropathic pain, referred to as "painful DPN." Appropriate treatment of painful DPN is important because this pain contributes to a poor quality of life by causing sleep disturbance, anxiety, and depression. The basic principle for the management of painful DPN is to control hyperglycemia and other modifiable risk factors, but these may be insufficient for preventing or improving DPN. Because there is no promising diseasemodifying medication for DPN, the pain itself needs to be managed when treating painful DPN. Drugs for neuropathic pain, such as gabapentinoids, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, alpha-lipoic acid, sodium channel blockers, and topical capsaicin, are used for the management of painful DPN. The U.S. Food and Drug Administration (FDA) has approved pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch as drugs for the treatment of painful DPN. Recently, spinal cord stimulation using electrical stimulation is approved by the FDA for the treatment for painful DPN. This review describes the currently available pharmacological and nonpharmacological treatments for painful DPN.
Topics: United States; Humans; Diabetic Neuropathies; Capsaicin; Quality of Life; Duloxetine Hydrochloride; Neuralgia; Diabetes Mellitus
PubMed: 37670573
DOI: 10.4093/dmj.2023.0018 -
Expert Review of Neurotherapeutics Jun 2023Generalized Anxiety Disorder (GAD) is a common psychiatric condition, characterized by the presence of general apprehensiveness and excessive worry. Current management... (Review)
Review
INTRODUCTION
Generalized Anxiety Disorder (GAD) is a common psychiatric condition, characterized by the presence of general apprehensiveness and excessive worry. Current management consists of a range of pharmacological and psychological treatments. However, many patients do not respond to first-line pharmacological treatments and novel anxiolytic drugs are being developed.
AREAS COVERED
In this review, the authors first discuss the diagnostic criteria and epidemiology of GAD. The effective pharmacological treatments for GAD and their tolerability are addressed. Current consensus guidelines for treatment of GAD are discussed, and maintenance treatment, the management of treatment resistance, and specific management of older adults and children/adolescents are considered. Finally, novel anxiolytics under development are discussed, with a focus on those which have entered clinical trials.
EXPERT OPINION
A range of effective treatments for GAD are available, particularly duloxetine, escitalopram, pregabalin, quetiapine, and venlafaxine. There is a limited evidence base to support the further pharmacological management of patients with GAD who have not responded to initial treatment. Although many novel anxiolytics have progressed to clinical trials, translation from animal models has been mostly unsuccessful. However, the potential of several compounds including certain psychedelics, ketamine, oxytocin, and agents modulating the orexin, endocannabinoid, and immune systems merits further study.
Topics: Humans; Anti-Anxiety Agents; Anxiety Disorders; Duloxetine Hydrochloride; Pregabalin; Treatment Outcome
PubMed: 37183813
DOI: 10.1080/14737175.2023.2211767 -
Revista de Neurologia May 2015Burning mouth syndrome (BMS) is mainly found in middle aged or elderly women and is characterized by intense burning or itching sensation of the tongue or other regions... (Review)
Review
Burning mouth syndrome (BMS) is mainly found in middle aged or elderly women and is characterized by intense burning or itching sensation of the tongue or other regions of the oral mucosa. It can be accompanied by xerostomia and dysgeusia. The syndrome generally manifests spontaneously, and the discomfort is typically of a continuous nature but increases in intensity during the evening and at night. Although BMS classically has been attributed to a range of factors, in recent years evidence has been obtained relating it peripheral (sensory C and/or trigeminal nerve fibers) or central neuropathic disturbances (involving the nigrostriatal dopaminergic system). The differential diagnosis requires the exclusion of oral mucosal lesions or blood test alterations that can produce burning mouth sensation. Patient management is based on the avoidance of causes of oral irritation and the provision of psychological support. Drug treatment for burning sensation in primary BMS of peripheral origin can consist of topical clonazepam, while central type BMS appears to improve with the use of antidepressants such as duloxetine, antiseizure drugs such as gabapentin, or amisulpride.
Topics: Adult; Age Distribution; Aged; Algorithms; Amisulpride; Antidepressive Agents; Burning Mouth Syndrome; Clonazepam; Deficiency Diseases; Dentures; Duloxetine Hydrochloride; Female; Humans; Male; Menopause; Middle Aged; Mood Disorders; Nerve Fibers, Unmyelinated; Orthodontic Appliances; Sex Distribution; Sulpiride; Tongue Habits
PubMed: 25952601
DOI: No ID Found -
Handbook of Experimental Pharmacology 2019This chapter covers antidepressants that fall into the class of serotonin (5-HT) and norepinephrine (NE) reuptake inhibitors. That is, they bind to the 5-HT and NE...
This chapter covers antidepressants that fall into the class of serotonin (5-HT) and norepinephrine (NE) reuptake inhibitors. That is, they bind to the 5-HT and NE transporters with varying levels of potency and binding affinity ratios. Unlike the selective serotonin (5-HT) reuptake inhibitors (SSRIs), most of these antidepressants have an ascending rather than a flat dose-response curve. The chapter provides a brief review of the chemistry, pharmacology, metabolism, safety and adverse effects, clinical use, and therapeutic indications of each antidepressant. Venlafaxine, a phenylethylamine, is a relatively weak 5-HT and weaker NE uptake inhibitor with a 30-fold difference in binding of the two transporters. Therefore, the drug has a clear dose progression, with low doses predominantly binding to the 5-HT transporter and more binding of the NE transporter as the dose ascends. Venlafaxine is metabolized to the active metabolite O-desmethylvenlafaxine (ODV; desvenlafaxine) by CYP2D6, and it therefore is subject to significant inter-individual variation in blood levels and response dependent on variations in CYP2D6 metabolism. The half-life of venlafaxine is short at about 5 h, with the ODV metabolite being 12 h. Both parent compound and metabolite have low protein binding and neither inhibit CYP enzymes. Therefore, both venlafaxine and desvenlafaxine are potential options if drug-drug interactions are a concern, although venlafaxine may be subject to drug-drug interactions with CYP2D6 inhibitors. At low doses, the adverse effect profile is similar to an SSRI with nausea, diarrhea, fatigue or somnolence, and sexual side effects, while venlafaxine at higher doses can produce mild increases in blood pressure, diaphoresis, tachycardia, tremors, and anxiety. A disadvantage of venlafaxine relative to the SSRIs is the potential for dose-dependent blood pressure elevation, most likely due to the NE reuptake inhibition caused by higher doses; however, this adverse effect is infrequently observed at doses below 225 mg per day. Venlafaxine also has a number of potential advantages over the SSRIs, including an ascending dose-antidepressant response curve, with possibly greater overall efficacy at higher doses. Venlafaxine is approved for MDD as well as generalized anxiety disorder, social anxiety disorder, and panic disorder. Desvenlafaxine is the primary metabolite of venlafaxine, and it is also a relatively low-potency 5-HT and NE uptake inhibitor. Like venlafaxine it has a favorable drug-drug interaction profile. It is subject to CYP3A4 metabolism, and it is therefore vulnerable to enzyme inhibition or induction. However, the primary metabolic pathway is direct conjugation. It is approved in the narrow dose range of 50-100 mg per day. Duloxetine is a more potent 5-HT and NE reuptake inhibitor with a more balanced profile of binding at about 10:1 for 5HT and NE transporter binding. It is also a moderate inhibitor of CYP2D6, so that modest dose reductions and careful monitoring will be needed when prescribing duloxetine in combination with drugs that are preferentially metabolized by CYP2D6. The most common side effects identified in clinical trials are nausea, dry mouth, dizziness, constipation, insomnia, asthenia, and hypertension, consistent with its mechanisms of action. Clinical trials to date have demonstrated rates of response and remission in patients with major depression that are comparable to other marketed antidepressants reviewed in this book. In addition to approval for MDD, duloxetine is approved for diabetic peripheral neuropathic pain, fibromyalgia, and musculoskeletal pain. Milnacipran is marketed as an antidepressant in some countries, but not in the USA. It is approved in the USA and some other countries as a treatment for fibromyalgia. It has few pharmacokinetic and pharmacodynamic interactions with other drugs. Milnacipran has a half-life of about 10 h and therefore needs to be administered twice per day. It is metabolized by CYP3A4, but the major pathway for clearance is direct conjugation and renal elimination. As with other drugs in this class, dysuria is a common, troublesome, and dose-dependent adverse effect (occurring in up to 7% of patients). High-dose milnacipran has been reported to cause blood pressure and pulse elevations. Levomilnacipran is the levorotary enantiomer of milnacipran, and it is pharmacologically very similar to the racemic compound, although the side effects may be milder within the approved dosing range. As with other NE uptake inhibitors, it may increase blood pressure and pulse, although it appears to do so less than some other medications. All medications in the class can cause serotonin syndrome when combined with MAOIs.
Topics: Antidepressive Agents; Desvenlafaxine Succinate; Duloxetine Hydrochloride; Humans; Serotonin; Serotonin and Noradrenaline Reuptake Inhibitors
PubMed: 30838456
DOI: 10.1007/164_2018_164 -
Nature Sep 2021Bacteria in the gut can modulate the availability and efficacy of therapeutic drugs. However, the systematic mapping of the interactions between drugs and bacteria has...
Bacteria in the gut can modulate the availability and efficacy of therapeutic drugs. However, the systematic mapping of the interactions between drugs and bacteria has only started recently and the main underlying mechanism proposed is the chemical transformation of drugs by microorganisms (biotransformation). Here we investigated the depletion of 15 structurally diverse drugs by 25 representative strains of gut bacteria. This revealed 70 bacteria-drug interactions, 29 of which had not to our knowledge been reported before. Over half of the new interactions can be ascribed to bioaccumulation; that is, bacteria storing the drug intracellularly without chemically modifying it, and in most cases without the growth of the bacteria being affected. As a case in point, we studied the molecular basis of bioaccumulation of the widely used antidepressant duloxetine by using click chemistry, thermal proteome profiling and metabolomics. We find that duloxetine binds to several metabolic enzymes and changes the metabolite secretion of the respective bacteria. When tested in a defined microbial community of accumulators and non-accumulators, duloxetine markedly altered the composition of the community through metabolic cross-feeding. We further validated our findings in an animal model, showing that bioaccumulating bacteria attenuate the behavioural response of Caenorhabditis elegans to duloxetine. Together, our results show that bioaccumulation by gut bacteria may be a common mechanism that alters drug availability and bacterial metabolism, with implications for microbiota composition, pharmacokinetics, side effects and drug responses, probably in an individual manner.
Topics: Animals; Antidepressive Agents; Bacteria; Bioaccumulation; Caenorhabditis elegans; Cells; Click Chemistry; Duloxetine Hydrochloride; Gastrointestinal Microbiome; Humans; Metabolomics; Models, Animal; Proteomics; Reproducibility of Results
PubMed: 34497420
DOI: 10.1038/s41586-021-03891-8 -
Journal of Orthopaedic Surgery and... Jul 2023The optimal dose of duloxetine in the management of fibromyalgia remains still controversial. Therefore, a systematic review and meta-analysis to investigate efficacy... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The optimal dose of duloxetine in the management of fibromyalgia remains still controversial. Therefore, a systematic review and meta-analysis to investigate efficacy and safety of duloxetine was conducted. The outcomes of interests were to assess changes in Fibromyalgia Impact Questionnaire (FIQ), Brief Pain Inventory (BPI), and Clinical Global Impression (CGI). The rate of of adverse events and those leading to therapy discontinuation were also investigated.
MATERIAL AND METHODS
This study followed the 2020 PRISMA guidelines. The literature search started in December 2022 accessing PubMed, Google scholar, Embase, and Scopus databases. All the RCTs investigating the efficacy and safety of daily administration of duloxetine for fibromyalgia were accessed. Studies reporting quantitative data under the outcomes of interest, and including a minimum of 10 patients who completed a minimum of 4 weeks follow-up, were included. Studies on combined pharmacological and non-pharmacological managements for fibromyalgia were not considered.
RESULTS
Data from 3432 patients (11 RCTs) were included. The mean age of the patients was 46.4 ± 10.7 years old, and the mean BMI 25.3 ± 3.2 kg/m. 90% (3089 of 3432 patients) were women. The 60 mg/daily cohort reported the higher FIQ, followed by the 30, 30-60, 120 mg/daily, and placebo groups, while the 60-120 mg /daily group performed the worst results. Concerning the CGI severity scale, placebo resulted in the lowest improvement, and no differences were found in the other groups. Concerning the BPI interference and severity pain scores, the 30-60 mg/daily group reported the worst result, along with the placebo group. The rate of adverse events leading to study discontinuation were lower in the 60-120 group, followed by the 30-60 and 30 mag/daily groups. Duloxetine was superior in all the comparisons to placebo, irrespective of the doses, in all endpoints analysed.
CONCLUSIONS
Duloxetine could help in improving symptoms of fibromyalgia. The dose of duloxetine should be customised according to individual patients. Irrespective of the doses, duloxetine was more effective than placebo in the management of fibromyalgia. The dose of duloxetine must be customised according to individual patients. Level of evidence I Meta-analysis of double-blind RCTs.
Topics: Humans; Female; Adult; Middle Aged; Male; Duloxetine Hydrochloride; Fibromyalgia; Thiophenes; Treatment Outcome; Pain; Randomized Controlled Trials as Topic
PubMed: 37461044
DOI: 10.1186/s13018-023-03995-z -
Daru : Journal of Faculty of Pharmacy,... Jun 2019Duloxetine and pregabalin are among the most widely used medications in the treatment of patients with fibromyalgia syndrome (FM). (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Duloxetine and pregabalin are among the most widely used medications in the treatment of patients with fibromyalgia syndrome (FM).
OBJECTIVES
To add to the very few lines of evidence that exist on the comparative safety and efficacy of these two medications.
METHODS
In this open-label randomized clinical trial, outpatient women, who were diagnosed with FM based on American College of Rheumatology 2010 criteria, and had an age range of 18-65 years old were assigned to either duloxetine 30-60 mg or pregabalin 75-150 mg per day for 4 weeks. Patients were excluded in cases of having used duloxetine, pregabalin, gabapentin, or antidepressants within 12 weeks prior to the study, having had a history of comorbid medical conditions that could provoke chronic pain, or having had comorbid neuropsychiatric disorders, except for major depressive/anxiety disorders. Primary outcomes were between-group differences in mean score changes from baseline to end point for Widespread Pain Index (WPI) and Beck Depression Inventory-II. Secondary outcomes were the same statistical estimates, but for Fibromyalgia Impact Questionnaire-Revised and 12-Item Short Form Survey. Descriptive statistics and independent samples t-test were the main methods of analysis. ( www.irct.ir ; IRCT2016030626935N1).
RESULTS
Among all the scales, only WPI scores improved with a statistically significant difference between the two treatment arms, favoring duloxetine (Mean difference in score change - 2.32, 95% CI, -4.46 to - 0.18; p = 0.034; Cohen's d 0.53 95% CI, 0.04 to 1.02). Drop out rate and cumulative incidence of nausea was significantly higher in the duloxetine arm compared to the pregabalin arm.
CONCLUSION
This study provides further evidence on higher efficacy of duloxetine compared to pregabalin for the treatment of pain in patients with fibromyalgia. Future comprehensive pragmatic clinical trials are warranted.
Topics: Adult; Chronic Pain; Depression; Drug Administration Schedule; Duloxetine Hydrochloride; Female; Fibromyalgia; Humans; Medication Adherence; Middle Aged; Pregabalin; Treatment Outcome; Young Adult
PubMed: 30877484
DOI: 10.1007/s40199-019-00257-4 -
Psychotherapy and Psychosomatics 2018Serotonin-noradrenaline reuptake inhibitors (SNRI) are widely used in medical practice. Their discontinuation has been associated with a wide range of symptoms. The aim... (Review)
Review
BACKGROUND
Serotonin-noradrenaline reuptake inhibitors (SNRI) are widely used in medical practice. Their discontinuation has been associated with a wide range of symptoms. The aim of this paper is to identify the occurrence, frequency, and features of withdrawal symptoms after SNRI discontinuation.
METHODS
PRISMA guidelines were followed to conduct a systematic review. Electronic databases included PubMed, the Cochrane Library, Web of Science, and MEDLINE from the inception of each database to June 2017. Titles, abstracts, and topics were searched using a combination of the following terms: "duloxetine" OR "venlafaxine" OR "desvenlafaxine" OR "milnacipran" OR "levomilnacipran" OR "SNRI" OR "second generation antidepressant" OR "serotonin norepinephrine reuptake inhibitor" AND "discontinuation" OR "withdrawal" OR "rebound." Only published trials in the English language were included.
RESULTS
Sixty-one reports met the criteria for inclusion. There were 22 double-blind randomized controlled trials, 6 studies where patients were treated in an open fashion and then randomized to a double-blind controlled phase, 8 open trials, 1 prospective naturalistic study, 1 retrospective study, and 23 case reports. Withdrawal symptoms occurred after discontinuation of any type of SNRI. The prevalence of withdrawal symptoms varied across reports and appeared to be higher with venlafaxine. Symptoms typically ensued within a few days from discontinuation and lasted a few weeks, also with gradual tapering. Late onset and/or a longer persistence of disturbances occurred as well.
CONCLUSIONS
Clinicians need to add SNRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with other types of psychotropic drugs. The results of this study challenge the use of SNRI as first-line treatment for mood and anxiety disorders.
Topics: Adrenergic Uptake Inhibitors; Desvenlafaxine Succinate; Duloxetine Hydrochloride; Humans; Mood Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Venlafaxine Hydrochloride
PubMed: 30016772
DOI: 10.1159/000491524