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Internal Medicine Journal Apr 2024Fibromyalgia is a common condition characterised by chronic widespread musculoskeletal pain and central sensitivity features. Appropriate management requires a...
BACKGROUND
Fibromyalgia is a common condition characterised by chronic widespread musculoskeletal pain and central sensitivity features. Appropriate management requires a multidisciplinary approach prioritising non-pharmacological strategies. Evidence-based fibromyalgia medications are not always easily available, effective or tolerated.
AIM
To characterise actual medication usage in Australian fibromyalgia patients.
METHODS
Demographic and clinical data, including medication use information, were gathered by chart review from patients attending the Monash Fibromyalgia Clinic between January 2019 and June 2022. Eligible patients were invited to complete an anonymous questionnaire between June and August 2022 to assess current therapeutic use. The questionnaire assessed fibromyalgia clinical features by using the Revised Fibromyalgia Impact Questionnaire and the 2016 modified American College of Rheumatology Fibromyalgia criteria.
RESULTS
The chart review included 474 patients, and 108 participants completed the questionnaire. Most chart review (78.7%) and questionnaire participants (85.2%) reported using at least one medication for their fibromyalgia. 48.5% of chart review patients and 58.3% of questionnaire participants reported using at least one evidence-based medication, usually amitriptyline, duloxetine or pregabalin. However, the most common individual medications for questionnaire participants were non-steroidal anti-inflammatory drugs (48.2%), paracetamol (59.3%) and opioids (34.3%), with most opioids being typical opioids. Among questionnaire participants, 14.8% reported using cannabinoids, and 70.4% reported using at least one supplement, vitamin or herbal/naturopathic preparation. Not all medication or substance use was recorded during clinic appointments.
CONCLUSION
Fibromyalgia patients engage in various pharmacotherapeutic strategies that are not always evidence-based or disclosed to their treating clinicians.
Topics: Humans; United States; Fibromyalgia; Australia; Pregabalin; Duloxetine Hydrochloride; Amitriptyline; Chronic Pain
PubMed: 37872879
DOI: 10.1111/imj.16257 -
Basic & Clinical Pharmacology &... Jan 2024Duloxetine is metabolized by cytochrome P450 (CYP)1A2 and CYP2D6. The aim of this study was to investigate the effect of the CYP2D6 genotype on duloxetine serum...
Duloxetine is metabolized by cytochrome P450 (CYP)1A2 and CYP2D6. The aim of this study was to investigate the effect of the CYP2D6 genotype on duloxetine serum concentration adjusting for age and sex. Patients were included retrospectively from a therapeutic drug monitoring service. Multiple linear regression analysis was used to investigate the effect of CYP2D6 genotype, age and sex on the duloxetine concentration-to-dose (C/D) ratio. In total, 269 patients were included and assigned to the following genotype-predicted phenotype subgroups: CYP2D6 poor metabolizers (PMs, n = 23), intermediate metabolizers (IMs, n = 121), normal metabolizers (NMs, n = 120) and ultrarapid metabolizers (UMs, n = 5). Multiple linear regression analysis revealed a 95% higher duloxetine C/D ratio in PMs compared with NMs (p = 0.009). Patients ≥65 years had a 56% higher C/D ratio than younger patients (p = 0.01), while women had a 46% higher C/D ratio than men (p = 0.04). In conclusion, the CYP2D6 PM phenotype is associated with a twofold higher concentration at recommended dosing compared with the NM phenotype. CYP2D6 PM females above 65 years are at particular risk of high duloxetine levels as they may obtain a threefold higher C/D ratio compared with younger, male NMs.
Topics: Humans; Male; Female; Cytochrome P-450 CYP2D6; Duloxetine Hydrochloride; Retrospective Studies; Genotype; Phenotype
PubMed: 37864290
DOI: 10.1111/bcpt.13954 -
The American Journal of Psychiatry Jan 2024The authors investigated the clinical outcomes of commonly used antidepressants among older adults who initiated first-time antidepressants for depression by analyzing...
OBJECTIVE
The authors investigated the clinical outcomes of commonly used antidepressants among older adults who initiated first-time antidepressants for depression by analyzing the 1-year risk of selected clinically relevant outcomes.
METHODS
This cohort study used nationwide Danish registry data and included all older adults who redeemed a first-time (since 1995) antidepressant prescription with an indication of depression between 2006 and 2017. Only the 10 most frequently redeemed antidepressants were included in the analyses. Outcomes included discontinuation, switching, augmentation, psychiatric hospital contacts, suicide attempt or self-harm, fall-related injuries, cardiovascular events, and all-cause mortality. Incidence rate ratios (IRRs) and 95% confidence intervals were estimated using Poisson regression models, controlling for potential confounders.
RESULTS
The study sample included 93,883 older adults (mean age, 78.0 years, SD=7.5 years; 56% female). The most frequently prescribed antidepressants were selective serotonin reuptake inhibitors (citalopram, 47.04%; escitalopram, 11.81%; fluoxetine, 0.55%; paroxetine, 0.52%; sertraline, 11.17%), serotonin-norepinephrine reuptake inhibitors (duloxetine, 0.71%; venlafaxine, 1.54%), a tricyclic antidepressant (amitriptyline, 1.86%), and two atypical antidepressants (mianserin, 1.93%; mirtazapine, 22.87%). Compared with users of sertraline (the reference drug in this analysis, as Danish guidelines recommend it as the first-choice treatment for depression), users of most of the other nine antidepressants had a significantly higher risk of discontinuation (e.g., mirtazapine: IRR=1.55, 95% CI=1.50-1.61; venlafaxine: IRR=1.22, 95% CI=1.12-1.32), switching (amitriptyline: IRR=1.45, 95% CI=1.15-1.81; venlafaxine: IRR=1.47, 95% CI=1.20-1.80), augmentation, cardiovascular events, and mortality. Overall, mirtazapine and venlafaxine users had the most adverse outcomes compared with sertraline users. These results remained consistent in analyses stratified by sex and age (≤75 years vs. >75 years).
CONCLUSIONS
This real-world evidence suggests that clinical outcomes may vary among initiators of commonly used antidepressants in older adults, which may inform benefit-risk evaluation at treatment initiation, and highlights the importance of careful selection of antidepressant treatment.
Topics: Female; Humans; Aged; Male; Venlafaxine Hydrochloride; Sertraline; Depression; Cohort Studies; Mirtazapine; Amitriptyline; Antidepressive Agents; Selective Serotonin Reuptake Inhibitors; Cardiovascular Diseases; Denmark
PubMed: 37849303
DOI: 10.1176/appi.ajp.20230356 -
Cell Biochemistry and Function Oct 2023Duloxetine, a selective reuptake inhibitor for serotonin and norepinephrine, is a medication widely used for major depression. Currently, duloxetine is also recommended...
Upregulation by duloxetine of the transforming growth factor-α-induced migration of hepatocellular carcinoma cells via enhancement of the c-Jun N-terminal kinase activity.
Duloxetine, a selective reuptake inhibitor for serotonin and norepinephrine, is a medication widely used for major depression. Currently, duloxetine is also recommended for pain related to chemotherapy-induced peripheral neuropathy or cancer. Previously, we showed that transforming growth factor-α (TGF-α) induces the migration of human hepatocellular carcinoma (HCC)-derived HuH7 cells through the activation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and AKT. In the present study, we investigate whether duloxetine affects cell migration and its mechanism. Duloxetine significantly enhanced the TGF-α-induced migration of HuH7 cells. Fluvoxamine and sertraline, specific inhibitors of serotonin reuptake, also upregulated the TGF-α-induced cell migration. On the contrary, reboxetine, a specific norepinephrine reuptake inhibitor, failed to affect cell migration. Duloxetine significantly amplified the TGF-α-stimulated phosphorylation of JNK, but not p38 MAPK and AKT. In addition, fluvoxamine and sertraline, but not reboxetine, enhanced the phosphorylation of JNK. SP600125, a JNK inhibitor, suppressed the enhancement by duloxetine, fluvoxamine, or sertraline of TGF-α-induced migration of HuH7 cells. Taken together, our results strongly suggest that duloxetine strengthens the TGF-α-induced activation of JNK via inhibition of serotonin reuptake in HCC cells, leading to the enhancement of cell migration.
Topics: Humans; Carcinoma, Hepatocellular; Duloxetine Hydrochloride; Fluvoxamine; JNK Mitogen-Activated Protein Kinases; Liver Neoplasms; Norepinephrine; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Serotonin; Sertraline; Transforming Growth Factor alpha; Up-Regulation
PubMed: 37814477
DOI: 10.1002/cbf.3831 -
FP Essentials Oct 2023Fibromyalgia is a chronic pain syndrome that is considered a pain processing disorder; its pathophysiology is not completely understood. The estimated prevalence in the...
Fibromyalgia is a chronic pain syndrome that is considered a pain processing disorder; its pathophysiology is not completely understood. The estimated prevalence in the general population varies from 0.5% to 12%, depending on the population studied and diagnostic criteria used. It is more common in females than males. There is no diagnostic laboratory test. The two currently used diagnostic methods are scoring criteria from the American College of Rheumatology (ACR) and the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION)-American Pain Society (APS). These diagnostic criteria include chronic widespread pain of at least 3 months' duration plus poor sleep and/or fatigue and other somatic symptoms. Other pain syndromes also should be considered in the differential diagnosis. A multimodal, targeted symptom management approach that emphasizes self-management is recommended. Nonpharmacotherapies include patient education, exercise, and cognitive behavior therapy. Pharmacotherapy should be based on predominant symptoms. Amitriptyline and pregabalin are effective for management of pain, fatigue, and sleep issues. Milnacipran (Savella) is effective for pain and fatigue. Duloxetine is effective for management of pain and depression. There is no evidence of benefit of analgesics. Common comorbidities, such as regional pain conditions and mental disorders, should be addressed.
Topics: Male; Female; Humans; Fibromyalgia; Chronic Pain; Pregabalin; Duloxetine Hydrochloride; Milnacipran; Fatigue
PubMed: 37812528
DOI: No ID Found -
Clinical NeuropharmacologyIn persons with narcolepsy type 1, sudden withdrawal of antidepressants can cause status cataplecticus. We describe a 77-year-old female patient with long-standing... (Review)
Review
In persons with narcolepsy type 1, sudden withdrawal of antidepressants can cause status cataplecticus. We describe a 77-year-old female patient with long-standing history of narcolepsy type 1 complaining of recurrent short sudden episodes of whole-body paralysis, with preserved consciousness and memory. Episodes started an hour after her family invited her to celebrate Mother's Day. One week prior, patient had abruptly discontinued duloxetine. Cataplectic episodes resolved within 24 hours after resumption of duloxetine and treatment of hypokalemia. Status cataplecticus has been reported after withdrawal of venlafaxine, fluoxetine, and clomipramine. This is the first report of status cataplecticus due to duloxetine withdrawal. We review the pathophysiology of antidepressant withdrawal-induced status cataplecticus. In persons with narcolepsy type 1, physicians discontinuing any antidepressant should counsel on adverse effects of antidepressant withdrawal and reduce the dose in tapering manner.
Topics: Female; Humans; Aged; Duloxetine Hydrochloride; Cataplexy; Narcolepsy; Antidepressive Agents; Venlafaxine Hydrochloride
PubMed: 37748003
DOI: 10.1097/WNF.0000000000000563 -
Dental Clinics of North America Oct 2023A patient with a past medical history significant for fibromyalgia presents for an incisional oral biopsy. The condition is being managed pharmacologically with... (Review)
Review
A patient with a past medical history significant for fibromyalgia presents for an incisional oral biopsy. The condition is being managed pharmacologically with duloxetine and ibuprofen. Given the patient's medical condition and medications, specific considerations were placed on chair positioning, muscle pain and tenderness, and achieving hemostasis through local measures. The patient was advised to follow up in 2 weeks for postoperative evaluation.
Topics: Humans; Fibromyalgia; Biopsy; Duloxetine Hydrochloride; Ibuprofen
PubMed: 37714615
DOI: 10.1016/j.cden.2023.06.002 -
Journal of Orthopaedic Surgery (Hong... 2023
Topics: Humans; Analgesics; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Duloxetine Hydrochloride; Pain, Postoperative
PubMed: 37694724
DOI: 10.1177/10225536231198768 -
International Journal of Molecular... Aug 2023Depression is a global mental health concern, and personalized treatment approaches are needed to optimize its management. This study aimed to investigate the influence...
Depression is a global mental health concern, and personalized treatment approaches are needed to optimize its management. This study aimed to investigate the influence of the CYP2D6 and CYP1A2 gene polymorphisms on the efficacy of duloxetine in reducing depressive and anxiety symptoms. A sample of 100 outpatients with major depression, who initiated monotherapy with duloxetine, were followed up. Polymorphisms in the CYP2D6 and CYP1A2 genes were assessed. The severity of depressive and anxiety symptoms was recorded using standardized scales. Adverse drug reactions (ADRs) were analyzed. Statistical analyses, including linear regression, were conducted to examine the relationships between genetic polymorphisms, clinical variables, and treatment outcomes. Patients with higher values of the duloxetine metabolic index (DMI) for CYP2D6, indicating a faster metabolism, achieved a greater reduction in anxiety symptoms. The occurrence of ADRs was associated with a lower reduction in anxiety symptoms. However, no significant associations were found between studied gene polymorphisms and reduction in depressive symptoms. No significant effects of the DMI for CYP1A2 were found. Patients with a slower metabolism may experience less benefit from duloxetine therapy in terms of anxiety symptom reduction. Personalizing treatment based on the CYP2D6 and CYP1A2 gene polymorphisms can enhance the effectiveness of antidepressant therapy and improve patient outcomes.
Topics: Humans; Cytochrome P-450 CYP2D6; Depressive Disorder, Major; Cytochrome P-450 CYP1A2; Duloxetine Hydrochloride; Depression; Drug-Related Side Effects and Adverse Reactions; Polymorphism, Genetic
PubMed: 37686266
DOI: 10.3390/ijms241713459 -
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