Efficacy of Duloxetine With Arthrocentesis in the Management of TMJ Internal Derangement.

Temporomandibular joint (TMJ) arthrocentesis is one of the most commonly used non-invasive surgical interventions in the treatment of refractory pain and dysfunction associated with internal derangement. Several adjunctive therapies have been used in combination with arthrocentesis in an attempt to increase its efficacy and long-term maintenance. Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor which is used in different chronic pain conditions. This study aimed to assess the efficacy of duloxetine in combination with arthrocentesis compared with arthrocentesis alone. Twenty-eight patients with chronic TMJ pain were included and randomly allocated into 2 groups (control and study groups). The control group included patients who underwent TMJ arthrocentesis only, and the study group included patients who underwent arthrocentesis followed by giving duloxetine (30 mg) orally twice daily for 3 months. Pain, maximum mouth opening, and level of anxiety and depression were assessed preoperatively and followed at regular intervals of 1 week, 1 month, 3 months, and 6 months postoperatively. Pain was significantly reduced in both groups at all postoperative intervals and was significantly lower in the study group than the control group at 6 months. Maximum mouth opening increased significantly in both groups, but the difference between them was not significant. Level of anxiety and depression was significantly decreased in both groups, with no statistically significant difference between them. The results of this study indicate that duloxetine in combination with arthrocentesis may provide effective and long-term pain control; however, its use is associated with a higher risk of adverse events.

The effect of earthquake on fibromyalgia: a comparison of patients on medication and without medication.

INTRODUCTION / OBJECTIVES: Stressful events like earthquakes might worsen the symptoms of fibromyalgia, although the influence of medications on these consequences is yet uncertain. The objective of this study was to examine the influence of an earthquake on the symptoms of fibromyalgia and evaluate the impacts of medications used to treat fibromyalgia on the clinical picture. METHOD: Ninety-five fibromyalgia patients were enrolled in a comparative study and divided into two groups: medication and non-medication. Three subcategories of medication groups were established: selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and gabapentinoid drugs (GDs). Before and after the earthquake, clinical evaluations were conducted using the Fibromyalgia Impact Questionnaire (FIQ), Hospital Anxiety and Depression Scale (HADS), and Jenkins Sleep Rating Scale (JSS). Statistical analyses were conducted to compare the scores before and after the earthquake and evaluate the differences between the groups. RESULTS: Statistically significant increases were observed in FIQ, HADS-anxiety, HADS-depression, and JSS scores in the medication and non-medication groups before and after the earthquake comparisons (p < 0.05). Non-medication group reported significantly higher post-earthquake changes in FIQ, HADS-anxiety, HADS-depression, and JSS compared to the medication group (p < 0.05). While HADS-anxiety, HADS-depression, and JSS changes after the earthquake differed according to the drug subgroups (p < 0.05), no statistically significant difference was observed in FIQ values (p > 0.05). The highest scores were detected in the GD subgroup. CONCLUSIONS: This study highlights the substantial impact of earthquakes on fibromyalgia patients. Medication use may assist in reducing the detrimental effects of stresses like earthquakes on fibromyalgia symptomatology. Future research with larger sample sizes and more extended follow-up periods is needed to explain these findings and optimize treatment regimens for fibromyalgia patients experiencing significant stressors.

How to treat chronic pain in rheumatic and musculoskeletal diseases (RMDs) - A pharmacological review.

INTRODUCTION: Chronic pain is a common symptom of rheumatic diseases that impacts patients' quality of life. While non-pharmacological approaches are often recommended as first-line treatments, pharmacological interventions are important for pain management. However, the effectiveness and safety of different pharmacological treatments for chronic pain in rheumatic diseases are unclear. METHODS: This review critically synthesizes the current evidence base to guide clinicians in selecting appropriate pharmacological treatments for their patients, considering the expected benefits and potential risks and side effects. RESULTS: For osteoarthritis, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, opioids, and antidepressants are commonly used, with NSAIDs being the most recommended. In addition, topical agents, such as topical NSAIDs, are recommended for localized pain relief. For fibromyalgia, amitriptyline, serotonin and noradrenaline reuptake inhibitors (SNRIs), and gabapentinoids are commonly used, with SNRIs being the most recommended. For back pain, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, opioids are used only for acute of flare-up pain, whereas neuropathic pain drugs are only used for chronic radicular pain. For inflammatory rheumatic diseases, disease-modifying antirheumatic drugs (DMARDs) and biological agents are recommended to slow disease progression and manage symptoms. CONCLUSION: While DMARDs and biological agents are recommended for inflammatory rheumatic diseases, pharmacological treatments for other rheumatic diseases only alleviate symptoms and do not provide a cure for the underlying condition. The use of pharmacological treatments should be based on the expected benefits and evaluation of side effects, with non-pharmacological modalities also being considered, especially for fibromyalgia.

Predictors of treatment response to serotonin and noradrenaline reuptake inhibitors in fibromyalgia.

INTRODUCTION: Fibromyalgia (FM) is often comorbid with anxiety and depression. Serotonin and noradrenaline reuptake inhibitors (SNRIs) are used in the treatment of FM, depression, and anxiety, but they are ineffective in a substantial number of patients. Recently, it has been reported that FM is associated with impaired glucose metabolism. OBJECTIVES: The aim of the study was to explore the associations between insulin resistance, psychiatric comorbidities, and treatment response to SNRIs in patients with FM. PATIENTS AND METHODS: A total of 59 patients with FM and 30 healthy controls (HCs) were recruited. The study patients were classified as treatment­nonresponsive if the SNRI treatment resulted in a reduction in reported pain by less than 30%. All participants were examined by a physician and completed self­report questionnaires. Blood samples were drawn to assess fasting glucose and insulin levels and to calculate the Homeostatic Model Assessment of Insulin Resistance (HOMA­IR) values. Multivariable logistic regression models were constructed to analyze the associations between insulin resistance, psychiatric comorbidies, and the lack of response to treatment with SNRIs. RESULTS: The SNRI nonresponders (FM [T-]) had higher body mass index (BMI), fasting insulin level, and HOMA­IR values than the responders (FM [T+]) and HCs. The FM [T+] patients did not significantly differ from HCs in terms of BMI, levels of fasting glucose and fasting insulin, and HOMA­IR values. Depression, anxiety, and personality disorders were significantly more prevalent in the FM [T-] than in the FM [T+] group. Insulin resistance, depression, anxiety, and personality disorders were identified as the predictors of nonresponse to SNRI treatment. The effect of BMI on the lack of response to SNRIs was fully mediated by insulin resistance. CONCLUSIONS: Increased values of certain clinical and metabolic parameters (BMI, fasting glucose, fasting insulin, HOMA­IR) as well as the presence of psychiatric comorbidities could affect the response to treatment with SNRIs in the patients with FM.

Pharmacotherapy for Spine-Related Pain in Older Adults.

As the population ages, spine-related pain is increasingly common in older adults. While medications play an important role in pain management, their use has limitations in geriatric patients due to reduced liver and renal function, comorbid medical problems, and polypharmacy. This review will assess the evidence basis for medications used for spine-related pain in older adults, with a focus on drug metabolism and adverse drug reactions. A PubMed/OVID search crossing common spine, neck, and back pain terms with key words for older adults and geriatrics was combined with common drug classes and common drug names and limited to clinical trials and age over 65 years. The results were then reviewed with identification of commonly used drugs and drug categories: nonsteroidal anti-inflammatories (NSAIDs), acetaminophen, corticosteroids, gabapentin and pregabalin, antispastic and antispasmodic muscle relaxants, tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tramadol, and opioids. Collectively, 138 double-blind, placebo-controlled trials were the focus of the review. The review found a variable contribution of high-quality studies examining the efficacy of medications for spine pain primarily in the geriatric population. There was strong evidence for NSAID use with adjustments for gastrointestinal and renal risk factors. Gabapentin and pregabalin had mixed evidence for neuropathic pain. SNRIs had good evidence for neuropathic pain and a more favorable safety profile than TCAs. Tramadol had some evidence in older patients, but more so in persons aged < 65 years. Rational therapeutic choices based on geriatric spine pain diagnosis are helpful, such as NSAIDs and acetaminophen for arthritic and myofascial-based pain, gabapentinoids or duloxetine for neuropathic and radicular pain, antispastic agents for myofascial-based pain, and combination therapy for mixed etiologies. Tramadol can be well tolerated in older patients, but has risks of cognitive and classic opioid side effects. Otherwise, opioids are typically avoided in the treatment of spine-related pain in older adults due to their morbidity and mortality risk and are reserved for refractory severe pain. Whenever possible, beneficial geriatric spine pain pharmacotherapy should employ the lowest therapeutic doses with consideration of polypharmacy, potentially decreased renal and hepatic metabolism, and co-morbid medical disorders.

Acetaminophen (paracetamol) is safe in older adults, but non-steroidal anti-inflammatories (e.g. ibuprofen) may be more effective for spine-related pain. Non-steroidal anti-inflammatories should be used in short-term lower dose courses with gastrointestinal precaution. Corticosteroids have the least evidence for treating nonspecific back pain. Gabapentin and pregabalin may cause dizziness or difficulty walking, but may have some benefit for neck and back nerve pain (e.g. sciatica) in older adults. They should be used in lower doses with smaller dose adjustments. Some muscle relaxants (carisoprodol, chlorzoxazone, cyclobenzaprine, metaxalone, methocarbamol, and orphenadrine) are avoided in older adults due to risk for sedation and falls. Others (tizanidine, baclofen, dantrolene) may be helpful for neck and back pain, with the most evidence for tizanidine and baclofen. These should be used in reduced doses, avoiding tizanidine with liver disease and reducing baclofen dosing with kidney disease. Older antidepressants are typically avoided in older adults due to their side effects, but nortriptyline and desipramine may be better tolerated for neck and back nerve pain at lower doses. Overall, newer antidepressants (namely duloxetine) have a better safety profile and good efficacy for spine-related nerve pain. Tramadol may be tolerated in older adults, but has risk for sedation, upset stomach, and constipation. It may be used in lower doses after alternative medications have failed, and works well with co-administered acetaminophen. Opioids are avoided due to their side effects and mortality risk, but low-dose opioid therapy may be helpful for severe refractory pain with close monitoring of patients clinically.

Depression and Long-Term Prescription Opioid Use and Opioid Use Disorder: Implications for Pain Management in Cancer.

OPINION STATEMENT: Preventing depression in cancer patients on long-term opioid therapy should begin with depression screening before opioid initiation and repeated screening during treatment. In weighing the high morbidity of depression and opioid use disorder in patients with chronic cancer pain against a dearth of evidence-based therapies studied in this population, patients and clinicians are left to choose among imperfect but necessary treatment options. When possible, we advise engaging psychiatric and pain/palliative specialists through collaborative care models and recommending mindfulness and psychotherapy to all patients with significant depression alongside cancer pain. Medications for depression should be reserved for moderate to severe symptoms. We recommend escitalopram/citalopram or sertraline among selective serotonin reuptake inhibitors (SSRIs), or the serotonin and norepinephrine reuptake inhibitors (SNRIs) duloxetine, venlafaxine, or desvenlafaxine if patients have a significant component of neuropathic pain or fibromyalgia. Tricyclic antidepressants (TCAs) (consider nortriptyline or desipramine, which have better anticholinergic profiles) should be considered for patients who do not respond to or tolerate SSRI/SNRIs. Existing evidence is inadequate to definitively recommend methylphenidate or novel agents, such as ketamine or psilocybin, as adjunctive treatments for cancer-related depression and pain. Physicians who treat patients with cancer pain should utilize universal precautions to limit the risk of non-medical opioid use (non-medical opioid use). Patients should be screened for non-medical opioid use behaviors at initial consultation and at regular intervals during treatment using a non-judgmental approach that reduces stigma. Co-management with an addiction specialist may be indicated for patients at high risk of non-medical opioid use and opioid use disorder. Buprenorphine and methadone are indicated for the treatment of opioid use disorder, and while they have not been systematically studied for treatment of opioid use disorder in patients with cancer pain, they do provide analgesia for cancer pain. While an interdisciplinary team approach to manage psychological stress may be beneficial, this may not be possible for patients treated outside of comprehensive cancer centers.

Treatment and diagnosis of chemotherapy-induced peripheral neuropathy: An update.

When peripheral neuropathy occurs due to chemotherapy treatment, it is referred to as chemotherapy-induced peripheral neuropathy (CIPN). Typically, symptoms are sensory rather than motor and include reduced feeling and heightened sensitivity to pressure, pain, temperature, and touch. The pathophysiology of CIPN is very complex, and it involves multiple mechanisms leading to its development which will be described specifically for each chemotherapeutic class. There are currently no approved or effective agents for CIPN prevention, and Duloxetine is the only medication that is an effective treatment against CIPN. There is an unavoidable necessity to develop preventative and treatment approaches for CIPN due to its detrimental impact on patients' lives. The purpose of this review is to examine CIPN, innovative pharmacological and nonpharmacological therapy and preventive strategies for this illness, and future perspectives for this condition and its therapies.

Low plasma serotonin linked to higher nigral iron in Parkinson's disease.

A growing body of evidence suggests nigral iron accumulation plays an important role in the pathophysiology of Parkinson's disease (PD), contributing to dopaminergic neuron loss in the substantia nigra pars compacta (SNc). Converging evidence suggests this accumulation might be related to, or increased by, serotonergic dysfunction, a common, often early feature of the disease. We investigated whether lower plasma serotonin in PD is associated with higher nigral iron. We obtained plasma samples from 97 PD patients and 89 controls and MRI scans from a sub-cohort (62 PD, 70 controls). We measured serotonin concentrations using ultra-high performance liquid chromatography and regional iron content using MRI-based quantitative susceptibility mapping. PD patients had lower plasma serotonin (p < 0.0001) and higher nigral iron content (SNc: p < 0.001) overall. Exclusively in PD, lower plasma serotonin was correlated with higher nigral iron (SNc: r(58) = - 0.501, p < 0.001). This correlation was significant even in patients newly diagnosed (< 1 year) and stronger in the SNc than any other region examined. This study reveals an early, linear association between low serotonin and higher nigral iron in PD patients, which is absent in controls. This is consistent with a serotonin-iron relationship in the disease process, warranting further studies to determine its cause and directionality.

Efficacy and safety of antidepressants for the treatment of back pain and osteoarthritis: systematic review and meta-analysis.

OBJECTIVE: To investigate the efficacy and safety of antidepressants for back and osteoarthritis pain compared with placebo. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane Central Register of Controlled Trials, CINAHL, International Pharmaceutical Abstracts, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform from inception to 15 November and updated on 12 May 2020. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials comparing the efficacy or safety, or both of any antidepressant drug with placebo (active or inert) in participants with low back or neck pain, sciatica, or hip or knee osteoarthritis. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data. Pain and disability were primary outcomes. Pain and disability scores were converted to a scale of 0 (no pain or disability) to 100 (worst pain or disability). A random effects model was used to calculate weighted mean differences and 95% confidence intervals. Safety (any adverse event, serious adverse events, and proportion of participants who withdrew from trials owing to adverse events) was a secondary outcome. Risk of bias was assessed with the Cochrane Collaboration's tool and certainty of evidence with the grading of recommendations assessment, development and evaluation (GRADE) framework. RESULTS: 33 trials (5318 participants) were included. Moderate certainty evidence showed that serotonin-noradrenaline reuptake inhibitors (SNRIs) reduced back pain (mean difference -5.30, 95% confidence interval -7.31 to -3.30) at 3-13 weeks and low certainty evidence that SNRIs reduced osteoarthritis pain (-9.72, -12.75 to -6.69) at 3-13 weeks. Very low certainty evidence showed that SNRIs reduced sciatica at two weeks or less (-18.60, -31.87 to -5.33) but not at 3-13 weeks (-17.50, -42.90 to 7.89). Low to very low certainty evidence showed that tricyclic antidepressants (TCAs) did not reduce sciatica at two weeks or less (-7.55, -18.25 to 3.15) but did at 3-13 weeks (-15.95, -31.52 to -0.39) and 3-12 months (-27.0, -36.11 to -17.89). Moderate certainty evidence showed that SNRIs reduced disability from back pain at 3-13 weeks (-3.55, -5.22 to -1.88) and disability due to osteoarthritis at two weeks or less (-5.10, -7.31 to -2.89), with low certainty evidence at 3-13 weeks (-6.07, -8.13 to -4.02). TCAs and other antidepressants did not reduce pain or disability from back pain. CONCLUSION: Moderate certainty evidence shows that the effect of SNRIs on pain and disability scores is small and not clinically important for back pain, but a clinically important effect cannot be excluded for osteoarthritis. TCAs and SNRIs might be effective for sciatica, but the certainty of evidence ranged from low to very low. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020158521.

Acupuncture for the Management of Low Back Pain.

PURPOSE OF REVIEW: This evidence-based systematic review will focus on the use of acupuncture and its role in the treatment of low back pain to help better guide physicians in their practice. It will cover the background and the burden of low back pain and present the current options for treatment and weigh the evidence that is available to support acupuncture as a treatment modality for low back pain. RECENT FINDINGS: Low back pain (LBP), defined as a disorder of the lumbosacral spine and categorized as acute, subacute, or chronic, can be a debilitating condition for many patients. Chronic LBP is more typically defined by its chronicity with pain persisting > 12 weeks in duration. Conventional treatment for chronic LBP includes both pharmacologic and non-pharmacologic options. First-line pharmacologic therapy involves the use of NSAIDs, then SNRI/TCA/skeletal muscle relaxants, and antiepileptics. Surgery is usually not recommended for chronic non-specific LBP patients. According to the 2016 CDC Guidelines for Prescribing Opioids for Chronic Pain and the 2017 American College of Physicians (ACP) clinical practice guidelines for chronic pain, non-pharmacologic interventions, acupuncture can be a first-line treatment for patients suffering from chronic low back pain. Many studies have been done, and most show promising results for acupuncture as an alternative treatment for low back pain. Due to non-standardized methods for acupuncture with many variations, standardization remains a challenge.

Screening for Anxiety in Adolescent and Adult Women: A Recommendation From the Women's Preventive Services Initiative.

DESCRIPTION: The Women's Preventive Services Initiative (WPSI), a national coalition of women's health professional organizations and patient representatives, developed a recommendation on screening for anxiety in adolescent and adult women to improve detection; achieve earlier diagnosis and treatment; and improve health, function, and well-being. The WPSI's recommendations are intended to guide clinical practice and coverage of services for the Health Resources and Services Administration and other stakeholders. The target audience for this recommendation includes all clinicians providing preventive health care to women, particularly in primary care settings. This recommendation applies to women and adolescent girls aged 13 years or older who are not currently diagnosed with anxiety disorders, including pregnant and postpartum women. METHODS: The WPSI developed this recommendation after evaluating results of a systematic review of the effectiveness of screening, accuracy of screening instruments, and benefits and harms of treatments in adolescent girls and adult women. No studies directly evaluated the overall effectiveness or harms of screening for anxiety. Twenty-seven screening instruments and their variations were moderately to highly accurate in identifying anxiety (33 individual studies and 2 systematic reviews; 171 studies total). Symptoms improved and relapse rates decreased with psychological therapies (246 randomized controlled trials [RCTs] in 5 systematic reviews) and with selective serotonin reuptake inhibitors or selective serotonin and norepinephrine reuptake inhibitors (126 RCTs in 3 systematic reviews). The WPSI also considered the effect of screening on symptom progression and identification of associated and underlying conditions, as well as implementation factors. RECOMMENDATION: The WPSI recommends screening for anxiety in women and adolescent girls aged 13 years or older who are not currently diagnosed with anxiety disorders, including pregnant and postpartum women. Optimal screening intervals are unknown, and clinical judgment should be used to determine frequency. When screening suggests the presence of anxiety, further evaluation is necessary to establish the diagnosis and determine appropriate treatment and follow-up.

Assessment of sleep quality of patients with panic disorder and generalized anxiety disorder during remission: a case-control study

Abstract Background Sleep disorders are common in psychiatric diseases. Panic disorder (PD) and generalized anxiety disorder (GAD) are two major anxiety disorders that are associated with sleep disorders. Objective We hypothesized that poor sleep quality continues in PD and GAD during remission. Therefore, in this study we aimed to compare the sleep quality of patients with PD and GAD to that of healthy controls. Methods The study included patients with PD (n = 42) and GAD (n = 40) who had been in remission for at least 3 months and healthy control volunteers (n = 45). The patients were administered the Pittsburgh Sleep Quality Index (PSQI), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI). Results The total PSQI scores of the GAD group were significantly increased in comparison to those of the PD (p = 0.009) and control (p < 0.001) groups. The rate of poor sleep quality in GAD during remission (77.5%) was greater than that of the PD (47.6%) and control (51.1%) groups (p = 0.011). Discussion GAD is a chronic and recurrent disease. In this study, it was found that the deterioration in sleep quality of patients with GAD may continue during remission. In the follow-up and treatment of patients, it is appropriate to question about sleep symptoms and to plan interventions according to these symptoms.

Effect of serotonin-norepinephrine reuptake inhibitors for patients with chemotherapy-induced painful peripheral neuropathy: A meta-analysis.

BACKGROUND: To compare the efficacy of serotonin-norepinephrine reuptake inhibitors (SNRIs) treatment for chemotherapy-induced peripheral neuropathy (CIPN) METHODS:: Two authors independently searched MEDLINE, Embase, Cochran Library, and Web of Science to identify and review articles published from January 1998 until December 2018 according to selection criteria. Outcomes were expressed as mean difference, the pooled odds ratio, or relative risk in a meta-analysis model. RESULTS: A total of 10 studies were included in this meta-analysis: 6 randomized-controlled studies and 4 observational studies. Meta-analysis showed that CIPN was improved after treatment with SNRI (standardized mean difference = 2.20; 95% confidence interval, 0.90-3.49; I = 93% in 3 randomized controlled studies). Somnolence and insomnia occurred in <15% of patients. Incidence of somnolence was lower than with pregabalin treatment, and insomnia was comparable to that in expectant management or pregabalin treatment. Incidence of nausea and vomiting was higher than in expectant management, but no significant difference was found when compared to expectant management. CONCLUSION: From the several available studies suitable for indirect comparison, SNRI shows excellent efficacy and tolerability to CIPN. SNRI could provide an important treatment option for CIPN.

Psychiatric Medication Use and Weight Outcomes One Year After Bariatric Surgery.

BACKGROUND: Given the high rates of psychiatric comorbidity in bariatric surgery patients, pharmacotherapy is common and could potentially influence weight loss outcomes. OBJECTIVE: We aimed to identify the impact of psychotropic medication use on percent total weight loss (%TWL) 1 year after bariatric surgery. METHODS: In this prospective cohort study, 190 patients were compared based on demographic variables (age, sex, relationship status, employment status), body mass index, %TWL, and psychotropic medication use before and 1 year after bariatric surgery. An analysis of variance test was used as a global test of significance for psychotropic medication comparisons related to %TWL. Significance of post hoc comparisons was calculated with the Tukey's Honestly Significance Difference test. RESULTS: Sixty-one of 190 (32.1%) patients were taking psychiatric medications before surgery; of those, 82% (50/61) continued to take psychiatric medications 1-year after surgery. %TWL did not significantly differ between patients taking no psychiatric medications, one medication, or more than one medication 1 year after surgery (31.4% vs. 29.9% vs. 34.4%, respectively). Among patients taking antidepressants, those taking serotonin-norepinephrine reuptake inhibitors had a significantly higher %TWL than those taking selective serotonin reuptake inhibitors (36.4% vs. 27.8%; P = 0.032). CONCLUSION: This longitudinal study suggests that psychiatric medication use was not associated with poorer %TWL at 1 year after bariatric surgery. Within class, antidepressant use may have differential effects on weight loss after bariatric surgery and warrants further investigation.

Platinum-induced peripheral neurotoxicity: From pathogenesis to treatment.

Platinum-induced peripheral neurotoxicity (PIPN) is a common side effect of platinum-based chemotherapy that may cause dose reduction and discontinuation, with oxaliplatin being more neurotoxic. PIPN includes acute neurotoxicity restricted to oxaliplatin, and chronic non-length-dependent sensory neuronopathy with positive and negative sensory symptoms and neuropathic pain in both upper and lower limbs. Chronic sensory axonal neuropathy manifesting as stocking-and-glove distribution is also frequent. Worsening of neuropathic symptoms after completing the last chemotherapy course may occur. Motor and autonomic involvement is uncommon. Ototoxicity is frequent in children and more commonly to cisplatin. Platinum-based compounds result in more prolonged neuropathic symptoms in comparison to other chemotherapy agents. Patient reported outcomes questionnaires, clinical evaluation and instrumental tools offer complementary information in PIPN. Electrodiagnostic features include diffusely reduced/abolished sensory action potentials, in keeping with a sensory neuronopathy. PIPN is dependent on cumulative dose but there is a large variability in its occurrence. The search for additional risk factors for PIPN has thus far yielded no consistent findings. There are currently no neuroprotective strategies to reduce the risk of PIPN, and symptomatic treatment is limited to duloxetine that was found effective in a single phase III intervention study. This review critically examines the pathogenesis, incidence, risk factors (both clinical and pharmacogenetic), clinical phenotype and management of PIPN.

Taxane and epothilone-induced peripheral neurotoxicity: From pathogenesis to treatment.

Taxane-induced peripheral neurotoxicity (TIPN) is the most common non-hematological side effect of taxane-based chemotherapy, and may result in dose reductions and discontinuations, having as such a detrimental effect on patients' overall survival. Epothilones share similar mechanism of action with taxanes. The typical TIPN clinical presentation is mainly comprised of numbness and paresthesia, in a stocking-and-glove distribution and may progress more proximally over time, with paclitaxel being more neurotoxic than docetaxel. Motor and autonomic involvement is less common, whereas an acute taxane-induced acute pain syndrome is frequent. Patient reported outcomes questionnaires, clinical evaluation, and instrumental tools offer complementary information in TIPN. Its electrodiagnostic features include reduced/abolished sensory action potentials, and less prominent motor involvement, in keeping with a length-dependent, axonal dying back predominately sensory neuropathy. TIPN is dose-dependent and may be reversible within months after the end of chemotherapy. The single and cumulative delivered dose of taxanes is considered the main risk factor of TIPN development. Apart from the cumulative dose, other risk factors for TIPN include demographic, clinical, and pharmacogenetic features with several single-nucleotide polymorphisms potentially linked with increased susceptibility of TIPN. There are currently no neuroprotective strategies to reduce the risk of TIPN, and symptomatic treatments are very limited. This review critically examines the pathogenesis, incidence, risk factors (both clinical and pharmacogenetic), clinical phenotype and management of TIPN.

Postpartum Bleeding in Pregnant Women Receiving SSRIs/SNRIs: New Insights From a Descriptive Observational Study and an Analysis of Data from the FAERS Database.

PURPOSE: To date, the available data on the relationship between the use of selective serotonin reuptake inhibitors (SSRIs) or the serotonin and norepinephrine reuptake inhibitor (SNRI) venlafaxine and postpartum hemorrhage (PPH) are conflicting and have not been extensively investigated, especially in terms of plasma drug concentrations. We performed data mining of antidepressant-induced PPH reported to the US Food and Drug Administration's Adverse Event Reporting System database, to assess the strength of the potential association between antidepressant pharmacotherapy and PPH in pregnant women. Concurrently, we carried out a descriptive observational population (pregnant women) analysis of the correlation between the plasma concentrations of SSRIs/SNRIs used during pregnancy and the extent of bleeding at delivery. METHODS: A disproportionality analysis of individual case study reports of PPH associated with SSRIs or venlafaxine in pregnant women was performed. Reporting odds ratio was used as a measure of disproportionality analysis. Pregnant women treated with an SSRI or SNRI (venlafaxine) for depressive or anxiety disorder and who consented to plasma drug concentration monitoring at the time of delivery were recruited. Plasma drug concentration assay was performed according to validated LC-MS/MS. Based on plasma drug concentrations, patients were classified into 1 of 2 groups, in therapeutic range or below therapeutic range for the drug administered, in accordance with the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie guideline, and correlations with blood loss were identified, with PPH defined as a blood loss of >500 mL. FINDINGS: Only 43 Individual Case Safety Reports (ICSRs) reported at least one SSRIs or venlafaxine as suspect drug in 14 years (database analyses). Forty-three women were enrolled in the study population (observational study). In 24 patients (55.8%) the plasma drug concentration was below the therapeutic threshold. Unexpectedly, the mean blood loss in the below-range group was significantly higher than that in the in-range group. PPH occurred in 30% of women: in 9.3% and in 20.7% of patients in the in-range and below-range groups, respectively. IMPLICATIONS: Although preliminary, these data indicate a rather good tolerability profile of SSRIs/SNRIs regarding postpartum bleeding. Moreover, they suggest that keeping the plasma levels of SSRIs/SNRIs low as a precautionary measure does not reduce postpartum bleeding, which was higher in the below-range group. The findings from this study suggest that the use of therapeutic drug monitoring in pregnancy, a period in which multiple variables affect drug metabolism, may allow for better treatment customization, with subsequent advantages in terms of tolerability and efficacy of treatment.

Diabetic neuropathy.

The global epidemic of prediabetes and diabetes has led to a corresponding epidemic of complications of these disorders. The most prevalent complication is neuropathy, of which distal symmetric polyneuropathy (for the purpose of this Primer, referred to as diabetic neuropathy) is very common. Diabetic neuropathy is a loss of sensory function beginning distally in the lower extremities that is also characterized by pain and substantial morbidity. Over time, at least 50% of individuals with diabetes develop diabetic neuropathy. Glucose control effectively halts the progression of diabetic neuropathy in patients with type 1 diabetes mellitus, but the effects are more modest in those with type 2 diabetes mellitus. These findings have led to new efforts to understand the aetiology of diabetic neuropathy, along with new 2017 recommendations on approaches to prevent and treat this disorder that are specific for each type of diabetes. In parallel, new guidelines for the treatment of painful diabetic neuropathy using distinct classes of drugs, with an emphasis on avoiding opioid use, have been issued. Although our understanding of the complexities of diabetic neuropathy has substantially evolved over the past decade, the distinct mechanisms underlying neuropathy in type 1 and type 2 diabetes remains unknown. Future discoveries on disease pathogenesis will be crucial to successfully address all aspects of diabetic neuropathy, from prevention to treatment.