Efficacy of patient education and duloxetine, alone and in combination, for patients with multisystem functional somatic disorder: Study protocol for the EDULOX trial.

BACKGROUND: Multisystem functional somatic disorder is characterized by specific patterns of persistent physical symptoms with a complex biopsychosocial etiology. The disorder can lead to disability and personal suffering. Current treatment options require specialized settings, therefore patients often wait a long time to receive specific treatment. Patient education is considered important in most treatment programs, but has only been investigated sparsely as a stand-alone treatment. Pharmacological treatment is limited to tricyclic antidepressants in low doses with no antidepressant properties. Duloxetine has been found effective in single organ functional disorders. As a treatment for multisystem functional somatic disorder, duloxetine could reduce symptoms and treat comorbid anxiety and depression. It may furthermore enhance the effect of patient education through a hypothesized effect on cognitive functioning. The purpose of the EDULOX trial is to study psycho-EDUcation and duLOXetine alone and in combination. METHODS: This is a nested study design. The parent trial "EDULOX1" (n = 424) will compare a patient education program with enhanced usual care in an open-labelled, randomized controlled trial. In addition to this, eligible participants will furthermore receive either duloxetine or active placebo in the nested, double-blinded, randomized controlled trial, "EDULOX2" (n = 212). Patient and clinician reported outcomes will be collected through questionnaires. CONCLUSION: The EDULOX trial may establish evidence for treatments applicable for the majority of patients with multisystem functional somatic disorder. If effective, duloxetine would be a more tolerable pharmacological treatment option that can target comorbid depression and anxiety, and potentially boost the effect of patient education. Trial registration number The study is registered at www. CLINICALTRIALS: gov (NCT06232473) and the internal list of research projects at the Region of Central Denmark (Case number 1-16-02-305-23). Approval from the Danish Medical Research Ethics Committees (Case number: 2212291) and the Danish Medicines Agency was obtained under EudraCT Number: 2022-002780-30 and Sponsor's Protocol Code Number: 9515.

Predicting acupuncture efficacy in fibromyalgia: results of a pragmatic open-label study.

OBJECTIVES: To identify the predictive factors of treatment response to acupuncture in patients with fibromyalgia (FM). METHODS: Patients with FM refractory to standard drug therapy underwent eight weekly acupuncture sessions. Significant improvement, defined as a reduction of at least 30% of the revised Fibromyalgia Impact Questionnaire (FIQR), was assessed at the end of the eight weeks (T1) of treatment and three months after the end of treatment (T2). Univariate analysis was conducted to identify predictors of significant improvement at T1 and T2. Variables that resulted to be significantly associated with clinical improvement at univariate analysis were included in multivariate models. RESULTS: Analyses were conducted on 77 patients (9 males, 11.7%). At T1, significant improvement in FIQR was recorded in 44.2% of patients. At T2, persistent significant improvement was recorded in 20.8% of patients. In the multivariate analysis, predictive variables of treatment failure were tender point count (TPC) (odds ratio [OR] =0.49, 95% confidence interval [95% CI]: 0.28-0.86, p=0.01) and pain magnification (OR=0.68, 95% CI: 0.47-0.99, p=0.04) assessed with the Pain Catastrophising Scale, at T1. At T2, the only predictive variable of treatment failure was concomitant duloxetine use (OR=0.21, 95% CI: 0.05-0.95, p=0.04). CONCLUSIONS: High TPC and a tendency for pain magnification predict immediate treatment failure, while duloxetine therapy predicts it three months after completion of the acupuncture course. The identification of clinical characteristics of unfavourable response to acupuncture could help to implement a cost-effective prevention of treatment failure in FM.

Efficacy and safety of different antidepressants and anticonvulsants in central poststroke pain: A network meta-analysis and systematic review.

OBJECTIVE: To evaluate the efficacy and safety of different antidepressants and anticonvulsants in the treatment of central poststroke pain (CPSP) by network meta-analysis and provide an evidence-based foundation for clinical practice. METHODS: PubMed, Cochrane Library, EMBASE, CNKI, APA PsycINFO, Wanfang, VIP and other databases were searched by computer to find clinical randomized controlled studies (RCTs) on drug treatment of CPSP. The retrieval time limit was from the establishment of each database to July 2022. The quality of the included RCTs was evaluated using the bias risk assessment tool recommended by Cochrane. Stata 14.0 was used for network meta-analysis. RESULTS: A total of 13 RCTs, 1040 patients and 9 drugs were finally included. The results of the network meta-analysis showed that the effectiveness ranking as rated by the visual analog scale (VAS) was gabapentin > pregabalin > fluoxetine > lamotrigine > duloxetine > serqulin > amitriptyline > carbamazepine > vitamin B. Ranking according to the numerical rating scale (NRS) was pregabalin > gabapentin > carbamazepine. Ranking derived from the Hamilton depression scale (HAMD) was pregabalin > duloxetine > gabapentin > amitriptyline. CONCLUSION: All nine drugs can relieve the pain of CPSP patients to different degrees; among them pregabalin and gabapentin have the most significant effect, and gabapentin and pregabalin also have the most adverse reactions. In the future, more multicenter, large sample, double-blind clinical randomized controlled trials need to be carried out to supplement and demonstrate the results of this study.

Predictors of Pain Reduction in Trials of Interventions for Aromatase Inhibitor-Associated Musculoskeletal Symptoms.

Background: Almost one-half of aromatase inhibitor (AI)-treated breast cancer patients experience AI-associated musculoskeletal symptoms (AIMSS); 20%-30% discontinue treatment because of severe symptoms. We hypothesized that we could identify predictors of pain reduction in AIMSS intervention trials by combining data from previously conducted trials. Methods: We pooled patient-level data from 3 randomized trials testing interventions (omega-3 fatty acids, acupuncture, and duloxetine) for AIMSS that had similar eligibility criteria and the same patient-reported outcome measures. Only patients with a baseline Brief Pain Inventory average pain score of at least 4 of 10 were included. The primary outcome examined was 2-point reduction in average pain from baseline to week 12. Variable cut-point selection and logistic regression were used. Risk models were built by summing the number of factors statistically significantly associated with pain reduction. Analyses were stratified by study and adjusted for treatment arm. Results: For the 583 analyzed patients, the 4 factors statistically significantly associated with pain reduction were Functional Assessment of Cancer Therapy Functional Well-Being greater than 24 and Physical Well-Being greater than 14 (higher scores reflect better function), and Western Ontario and McMaster Universities Osteoarthritis Index less than 50 and Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands less than 33 (lower scores reflect less pain). Patients with all 4 factors were greater than 6 times more likely to experience at least a 2-point pain reduction (odds ratio = 6.37, 95% confidence interval = 2.31 to 17.53, 2-sided P < .001); similar results were found for secondary 30% and 50% pain reduction endpoints. Conclusions: Patients with AIMSS who have lower symptom and functional distress at study entry on AIMSS intervention trials are more likely to experience meaningful pain reduction. Baseline symptom and functional status should be considered as stratification factors in future interventional trials.

Second-generation antidepressants for treatment of seasonal affective disorder.

BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent depressive episodes that is often treated with second-generation antidepressants (SGAs), light therapy, or psychotherapy. OBJECTIVES: To assess the efficacy and safety of second-generation antidepressants (SGAs) for the treatment of seasonal affective disorder (SAD) in adults in comparison with placebo, light therapy, other SGAs, or psychotherapy. SEARCH METHODS: This is an update of an earlier review first published in 2011. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 1) in the Cochrane Library (all years), Ovid MEDLINE, Embase, and PsycINFO (2011 to January 2020), together with the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR) (all available years), for reports of randomised controlled trials (RCTs). We hand searched the reference lists of all included studies and other systematic reviews. We searched ClinicalTrials.gov for unpublished/ongoing trials. We ran a separate update search for reports of adverse events in the Ovid databases.  SELECTION CRITERIA: For efficacy we included RCTs of SGAs compared with other SGAs, placebo, light therapy, or psychotherapy in adult participants with SAD. For adverse events we also included non-randomised studies. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts and full-text publications against the inclusion criteria. Data extraction and 'Risk of bias' assessment were conducted individually. We pooled data for meta-analysis where the participant groups were similar, and the studies assessed the same treatments with the same comparator and had similar definitions of outcome measures over a similar duration of treatment. MAIN RESULTS: In this update we identified no new RCT on the effectiveness of SGAs in SAD patients. We included 2 additional single-arm observational studies that reported on adverse events of SGAs.  For efficacy we included three RCTs of between five and eight weeks' duration with a total of 204 participants. For adverse events we included two RCTs and five observational (non-randomised) studies of five to eight weeks' duration with a total of 249 participants. All participants met the DSM (Diagnostic and Statistical Manual of Mental Disorders) criteria for SAD. The average age ranged from 34 to 42 years, and the majority of participants were female (66% to 100%). Results from one trial with 68 participants showed that fluoxetine (20/36) was numerically superior to placebo (11/32) in achieving clinical response; however, the confidence interval (CI) included both a potential benefit as well as no benefit of fluoxetine (risk ratio (RR) 1.62, 95% CI 0.92 to 2.83, very low-certainty evidence). The number of adverse events was similar in both groups (very low-certainty evidence). Two trials involving a total of 136 participants compared fluoxetine versus light therapy. Meta-analysis showed fluoxetine and light therapy to be approximately equal in treating seasonal depression: RR of response 0.98 (95% CI 0.77 to 1.24, low-certainty evidence), RR of remission 0.81 (95% CI 0.39 to 1.71, very low-certainty evidence). The number of adverse events was similar in both groups (low-certainty evidence). We did not identify any eligible study comparing SGA with another SGA or with psychotherapy. Two RCTs and five non-randomised studies reported adverse event data on a total of 249 participants who received bupropion, fluoxetine, escitalopram, duloxetine, nefazodone, reboxetine, light therapy, or placebo. We were only able to obtain crude rates of adverse events, therefore caution is advised regarding interpretation of this information. Between 0% and 100% of participants who received an SGA suffered an adverse event, and between 0% and 25% of participants withdrew from the study due to adverse events. AUTHORS' CONCLUSIONS: Evidence for the effectiveness of SGAs is limited to one small trial of fluoxetine compared with placebo showing a non-significant effect in favour of fluoxetine, and two small trials comparing fluoxetine against light therapy suggesting equivalence between the two interventions. The lack of available evidence precluded us from drawing any overall conclusions on the use of SGAs for SAD. Further, larger RCTs are required to expand and strengthen the evidence base on this topic, and should also include comparisons with psychotherapy and other SGAs. Data on adverse events were sparse, and a comparative analysis was not possible. The data we obtained on adverse events is therefore not robust, and our confidence in the data is limited. Overall, up to 25% of participants treated with SGAs for SAD withdrew from the study early due to adverse events.

Analgesic Effects of Sokeikakketsuto on Chemotherapy-Induced Mechanical Allodynia and Cold Hyperalgesia in Rats.

The anticancer agents including oxaliplatin, paclitaxel, and bortezomib cause severe peripheral neuropathy. The Kampo medicine Sokeikakketsuto (SOKT) has been widely used to treat several types of pain. In this study, the analgesic effects of SOKT on oxaliplatin-, paclitaxel-, and bortezomib-induced peripheral neuropathy were investigated in rat models. Rats were treated with oxaliplatin (4 mg/kg, intraperitoneally (i.p.), twice a week for four weeks), paclitaxel (4 mg/kg, i.p., twice a week for two weeks), or bortezomib (0.2 mg/kg, i.p., twice a week for two weeks). SOKT (0.3 or 1.0 g/kg) or duloxetine hydrochloride (30 mg/kg, as a positive control) was administered orally after neuropathy developed. Mechanical allodynia and cold hyperalgesia were assessed using the von Frey test and the acetone test, respectively. These tests were performed immediately before and 30, 60, 90, and 120 min after the administration of the drugs. Repeated treatment of oxaliplatin induced mechanical allodynia and cold hyperalgesia. A single administration of SOKT (1 g/kg, per os (p.o.)), as well as duloxetine, temporarily reversed both the mechanical allodynia and the cold hyperalgesia. Repeated administration of paclitaxel and bortezomib also induced the mechanical allodynia. SOKT and duloxetine reversed the mechanical allodynia caused by bortezomib, but not by paclitaxel. SOKT might have the potential to become a new drug to relieve the symptom of oxaliplatin- or bortezomib-induced peripheral neuropathy.

Tratamiento conservador de la artrosis de cadera / Conservative treatment of hip osteoarthritis

Ante un escenario clínico de coxalgia por artrosis de cadera se planteó la necesidad de conocer los tratamientos con-servadores más seguros y efectivos para el manejo del dolor. El tratamiento de la artrosis requiere un enfoque integral e individualizado en función de las preferencias del paciente para lograr el máximo beneficio clínico. Existen numerosas estrategias útiles para el manejo del dolor en pacientes con artrosis de cadera siendo fuertemente recomendados de inicio la actividad física, los antiinflamatorios no esteroideos (AINE) orales y en ciertos casos los corticoides intraarticulares, tramadol o duloxetina, siempre asociado con la actividad física. Los ejercicios más recomendados son los aeróbicos y el Tai Chi o yoga. (AU)

Faced with a clinical scenario of coxalgia due to hip osteoarthritis, the need to know the safest and most effective conservative treatments for pain management arose. The treatment of osteoarthritis requires a comprehensive and individualised approach based on the patient's preferences to achieve maximum clinical benefit. There are numerous useful strategies for pain management in patients with hip osteoarthritis being strongly recommended from the beginning such as physical activity, oral non-steroidal anti-inflammatory drugs (NSAID) and in certain cases intra-articular corticosteroids, tramadol or duloxetine, always associated with physical activity. The most recommended exercises are aerobics and Tai Chi or yoga. (AU)

Effects of the publication of Clinical Guidelines for the Management of Chemotherapy-Induced Peripheral Neuropathy on the Administration Preferences of Oncology Specialists: Japanese Association of Supportive Care in Cancer.

OBJECTIVE: We conducted a questionnaire survey of oncology specialists to investigate the frequency of administration of different drugs for the management of chemotherapy-induced peripheral neuropathy in Japan in 2015. Our group published Clinical Guidelines for the Management of Chemotherapy-Induced Peripheral Neuropathy in 2017 (CIPN-GL2017). In these guidelines, we recommended duloxetine only. To verify the effect of the publication of the CIPN-GL2017, we conducted a questionnaire survey in 2019. METHODS: In 2015 and again in 2019, we investigated the use of vitamin B12, antiepileptic agents, duloxetine, antidepressants other than duloxetine, non-steroidal anti-inflammatory drugs, opioids and the Kampo compound (goshajinkigan) in a questionnaire employing a three-point scale wherein A implies routine or prophylactic administration, B implies occasional administration and C implies infrequent administration. RESULTS: We sent the questionnaires via email to 971 diplomates of the Subspecialty Board of Japanese Society of Medical Oncology in 2015 and 1239 diplomates in 2019. The administration ratio (A + B) of duloxetine for numbness and pain was 46.8 and 31.7%, respectively, in 2015 and 68.9% (P < 0.01) and 73.1% (P < 0.01) in 2019. In response to the question regarding awareness of the CIPN-GL2017, 53.2% of respondents to the 2019 questionnaire were aware of the CIPN-GL2017. Among the respondents with an awareness of the CIPN-GL2017, the prescription rate of duloxetine (78.3%) for pain was significantly higher than that among respondents without any awareness (67.4%). CONCLUSIONS: It is possible that the publication of CIPN-GL2017 influenced administration preferences of oncology specialists.

DUOX2, a common modulator in preventive effects of monoamine-based antidepressants on water immersion restraint stress- and indomethacin- induced gastric mucosal damage.

Multiple kinds of monoamine-based antidepressants have been shown prophylactic effects in experimentally induced gastric ulcer. The loss of redox homeostasis plays a principle role in the development of peptic mucosal damage. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are one of the most important sources of reactive oxygen species within the gastrointestinal tract. It is unclear whether there are some common NADPH oxidases modulated by monoamine-based antidepressants in different gastric mucosal damage models. We explored the effects of selective serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine on the reactive oxygen species production and antioxidant capacity in the gastric mucosa of water immersion restraint (WIRS) or indomethacin treated rats, and examined the role of NADPH oxidases in the protective effects. Pretreated duloxetine prevented the increase of gastric mucosal NADPH oxidase activity and NADPH oxidase inhibitor apocynin dose-dependently protected gastric mucosa from damage by the two factors. Furthermore, dual oxidase 2 (DUOX2) and NADPH oxidase4 (NOX4) are involved in the protective effects of duloxetine in both models. We then examined NADPH oxidases expression modulated by the other monoamine-based antidepressants including selective serotonin reuptake inhibitor (SSRIs) fluoxetine, tricyclic agent (TCAs) amitriptyline and monoamine oxidase inhibitor (MAOs) moclobemide in the two models, and all the three antidepressants reduced the DUOX2 expression in the gastric mucosa. So DUOX2 was a common modulator in the preventive effects of all the monoamine-based antidepressants on WIRS- and indomethacin-induced gastric lesion. Our work provided a peripheral joint molecular target for monoamine modulatory antidepressants, which may be helpful to reveal the mechanisms of this kind of drugs more than monoamine regulation.

Analgesic Effect of Duloxetine on an Animal Model of Monosodium Iodoacetate-Induced Hip Osteoarthritis.

We investigated the efficacy of duloxetine on hyperalgesia, histopathological and radiographic findings, pain-related sensory innervation of dorsal-root ganglia (DRG), and spinal changes in a rat model of induced hip osteoarthritis (OA). The right hip joints of male Sprague-Dawley rats (n = 6 rats/group) in the Sham group were injected with 25 µl of sterile saline and 25 µl of sterile saline with 2 mg of monosodium iodoacetate (MIA) were injected to the MIA + Vehicle and MIA + Duloxetine groups. We injected duloxetine 20 mg/kg intraperitoneally in the MIA + Duloxetine group 28 days after injection, whereas rats in the MIA + Vehicle group were injected with 0.5 ml of 20% dimethyl sulfoxide. We assessed hyperalgesia, histopathological changes, immunoreactive (-ir) neurons for calcitonin gene-related peptide and activating transcription factor 3 in DRG, and immunoreactive neurons for ionized-calcium-binding adaptor molecule 1 (Iba1) in the dorsal horn of the spinal cord. MIA administration into the hip joint let to mechanical hyperalgesia of the ipsilateral hind paw (p < 0.05). A single injection of duloxetine significantly attenuated it in induced hip OA (p < 0.05) and suppressed the number of Iba1-ir microglia of the ipsilateral dorsal horn (p < 0.05). These results suggest that a single injection of duloxetine suppressed mechanical hyperalgesia and may influence the expression of Iba1 in the microglia of the ipsilateral dorsal horn in the MIA-induced hip OA. This finding implies the inhibitory effects of duloxetine against neuropathic pain, which may lead to a change of microglial activities. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:422-430, 2020.

Okada Purifying Therapy in combination with duloxetine vs. duloxetine alone in patients with TMD and fibromyalgia: a randomized clinical study.

OBJECTIVES: This randomized study was aimed at evaluating the additional analgesic effect of Okada Purifying Therapy (OPT) when administered in combination with duloxetine in patients with Temporomandibular Disorders (TMDs) and Fibromyalgia (FM). METHODS: Patients with TMDs visited at Department of Oral and Maxillofacial Sciences, Sapienza University of Rome who were diagnosed with FM were selected for the study. The final sample was composed of 31 patients: 15 patients were treated only with duloxetine (Group I) and 16 patients underwent also OPT treatment (Group II), for eight weeks. Craniomandibular index, total tenderness score, Brief Pain Inventory Modified Short Form, Fibromyalgia Impact Questionnaire, Beck Depression Inventory and State and Trait Anxiety Inventory-1 were assessed at the beginning (T0), during the course (T1) and after therapy (T2). Descriptive and inferential statistics were performed. RESULTS: In all the data analyzed, both groups showed an improvement in particular between T0 and T1. No statistically significant differences were observed between the two groups during the trial, except for the interaction between treatment and time as to the ability of walking at the BPI-I (F=7.57, p=0.002). No side effects due to the duloxetine were recorded in group II compared to group I. CONCLUSION: The additional complementary treatment (OPT) did not appear to give the patients with TMDs and FM any further benefit but it might improve pharmacological tolerability of the traditional medication.

Treatment of Poststroke Pathologic Laughing With Duloxetine: A Case Series.

OBJECTIVES: Pathologic laughing is characterized by episodes of uncontrollable laughter caused by underlying neurologic disturbances, such as stroke. Several types of medication, including selective serotonin reuptake inhibitors, have demonstrated only limited success at treating the condition. Duloxetine, a dual serotonin-norepinephrine reuptake inhibitor, is reportedly effective in treating the symptoms of mood disorders. We herein introduce a prospective consecutive sample of stroke patients with pathologic laughing treated with duloxetine. METHODS: We enrolled patients without a history of psychological illness who exhibited poststroke pathologic laughter. Duloxetine administration was commenced at an initial dose of 30 mg once daily. The dose was increased to 60 mg once daily within 2 weeks for all patients except 2. The effect of the treatment was assessed by means of the Pathological Laughter and Crying Scale. RESULTS: A total of 7 patients were included in the study. Improvements were observed within an average of 10 days after duloxetine administration. Pathological Laughter and Crying Scale score decreased after duloxetine administration in all patients, and 4 patients demonstrated a decrease in score of more than 50%. All patients reported subjective improvement of symptoms, and no adverse effects were observed. CONCLUSIONS: This case series demonstrates that duloxetine could attenuate pathologic laughing exhibited by stroke patients; however, further randomized controlled studies are necessary to validate our findings.

Duloxetine Improves Spinal Cord Stimulation Outcomes for Chronic Pain.

OBJECTIVE: Spinal cord stimulation (SCS) has been shown to be effective in treating chronic pain in patients with varying etiologies. However, the impact of pharmacological treatment on augmenting response to SCS has not been previously studied. METHODS: We enrolled 108 patients who had undergone SCS surgery and documented their pain preoperatively and at 12 months postoperatively using the Numeric Rating Scale (NRS), McGill Pain Questionnaire (MPQ), Beck Depression Inventory (BDI), Oswestry Disability Index (ODI), Pain Catastrophizing Scale (PCS), and Global Impression of Change (GIC). Pain outcomes were compared between patients receiving SCS alone and in addition to duloxetine. RESULTS: At 1-year follow-up, patients receiving duloxetine and SCS (n = 41) had better pain relief in the affective component of MPQ (p < 0.05) than those receiving SCS alone (n = 71). Patients on duloxetine with SCS also were significantly more willing to receive SCS again (p < 0.01). This willingness appeared to be duloxetine dose dependent (p < 0.05). Patients receiving pregabalin or gabapentin with SCS did not have significantly more pain relief than patients receiving SCS alone. CONCLUSION: This study shows the combination therapy to be an effective strategy to provide more holistic pain relief and further improve the quality of life of SCS patients.

What Interventions Improve Outcomes for the Patient Who Is Depressed and in Pain?

SPECIFIC CLINICAL ISSUE: The purpose of this clinical consultation is to offer nurses evidence-based strategies to provide holistic care to their patients with comorbid depression and pain. The combination of depression and pain is common and, if not managed effectively, has negative outcomes. Treatment-resistance is one negative outcome. The worst-case scenario for unrelieved depression and/or pain is suicide. MAJOR PRACTICE RECOMMENDATIONS BASED ON BEST EVIDENCE: Antidepressants, particularly duloxetine, have had efficacy for pain and depression. Cognitive behavioral therapy, an evidence-based treatment for depression, has been found to decrease pain. Examples of additional interventions include exercise, relaxation techniques, mindfulness, and music. Providing holistic nursing care and working with other disciplines optimizes more effective management of these co-occurring conditions.

The evaluation of changes in peripheral neuropathy and quality-of-life using low-frequency electrostimulation in patients treated with chemotherapy for breast cancer: a study protocol.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a progressive, enduring, and sometimes irreversible neurotoxic symptom that occurs in 30-40% of chemotherapy-treated cancer patients. CIPN negatively affects both the patient's abilities to perform daily activities and their health-related quality of life (HRQOL) after chemotherapy treatment. Although this neuropathy has been treated with duloxetine and/or gabapentin, limited therapeutic benefits have been reported, thereby necessitating the development of an integrated approach that combines pharmacological management and complementary methods such as acupuncture and electric nerve stimulation. Therefore, this study is designed to examine the effect of a portable, low-frequency electrostimulation (ES) device on CIPN symptoms and HRQOL of female patients diagnosed with CIPN immediately after chemotherapy for breast cancer. METHODS: This study is a single-center, randomized, placebo-controlled trial with two parallel groups and a 2-week follow-up. We will enroll 80 breast cancer patients who are newly diagnosed with CIPN after chemotherapy. Duloxetine or pregabalin will be prescribed to all participants from the initial assessment. Half of the patients will be assigned into the experimental group and the other half to the control group. The CarebandR (Piomed Inc., Seoul, Korea), a wearable wristband that generates low-frequency electrostimulation, will be administered only to the experimental group. Electrostimulation will be administered on the unilateral PC6 acupoint. A numerical rating scale will be used to assess the overall intensity of CIPN symptoms. The key secondary outcome variables include patient-reported CIPN symptom distress tested by a self-rated questionnaire, physician-rated symptom severity assessed by the Total Neuropathy Score, and HRQOL. DISCUSSION: It is expected that the combination of a low-frequency electrostimulation device and pharmacological intervention (duloxetine or pregabalin) will produce synergistic effects in breast cancer patients with CIPN after treatment. To our knowledge, this is the first study to investigate the beneficial effect of a new integrated approach for CIPN management after breast cancer treatment. The study findings can expand our knowledge and understanding of the occurrence of CIPN and the efficacy of integrated intervention efforts to ameliorate CIPN symptoms. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), Republic of Korea, ID: KCT0002357 . Registered retrospectively on 13 June 2017.

[Hyponatremia associated with SSRI/NRSI: Descriptive and comparative epidemiological study of the incidence rates of the notified cases from the data of the French National Pharmacovigilance Database and the French National Health Insurance]. / Les hyponatrémies sous ISRS/IRSNA : étude épidémiologique descriptive et comparative des taux d'incidence de cas notifiés à partir des données de la Banque nationale de pharmacovigilance et de l'Assurance maladie.

INTRODUCTION: Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) are frequently prescribed. These antidepressants can potentially induce serious hyponatremia through the SIADH syndrome. That seems to concern all molecules of these classes but the individual risk of each molecule is not well known. The aims of the study were to compare the incidence rate of each molecule in order to identify the existence of molecules more at risk of inducing hyponatremia and to characterize a profile of patients at risk for hyponatremia during a treatment with a SSRI or a SNRI. METHOD: The cases of hyponatremia under SSRI/SNRI were extracted from the French pharmacovigilance database (BPNV). The exposition to the different SSRIs/SNRIs in the French population was estimated from the French National Health Insurance database (SNIIRAM) using a sampled database (Echantillon Généralistes des Bénéficiaires). The study ran from 01/01/2011 to 31/12/2013. The primary study endpoint was the incidence rate of notifications of the hyponatremia cases in patients treated by SSRI/SNRI and recorded into the BNPV database, related to the average annual number of corresponding treatments initiated during the same period. RESULTS: The number of cases of hyponatremia included in the study was 169 for 3 749 800 adult patients initiating treatment. The incidence rate of cases was 1.64 for 100 000 persons per year (PY). The standardized incidence rates between the different molecules showed no difference except for duloxetine (2.79/100 000 PY p > 0.03). Identified risk factors were age, with a large increase of incidence rate from 75 years old (incidence 12.5 higher) and female gender. CONCLUSIONS: Comparison of the incidence rates from spontaneous reports indicates a greater risk of hyponatremia for duloxetine for 2011-2013. This result needs to be confirmed by other studies. The advanced age and female sex are risk factors, irrespective of the molecule.

Chemotherapy-induced peripheral neuropathy: a review of recent findings.

PURPOSE OF REVIEW: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, frequently chronic condition characterized by pain and decreased function. Given the growing number of cancer survivors and an increasing recognition of opioid therapy limitations, there is a need for critical analysis of the literature in directing an informed and thoughtful approach for the management of painful CIPN. RECENT FINDINGS: A PubMed search for 'chemotherapy-induced peripheral neuropathy AND pain' identifies 259 publications between 1 January 2016 and 31 March 2017. Based on review of this literature, we aim to present a clinically relevant update of painful CIPN. Notably, the use of duloxetine as a first-line agent in treatment of CIPN is confirmed. Moreover, clinical trials focus on nonpharmacologic strategies for managing painful CIPN. SUMMARY: Despite the volume of recent publications, there are limited preventive or therapeutic strategies for CIPN supported by high-level evidence. Duloxetine remains the only pharmacologic agent with demonstrated benefit; its clinical use should be routinely considered. Moving forward, nonopioid analgesic therapies will likely play an increasing role in CIPN treatment, but further research is necessary to confirm their utility. Promising therapies include vitamin B12 supplementation, physical therapy, and various forms of neuromodulation.

Análisis de costo-efectividad de los medicamentos utilizados para el tratamiento de pacientes con dolor neuropático en Colombia / Cost-effectiveness analysis of drugs used for the treatment of patients with neuropathic pain in Colombia

INTRODUCCIÓN: El análisis de costo-efectividad de ácido tióctico, acetaminofén y tramadol, acetaminofén e hidrocodona, tramadol, amitriptilina, imipramina, valproato, acetaminofén y codeína, buprenorfina, capsaicina, carbamazepina, parches de fentanyl, tapentadol, duloxetina, gabapentina, parches de lidocaína, oxcarbazepina, pregabalina para el tratamiento de pacientes con dolor neuropatico en Colombia, se desarrolla en el marco del mecanismo técnico-científico para la ampliación progresiva del plan de beneficios y la definición de la lista de exclusiones, establecido en el artículo 15 de la Ley 1751 de 2015. Estas tecnologías fueron seleccionadas por la Dirección de Beneficios, Costos y Tarifas del Aseguramiento en Salud del Ministerio de Salud y Protección Social (MinSalud), y remitidas al Instituto de Evaluación Tecnológica en Salud (IETS) para su evaluación. Con respecto a la condición de salud de interés, la asociación internacional para el estudio del dolor (IASP 2011) definió el dolor neuropático como dolor causado por consecuencia directa de una lesión o enfermedad del sistema nervioso somatosensitivo. El mecanismo generador del dolor neuropático se halla en cualquier sitio a lo largo del recorrido de las vías nociceptivas (las vías que conducen la información de tipo doloroso), sin estimular inicialmente a los nociceptores (los receptores de dolor), a diferencia de lo que sucede con el dolor nociceptivo o fisiológico. El dolor neuropático es causado por diversos trastornos que afectan el sistema nervioso central y perifér