A comparative study on efficacy and safety of tablet duloxetine 60 mg and tablet gabapentin 300 mg among patients with diabetic polyneuropathy – A randomized double-blind study

Background: Diabetic peripheral neuropathy is defined as the presence of symptoms and signs of peripheral nerve damage among patients with diabetes, after ruling out other potential causes. Diabetic neuropathies are one among the most common long-term complications of diabetes. About 60% of diabetic patients are affected by neuropathy. Aim and Objectives: This study aims to study the efficacy and safety of tablet duloxetine 60 mg and tablet gabapentin 300 mg among patients with diabetic polyneuropathy. Materials and Methods: This study was randomized, comparative, double-blind parallel group study which was conducted for a period of 6 months. Sixty patients with diabetic polyneuropathic pain were randomly allocated into two groups. One group received duloxetine 60 mg and other group received gabapentin 300 mg. Efficacy was assessed using visual analog scale (VAS), short form of McGill pain questionnaire, and patients global impression of change score. Safety was assessed using adverse drug reaction profile. Results: In the duloxetine group, the mean VAS score at the baseline was 54.97 ± 6.75, and at 3 months, it was 20.07 ± 5.32 which was statistically significant. In the gabapentin group, the mean score at baseline was 53.57 ± 7.85, and at 3 months, it was 26.57 ± 4.39 which was also statistically significant. The difference between the baseline and 3rd month mean McGill score in both groups was statistically significant. Conclusions: We found that both duloxetine 60 mg once daily and gabapentin 300 mg once daily are effective in the treatment of diabetic polyneuropathic pain. However, duloxetine 60 mg once daily is more efficacious than gabapentin 300 mg once daily in the treatment of diabetic neuropathic pain. Both the drugs are well tolerated but gabapentin is better tolerated than duloxetine.

Structural elucidation and mechanism study for Hofmann-Martius-like rearrangement products in duloxetine hydrochloride under the process condition / 中国药科大学学报

@#Two Hofmann-Martius-like rearrangement products generated in the production of duloxetine hydrochloride were studied. The structures and generation mechanism of the two Hofmann-Martius rearrangement products were analyzed by LC-MS and NMR. The results showed that under the acidic conditions, the naphthol ether bond of duloxetine would break down and the intermediates of naphthol and the alkyl thiophene cation was generated; the two Hofmann-Martius-like rearrangement products were proven to be a pair of isomers produced by nucleophilic substitution between the naphthol intermediate state and the alkyl thiophene cation intermediate state at the ortho or the para position, respectively. The production of two isomers was related to the strong acidic and protic solvent environment. Therefore, in the salting process of duloxetine hydrochloride, the pH value should be controlled in the range of 3-7 and temperature should be maintained below 50 °C, as well as the nonprotic solvent acetone is chosen to avoid generation of the two isomers.

Comparison of the effects of duloxetine and pregabalin on pain and associated factors in patients with knee osteoarthritis

SUMMARY OBJECTIVES: This study aimed to investigate the effects of duloxetine and pregabalin primarily on pain and functional status in patients with knee osteoarthritis and secondarily on quality of life, depression, anxiety, and sleep disturbance. METHODS: A total of 66 patients with knee osteoarthritis were randomized to use duloxetine or pregabalin. Patients were evaluated by Visual Analog Scale, Neuropathic Pain Diagnostic Questionnaire, Western Ontario and McMaster University Osteoarthritis Index, Short Form-36, Beck Depression Inventory, Beck Anxiety Inventory, and Pittsburg Sleep Quality Index before the treatment and after 4 and 12 weeks of treatment. RESULTS: Improvements occurred in Visual Analog Scale, Neuropathic Pain Diagnostic Questionnaire, Western Ontario and McMaster University Osteoarthritis Index, Short Form-36 (with an exception of the mental health subgroup scores in duloxetine-treated group), Beck Depression Inventory, and Beck Anxiety Inventory scores in both groups from 4 weeks after baseline. Pittsburg Sleep Quality Index total scores and SF-36 mental health subgroup scores started to improve on the 4th and 12th weeks in pregabalin- and duloxetine-treated groups, respectively. CONCLUSION: Osteoarthritis pain, a complex outcome with nociceptive and neuropathic components, leads to central sensitization in a chronic phase. Using centrally acting drugs in the control of pain and associated symptoms would increase the probability of treatment success.

Hyperprolactinemia and galactorrhea associated with the use of duloxetine to treat chronic neuropathic pain. Case report / Hiperprolactinemia e galactorreia associada ao uso de duloxetina para tratamento de dor neuropática crônica. Relato de caso

ABSTRACT BACKGROUND AND OBJECTIVES: The association of the use of some drugs with hyperprolactinemia and galactorrhea has been reported in the literature, but information on the role of duloxetine in these alterations is scarce. Therefore, the aim of this study was to highlight this adverse effect and discuss the pathophysiological causes of galactorrhea associated with the use of duloxetine in a patient undergoing treatment for chronic pain. CASE REPORT: Female patient, 70 years old, with herpetic neuropathy diagnosis. She developed refractory pain after drug treatment and was referred to the pain clinic. Duloxetine (60mg) taken once a day was maintained and associated with blocks with local anesthetic in regions of herpetic pain. The patient complained of galactorrhea and changes in weight and showed an increase in serum prolactin. Then, the possibility of hyperprolactinemia due to duloxetine was raised. Duloxetine was suspended, and after one month, a significant reduction in serum prolactin levels and end of galactorrhea were observed. CONCLUSION: The treatment of patients with neuropathic pain is extremely challenging and the detailed understanding, especially of the pharmacological strategy and its possible adverse effects, is fundamental for the better management of patients and their well-being. Therefore, it is concluded that duloxetine, although rarely, can cause an increase in serum prolactin and galactorrhea in users.

RESUMO JUSTIFICATIVA E OBJETIVOS: A associação do uso de alguns fármacos com hiperprolactinemia e galactorreia tem sido relatada na literatura, mas são escassas as informações sobre o papel da duloxetina nestas alterações. Portanto, o objetivo deste estudo foi destacar este efeito adverso e discutir as causas fisiopatológicas da galactorreia associada ao uso de duloxetina no tratamento da dor crônica. RELATO DO CASO: Paciente do sexo feminino, 70 anos, com diagnóstico de neuropatia herpética. Evoluiu com refratariedade álgica após tratamento farmacológico, sendo encaminhada à clínica de dor. Optou-se por manter a duloxetina (60 mg) uma vez ao dia e associar bloqueios com anestésico local em regiões de dor herpética. A paciente queixou-se de galactorreia e alteração de peso e apresentou elevação da prolactina sérica. Foi aventada, então, a possibilidade de hiperprolactinemia pela duloxetina. Foi, então, realizada a suspensão da duloxetina e, após um mês, foi observada redução expressiva dos níveis séricos da prolactina e cessação da galactorreia. CONCLUSÃO: O tratamento de pacientes com dor neuropática é extremamente desafiador e a compreensão detalhada do processo, em destaque para a estratégia farmacológica e seus possíveis efeitos adversos é fundamental para o melhor manejo dos pacientes e manutenção do bem-estar. Diante disso, concluiu-se que a duloxetina, apesar de acontecer raramente, pode causar aumento da prolactina sérica e galactorreia em usuários.

Spontaneous Ejaculation Due to Duloxetine: A Case Report

ABSTRACT Ejaculation is controlled by both the sympathetic and parasympathetic system and consists of an emission and expulsion phase. Ejaculation latency time is regulated by the sympathetic system. Hypothetically, by reducing ejaculatory latency time, spontaneous ejaculation can occur. Extending the duration of ejaculation is a well-known side effect of antidepressants, especially selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors and noradrenergic reuptake inhibitors. Adrenergic drugs are sometimes used as treatment for delayed ejaculation. A spontaneous ejaculation due to the use of these drugs has rarely been reported. Although most reports of spontaneous ejaculations are related to the use of venlafaxine and reboxetine, this study is based on a case of the side effect of duloxetine.

Effects of duloxetine, fluoxetine and pregabalin on fentanyl-induced hyperalgesia in rattus novergicus / Efeitos da duloxetina, fluoxetina e pregabalina sobre a hiperalgesia induzida por fentanil em rattus novergicus

ABSTRACT BACKGROUND AND OBJECTIVES: Opioids are drugs used to relieve pain, but may cause increased pain sensitivity, known as opioid-induced hyperalgesia, which adversely affects pain management. This study aimed to check if fentanyl, an opioid widely used in the clinical practice, produces hyperalgesia that can be attenuated by duloxetine, fluoxetine and pregabalin. METHODS: Thirty male Wistar rats were divided into six groups. The animals in group 1 received 1mL of 0.9% saline solution intraperitoneally (IP) and gavage; group 2 received fentanyl at a dose of 100µg.kg-1 IP and 0.9% saline solution per gavage; groups 3, 4 and 5 received fentanyl at the dose of 100µg.kg-1 IP, and gavage with duloxetine, 40mg.kg-1, fluoxetine, 40mg.kg-1 and pregabalin, 40mg.kg-1, respectively. Under general anesthesia with isoflurane, all animals were submitted to plantar surgical incision. The application of Von Frey filaments assessed hyperalgesia at the second hour, one, three, five and seven days after treatment. RESULTS: Two hours after the procedure, no differences were observed between G1 and G2, although G3, G4, and G5 showed less hyperalgesia. On day one and day three, a greater hyperalgesic effect was observed in G2 when compared to G1, G3, G4 and G5. On day five, there was a hyperalgesic effect on G2, and on day seven, there were no differences among the groups. CONCLUSION: The results suggest that fentanyl induces hyperalgesia and the efficacy of duloxetine, fluoxetine, and pregabalin in reducing it.

RESUMO JUSTIFICATIVA E OBJETIVOS: Opioides são fármacos utilizados para o alívio da dor, porém, podem causar aumento da sensibilidade dolorosa, denominada hiperalgesia induzida por opioides, que afeta negativamente o tratamento da dor. O objetivo deste estudo foi avaliar se o fentanil, opioide amplamente utilizado na prática clínica, produz hiperalgesia que pode ser atenuada pela duloxetina, fluoxetina e pregabalina. MÉTODOS: Trinta ratos Wistar machos, foram divididos em 6 grupos. No grupo 1, os animais receberam 1mL de solução fisiológica (SF) a 0,9% por via intraperitoneal (IP) e por gavagem; no grupo 2, fentanil na dose de 100µg.kg-1 IP e SF a 0,9% por gavagem; nos grupos 3, 4 e 5 os animais receberam fentanil na dose de 100µg.kg-1 IP e, por gavagem, receberam respectivamente duloxetina, 40mg.kg-1, fluoxetina, 40mg.kg-1 e pregabalina, 40mg.kg-1. A avaliação da hiperalgesia e sua atenuação foi feita pela aplicação de filamentos de Von Frey, na 2ª hora e nos dias 1, 3, 5 e 7, após o tratamento. RESULTADOS: Na 2ª hora pós-procedimento não foram observadas diferenças entre G1 e G2, entretanto, G3, G4 e G5 se mostraram com menor hiperalgesia. No 1º e 3º dias foi observado maior efeito hiperalgésico em G2 quando comparado com G1, G3, G4 e G5. No 5º dia foi observado efeito hiperalgésico no G2, e no 7º dia não houve diferenças entre os grupos. CONCLUSÃO: Os resultados sugerem que o fentanil induz hiperalgesia e eficácia da duloxetina, fluoxetina e pregabalina na sua redução.

Effects of aripiprazole combined with duloxetine on the treatment effect and VEGF level in patients with refractory depression / 中国临床药理学与治疗学

AIM: To explore the effects of aripiprazole and duloxetine on refractory depression and the change of VEGF concentration during treatment. METHODS: Ninety patients with refractory depression who were treated at the Fourth People's Hospital of Jiande from February 2017 to February 2019 were selected, and 40 healthy volunteers were recruited as healthy control groups. Random numbers table was used to divide patients into aripiprazole combined with duloxetine treatment group (combined treatment group) and duloxetine treatment group (monotherapy group). After 4 weeks of treatment, the differences in efficacy and adverse reactions between the two groups were evaluated. The difference of VEGF level between each group was compared. RESULTS: The effective rate was 88.8% in the combined treatment group and 80.0% in the monotherapy group. The effective rate between the two groups was not statistically significant (P<0.05). After 4 weeks of treatment, the HAMD score in the combined treatment group was lower than that in the monotherapy group, the difference was statistically significant (P<0.05). The difference in adverse reactions between the two groups was not statistically significant (R=0.641, P=0.624). The level of VEGF before treatment in the two treatment groups was higher than that in the healthy control group, and the difference was statistically significant (P<0.01). After treatment, the VEGF level of the two groups decreased compared with before treatment, and the difference was statistically significant (P<0.01). The level of VEGF in the combined treatment group was lower than that in the monotherapy group, and the difference was statistically significant (P<0.05). Pearson correlation analysis showed that the level of VEGF before treatment was positively correlated with the HAMD score (R=0.403, P<0.01), and VEGF decline level is positively correlated with HAMD score reduction rate (R=0.330, P<0.01). CONCLUSION: Aripiprazole combined with duloxetine has a better effect on refractory depression than duloxetine alone, and can significantly reduce the level of VEGF in peripheral blood.

Comparing the efficacy and safety of duloxetine and amitriptyline in the treatment of fibromyalgia: overview of systematic reviews

Abstract Background: Duloxetine and amitriptyline are antidepressants used in the treatment of fibromyalgia. In published systematic reviews, there is no agreement about which drug is more effective and safer. This study aimed to compare evidence of the efficacy and safety of duloxetine compared with amitriptyline in the treatment of adult patients with fibromyalgia. This work contributes to guiding clinicians on the use of duloxetine or amitriptyline for the treatment of fibromyalgia and provides information for public health decision-makers. Methods: Overview of systematic reviews of clinical trials comparing duloxetine and amitriptyline in the treatment of fibromyalgia. The reviews were screened in Cochrane, PubMed, EMBASE, and SRDR with no restrictions on language and year of publication, considering that the research was conducted in July 2018 and updated until May 2020. The selection was based on the following criteria: adult patients with a diagnosis of fibromyalgia treated with duloxetine or amitriptyline, comparing the efficacy and safety in pain, fatigue, sleep, and mood disorder symptoms and quality of life, in addition to the acceptability of these antidepressants. The methodological quality and strength of evidence were assessed using the AMSTAR and GRADE instruments. Results: Eight systematic reviews were selected. Amitriptyline had low evidence for pain, moderate evidence for sleep and fatigue, and high evidence for quality of life. Duloxetine had high quality of evidence in patients with mood disorders. With low evidence, duloxetine has higher acceptability, but is safer in older patients, while amitriptyline is safer for non-elderly individuals. Conclusion: Both antidepressants are effective in the treatment of fibromyalgia, differing according to the patient's symptoms and profile. Registration: PROSPERO: CRD42019116101.(AU)

Efficacy and Safety of Duloxetine in the Improvement of Pain Symptoms of Knee Osteoarthritis ：A Meta-analysis / 中国药房

OBJECTIVE：To systematically e valuate the efficacy and safety of duloxetine in the improvement of pain symptoms of knee osteoarthritis （KOA），and to provide evidence-based reference for clinical treatment of KOA. METHODS ：Retrieved from PubMed，Embase，Medline，Cochrane Library ，CNKI，VIP and Wanfang database ，during the establishment of the database to Sept. 2019，RCTs about duloxetine （trial group ）vs. placebo （control group ）in the improvement of pain symptoms of KOA were collected. After data extraction and quality evaluation using Cochrane system evaluator ’s manual 5.1.0，Meta-analysis was performed by using Stata 14.0 software for WOMAC total score ，WOMAC pain score ，WOMAC stiffness score ，WOMAC function score and BPI-S score ，as well as the incidence of adverse reaction such as dry mouth ，somnolence and nausea. RESULTS：A total of 6 RCTs were included ，involving 2 059 patients. Meta-analysis results showed that WOMAC total score [MD＝－0.34，95％CI（－0.48，－0.20），P＜0.05]，WOMAC pain score [MD ＝－0.41，95％CI（－0.54，－0.29），P＜0.05]， WOMAC stiffness score [MD ＝－0.24，95％ CI（－0.37，－0.12），P＜0.05]，WOMAC function score [MD ＝－0.43，95％CI （－0.55，－0.31），P＜0.05]，BPI-S score [MD ＝－0.38，95％CI（－0.48，－0.28），P＜0.05] of trial group were significantly lower than those of control group ；the incidence of dry mouth [RR ＝3.55，95％CI（2.00，6.29），P＜0.05]，somnolence [RR ＝3.23， 95％CI（1.88，5.54），P＜0.05] and nausea [RR ＝6.95，95％CI（2.99，16.15），P＜0.05] in trial group were significantly higher than control group ，with significant difference. CONCLUSIONS ：Duloxetine can relieve the pain and improve knee function in patients with KOA ，but it is necessary to pay attention to its adverse reactions.

Efeitos citotóxicos da duloxetina nas linhagens celulares MKN45 e NIH3T3 e efeitos genotóxicos em linfócitos sanguíneos periféricos humanos / Cytotoxic effects of duloxetine on mkn45 and nih3t3 cell lines and genotoxic effects on human peripheral blood lymphocytes

ABSTRACT BACKGROUND: Gastric cancer is the second leading cause of cancer-related death globally. Unfortunately, the survival rate of the gastric cancer patients who underwent chemotherapy following surgery has been less than a half. Besides, chemotherapy has many side effects. Current evidence suggests that some antidepressants like duloxetine have growth-inhibiting effects against a number of cancer cell lines. OBJECTIVE: Thus, the aim of this study was to determine the cytotoxic and genotoxic effects of duloxetine on gastric cancer. METHODS: In this regard, the cytotoxicity and genotoxicity of duloxetine were investigated in MKN45 and NIH3T3 cell lines by MTT assay and on peripheral blood lymphocytes by MN assay. For this purpose, cells were cultured in 96 wells plate. Stock solutions of duloxetine and cisplatin were prepared. After cell incubation with different concentrations of duloxetine (1, 10, 25, 50, 100 and 200 μL), MTT solution was added. For micronucleus assay fresh blood was added to RPMI culture medium 1640 supplemented, and different concentrations of duloxetine (1, 10, 25, 50, 100 and 200 μL) were added. RESULTS: The cytotoxicity of duloxetine on MKN45 cancer cell line and NIH3T3 normal cell line were studied followed by MTT assay. duloxetine exhibited higher IC50 in the MKN45 cells in comparison with the NIH3T3 cells. In addition, genotoxic effect of duloxetine was evaluated by micronucleus assay. The results revealed that duloxetine induced more DNA damage at 100 and 200 μM and no significant difference at 200 μM with respect to cisplatin, but it had less genotoxic effects at 100 and 50 μM concentrations. CONCLUSION: Although, in this study, duloxetine had less genotoxicity than cisplatin in concentrations under 200 μM and showed cytotoxic effects as well, due to its IC50, it cannot be considered as a better choice for gastric cancer therapies with respect to cisplatin as a common anticancer drug.

RESUMO CONTEXTO: O câncer gástrico é a segunda principal causa de morte relacionada ao câncer globalmente. Infelizmente, a taxa de sobrevivência dos pacientes com câncer gástrico que se submeteram à quimioterapia após a cirurgia, tem sido inferior à metade. Além disso, a quimioterapia tem muitos efeitos colaterais. Evidências atuais sugerem que alguns antidepressivos como a duloxetina têm efeitos inibidores de crescimento contra um número de linhas de células cancerosas. OBJETIVO: Assim, o objetivo deste estudo foi determinar os efeitos citotóxicos e genotóxicos da duloxetina sobre o câncer gástrico. MÉTODOS: A este respeito, a citotoxicidade e a genotoxicidade da duloxetina foram investigadas em linhas celulares MKN45 e NIH3T3 por ensaio de MTT e por ensaio de MN em linfócitos periféricos de sangue. Para este efeito, as células foram cultivadas em 96 placas. Soluções de estoque de duloxetina e cisplatina foram preparadas. Após incubação celular com diferentes concentrações de duloxetina (1, 10, 25, 50, 100 e 200 μL), a solução de MTT foi adicionada. Para o teste do micronúcleo o sangue fresco foi adicionado ao meio de cultura RPMI 1640 suplementado, e as concentrações diferentes de duloxetina (1, 10, 25, 50, 100 e 200 μL) foram adicionadas. RESULTADOS: A citotoxicidade da duloxetina na linha celular cancerosa MKN45 e NIH3T3 linha celular normal foram estudadas e seguidas pelo ensaio de MTT. A duloxetina exibiu maior IC50 nas células MKN45 em comparação com as células NIH3T3. Além disso, o efeito genotóxico da duloxetina foi avaliado pelo ensaio de micronúcleos. Os resultados revelaram que a duloxetina induziu mais dano de DNA em 100 e 200 μM e não houve diferença significativa em 200 μM em relação à cisplatina, mas teve menos efeitos genotóxicos nas concentrações de 100 e 50 μM. CONCLUSÃO: Embora, neste estudo, a duloxetina tenha menos genotoxicidade do que a cisplatina em concentrações inferiores a 200 μm e também tenha mostrado efeitos citotóxicos, devido ao seu IC50, não pode ser considerada como uma escolha terapêutica melhor para o câncer gástrico no que diz respeito à cisplatina como uma droga anticâncer comum.

Development And Validation Of Uv-Visible Spectrophotometric Method For Determination Of Duloxetine

Objective: The aim of the present work was to develop and validate a simple UV spectroscopic method for the determination of duloxetine, which is a thiophene derivative and a selective neurotransmitter reuptake inhibitor for serotonin, norepinephrine, and to lesser degree dopamine. Methods: The UV Spectrophotometric analysis was performed using Shimadzu UV-1800 and Shimadzu UV-1700 spectrophotometer by using solvent system acetonitrile and water in the ratio of 8:2. Detection was performed at a wavelength of 290 nm. Method validation was carried out according to ICH Q2R1 guidelines by taking the parameters linearity, accuracy, precision, ruggedness, and robustness, LOD and LOQ. Results: The UV Spectrophotometric method was found linear in the range of 10-50 μg/ml. The method was rugged and robust with % relative standard deviation less than 2. The extraction recoveries were found to be higher than 99% in all experimental conditions. Conclusion: Based upon the performance characteristics, the proposed method was found accurate, precise and rapid and suitable for the determination of Duloxetine for routine analysis.

Efficacy and Safety of Duloxetine in the Treatment of Major Depressive Disorder ：a Meta-analysis / 中国药房

OBJECTIVE： To systematically evaluate the efficacy and safety of duloxetine in the treatment of major depressive disorder （MDD）， and to provide evidence-based reference for clinical drug use. METHODS： Retrieved from the Cochrane Library， PubMed， Embase， CNKI databases， CBM and VIP databases， randomized controlled trials（RCTs） about duloxetine （trial group） versus placebo （control group）in the treatment of MDD were collected. After literature screening and data extraction， the quality of included studies was evaluated by using Cochrane systematic evaluator manual 5.1.0. Rev Man 5.3 software was used for Meta-analysis. RESULTS： A total of 8 RCTs were included， involving a total of 2 772 cases. Meta-analysis showed that the decrease of Montgomery-Asberg Depression Rating Scale [MD＝－3.97，95％CI（－4.71，－3.24），P＜0.000 01]， the decrease of Hamilton Anxiety Rating Scale[MD＝－2.12，95％CI（－3.66，－0.57），P＝0.007]， the decrease of Clinical Global Impression-Severity [MD＝－0.47，95％CI（－0.73，－0.21），P＝0.000 4]， the decrease of Clinical Global Impression-Improvement Scale [MD＝－0.58，95％CI（－0.92，－0.25），P＝0.000 6] and the decrease of Sheehan Disability Scale [MD＝－2.82，95％CI（－4.55，－1.09），P＝0.001] in trial group were significantly more than control group. The incidence of nausea， dry mouth， constipation， vomiting， dizziness， drowsiness， insomnia， hyperhidrosis and anorexia in the trial group was significantly higher than control group （P＜0.05）. There was no statistical significance in the incidence of serious ADR， diarrhea， headache and dyspepsia between 2 groups （P＞0.05）. CONCLUSIONS： Duloxetine shows significant therapeutic efficacy for the treatment of MDD， but it will increase the occurrence of common mild ADR.

The current treatment of fibromyalgia / O tratamento atual da fibromialgia

ABSTRACT BACKGROUND AND OBJECTIVES: Fibromyalgia is a highly relevant theme for research considering its impressive 2% worldwide prevalence, diffuse pain and suffering, largely unknown pathophysiology, scarce odds of cure and, more often than not, poor symptom control. This study aims to review the main options of treatment for fibromyalgia, including some novel alternatives. CONTENTS: The pharmacological treatment for fibromyalgia can be prescribed in monotherapy or combination of drugs, which comprises antidepressants, muscle relaxants, anticonvulsants, cannabinoids, opioids, N-methyl D-Aspartate antagonists, melatoninergic agonists, peptidergic substances among others. Non-pharmacological therapies include acupuncture, behavioral (or psychobehavioral) and psychological (or psychotherapy) interventions, physical activity programs, hyperbaric oxygen therapy, ozone therapy, transcranial magnetic stimulation, stretching exercises associated to low intravenous curare doses, among others. Treatment modalities are presented according to possible mechanisms of action, level of scientific evidence and recommendation. CONCLUSION: Fibromyalgia therapy should be individualized, and it does not aim the cure. Its objective is to reduce the subject's suffering; provide function improvement and, as much as possible, the individual's autonomy and quality of life. There is much in common in most approach recommendations, yet there are some divergence and changes as knowledge is acquired about a theme where consensus is far from being achieved.

RESUMO JUSTIFICATIVA E OBJETIVOS: A impressionante prevalência de 2% da fibromialgia na população mundial, associada ao sofrimento a ela atribuída, à sua fisiopatologia ainda não integralmente desvendada, ao prognóstico reservado em relação à possibilidade de cura, e, aos resultados insatisfatórios no controle de seus sintomas, mormente os dolorosos; fazem dela um tema preferencial para investigação e estudo. O objetivo deste estudo foi apresentar uma revisão sobre os principais tratamentos sugeridos para os portadores de fibromialgia, incluindo alguns emergentes. CONTEÚDO: O tratamento farmacológico da fibromialgia pode ser aplicado em monoterapia ou combinar fármacos, inclusive antidepressivos, relaxantes musculares, anticonvulsivantes, canabinoides, opioides, antagonistas N-metil D-Aspartato, agonistas melatoninérgicos, substâncias peptidérgicas entre outras. Os tratamentos classificados como não farmacológicos incluem a acupuntura, intervenções comportamentais (ou psicocomportamentais), psicológicas (ou psicoterápicas), programas de atividade física, oxigenoterapia hiperbárica, ozonioterapia, estimulação magnética transcraniana, relaxamento muscular com baixas doses de curare por via venosa associado a alongamento e realongamento, entre outros. Os tratamentos são apresentados e situados em relação aos respectivos possíveis mecanismos de ação, evidência científica e graus de recomendação. CONCLUSÃO: O tratamento da fibromialgia é individualizado, e, não propõe sua cura. O objetivo é a redução do sofrimento de seus portadores, a melhora da funcionalidade, e na medida do possível, da autonomia pessoal e da qualidade de vida. A maioria das condutas e recomendações possuem muito em comum, porém não são totalmente congruentes, mostram dinamismo e mudanças à medida em que se acumula conhecimento sobre um assunto sobre o qual o consenso ainda está muito longe de ocorrer.

Combined Use of Duloxetine and Olanzapine in the Treatment of Urologic Chronic Pelvic Pain Syndromes Refractory to Conventional Treatment: A Case Report

Patients with urologic chronic pelvic pain syndromes (UCPPS) report interstitial cystitis/bladder pain syndrome and/or chronic prostatitis/chronic pelvic pain syndrome. The pathogenesis of these syndromes remains unclear and there is currently no standard treatment. UCPPS is, therefore, often misdiagnosed and its management is complex. The present case report involves a 62-year-old male patient with UCPPS whose main presentation is painful bladder filling and painful urgency refractory to conventional treatment with medication, which was successfully treated with the combined use of duloxetine and olanzapine. The combined use of duloxetine and olanzapine may become a new therapeutic option in the management of UCPPS.

Effectiveness and Safety of Escitalopram and Duloxetine in the Treatment of Depression:a Meta-analysis / 中国药房

OBJECTIVE:To systematically evaluate the effectiveness and safety of escitalopram and duloxetine in the treatment of depression, and provide evidence-based reference for clinical treatment. METHODS:Retrieved from PubMed, Wanfang database,VIP,CNKI and CBM,randomized controlled trials (RCTs) about escitalopram (trial group) and duloxetine (control group) in the treatment of depression were collected. Meta-analysis was conducted by using Rev Man 5.3 software after data extraction and quality evaluation according to bias risk assessment tool recommended by system evaluator manual 5.3. RESULTS:Finally 25 RCTs were included,involving 2621 patients. The results of Meta-analysis showed that there was no statistical significance in total response rate between 2 groups after 1,2,4,6,8 weeks of treatment or cure rate between 2 groupsafter 4,6,8 weeks of treatment (P>0.05). There was no statistical significance in total response rate [RR=0.96,95％CI(0.88, 1.05),P=0.42] or cure rate [RR=0.91,95％CI(0.78,1.06),P=0.24] of female patients,as well as total response rate [RR=0.96, 95％CI(0.84,1.11),P=0.61] or cure rate [RR=0.90,95％CI(0.54,1.49),P=0.69] of elderly patients between 2 groups. The incidence of constipation [RR=0.59,95％CI (0.42,0.81),P=0.001],dry mouth [RR=0.65,95％CI(0.51,0.82),P=0.0004], nausea [RR=0.68,95％CI(0.56,0.83),P=0.0002] and decreased appetite [RR=0.74,95％CI(0.55,0.99),P=0.04] in trial group were significantly lower than control group,with statistical significance. CONCLUSIONS:The effectiveness of escitalopram is similar to duloxetine in the treatment of depression,but the safety of escitalopram is better than duloxetine.

Efficacy and safety of duloxetine for depression in China :a meta-analysis / 中华行为医学与脑科学杂志

Objective To systematically evaluate the efficacy and adverse effects of duloxetine in the treatment of domestic depression patients,and compare with those who were treated with SSRIs drugs in the same period to explore the difference between them to guide the clinical medication.Methods A search was conducted in CBMdisc,Wanfang database,CNKI,VIP,Pubmed.The double-blind randomized controlled trials on duloxetine for depression in China were collected.The quality of the included trials was assessed according to the Cochrane Handbook 5.0,and the systematic analysis was conducted by using RevMan 5.3 soft ware.Results Seven double-blind randomized controlled trials (two of duloxetine versus fluoxetine,five of duloxetine versus paroxetine) involving 1 193 patients were included.The results of rmeta-analysis showed that:①After 6-8 weeks of treatment,there were no significant differences in the effective rate (RR =1.02,95％CI=0.78-1.32,Z=0.12,P=0.90),and the final cure rate (RR=0.95,95％CI=0.75-1.19,Z=0.47,P=0.64) between the duloxetine and fluoxetine/paroxetine groups.②Adverse reactions:the incidence rate was not significantly different between duloxetine and fluoxetine/paroxetine groups (RR =1.03,95％ CI =0.86-1.23,Z=0.32,P=0.75).Conclusion After 6-8 weeks of treatment,there are no significant differences in the effective rate and the final cure rate between duloxetine and fluoxetine/paroxetine.There is no significantly difference in common adverse reactions.

Protective Effects of Duloxetine on Arrhythmia in Rats with Myocardial Ischemia Reperfusion Injury / 医学研究杂志

Objective To explore the protective effects of duloxetine on ventricular arrhythmia in rats with ischemia reperfusion injury.Methods Thirty Sprague Dawley (SD) rats were randomly divided into 3 groups:Sham group,ischemia reperfusion group (IR group),duloxetine-treated group (Dulo group).The rats in IR group were subjected to 30min-ischemia of left anterior descending artery ligation followed by 120min of reperfusion,while intraperitoneal injection of duloxetine 40mg/kg were give prior ischemia in Dulo group,and the remaining experiment protocols were same as IR group.The left anterior descending artery of rats in sham group was exposed without being clamped.Two biopotential leads ECG monitor was used to record the arrhythmia in each group,and ECG parameters were analyzed by LabChart 8 software.Triphenyltetrazolium chloride (TTC) was used for determination of infarct area.The protein expressions of Akt,extracellular regulated protein kinases (Erk),caspase-3,superoxide dismutase (SOD) 1,SOD2 and Connexin 43 (Cx 43) were measured by western blot analysis.Results As compared to IR group,the incidences of both ventricular extrasystoles and tachycardia were decreased during ischemic period (P ＜0.05),and the incidence of ventricular tachycardia was decreased with no significant changes in ventricular extrasystoles during reperfusion period in Dulo group (P ＜ 0.05).Duloxetine decreased the prolonged QTc and infraeted area during IR injury (P ＜ 0.05).Duloxetine inhibited the phosphorylation of Akt and Erk,and downregulated the protein expressions of cleaved caspase-3,cytochrome C,while upregulated SOD1,SOD2 and Cx 43 protein expression during I/R injury (P ＜ 0.05).Conclusion Duloxetine decreases the phosphorylation of Akt and Erk,inhibits oxidative stress and apoptosis,exerts anti-arrhythmogenic effects and decreases the occurrence of ventricular arrhythmia and infracted area induced by myocardial IR.

Efficacy and safety of duloxetine versus sertraline for Chinese depression patients: a meta-analysis / 中华全科医师杂志

Objective To systematically evaluate the efficacy and safety of duloxetine and sertraline for Chinese depression patients.Methods The randomized controlled trials(RCTs)comparing the efficacy and safety of duloxetine and sertraline in the treatment of depression were retrieved from databases and the quality of literature was evaluated.Meta-analysis was performed with the software Revman 5.2.Results Eighteen RCTs involving 1 557 Chinese depression patients were included.The results of Meta-analysis showed that there were no significant differences in efficacy and cure rate between duloxetine and sertraline groups(OR=1.28, 95%CI:0.94 -1.73, P =0.11; OR =1.25,95%CI:0.97 -1.62,P =0.09, respectively).The Hamilton Depression Scale(HAMD)scores were significantly lower in duloxetine group than those in sertraline group at 1,2 weeks after treatment;however,there were no significant differences at 8-weeks after treatment between duloxetine and sertraline groups.The score of Medical Outcomes Study Pain Measures(MOSPM)in duloxetine group was significantly lower than that in sertraline group(P<0.01). The rate of insomnia in duloxetine group was significantly lower than that in sertraline group(RR=0.57, 95%CI:0.32 -1.00, P=0.04).There were no significant differences in other common side reactions between the two groups(P>0.05).Conclusions Duloxetine has similar long term treatment effect as sertraline,but it has a rapid-action profile.Duloxetine is more effective than sertraline in depression with painful physical symptoms;besides,duloxetine is less likely to induce insomnia.

Neuroprotective Effect of Duloxetine on Chronic Cerebral Hypoperfusion-Induced Hippocampal Neuronal Damage

Chronic cerebral hypoperfusion (CCH), which is associated with onset of vascular dementia, causes cognitive impairment and neuropathological alterations in the brain. In the present study, we examined the neuroprotective effect of duloxetine (DXT), a potent and balanced serotonin/norepinephrine reuptake inhibitor, on CCH-induced neuronal damage in the hippocampal CA1 region using a rat model of permanent bilateral common carotid arteries occlusion. We found that treatment with 20 mg/kg DXT could attenuate the neuronal damage, the reduction of phosphorylations of mTOR and p70S6K as well as the elevations of TNF-α and IL-1β levels in the hippocampal CA1 region at 28 days following CCH. These results indicate that DXT displays the neuroprotective effect against CCH-induced hippocampal neuronal death, and that neuroprotective effect of DXT may be closely related with the attenuations of CCH-induced decrease of mTOR/p70S6K signaling pathway as well as CCH-induced neuroinflammatory process.

Comparative study of duloxetine pharmacokinetics in normal and diabetic rats / 药学学报

The study was aimed to establish a liquid chromatography-tandem mass spectrometric method for the determination of the duloxetine concentration in rat plasma, and compare the pharmacokinetics in normal and diabetes mellitus rat models. Diazepam was used as an internal standard. The separation was achieved on a Waters Xterra® RP18 column (100 mm × 4.6 mm, 3.5 μm) with a mobile phase consisting of methanol -0.3% formic acid containing 5 mmol·L-1 ammonium acetate (75:25) at the flow rate of 0.6 mL·min-1. Electrospray ionization source was applied and operated in the positive multiple reaction monitoring mode. A good linearity of duloxetine was obtained in the concentration range of 10-5 000 ng·mL-1. The rat models of diabetes mellitus were established by intraperitoneal injection of streptozotocin. The same dose of duloxetine (40 mg·kg-1) was given by intragastric administration to the normal and diabetic rats. Blood samples were collected from the orbital venous plexus to determinate duloxetine concentration in the plasma. The pharmacokinetic parameters were calculated by DAS software. Statistical analysis was performed by SPSS software. The major pharma-cokinetic parameters of diabetes group were as follows: Cmax was 1 185 ± 190.0 ng·mL-1; AUC0-∞ was 8 398 ± 1 835 ng·mL-1·h; tmax was 1.6 ± 0.4 h; t1/2z was 3.6 ± 0.9 h. The major pharmacokinetic parameters of normal group were as follows: Cmax was 368.1 ± 40.7 ng·mL-1; AUC0-∞ was 4145 ± 640.1 ng·mL-1·h; tmax was 1.6 ± 0.3 h; t1/2z was 4.1 ± 0.8 h. The results of pharmacokinetic experiments suggest that the exposure amount of duloxetine in diabetic rats is twice higher than that in normal rats.