A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder. A pragmatic 12-week, randomized trial of duloxetine versus generic selective serotonin-reuptake inhibitors in the treatment of adult outpatients in a moderate-to-severe depressive episode The evidence for pharmacological treatment of neuropathic pain Effectiveness of the psychological and pharmacological treatment of catastrophization in patients with fibromyalgia: a randomized controlled trial Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial. Effects of duloxetine on painful physical symptoms associated with depression. Double-Blind Comparison of Escitalopram and Duloxetine in the Acute Treatment of Major Depressive Disorder Efficacy and tolerability of duloxetine in the treatment of patients with borderline personality disorder: a pilot study Open‐Label Support for Duloxetine for the Treatment of Panic Disorder Duloxetine vs. placebo in patients with painful diabetic neuropathy Pharmacological management of chronic neuropathic pain - consensus statement and guidelines from the Canadian Pain Society. Efficacy and Safety of Duloxetine in Patients With Chronic Low Back Pain Treatments for Poststroke Motor Deficits and Mood Disorders: A Systematic Review for the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Guidelines for Stroke Rehabilitation A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain Aripiprazole as an augmentor of selective serotonin reuptake inhibitors in depression and anxiety disorder patients Guidelines for the pharmacological treatment of anxiety disorders, obsessive–compulsive disorder and posttraumatic stress disorder in primary care Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. Comparative study of the effects of venlafaxine and duloxetine on chemotherapy-induced peripheral neuropathy Duloxetine in the treatment of depression: A double-blind placebo-controlled comparison with paroxetine Duloxetine 60 mg once-daily in the treatment of painful physical symptoms in patients with major depressive disorder. Efficacy and safety of duloxetine in the treatment of generalized anxiety disorder: a flexible‐dose, progressive‐titration, placebo‐controlled trial Duloxetine in the treatment of major depressive disorder: an open-label study A Review of Vilazodone, Serotonin, and Major Depressive Disorder
OBJECTIVE To assess the efficacy and safety of duloxetine , a serotonin and norepinephrine reuptake inhibitor , in subjects with primary fibromyalgia , with or without current major depressive disorder . METHODS This study was a r and omized , double-blind , placebo-controlled trial conducted in 18 outpatient research centers in the US . A total of 207 subjects meeting the American College of Rheumatology criteria for primary fibromyalgia were enrolled ( 89 % female , 87 % white , mean age 49 years , 38 % with current major depressive disorder ) . After single-blind placebo treatment for 1 week , subjects were r and omly assigned to receive duloxetine 60 mg twice a day ( n = 104 ) or placebo ( n = 103 ) for 12 weeks . Co- primary outcome measures were the Fibromyalgia Impact Question naire ( FIQ ) total score ( score range 0 - 80 , with 0 indicating no impact ) and FIQ pain score ( score range 0 - 10 ) . Secondary outcome measures included mean tender point pain threshold , number of tender points , FIQ fatigue , tiredness on awakening , and stiffness scores , Clinical Global Impression of Severity ( CGI-Severity ) scale , Patient Global Impression of Improvement ( PGI-Improvement ) scale , Brief Pain Inventory ( short form ) , Medical Outcomes Study Short Form 36 , Quality of Life in Depression Scale , and Sheehan Disability Scale . RESULTS Compared with placebo-treated subjects , duloxetine-treated subjects improved significantly more ( P = 0.027 ) on the FIQ total score , with a treatment difference of -5.53 ( 95 % confidence interval -10.43 , -0.63 ) , but not significantly more on the FIQ pain score ( P = 0.130 ) . Compared with placebo-treated subjects , duloxetine-treated subjects had significantly greater reductions in Brief Pain Inventory average pain severity score ( P = 0.008 ) , Brief Pain Inventory average interference from pain score ( P = 0.004 ) , number of tender points ( P = 0.002 ) , and FIQ stiffness score ( P = 0.048 ) , and had significantly greater improvement in mean tender point pain threshold ( P = 0.002 ) , CGI-Severity ( P = 0.048 ) , PGI-Improvement ( P = 0.033 ) , and several quality -of-life measures . Duloxetine treatment improved fibromyalgia symptoms and pain severity regardless of baseline status of major depressive disorder . Compared with placebo-treated female subjects ( n = 92 ) , duloxetine-treated female subjects ( n = 92 ) demonstrated significantly greater improvement on most efficacy measures , while duloxetine-treated male subjects ( n = 12 ) failed to improve significantly on any efficacy measure . The treatment effect on significant pain reduction in female subjects was independent of the effect on mood or anxiety . Duloxetine was safely administered and well tolerated . CONCLUSION In this r and omized , controlled , 12-week trial ( with a 1-week placebo lead-in phase ) , duloxetine was an effective and safe treatment for many of the symptoms associated with fibromyalgia in subjects with or without major depressive disorder , particularly for women , who had significant improvement across most outcome measures Some evidence suggests that medications that modulate both serotonin and norepinephrine may be more effective than selective serotonin-reuptake inhibitors ( SSRIs ) in severe major depressive disorder ( MDD ) . This prospect i ve pragmatic trial tests this hypothesis . Patients with severe MDD were r and omly assigned to either duloxetine ( a serotonin and norepinephrine-reuptake inhibitor ) or physicians ’ choice of four generic SSRIs . Nonblinded , flexibly dosed treatment was used to mimic clinical practice . To address potential investigator bias , the patient-reported Quick Inventory of Depressive Symptomatology Self-Report ( QIDS-SR ) was used as the primary efficacy outcome measure . A total of 750 out patients ( 19.2 % , African descent ; 14.8 % , Hispanic ) were r and omized . The primary outcome , remission at week 12 by QIDS-SR , was numerically greater for duloxetine compared with SSRIs ( 36 vs. 32 % ) , but this difference was not statistically significant . Mean changes in secondary outcomes were significantly superior in favor of duloxetine for the Hamilton Depression Scale-17 item , the Brief Pain Inventory , and the Sheehan Disability Scale . Remission superiority on the QIDS-SR was not achieved . Significantly greater benefit for duloxetine compared with SSRIs was demonstrated on measures of pain and functioning . Study demographics suggest a more generalizable racial and ethnic population than is typical in r and omized clinical trials & NA ; R and omized , double‐blind , placebo‐controlled trials on neuropathic pain treatment are accumulating , so an up date d review of the available evidence is needed . Studies were identified using MEDLINE and EMBASE search es . Numbers needed to treat ( NNT ) and numbers needed to harm ( NNH ) values were used to compare the efficacy and safety of different treatments for a number of neuropathic pain conditions . One hundred and seventy‐four studies were included , representing a 66 % increase in published r and omized , placebo‐controlled trials in the last 5 years . Painful poly‐neuropathy ( most often due to diabetes ) was examined in 69 studies , postherpetic neuralgia in 23 , while peripheral nerve injury , central pain , HIV neuropathy , and trigeminal neuralgia were less often studied . Tricyclic antidepressants , serotonin noradrenaline reuptake inhibitors , the anticonvulsants gabapentin and pregabalin , and opioids are the drug classes for which there is the best evidence for a clinical relevant effect . Despite a 66 % increase in published trials only a limited improvement of neuropathic pain treatment has been obtained . A large proportion of neuropathic pain patients are left with insufficient pain relief . This fact calls for other treatment options to target chronic neuropathic pain . Large‐scale drug trials that aim to identify possible subgroups of patients who are likely to respond to specific drugs are needed to test the hypothesis that a mechanism‐based classification may help improve treatment of the individual patients Abstract Background Fibromyalgia is a prevalent and disabling disorder characterized by widespread pain and other symptoms such as insomnia , fatigue or depression . Catastrophization is considered a key clinical symptom in fibromyalgia ; however , there are no studies on the pharmacological or psychological treatment of catastrophizing . The general aim of this study is to assess the effectiveness of cognitive-behaviour therapy and recommended pharmacological treatment for fibromyalgia ( pregabalin , with duloxetine added where there is a comorbid depression ) , compared with usual treatment at primary care level . Method / design Design : A multi-centre , r and omized controlled trial involving three groups : the control group , consisting of usual treatment at primary care level , and two intervention groups , one consisting of cognitive-behaviour therapy , and the other consisting of the recommended pharmacological treatment for fibromyalgia . Setting : 29 primary care health centres in the city of Zaragoza , Spain . Sample : 180 patients , aged 18–65 years , able to underst and and read Spanish , who fulfil criteria for primary fibromyalgia , with no previous psychological treatment , and no pharmacological treatment or their acceptance to discontinue it two weeks before the onset of the study . Intervention : Psychological treatment is based on the manualized protocol developed by Prof. Escobar et al , from the University of New Jersey , for the treatment of somatoform disorders , which has been adapted by our group for the treatment of fibromyalgia . It includes 10 weekly sessions of cognitive-behaviour therapy . Pharmacological therapy consists of the recommended pharmacological treatment for fibromyalgia : pregabalin ( 300–600 mg/day ) , with duloxetine ( 60–120 mg/day ) added where there is a comorbid depression ) . Measurements : The following socio-demographic data will be collected : sex , age , marital status , education , occupation and social class . The diagnosis of psychiatric disorders will be made with the Structured Polyvalent Psychiatric Interview . Other instruments to be administered are the Pain Catastrophizing Scale , the Hamilton tests for Anxiety and for Depression , the Fibromyalgia Impact Question naire ( FIQ ) , the EuroQuol-5 domains ( EQ-5D ) , and the use of health and social services ( CSRI ) . Assessment s will be carried out at baseline , 1 , 3 , and 6 months . Main variable : Pain catastrophizing . Analysis : The analysis will be per intent to treat . We will use the general linear models of the SPSS version 15 statistical package , to analyse the effect of the treatment on the result variable ( pain catastrophizing ) . Discussion It is necessary to assess the effectiveness of pharmacological and psychological treatments for pain catastrophizing in fibromyalgia . This r and omized clinical trial will determine whether both treatments are effective for this important prognostic variable in patients with fibromyalgia . Trial registration Current Controlled Trials IS RCT BACKGROUND Duloxetine hydrochloride , a dual reuptake inhibitor of serotonin and norepinephrine , was evaluated for therapeutic efficacy and safety/tolerability in the treatment of major depression . METHOD In an 8-week multicenter , double-blind , placebo-controlled study , 173 patients ( aged 18 - 65 years ) with DSM-IV major depressive disorder were r and omly allocated to receive placebo ( N = 70 ) , duloxetine ( N = 70 ) , or fluoxetine , 20 mg q.d . ( N = 33 ) . Duloxetine dose was titrated in the first 3 weeks in a forced-titration regimen from 40 mg ( 20 mg b.i.d . ) to 120 mg/day ( 60 mg b.i.d . ) . Patients were required to have a Clinical Global Impressions (CGI)-Severity of Illness scale score of at least moderate severity ( > or = 4 ) and a 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) total score of at least 15 . Patients could not have had any current primary DSM-IV Axis I diagnosis other than major depressive disorder , or any anxiety disorder as a primary diagnosis within the past year , excluding specific phobias . The primary efficacy measurement was the HAM-D-17 total score , and secondary measures included the Montgomery-Asberg Depression Rating Scale , CGI-Severity of Illness and CGI-Improvement , and Patient Global Impression of Improvement . Safety was evaluated by recording the occurrence of discontinuation rates and treatment-emergent adverse events and by measurement of vital signs and laboratory analytes . RESULTS Duloxetine was superior to placebo in change on the HAM-D-17 ( p = .009 ) . Estimated probabilities of response and remission were 64 % and 56 % , respectively , for duloxetine , compared with 52 % and 30 % for fluoxetine and 48 % and 32 % for placebo . Duloxetine was numerically superior to fluoxetine on the primary and most of the secondary outcome measures . In general , duloxetine was well tolerated ; 76 % of patients achieved the maximum dose , and insomnia and asthenia were the only adverse events reported statistically significantly ( p < .05 ) more frequently by duloxetine-treated patients compared with placebo-treated patients . CONCLUSION These data indicate that duloxetine is efficacious for the treatment of major depressive disorder and is well tolerated and safe Painful physical symptoms are common features of major depressive disorder and may be the presenting complaints in primary care setting s. The effect of the dual serotonin ( 5-HT ) and norepinephrine reuptake inhibitor duloxetine on emotional and painful physical symptoms in out patients with major depressive disorder was evaluated in three r and omized , double-blind , placebo-controlled trials . The trials ' primary objective was to evaluate the effect of duloxetine on mood , and subjects were not enrolled on the basis of presence , type , or severity of pain . However , the pain-relieving effects of duloxetine were evaluated by a priori defined analyses of results from a visual analogue scale and the Somatic Symptom Inventory . Compared with placebo , duloxetine was associated with significant reduction in pain severity . The authors concluded that duloxetine reduces the painful physical symptoms of depression Abstract Background and objective : Escitalopram is the most selective serotonin reuptake inhibitor antidepressant ; in contrast , duloxetine inhibits both serotonin and norepinephrine reuptake . Double-blind comparison studies may help guide treatment decisions by revealing the relative benefits of different therapeutic approaches . This study evaluated the efficacy and safety of escitalopram versus duloxetine in the acute treatment of patients with moderate to severe major depressive disorder . Methods : A 1-week , single-blind , placebo lead-in period followed by an 8-week , r and omised , double-blind , multicentre , parallel-group comparison was conducted from 20 April 2005 to 10 March 2006 in independent psychiatric research facilities with principal investigators who were board certified in psychiatry . A total of 278 out patients of 382 patients screened with Diagnostic and Statistical Manual of Mental Disorders ( 4th edition)-diagnosed major depressive disorder ( Montgomery-Åsberg Depression Rating Scale [ MADRS ] total score ≥26 ) were r and omised to the two treatment groups . Eight patients received no medication and were excluded from the safety group . Patients were treated with either escitalopram 10–20 mg/day ( fixed at 10 mg/day for the first 4 weeks ) or duloxetine 60 mg/day . The primary efficacy variable was change from baseline at week 8 in MADRS total score using the last observation carried forward ( LOCF ) approach . Efficacy , safety and tolerability measures were prospect ively defined in the statistical analysis plan prior to study initiation unless otherwise specifically noted as conducted post hoc . Results : A significantly greater proportion of escitalopram-treated patients completed the 8-week study compared with duloxetine-treated patients ( 87 % vs 69 % , respectively ; p < 0.01 ) . Mean baseline MADRS total scores were 31.0 for the escitalopram group and 31.6 for the duloxetine group . At week 8 , escitalopram treatment result ed in significantly greater improvement compared with duloxetine on the prospect ively defined primary efficacy endpoint of mean change from baseline in MADRS total score using the LOCF approach ( least-squares mean difference [ LSMD ] −2.42 ; 95 % CI −4.73 , −0.11 ; p < 0.05 ) . There was no difference between treatment groups in the observed cases ( OC ) analysis ( LSMD −0.32 ; 95 % CI −2.71 , 2.07 ; p = 0.79 ) . Significantly fewer escitalopram-treated patients discontinued because of adverse events  compared with duloxetine ( 2 % vs 13 % , respectively ; p < 0.01 ) . Conclusion : These findings suggest that escitalopram is better tolerated and at least as effective as the serotonin-norepinephrine reuptake inhibitor duloxetine in the treatment of major depressive disorder Guidelines of the American Psychiatric Association for borderline personality disorder ( BPD ) indicate selective serotonin reuptake inhibitors and the serotonin and noradrenaline reuptake inhibitor ( SNRI ) venlafaxine for treating affective dysregulation and impulsive behavioural dyscontrol symptoms . The SNRI duloxetine has been studied in patients with major depression , generalized anxiety disorder and fibromyalgia , showing particular efficacy on somatic complaints . This study investigates duloxetine in the treatment of patients with BPD . Eighteen out patients with a DSM-IV-TR diagnosis of BPD were treated with open-label duloxetine , 60 mg/day , for 12 weeks . Patients were assessed at baseline , week 4 and 12 with the CGI Severity item , the BPRS , the HAM-D , the HAM-A , the SOFAS , the BPD Severity Index ( BPDSI ) and the HSCL-90-Somatization Subscale ( HSCL-90 SOM ) . Adverse effects were evaluated using the Dosage Record Treatment Emergent Symptom Scale . Statistics were performed with the analysis of variance . Significant P values were ≤0.05 . Fourteen patients completed the study . Four patients ( 22.2 % ) discontinued treatment in the first 4 weeks because of non-compliance . A significant change was found for : BPRS , HAM-D , SOFAS , BPDSI total score and items ‘ impulsivity ’ , ‘ outbursts of anger ’ and ‘ affective instability ’ and HSCL-90 SOM . Adverse effects were mild headache and nausea . Initial results suggest that duloxetine is an effective and well-tolerated treatment for BPD , with positive effects on somatic symptoms Panic disorder with or without agoraphobia is a common , often chronic and refractory anxiety disorder . Although a number of pharmacotherapies are now indicated for panic disorder , many patients do not respond to available interventions . We hypothesized that duloxetine , a serotonin‐norepinephrine reuptake inhibitor ( SNRI ) that has greater initial noradrenergic effects than venlafaxine , would have broad efficacy for individuals with panic disorder . Fifteen individuals with panic disorder with or without agoraphobia received 8 weeks of open label duloxetine flexibly dosed from 60 to 120 mg per day . Duloxetine treatment result ed in significant anxiolysis as measured by the primary outcome measure , the Panic Disorder Severity Scale ( PDSS ) ( paired t(df ) = 4.02(14 ) , P= 0.0013 ) , as well as measures of generalized anxiety , depression and quality of life ( all P < 0.05 ) . Although definitive conclusions are limited due to its small open‐label nature , this first prospect i ve study provides preliminary support for the efficacy of duloxetine for panic disorder and suggests larger r and omized controlled study is warranted & NA ; The aim of this study was to examine the efficacy and safety of duloxetine , a balanced and potent dual reuptake inhibitor of serotonin and norepinephrine , in the management of  diabetic peripheral neuropathic pain . Serotonin and norepinephrine are thought to inhibit pain via descending pain pathways . In a 12‐week , multicenter , double‐blind study , 457 patients experiencing pain due to polyneuropathy caused by Type 1 or Type 2 diabetes mellitus were r and omly assigned to treatment with duloxetine 20 mg/d ( 20 mg QD ) , 60 mg/d ( 60 mg QD ) , 120 mg/d ( 60 mg BID ) , or placebo . The diagnosis was confirmed by a score of at least 3 on the Michigan Neuropathy Screening Instrument . The primary efficacy measure was the weekly mean score of the 24‐h Average Pain Score , which was rated on an 11‐point ( 0–10 ) Likert scale ( no pain to worst possible pain ) and computed from diary scores between two site visits . Duloxetine 60 and 120 mg/d demonstrated statistically significant greater improvement compared with placebo  on the 24‐h Average Pain Score , beginning 1 week after r and omization and continuing through the 12‐week trial . Duloxetine also separated from placebo on nearly all the secondary measures including health‐related outcome measures . Significantly more patients in all three active‐treatment groups achieved a 50 % reduction in the 24‐h Average Pain Score  compared with placebo . Duloxetine treatment was considered to be safe and well tolerated with less than 20 percent discontinuation due to adverse events . Duloxetine at 60 and 120 mg/d was safe and effective in the management of diabetic peripheral neuropathic pain Neuropathic pain ( NeP ) , generated by disorders of the peripheral and central nervous system , can be particularly severe and disabling . Prevalence estimates indicate that 2 % to 3 % of the population in the developed world suffer from NeP , which suggests that up to one million Canadians have this disabling condition . Evidence -based guidelines for the pharmacological management of NeP are therefore urgently needed . R and omized , controlled trials , systematic review s and existing guidelines focusing on the pharmacological management of NeP were evaluated at a consensus meeting . Medications are recommended in the guidelines if their analgesic efficacy was supported by at least one method ologically sound , r and omized , controlled trial showing significant benefit relative to placebo or another relevant control group . Recommendations for treatment are based on degree of evidence of analgesic efficacy , safety , ease of use and cost-effectiveness .  Analgesic agents recommended for first-line treatments are certain antidepressants ( tricyclics ) and anticonvulsants ( gabapentin and pregabalin ) . Second-line treatments recommended are serotonin noradrenaline reuptake inhibitors and topical lidocaine . Tramadol and controlled-release opioid analgesics are recommended as third-line treatments for moderate to severe pain . Recommended fourth-line treatments include cannabinoids , methadone and anticonvulsants with lesser evidence of efficacy , such as lamotrigine , topiramate and valproic acid . Treatment must be individualized for each patient based on efficacy , side-effect profile and drug accessibility , including cost . Further studies are required to examine head-to-head comparisons among analgesics , combinations of analgesics , long-term outcomes , and treatment of pediatric and central Study Design . This was a r and omized , double-blind , placebo-controlled clinical trial . Objective . To assess the efficacy and safety of duloxetine in the treatment of chronic low back pain ( CLBP ) . Summary of Background Data . Imbalance of serotonin and norepinephrine within modulatory pain pathways has been implicated in the development and maintenance of chronic pain . Duloxetine , a selective reuptake inhibitor of serotonin and norepinephrine , has demonstrated clinical efficacy in 3 distinct chronic pain conditions : diabetic peripheral neuropathic pain , fibromyalgia , and chronic pain because of osteoarthritis . Methods . In this r and omized double-blind trial , adult nondepressed patients with a non-neuropathic CLBP and a weekly mean of the 24-hour average pain score ≥4 at baseline ( 0–10 scale ) were treated with either duloxetine or placebo for 13 weeks . The dose of duloxetine during first 7 weeks was 60 mg once daily . At week 7 , patients reporting < 30 % pain reduction had their dose increased to 120 mg . The primary outcome measure was the Brief Pain Inventory ( BPI ) 24-hour average pain rating . Secondary measures included Rol and -Morris Disability Question naire-24 ; Patient 's Global Impressions of Improvement ; Clinical Global Impressions-Severity ( CGI-S ) ; BPI-Severity and -Interference ( BPI-I ) ; and weekly means of the 24-hour average pain , night pain , and worst pain scores from patient diaries . Quality -of-life , safety , and tolerability outcomes were also assessed . Results . Compared with placebo-treated patients ( least-squares mean change of −1.50 ) , patients on duloxetine ( least-squares mean change of −2.32 ) had a significantly greater reduction in the BPI 24-hour average pain from baseline to endpoint ( P = 0.004 at week 13 ) . Additionally , the duloxetine group significantly improved on Patient 's Global Impressions of Improvement ; Rol and -Morris Disability Question naire-24 ; BPI-Severity and average BPI-Interference ; weekly mean of the 24-hour average pain , night pain , and worst pain . Significantly more patients in the duloxetine group ( 13.9 % ) compared with placebo ( 5.8 % ) discontinued because of adverse events ( P = 0.047 ) . The most common treatment-emergent adverse events in the duloxetine group included nausea , dry mouth , fatigue , diarrhea , hyperhidrosis , dizziness , and constipation . Conclusion . Duloxetine significantly reduced pain and improved functioning in patients with CLBP . The safety and tolerability were similar to those reported in earlier studies Background Early rehabilitation after stroke is essential to help reduce disability . Purpose To summarize evidence on the benefits and harms of nonpharmacologic and pharmacologic treatments for motor deficits and mood disorders in adults who have had stroke . Data Sources English- language search es of multiple electronic data bases from April 2009 through July 2018 ; targeted search es to December 2018 for studies of selective serotonin reuptake inhibitors ( SSRIs ) or serotonin-norepinephrine reuptake inhibitors . Study Selection 19 systematic review s and 37 r and omized controlled trials addressing therapies for motor deficits or mood disorders in adults with stroke . Data Extraction One investigator abstract ed the data , and quality and GRADE assessment were checked by a second investigator . Data Synthesis Most interventions ( for example , SSRIs , mental practice , mirror therapy ) did not improve motor function . High- quality evidence did not support use of fluoxetine to improve motor function . Moderate- quality evidence supported use of cardiorespiratory training to improve maximum walking speed and repetitive task training or transcranial direct current stimulation to improve activities of daily living ( ADLs ) . Low- quality evidence supported use of robotic arm training to improve ADLs . Low- quality evidence indicated that antidepressants may reduce depression , whereas the frequency and severity of antidepressant-related adverse effects was unclear . Low- quality evidence suggested that cognitive behavioral therapy and exercise , including mind-body exercise , may reduce symptoms of depression and anxiety . Limitation Studies were of poor quality , interventions and comparators were heterogeneous , and evidence on harms was scarce . Conclusion Cardiorespiratory training , repetitive task training , and transcranial direct current stimulation may improve ADLs in adults with stroke .  Cognitive behavioral therapy , exercise , and SSRIs may reduce symptoms of poststroke depression , but use of SSRIs to prevent depression or improve motor function was not supported . Primary Funding Source U.S. Department of Veterans Affairs , Veterans Health Administration Background : Serotonin ( 5-HT ) and norepinephrine ( NE ) are involved in pain modulation via descending inhibitory pathways in the brain and spinal cord . Objective : To assess the efficacy of duloxetine , a dual reuptake inhibitor of 5-HT and NE , on the reduction of pain severity , as well as secondary outcome measures in patients with diabetic peripheral neuropathic pain ( DPNP ) . Methods : In this double-blind study , patients with DPNP and without comorbid depression were r and omly assigned to treatment with duloxetine 60 mg once daily ( QD ) , duloxetine 60 mg twice daily ( BID ) , or placebo for 12 weeks . The primary outcome measure was the weekly mean score of 24-hour average pain severity on the 11-point Likert scale . Secondary measures and health outcome measures were also assessed . Results : Duloxetine 60 mg QD and 60 mg BID demonstrated improvement in the management of DPNP and showed rapid onset of action , with separation from placebo beginning at week 1 on the 24-hour average pain severity score . For all secondary measures for pain ( except allodynia ) , mean changes showed an advantage of duloxetine over placebo , with no significant difference between 60 mg QD and 60 mg BID . Clinical Global Impression of Severity and Patient ’s Global Impression of Improvement evaluation demonstrated greater improvement on duloxetine- vs placebo-treated patients . Duloxetine showed no notable interference on diabetic controls , and both doses were safely administered . Conclusions : This study confirms previous findings that duloxetine at 60 mg QD and 60 mg BID is effective and safe in the management of diabetic peripheral neuropathic pain More than half of anxiety and depression patients treated with an adequate course of antidepressants fail to fully improve . We retrospectively examined whether treatment-resistant depression and anxiety disorder patients responded to and tolerated augmentation with the atypical antipsychotic , aripiprazole . We report on patients with depression and anxiety disorders , including panic disorder , generalized anxiety disorder , social anxiety and post-traumatic stress disorder , who had an incomplete response to a variety of selective serotonin reuptake inhibitors ( SSRIs ) and who received augmentation with aripiprazole .  The primary outcome measure was the Clinical Global Impression of Improvement ( CGI-I ) . In the intent-to-treat analysis , the mean±SD CGI-S was 3.8±1.3 at endpoint . Fifty-nine percent of subjects received CGI-I ratings of 1 or 2 , ‘ much improved ’ or ‘ very much improved , ’ in terms of their depression and anxiety symptoms at the end of 12 weeks . Several patients showed an early ( weeks 1–5 ) , as well as sustained , response to augmentation with doses of aripiprazole between 15 and 30 mg/day . The results suggest that aripiprazole may be effective as an augmentation for patients with persistent depressive and anxiety disorders despite initial SSRI treatment . Because this is a retrospective case review , further prospect i ve studies are required to confirm these findings Abstract Objective . Anxiety disorders are frequently under-diagnosed conditions in primary care , although they can be managed effectively by general practitioners . Methods . This paper is a short and practical summary of the World Federation of Biological Psychiatry ( WFSBP ) guidelines for the pharmacological treatment of anxiety disorders , obsessive – compulsive disorder ( OCD ) and posttraumatic stress disorder ( PTSD ) for the treatment in primary care . The recommendations were developed by a task force of 30 international experts in the field and are based on r and omized controlled studies . Results . First-line pharmacological treatments for these disorders are  selective serotonin reuptake inhibitors  ( for all disorders ) ,  serotonin-norepinephrine reuptake inhibitors  ( for some ) and  pregabalin  ( for generalized anxiety disorder only ) . A combination of  medication and cognitive behavior/exposure therapy  was shown to be a clinical ly desired treatment strategy . Conclusions . This short version of an evidence -based guideline may improve treatment of anxiety disorders , OCD , and PTSD in primary care BACKGROUND Despite treatment advances , major depressive disorder ( MDD ) is still a significant cause of morbidity and mortality . Current therapies frequently fall short of providing full remission . In addition , physical symptoms are commonly seen in MDD patients , increasing overall morbidity and health care utilization . Duloxetine hydrochloride , a dual reuptake inhibitor of serotonin and norepinephrine , was evaluated for efficacy and tolerability/safety in the treatment of MDD and associated physical symptoms . METHOD In this multicenter , double-blind , parallel-group study , adult patients with DSM-IV MDD were r and omly assigned to receive placebo ( N = 122 ) or duloxetine ( 60 mg/day , N = 123 ) for 9 weeks . The primary efficacy measure was the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) total score . Painful physical symptoms were assessed using visual analog scales , and global illness and quality of life were evaluated using the Clinical Global Impressions-Severity scale , the Patient Global Impressions-Improvement scale , and the Quality of Life in Depression Scale . Safety and tolerability were determined by monitoring discontinuation rates , adverse events , vital signs , and laboratory results . RESULTS Duloxetine was significantly superior to placebo ( p < .001 ) in reducing HAM-D-17 total scores , starting at week 2 . The estimated probability of remission for duloxetine-treated patients ( 44 % ) was almost 3 times that of placebo patients ( 16 % ) . Duloxetine significantly reduced painful physical symptoms in comparison with placebo .  Discontinuation due to adverse events for duloxetine-treated patients ( 13.8 % ) compared favorably with the rates reported for SSRIs in other studies . Nausea , dry mouth , and somnolence were the most common adverse events ; no significant incidence of hypertension was seen . CONCLUSION Duloxetine , 60 mg/day , is a well-tolerated and effective treatment for MDD that reduces painful physical symptoms . These findings suggest that duloxetine may be a first-line treatment for patients with MDD and associated painful physical symptoms Objective One of the complications of chemotherapy is peripheral neuropathy . Various studies have shown that potent norepinephrine and serotonin reuptake inhibitors such as gabapentin , venlafaxine and duloxetine have therapeutic effects on neuropathy . The aim of this study was to compare the effects of venlafaxine vs. duloxetine on chemotherapy-induced peripheral neuropathy . Methods In this clinical trial , cancer patients who were suffering from chemotherapy-induced peripheral neuropathy comprised the study population . They were r and omly assigned to three pharmacotherapy groups including venlafaxine , duloxetine and placebo . Cranial , sensory , motor neuropathies as well as neuropathic pain were evaluated on day 1 , week 2 , and week 4 after enrollment . Results Grade of cranial , motor , sensory and neuropathic pain decreased significantly in venlafaxine and duloxetine groups . This reduction was more considerable in duloxetine group compared to venlafaxine group ( P < 0.05 ) . Conclusion Duloxetine seems to be more effective than venlafaxine in decreasing the symptoms of chemotherapy-induced peripheral neuropathy .  Duloxetine was more effective than venlafaxine in decreasing motor neuropathy and neuropathic pain grade CONTEXT Major depressive disorder causes significant morbidity and mortality . Current therapies fail to fully treat both emotional and physical symptoms of major depressive disorder . OBJECTIVE To evaluate duloxetine , a dual reuptake inhibitor of serotonin and norepinephrine , on improvement of emotional and painful physical symptoms . DESIGN R and omized , double-blind , evaluation of duloxetine at 40 mg/d ( 20 mg twice daily ) and 80 mg/d ( 40 mg twice daily ) versus placebo and paroxetine 20 mg/d in depressed out patients . MAIN OUTCOME MEASURES The primary efficacy measure was the 17-item Hamilton Depression Rating Scale . Visual Analog Scales for pain , Clinical Global Impression of Severity , Patient 's Global Impression of Improvement , and Quality of Life in Depression Scale were also used . Safety was evaluated by assessing discontinuation rates , adverse event rates , vital signs , and laboratory tests . RESULTS Duloxetine 80 mg/d was superior to placebo on mean 17-item Hamilton Depression Rating Scale total change by 3.62 points ( 95 % CI 1.38 , 5.86 ; P = 0.002 ) . Duloxetine at 40 mg/d was also significantly superior to placebo by 2.43 points ( 95 % CI 0.19 , 4.66 ; P = 0.034 ) , while paroxetine was not ( 1.51 points ; 95 % CI -0.55 , 3.56 ; P = 0.150 ) . Duloxetine 80 mg/d was superior to placebo for most other measures , including overall pain severity , and was superior to paroxetine on 17-item Hamilton Depression Rating Scale improvement ( by 2.39 points ; 95 % CI 0.14 , 4.65 ; P = 0.037 ) and estimated probability of remission ( 57 % for duloxetine 80 mg/d , 34 % for paroxetine ; P = 0.022 ) . The only adverse event reported significantly more frequently for duloxetine 80 mg/d than for paroxetine was insomnia ( 19.8 % for duloxetine 80 mg/d , 8.0 % for paroxetine ; P = 0.031 ) . Hypertension incidence was not affected by any treatment . CONCLUSION Duloxetine therapy was efficacious for emotional and physical symptoms of depression , with a selective serotonin reuptake inhibitor-like profile of side effects BACKGROUND While emotional symptoms such as depressed mood and loss of interest have traditionally been considered to constitute the core symptoms of major depressive disorder ( MDD ) , the prevalence and importance of painful physical symptoms such as back pain , abdominal pain , and musculoskeletal pain is becoming increasingly appreciated . Antidepressants possessing dual serotonin/norepinephrine ( 5-HT/NE ) reuptake inhibition may demonstrate greater efficacy in the alleviation of pain . The efficacy of duloxetine , a balanced and potent dual reuptake inhibitor of 5-HT and NE , was evaluated within a cohort of depressed patients with associated painful physical symptoms . METHODS In this multicenter , double-blind , placebo-controlled study , patients meeting DSM-IV criteria for MDD were r and omized to receive placebo ( N=141 ) or duloxetine 60 mg QD ( N=141 ) . Patients were required to have a 17-item Hamilton Rating Scale for Depression ( HAMD17 ) total score 15 , a Clinical Global Impression of Severity ( CGI-S ) score 4 , and a Brief Pain Inventory ( BPI ) Average Pain score 2 at baseline . The primary efficacy measure was the BPI Average Pain score , while secondary measures included other BPI items , the HAMD17 total score , CGI-S , the Patient Global Impression of Improvement ( PGI-I ) scale , Visual Analog Scales ( VAS ) for pain , and the Symptom Question naire , Somatic Subscale ( SQSS ) . Safety was evaluated by recording treatment-emergent adverse events ( spontaneously reported ) , vital signs , and laboratory analytes . RESULTS Mean changes in BPI Average Pain for duloxetine- and placebo-treated patients differed significantly at most visits , but only approached significance at endpoint p=0.066 . For the main effect of treatment ( pooling all visits ) , significant advantages for duloxetine-treated patients were found in 10 of 11 assessed BPI pain severity and pain interference items , in addition to VAS overall pain and back pain . Mean changes in pain measures for duloxetine-treated patients corresponded to improvements of 25 - 50 % , compared with 19 - 39 % for placebo . Mean changes at endpoint in depression rating scales ( HAMD17 , CGI-S , PGI-I ) did not differ significantly between duloxetine and placebo treatment groups due to unusually high placebo response . The magnitude of placebo treatment effects ( as measured by HAMD17 total score and Maier subscale ) was significantly smaller in patients with 1 previous depressive episode , compared to those patients with no previous episodes . In patients with 1 previous depressive episode the advantage of duloxetine over placebo was similar to previous studies . Rates of discontinuation due to adverse events were 14.2 % vs. 2.1 % for duloxetine and placebo , respectively p<0.001 . Treatment-emergent adverse events reported at a significantly higher rate by duloxetine-treated patients included nausea , dry mouth , fatigue , and decreased appetite . CONCLUSIONS In this study , duloxetine ( 60 mg QD ) was shown to be an effective treatment for the painful physical symptoms which are frequently associated with depression . Improvements in pain severity occurred independently of changes in depressive symptom severity Generalized anxiety disorder ( GAD ) , a prevalent and chronic illness , is associated with dysregulation in both serotonergic and noradrenergic neurotransmission . Our study examined the efficacy , safety , and tolerability of duloxetine hydrochloride , a dual reuptake inhibitor of serotonin and norepinephrine , for short‐term treatment of adults with GAD . In a 10‐week , double‐blind , progressive‐titration , flexible‐dose trial , 327 adult out patients with a DSM‐IV – defined GAD diagnosis were r and omized to duloxetine 60–120 mg ( DLX , N=168 ) or placebo ( PLA , N=159 ) treatment . The primary efficacy measure was mean change from baseline to endpoint in Hamilton Anxiety Scale ( HAMA ) total score . Secondary outcome measures included response rate ( HAMA total score reduction ≥50 % from baseline ) , Clinician Global Impression — Improvement ( CGI‐I ) scores , and Sheehan Disability Scale ( SDS ) scores . Patients who received duloxetine treatment demonstrated significantly greater improvement in HAMA total scores ( P=.02 ) ; a higher response rate ( P=.03 ) , and greater improvement ( P=.04 ) than patients who received placebo . Duloxetine‐treated patients were also significantly more improved than placebo‐treated patients on SDS global functional ( P<.01 ) and work , social , and family/home impairment scores ( P<.05 ) . The rate of discontinuation due to adverse events ( AEs ) was higher for the duloxetine group compared with the placebo group ( P=.002 ) . The AEs most frequently associated with duloxetine were nausea , dizziness , and somnolence . Duloxetine was an efficacious , safe , and well‐tolerated treatment that result ed in clinical ly significant improvements in symptom severity and functioning for patients with GAD . Depression and Anxiety 0:1–8 , 2007 . © 2007 Wiley‐Liss , Background Major depressive disorder ( MDD ) is a chronic and highly disabling condition . Existing pharmacotherapies produce full remission in only 30 % to 40 % of treated patients . Antidepressants exhibiting dual reuptake inhibition of both serotonin ( 5-HT ) and norepinephrine ( NE ) may achieve higher rates of remission compared with those acting upon a single neurotransmitter . In this study , the safety and efficacy of duloxetine , a potent dual reuptake inhibitor of 5-HT and NE , were examined . Methods Patients ( N = 533 ) meeting DSM-IV criteria for MDD received open-label duloxetine ( 60 mg once a day [ QD ] ) for 12 weeks during the initial phase of a relapse prevention trial . Patients were required to have a 17-item Hamilton Rating Scale for Depression ( HAMD17 ) total score ≥18 and a Clinical Global Impression of Severity ( CGI-S ) score ≥4 at baseline . Efficacy measures included the HAMD17 total score , HAMD17 subscales , the CGI-S , the Patient Global Impression of Improvement ( PGI-I ) scale , Visual Analog Scales ( VAS ) for pain , and the Symptom Question naire , Somatic Subscale ( SQ-SS ) . Quality of life was assessed using the Sheehan Disability Scale ( SDS ) and the Quality of Life in Depression Scale ( QLDS ) . Safety was evaluated by recording spontaneously-reported treatment-emergent adverse events , changes in vital signs and laboratory analytes , and the Patient Global Impression of Sexual Function ( PGI-SF ) scale . Results The rate of discontinuation due to adverse events was 11.3 % . Treatment-emergent adverse events reported by ≥10 % duloxetine-treated patients were nausea , headache , dry mouth , somnolence , insomnia , and dizziness . Following 12 weeks of open-label duloxetine therapy , significant improvements were observed in all assessed efficacy and quality of life measures . In assessment s of depression severity ( HAMD17 , CGI-S ) the magnitude of symptom improvement continued to increase at each study visit , while for painful physical symptoms the onset of improvement was rapid and reached a maximum after 2 to 3 weeks of treatment . Conclusion In this open-label phase of a relapse prevention study , duloxetine ( 60 mg QD ) was shown to be safe and effective in the treatment of MDD.Trial registration NCT00036309 Objective : To review the mechanism of selective serotonin reuptake inhibitor (SSRI)–mediated serotonergic neurotransmission , focusing on serotonin 1A ( 5-HT1A ) autoreceptors , which are proposed to be involved in delaying therapeutic efficacy . Vilazodone was specifically design ed to function both as an SSRI and a partial agonist at 5-HT1A receptors . This combined mechanism is proposed to decrease time to efficacy , minimize sexual side effects , and provide concomitant anxiolytic properties . Data Sources : A PubMed search of all English- language articles from January 1990 to January 2013 was conducted using the search terms depression and 5-HT1A , depression and buspirone , depression and pindolol , and vilazodone . Study Selection : We found 47 articles and abstract s that were selected for inclusion on the basis of information about the pharmacology of 5-HT1A receptors and the clinical data on pindolol , buspirone , and vilazodone in depression . Data Extraction : This review summarizes current literature involving antidepressant activity , the role of 5-HT1A autoreceptors , and clinical trials involving serotonin reuptake inhibition in conjunction with 5-HT1A agonists and partial agonists , with a focus on vilazodone . Results : Vilazodone has demonstrated efficacy in 2 large , r and omized , double-blind , placebo-controlled trials in major depressive disorder . Results suggest that vilazodone has a low incidence of sexual side effects and is effective in patients with high levels of anxiety . A pooled analysis shows evidence of significant symptom reduction after only 1 week of therapy . Conclusions : If future studies corroborate the clinical benefits attributed to its mechanism of action , vilazodone may show potential advantages in terms of onset of action , sexual side effects , and anxiolytic activity in patients with major depressive disorder
Results : Duloxetine may be an effective treatment for mood spectrum disorders , panic disorder , several symptom clusters of borderline personality , and as add-on drug in schizophrenia .
Modest or conflicting results have been found for the efficacy of duloxetine in obsessive-compulsive disorder , posttraumatic stress disorder , eating , and sexual disorders .
Background : Duloxetine hydrochloride ( DUL ) is an antidepressant included in the pharmacological class of serotonin-norepinephrine reuptake inhibitors approved for the treatment of major depressive disorder , generalized anxiety disorder , diabetic peripheral neuropathic pain , fibromyalgia , and chronic musculoskeletal pain .
The aim of this review was to eluci date current evidence s on the use of DUL in the treatment of a variety of psychiatric disorders .