A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain Duloxetine 60 mg once-daily in the treatment of painful physical symptoms in patients with major depressive disorder. Duloxetine in the treatment of major depressive disorder: an open-label study Efficacy and safety of duloxetine in the treatment of generalized anxiety disorder: a flexible‐dose, progressive‐titration, placebo‐controlled trial Duloxetine vs. placebo in patients with painful diabetic neuropathy A double-blind, randomized multicenter trial comparing duloxetine with placebo in the management of diabetic peripheral neuropathic pain. Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial. Duloxetine 60 mg once daily dosing versus placebo in the acute treatment of major depression. Efficacy and tolerability of duloxetine in the treatment of patients with borderline personality disorder: a pilot study Effects of duloxetine on painful physical symptoms associated with depression. Acute and long-term treatment of late-life major depressive disorder: duloxetine versus placebo. Duloxetine versus placebo in the treatment of patients with diabetic neuropathic pain in China. Efficacy of duloxetine for the treatment of generalized anxiety disorder: implications for primary care physicians. Efficacy and Safety of Duloxetine in Patients With Chronic Low Back Pain Duloxetine in the treatment of major depressive disorder Duloxetine in the acute and long-term treatment of major depressive disorder: a placebo- and paroxetine-controlled trial
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 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 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 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 , & 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 OBJECTIVE Assess efficacy and safety of duloxetine , a selective serotonin and norepinephrine reuptake inhibitor , on the reduction of pain severity , in patients with diabetic peripheral neuropathic pain ( DPNP ) . METHODS This was a multicenter , parallel , double-blind , r and omized , placebo-controlled trial that enrolled 348 patients with pain due to peripheral neuropathy caused by type 1 or type 2 diabetes mellitus . Patients ( N = 116 per group ) were r and omly assigned to receive 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 evaluated on an 11-point Likert scale . Secondary outcome measures and safety were evaluated . RESULTS Compared with placebo-treated patients , both duloxetine-treated groups improved significantly more ( P < 0.001 ) on the 24-hour average pain score .  Duloxetine demonstrated superiority to placebo in all secondary analyses of the primary efficacy measure . A significant treatment effect for duloxetine was observed in most secondary measures for pain . Discontinuations due to adverse events were more frequent in the duloxetine 60 mg BID- ( 12.1 % ) versus the placebo- ( 2.6 % ) treated group . Duloxetine showed no adverse effects on diabetic control , and both doses were safely administered and well tolerated . CONCLUSIONS In this clinical trial , duloxetine 60 mg QD and duloxetine 60 mg BID were effective and safe in the management of DPNP 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 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 Existing therapies for major depressive disorder ( MDD ) have either limited efficacy and /or poor tolerability . The present study examined the effects of duloxetine , a potent and balanced dual reuptake inhibitor of serotonin ( 5-HT ) and norepinephrine ( NE ) , in patients with MDD . Adult patients ( N = 267 ) with MDD were r and omly assigned to receive duloxetine ( 60 mg/day ) or placebo in this 9-week , multi-center , double-blind , parallel-group clinical trial . Efficacy was evaluated using the 17-item Hamilton Depression Rating Scale ( HAMD(17 ) ) , Visual Analog Scales ( VAS ) for pain , Clinical Global Impression of Severity ( CGI-S ) , Patient 's Global Impression of Improvement ( PGI-I ) , and Quality of Life in Depression Scale ( QLDS ) . Safety was evaluated by assessing discontinuation rates , adverse event rates , vital signs , and laboratory tests .  Duloxetine ( 60 mg QD ) significantly reduced the HAMD(17 ) total score compared with placebo at the end of 9-week therapy . Estimated probabilities of response and remission were 65 and 43 % , respectively , for duloxetine compared with 42 and 28 % for placebo . Duloxetine also reduced overall pain , back pain , shoulder pain and time in pain while awake significantly more than placebo . Global measures of improvement , including PGI-I and QLDS , were significantly improved by duloxetine compared with placebo .  Discontinuations due to adverse events were more frequent for duloxetine-treated patients ( 12.5 % ) than for placebo-treated patients ( 4.3 % ) . Nausea , dry mouth , dizziness , and constipation were more frequent for duloxetine than placebo . There was no significant incidence of hypertension , nor any other safety issues . Duloxetine 60 mg administered once daily appears to be a safe and effective treatment for MDD 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 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 OBJECTIVE To compare the efficacy of duloxetine with placebo on depression in elderly patients with major depressive disorder . DESIGN Multicenter , 24-week ( 12-week short-term and 12-week continuation ) , r and omized , placebo-controlled , double-blind trial . SETTING United States , France , Mexico , Puerto Rico . PARTICIPANTS Age 65 years or more with major depressive disorder diagnosis ( one or more previous episode ) ; Mini-Mental State Examination score ≥20 ; Montgomery-Asberg Depression Rating Scale total score ≥20 .  INTERVENTION Duloxetine 60 or 120 mg/day or placebo ; placebo rescue possible . MEASUREMENTS Primary -Maier subscale of the 17-item Hamilton Depression Rating Scale ( HAMD-17 ) at week 12 . Secondary -Geriatric Depression Scale , HAMD-17 total score , cognitive measures , Brief Pain Inventory ( BPI ) , Numeric Rating Scales ( NRS ) for pain , Clinical Global Impression-Severity scale , Patient Global Impression of Improvement in acute phase and acute plus continuation phase of treatment . RESULTS Compared with placebo , duloxetine did not show significantly greater improvement from baseline on Maier subscale at 12 weeks , but did show significantly greater improvement at weeks 4 , 8 , 16 , and 20 . Similar patterns for Geriatric Depression Scale and Clinical Global Impression-Severity scale emerged , with significance also seen at week 24 . There was a significant treatment effect for all BPI items and 4 of 6 NRS pain measures in the acute phase , most BPI items and half of the NRS measures in the continuation phase . More duloxetine-treated patients completed the study ( 63 % versus 55 % ) . A significantly higher percentage of duloxetine-treated patients versus placebo discontinued due to adverse event ( 15.3 % versus 5.8 % ) . CONCLUSIONS Although the antidepressant efficacy of duloxetine was not confirmed by the primary outcome , several secondary measures at multiple time points suggested efficacy . Duloxetine had significant and meaningful beneficial effects on pain BACKGROUND Duloxetine , a selective serotonin and noradrenaline reuptake inhibitor , has been shown to be effective in treatment of diabetic peripheral neuropathic pain and approved for the management of patients with diabetic peripheral neuropathic pain ( DPNP ) in the United States , European Union , and many other countries . This study assessed the efficacy and safety of duloxetine in Chinese patients with diabetic peripheral neuropathic pain . METHODS This double-blind , r and omized , placebo-controlled , flexible-dose study treated adult patients with diabetic peripheral neuropathic pain and baseline Brief Pain Inventory ( BPI ) 24-hour average pain severity ratings ≥ 4 with duloxetine 60 mg to 120 mg once daily or placebo for 12 weeks . Dose adjustments of duloxetine or matching placebo were based upon investigator 's judgment of clinical response . Change from baseline to endpoint in BPI average pain was the primary efficacy outcome . Secondary outcome measures included BPI-severity and -Interference , Patient Global Impression of Improvement , Clinical Global Impressions of Severity , EuroQol : 5 Dimensions , Athens Insomnia Scale , and safety measures . RESULTS Of 215 patients r and omized , 88.4 % and 82.1 % of patients in placebo and duloxetine groups , respectively , completed the study . Mean change from baseline to endpoint in BPI average pain was not statistically different between the treatment groups ( P = 0.124 ) . Duloxetine- treated patients showed significantly greater pain reduction compared with those in placebo group at weeks 1 , 2 , and 4 ( P = 0.004 , P = 0.009 , and P = 0.006 , respectively ) , but not at weeks 8 ( P = 0.125 ) and 12 ( P = 0.107 ) . Duloxetine-treated patients experienced statistically significant improvement in Patient Global Impression of Improvement , Clinical Global Impression of Severity , area under the curve for pain relief , BPI-severity pain right now , and BPI-interference walking ability . Patients treated with duloxetine 120 mg once daily showed significantly greater pain reduction on the Brief Pain Inventory average pain score relative to placebo . Duloxetine-treated patients reported nausea , somnolence , anorexia , and dysuria significantly more than placebo . CONCLUSIONS Although the primary study endpoint was not achieved , the overall observed response pattern suggests the efficacy of duloxetine in the treatment of Chinese patients with diabetic peripheral neuropathic pain . The safety profile for duloxetine is similar to that reported in other global trials OBJECTIVE This study examined the efficacy and tolerability of duloxetine , a dual reuptake inhibitor of serotonin and norepinephrine , for the treatment of patients with generalized anxiety disorder ( GAD ) . METHOD Patients were ≥ 18 years old and recruited from 5 European countries , the United States , and South Africa . The study had a 9-week , multicenter , r and omized , double-blind , fixed-dose , placebo-controlled , parallel-group design . A total of 513 patients ( mean age = 43.8 years ; 67.8 % female ) with a DSM-IV-defined GAD diagnosis received treatment with duloxetine 60 mg/day ( N = 168 ) , duloxetine 120 mg/day ( N = 170 ) , or placebo ( N = 175 ) . The primary efficacy measure was the Hamilton Rating Scale for Anxiety ( HAM-A ) total score . Secondary measures included the Sheehan Disability Scale , HAM-A psychic and somatic anxiety factor scores , and HAM-A response , remission , and sustained improvement rates . The study was conducted from July 2004 to September 2005 . RESULTS Both groups of duloxetine-treated patients demonstrated significantly greater improvements in anxiety symptom severity compared with placebo-treated patients as measured by HAM-A total score and HAM-A psychic and somatic anxiety factor scores ( p values ranged from ≤ .01 to ≤ .001 ) . Duloxetine-treated patients had greater functional improvements in Sheehan Disability Scale global and specific domain scores ( p ≤ .001 ) than placebo-treated patients . Both duloxetine doses also result ed in significantly greater HAM-A response , remission , and sustained improvement rates compared with placebo ( p values ranged from ≤ .01 to ≤ .001 ) . The rate of study discontinuation due to adverse events was 11.3 % for duloxetine 60 mg and 15.3 % for duloxetine 120 mg versus 2.3 % for placebo ( p ≤ .001 ) . CONCLUSION The results of this study demonstrate that duloxetine 60 mg/day and 120 mg/day were efficacious and well tolerated and thus may provide primary care physicians with a useful pharmacologic intervention for GAD . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00122824 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 Since depression impacts all body systems , antidepressant treatments should relieve both the emotional and physical symptoms of depression . Duloxetine demonstrated antidepressant efficacy at a dose of 60 mg qd in two placebo-controlled , r and omized , double-blind studies and significantly improved remission rates compared with placebo . Duloxetine-treated patients had significant reduction in severity of the symptoms of depression as assessed by the HAM-D17 , anxious symptoms as measured by the HAM-A and quality of life measures compared to placebo . Duloxetine also improved somatic symptoms , particularly painful symptoms which may have contributed to significantly improved remission rates compared to placebo . Approximately 10 % of the 1139 patients with major depressive disorder in placebo-controlled trials discontinued treatment due to an adverse event , compared to 4 % of the 777 patients receiving placebo .  In addition to nausea ( 1.4 % incidence ) , which was the most common reason for discontinuation , dizziness , somnolence , and fatigue were the most common AEs reported as reasons for discontinuation and all were considered drug-related . Duloxetine treatment lacks effects on ECG , increases heart rate , and has little effect on blood pressure or weight BACKGROUND Duloxetine is a balanced and potent dual reuptake inhibitor of serotonin ( 5-HT ) and norepinephrine ( NE ) that has previously been shown to be effective in the acute treatment of major depressive disorder ( MDD ) . This placebo-controlled study assesses the safety and efficacy of duloxetine ( 80 or 120 mg/day ) and paroxetine ( 20 mg QD ) during an initial 8-week acute phase and subsequent 6-month continuation phase treatment of MDD . METHOD In this r and omized , double-blind , placebo-controlled trial , adult out patients ( age > or= 18 years ) meeting DSM-IV criteria for MDD received placebo ( n = 93 ) , duloxetine 80 mg/day ( 40 mg BID ; n = 95 ) , duloxetine 120 mg/day ( 60 mg BID ; n = 93 ) , or paroxetine ( 20 mg QD ; n = 86 ) for 8 weeks . Patients who had a > or= 30 % reduction from baseline in HAMD(17 ) total score during the acute phase were allowed to continue on the same ( blinded ) treatment for a 6-month continuation phase . Efficacy measures included the 17-item Hamilton Rating Scale for Depression ( HAMD(17 ) ) total score , HAMD(17 ) subscales , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Hamilton Anxiety Rating Scale ( HAMA ) , Visual Analog Scales ( VAS ) for pain , the Clinical Global Impression of Severity ( CGI-S ) and Patient Global Impression of Improvement ( PGI-I ) scales , the 28-item Somatic Symptom Inventory ( SSI ) , and the Sheehan Disability Scale ( SDS ) . Safety and tolerability were assessed using treatment-emergent adverse events , discontinuations due to adverse events , vital signs , ECGs , laboratory tests , and the Arizona Sexual Experiences Scale ( ASEX ) . RESULTS During the acute phase , patients receiving duloxetine 80 mg/day , duloxetine 120 mg/day , or paroxetine 20 mg QD had significantly greater reductions in HAMD(17 ) total score compared with placebo . Both duloxetine ( 80 and 120 mg/day ) and paroxetine treatment groups had significantly greater improvement , compared with placebo , in MADRS , HAMA , CGI-S , and PGI-I scales . Estimated probabilities of remission at week 8 for patients receiving duloxetine 80 mg/day ( 51 % ) , duloxetine 120 mg/day ( 58 % ) , and paroxetine ( 47 % ) were significantly greater compared with those receiving placebo ( 30 % ) . The rate of discontinuation due to adverse events among duloxetine-treated patients ( 80 and 120 mg/day ) did not differ significantly from the rate in the placebo group . Treatment-emergent adverse events reported significantly more frequently by duloxetine-treated patients than by patients receiving placebo were constipation ( 80 and 120 mg/day ) , increased sweating ( 120 mg/day ) , and somnolence ( 120 mg/day ) . The incidence of acute treatment-emergent sexual dysfunction in duloxetine- and paroxetine-treated patients was 46.5 % and 62.8 % , respectively . During the 6-month continuation phase , duloxetine ( 80 and 120 mg/day ) and paroxetine treatment groups demonstrated significant improvement in HAMD(17 ) total score . Treatment-emergent adverse events occurring most frequently in each active treatment group during the continuation phase were viral infection  ( duloxetine 80 mg/day ) , diarrhea  ( duloxetine 120 mg/day ) , and headache  ( paroxetine 20 mg QD ) . CONCLUSION These data support previous findings that duloxetine is safe , efficacious , and well tolerated in the acute treatment of MDD . Furthermore , these data provide the first demonstration under double-blind , placebo-controlled conditions that the efficacy and tolerability of duloxetine are maintained during chronic treatment
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 .