***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 Previous studies have shown a positive association between pain and depression  , though evidence supporting a direct link between these two variables is less robust . Using a placebo-controlled trial , the authors examined the analgesic and antidepressant efficacy of paroxetine ( 20 mg ) in chronic low back pain sufferers . The authors examined the associations among pain , depression , disability , and illness attitudes .  Paroxetine showed no effects on pain or depression compared with placebo ; however , subjects r and omized to paroxetine were more likely to reduce concomitant analgesic medication . The cross-sectional association of depression and pain at baseline ( r = 0.2 , P = 0.02 ) was weaker than the association between depression and disability ( r = 0.3 , P = 0.004 ) . Similarly , the association of change in depression scores with change in pain ( r = 0.25 , P = 0.016 ) was weaker than change between depression and disability ( r = 0.49 , P<0.0005 ) . Whereas the relationship between pain and depression became nonsignificant when disability and illness attitudes were controlled , the relationship between depression and disability remained highly significant when pain and illness attitudes were controlled . These data are consistent with the association between pain and depression being wholly modulated by disability and illness attitudes , with no direct relationship between pain and depression The reduction of pain by two antidepressants , clomipramine and mianserin , was , in this study on 253 patients with chronic idiopathic pain syndrome , found to be not better than a placebo when all patients were compared independently of the classification of pain . The improvement rate was around 40 % after 6 weeks of treatment when using a 50 % or better reduction in pain level . However , in patients who fulfilled a checklist definition of minor to major depression ( 30 % of the total patient material ) clomipramine was superior to mianserin and placebo with an improvement rate of 75 % after 6 weeks . Using pain curves over time as outcome measure in the various clinical pain categories it was found that both mianserin and clomipramine seemed superior to placebo in patients with tension headache , but in patients with low back pain syndrome placebo was superior to the two antidepressants . No difference among the three treatments was found in patients with burning mouth syndrome or in patients with abdominal pain . These differences underline the importance of study ing specific pain syndromes rather than composite groups of patients with idiopathic pain . The clinical significance of these pain curves needs further placebo controlled investigations Abstract Although lumbar radicular pain is the most common chronic neuropathic pain syndrome , there have been few r and omized studies of drug treatments . We compared the efficacy of morphine ( 15–90 mg ) , nortriptyline ( 25–100 mg ) , their combination , and a benztropine “ active placebo ” ( 0.25–1 mg ) in patients with chronic sciatica . Each period consisted of 5 weeks of dose escalation , 2 weeks of maintenance at the highest tolerated doses , and 2 weeks of dose tapering . The primary outcome was the mean daily leg pain score on a 0–10 scale during the maintenance period . Secondary outcomes included a 6‐point ordinal global pain relief scale , the Beck Depression Inventory ( BDI ) , the Oswestry Back Pain Disability Index ( ODI ) and the SF‐36 . In the 28 out of 61 patients who completed the study , none of the treatments produced significant reductions in average leg pain or other leg or back pain scores . Pain reduction , relative to placebo treatment was , 14 % for nortriptyline ( 95 % CI = [ −2 % , 30 % ] ) , 7 % for morphine ( 95 % CI = [ −8 % , 22 % ] ) , and 7 % for the combination treatment ( 95 % CI = [ −4 % , 18 % ] ) . Mean doses were : nortriptyline alone , 84 ± 24.44 ( SD ) mg/day ; morphine alone , 62 ± 29 mg/day ; and combination , morphine , 49 ± 27 mg/day plus nortriptyline , 55 mg ± 33.18 mg/day . Over half of the study completers reported some adverse effect with morphine , nortriptyline or their combination . Within the limitations of the modest sample size and high dropout rate , these results suggest that nortriptyline , morphine and their combination may have limited effectiveness in the treatment of chronic sciatica & NA ; To assess the efficacy of nortriptyline , a tricyclic antidepressant , as an analgesic in chronic back pain without depression , we conducted a r and omized , double‐blind , placebo‐controlled , 8‐week trial in 78 men recruited from primary care and general orthopedic setting s , who had chronic low back pain ( pain at T‐6 or below on a daily basis for 6 months or longer ) . Of these 57 completed the trial ; of the 21 who did not complete , four were withdrawn because of adverse effects . The intervention consisted of inert placebo or nortriptyline titrated to within the therapeutic range for treating major depression ( 50–150 ng/ml ) . The main outcome endpoints were pain ( Descriptor Differential Scale ) , disability ( Sickness Impact Profile ) , health‐related quality of life ( Quality of Well‐Being Scale ) , mood ( Beck Depression Inventory , Spielberger State Anxiety Inventory , Hamilton Anxiety/Depression Rating Scales ) , and physician rated outcome ( Clinical Global Impression ) . Reduction in pain intensity scores was significantly greater for participants r and omized to nortriptyline ( difference in mean change 1.68 , 95 % −0.001 , CI −3.36 , P=0.050 ) , with a reduction of pain by 22 % compared to 9 % on placebo . Reduction in disability marginally favored nortriptyline ( P=0.055 ) , but health‐related quality of life , mood , and physician ratings of overall outcome did not differ significantly between treatments . Subgroup analyses of study completers supported the intent‐to‐treat analysis . Also , completers with radicular pain on nortriptyline ( n=5 ) had significantly ( P<0.05 ) better analgesia and overall outcome than did those on placebo ( n=6 ) . The results suggest noradrenergic mechanisms are relevant to analgesia in back pain . This modest reduction in pain intensity suggests that physicians should carefully weigh the risks and benefits of nortriptyline in chronic back pain without depression Sixty patients with chronic pain of the low back or cervical spine concomitant with clinical depression were studied in a 6-week , r and omized , double-blind comparison of doxepin and placebo . Significant improvements in the doxepin-treated group compared to placebo or to baseline values were seen on Hamilton depression scores , Global Assessment Scale scores , pain severity , percent of time pain felt , and effect of pain on activity , sleep , and muscle tension . Some improvements were observed after 1 week of treatment ; the most improvement occurred at 6 weeks , when the mean doxepin dosage was approximately 200 mg/day and plasma doxepin and nordoxepin averaged 80 ng/ml . No significant harmful effects were observed . Neither plasma beta-endorphin nor enkephalin-like activity demonstrated significant differences from baseline . These data indicate that doxepin is a valuable treatment for patients with chronic pain and depression Objective : Although antidepressants are widely prescribed as analgesics in chronic back pain , their clinical pharmacology is not well established . Norepinephrine transporter blockade seems to be essential for analgesia , but optimal concentrations are unknown . Fixed-dose studies of serotonin reuptake inhibitors are generally negative , but such studies can not be interpreted clearly because efficacy might be detected if concentration-response relationships were known . We evaluated ( 1 ) the feasibility of conducting a controlled-concentration study of a norepinephrine ( desipramine ) and a serotonin reuptake ( fluoxetine ) inhibitor and ( 2 ) the relationship between achieved concentrations and analgesic response . Methods : This single-center , 12-week , double-blind , prospect i ve , controlled-concentration study r and omized 121 chronic back pain patients without major depression to active placebo ( benztropine mesylate )  or  to predetermined low , medium , or high concentrations of desipramine ( targets were 50 , 110 , and 150 ng/mL , respectively ) or fluoxetine ( targets were 100 , 200 , and 400 ng/mL , respectively ) . Of these , 83 completed the trial : 38 withdrew primarily due to side effects . Results : Manipulation check revealed significant overlap of assigned and achieved concentrations related to drug intolerability . Completers ' analysis of achieved concentrations revealed reduction in pain intensity was significantly greater for low-concentration desipramine ( < 60 ng/mL , mean Descriptor Differential Scale [ DDS ] , 4.5 ) compared with placebo ( DDS 6.2 ) , higher concentrations of desipramine ( > 60 ng/mL , DDS 7.9 ) , and all concentrations of fluoxetine ( P < 0.05 , DDS 7.1 ) . Significant improvement in everyday function mirrored findings for pain intensity . Conclusions : Preliminary evidence for a low-concentration " therapeutic window " for noradrenergic analgesia may warrant additional study Thirty-nine patients with acute low back pain were treated with amitriptyline ( 150 mg/d ) or acetaminophen ( 2,000 mg/d ) in a controlled double-blind design for 5 weeks . Both groups revealed mild depression , normal coping , and increased anxiety at the beginning , with significant improvement in anxiety state and pain at the end of treatment . A repeated measures analysis of variance demonstrated that amitriptyline was more effective than acetaminophen in reducing pain intensity from the second week of treatment . Age and depression were the only significant pretreatment predictors of posttreatment pain . The study evaluates the significance of these findings UNLABELLED Clinical trials of the efficacy of antidepressant drugs in patients with chronic low back pain have had mixed results , possibly because of the different mechanisms of action of the drugs that have been studied . Because bupropion has a mechanism of action 
    Output:
    
The qualitative analyses found conflicting evidence on the effect of antidepressants on pain intensity in chronic low-back pain , and no clear evidence that antidepressants reduce depression in chronic low-back pain patients .
There is no clear evidence that antidepressants are more effective than placebo in the management of patients with chronic low-back pain .
These findings do not imply that severely depressed patients with back pain should not be treated with antidepressants ; furthermore , there is evidence for their use in other forms of chronic pain