***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: & NA ; Dysesthetic pain following traumatic myelopathy is characterized by diffuse burning and tingling sensations distal to the level of spinal injury . The dysesthetic pain syndrome ( DPS ) can compromise performance of functional abilities and inhibit participation in rehabilitation programs . Recent laboratory evidence suggests that antidepressant medications with selective inhibition of serotonin reuptake in the brain may be associated with superior analgesic effect compared to such non‐selective agents as amitriptyline . Trazodone hydrochloride is a potent presynaptic serotonin reuptake blocker with few anticholinergic and cardiovascular side effects . This study was a r and omized , double‐blind , placebocontrolled trial of trazodone hydrochloride for the treatment of DPS . Following a 2‐week placebo lead‐in period , patients were r and omized to a 6‐week course of 150 mg trazodone hydrochloride/day or placebo .  Evaluations of pain quality and intensity were performed at 2‐week intervals , utilizing the McGill Pain Question naire , Sternbach Pain Intensity Scale , and Zung Pain and Distress Index . Neurologic examination and assessment of side effects were performed at each evaluation session . No significant changes were noted in reported pain measures between patients allocated to the active drug group and those given placebo during the course of the protocol . However , significantly more patients r and omized  to trazodone complained of side effects and prematurely terminated their participation in the study . The results of this investigation are consistent with those of other earlier trials which indicate that such antidepressant medications as trazodone hydrochloride which selectively inhibit presynaptic reuptake of serotonin , may not be effective in the control of certain pain syndromes . These results do not preclude the possible utility of these agents in the treatment of other pain syndromes or at higher doses than previously studied Fifty-nine patients referred for painful diabetic neuropathy of the lower extremities were evaluated for depression and response to antidepressant drug therapy in a double-blind controlled study . All patients were found to have substantial degrees of depression during psychiatric interview and by Kupfer-Detre test scores ( 8.1 + /- 0.6 , as compared with control values of 4.0 to 4.3 + /- 0.2 ) . Treatment with imipramine hydrochloride or amitriptyline hydrochloride result ed in complete remission of lower extremity pains in all patients in 10 + /- 2 weeks , with concomitant relief of depression and return of depression test scores to 3.8 . These results suggest that the syndrome of painful diabetic neuropathy of the lower extremities represents a depressive equivalent in a large proportion of cases and that treatment with imipramine or amitriptyline is a successful mode of therapy for such persons & NA ; The efficacy of amitriptyline was evaluated in 28 patients with chronic oral‐facial pain . Most of the patients had evidence of musculoskeletal pain while some had a history suggesting pain of neurogenic origin . Two patients had mixed elements of neurogenic and musculoskeletal pain .  Amitriptyline was more effective than placebo in reducing pain after 4 weeks of treatment . No effect was found after only 1 week of drug administration in either dose range . When the patients were divided into depressed and non‐depressed groups based on their Hamilton depression scores , amitriptyline  reduced pain in the depressed and in the non‐depressed groups as compared to placebo . Amitriptyline  reduced the depression scores in the depressed group but had no effect on the depression scores in the non‐depressed group . Thus , pain reduction was not associated with a change in mood in the non‐depressed group . Amitriptyline had no effect on patients ' ratings of the intensity of experimental heat stimuli . We conclude that amitriptyline is effective in the treatment of chronic oral‐facial pain and that its efficacy is independent of its effects on depression . It appears that tricyclic antidepressants act in a fashion different from opiate drugs that alter the sensory discriminative component of pain An account is given of a two-centre controlled clinical trial to assess the efficacy of dothiepin ( Prothiaden ) against placebo and a soft bite-guard in the treatment of psychogenic facial pain . The results confirm the superiority of the dothiepin to placebo in achieving pain relief , but show no benefit from the use of mechanical treatment . Short-term relapse of pain which occurred in the follow-up period was not associated with recurrence of psychiatric symptoms but appeared to be directly related to withdrawal of dothiepin & NA ; Amitriptyline ( AT ) relieves some patients with postherpetic neuralgia ( PHN ) .  Many patients suffer side effects and better therapies are necessary . The aim of this study was to evaluate the efficacy of maprotiline ( MT ) ( noradrenergic ) compared to AT ( mixed noradrenergic and serotonergic ) in this disorder . Thirty‐five patients entered a r and omized , double‐blind , crossover trial of these two agents . We found that MT  relieved PHN in many patients but was not as effective as AT .  Side effects were troublesome with both agents . Relief of steady pain , brief pain and pain on tactile stimulation occurred . Four groups of responses were identified . Some patients reported relief with both agents , some with neither agent and others with only one of the drugs . Most patients were not depressed and analgesia was observed to occur without change in depression ratings in most patients who responded . This result provides evidence that in some patients AT may act via a selective noradrenergic mechanism in relieving PHN and that individuals may differ in the balance and type of neurotransmitters inhibiting pain . Selective noradrenergic agents may be effective if AT fails BACKGROUND Amitriptyline reduces the pain caused by peripheral-nerve disease , but treatment is often limited by side effects related to the drug 's many pharmacologic actions . Selective agents might be safer and more effective . METHODS We carried out two r and omized , double-blind , crossover studies in patients with painful diabetic neuropathy , comparing  amitriptyline with the relatively selective blocker of norepinephrine reuptake desipramine in 38 patients , and comparing the selective blocker of serotonin reuptake fluoxetine with placebo in 46 patients . Fifty-seven patients were r and omly assigned to a study as well as to the order of treatment , permitting comparison among all three drugs and placebo as the first treatment . The patients rated the degree of pain present each day using verbal descriptors , and they also assessed the extent of pain relief globally at the end of each treatment period . RESULTS After individual dose titration , the mean daily doses of the drugs were as follows : amitriptyline , 105 mg ; desipramine , 111 mg ; and fluoxetine , 40 mg . There was moderate or greater relief of pain in 28 of the 38 patients ( 74 percent ) who received amitriptyline , 23 of the 38 patients ( 61 percent ) who received desipramine , 22 of the 46 patients ( 48 percent ) who received fluoxetine , and 19 of the 46 patients ( 41 percent ) who received placebo . The differences in responses between amitriptyline and desipramine and between fluoxetine and placebo were not statistically significant , but both amitriptyline and desipramine were superior to placebo .  Amitriptyline and desipramine were as effective in patients who were not depressed as in depressed patients , but fluoxetine was effective only in depressed patients . CONCLUSIONS Desipramine relieves pain caused by diabetic neuropathy with efficacy similar to that of amitriptyline , offering an alternative for patients unable to tolerate the latter . Blockade of norepinephrine reuptake is likely to mediate the analgesic effect of these antidepressant drugs in diabetic neuropathy . Fluoxetine , which blocks serotonin uptake , is no more effective than placebo for the relief of pain The analgesic efficacy of amitriptyline 25 mg was compared with placebo in 41 patients with chronic ( more than 3 months ) nonmalignant pain , using a double‐blind r and omised multiple‐dose 3‐week treatment period crossover design . Amitriptyline 25 mg provided significantly greater efficacy than placebo , with significant differences evident within the first week . There was no significant difference on mood scores between amitriptyline and placebo . The results suggest that surprisingly low doses of amitriptyline may be effective without substantial adverse effects , that the effect is evident early , and that the effect is distinguishable from any effect of the amitriptyline on mood Summary The effect of the non-tricyclic antidepressant mianserin on symptoms of  diabetic neuropathy  has been studied in 18 patients in a double-blind , cross-over study with imipramine as a positive control . The patients were treated with placebo , mianserin , and imipramine , each for two weeks , in r and omized order , with 1–3 weeks between the treatments . The symptoms were assessed by observer and self-rating scales . Mianserin was given in the fixed dosage of 60 mg per day , whereas the dose of imipramine was adjusted to yield the optimal plasma concentration of imipramine plus desipramine of 400–600 nmol · l−1 . The mianserin plus desmethylmianserin plasma concentration ranged from 85 to 850 nmol · l− ' , with the highest concentration in a patient who was a poor metabolizer of both sparteine and mephenytoin . The symptoms of neuropathy were significantly reduced during imipramine treatment , although somewhat less than in earlier studies . In contrast , mianserin produced no change in symptoms in comparison with placebo . As there was no evidence that higher mianserin ( plus metabolite ) steady-state concentrations were associated with a more favourable effect , the negative outcome appeared not to be related to underdosing with mianserin . In contrast to drugs with documented effects on the symptoms of diabetic neuropathy , mianserin has a very weak or no inhibitory effect on 5-HT and noradrenaline reuptake and this may explain its poor clinical effect Abstract Antidepressant drugs are increasingly used in the management of  chronic pain .  They are mainly prescribed for cancer‐related pain and central pain , e.g. phantom or stump pain , post‐herpetic neuropathy . However , no controlled clinical trials have vali date d their in either pathology . Thus , physicians still do not know whether antidepressants are really effective and which might be best . It is still debated whether the effect of antidepressants in the management of chronic pain is limited to the amelioration of frequently concomitant depression or extends to pain itself . To verify both the analgesic effect of tricyclic antidepressants , and the possible relationship between their antidepressant effect and the relief of central pain , we carried out a r and omized , within‐patient ( cross‐over ) placebo‐controlled study in patients suffering from central pain . The results clearly indicate the better analgesic effect of tricyclic antidepressants over placebo ( p < 0.0001 ) . Within the antidepressants tested , chlorimipramine , a blocker of serotonin reuptake , is significantly more effective ( p < 0.0001 ) than nortriptyline , a blocker of noradrenaline reuptake . Finally , the antinociceptive effect is independent of the effects of the two drugs on the symptoms of depression & NA ; A double‐blind , 3‐phase , cross‐over , placebo‐controlled trial of the pain‐relieving effect of amitriptyline and carbamazepine was carried out in 15 patients with central post‐stroke pain ( CPSP ) but without signs of depression . Treatment was given , in r and omized order , for periods of 4 weeks , separated by 1 week wash‐out . The final doses were 75 and 800 mg/day , respectively , for amitriptyline and carbamazepine . The treatment effects were assessed by daily ratings of pain intensity on a 10‐step verbal scale and at the end of each treatment period by a global rating of the analgesic effect on a 5‐step verbal scale . For the assessment of depression the Comprehensive Psychopathological Rating Scale ( CPRS ) was used . Amitriptyline produced a statistically significant reduction of pain when compared to placebo . According to the global rating , 10 of the 15 patients were responders to this drug . The effect could already be noticed during the second treatment week and it appeared to be correlated to the plasma concentration , since the median total ami‐ and nortriptyline concentrations were 497 and 247 nmol/1 , respectively , for responders and non‐responders . The early onset , together with the fact that the patients were not depressed , nor did they obtain reduced scores on ratings of depressive symptoms and signs , provides strong support for the conclusion that the pain relief was not caused by an antidepressive effect . Five of the 14 patients treated with carbamazepine  reported some pain relief , but the effect did not reach statistical significance when compared to placebo . No correlation was found between effect and plasma concentration . In general , the patients tolerated the planned final dose of amitriptyline well . No final dose reduction was necessary . Carbamazepine caused more side effects and the final dose had to be reduced in 4 patients . However , only 1 patient had to be taken off medication , on day 25 , due to drug interaction OBJECTIVE To compare the sensitivity , precision , and the costs in time of search ing by h and and by MEDLINE to identify r and omized controlled trials ( RCTs ) for systematic review s. DESIGN Nine anesthetic and pain journals were search ed by both MEDLINE and by h and for the years 1970 , 1 
    Output:
    
Comparisons of tricyclic antidepressants did not show any significant difference between them ; they were significantly more effective than benzodiazepines in the three comparisons available .
Paroxetine and mianserin were less effective than imipramine .
Antidepressants are effective in relieving neuropathic pain .
With very similar results for anticonvulsants it is still unclear which drug class should be first choice .
Treatment would be improved if we could harness the dramatic improvement seen on placebo in some of the trials