***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 
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    ***EXAMPLES*** 
    Input: Objectives This study aims to evaluate the efficacy of methadone as substitute for morphine and to investigate if the addition of acetaminophen could reduce the time to attain an equianalgesic dose of methadone and /or to improve the level of pain control in oncologic patients . Patients and methods Fifty patients on stable doses of morphine for 1 week were switched to methadone using a “ stop – start ” strategy and r and omized in a double-blind fashion to receive either acetaminophen ( 750 mg PO every 6 hours ) or placebo for a 7-day period . We collected data regarding level of pain , side effects , and quality of life . Results Substitution of morphine for methadone result ed in a significant reduction in constipation ( p < 0.001 ) and xerostomia ( p = 0.03 ) . There was also an improvement in the numeric pain scale ( p = 0.03 ) as well as a significant improvement in the functional level and symptomatology according to the QLQ-C30 question naire . Addition of acetaminophen did not improve pain control or reduce the time of stabilization of analgesia once methadone was introduced . At the end of the study , most patients ( 70.8 % , p = 0.001 ) preferred methadone to morphine . Conclusions Early switching from morphine to methadone was a safe and efficient strategy for the reduction of side effects and improvement of analgesia , allowing for a comfortable dosing regimen . In this scenario , the association with acetaminophen did not improve pain control or reduce the time to achieve an equianalgesic dose of methadone AIM Opioid switching is a treatment strategy in cancer patients with unacceptable pain and /or adverse effects ( AEs ) . We investigated whether patients switched to methadone by the stop and go ( SAG ) strategy have lower pain intensity ( PI ) than the patients switched over three days ( 3DS ) , and whether the SAG strategy is as safe as the 3DS strategy . METHODS In this prospect i ve , open , parallel-group , multicentre study , 42 cancer patients on morphine or oxycodone were r and omised to the SAG or 3DS switching- strategy to methadone . The methadone dose was calculated using a dose-dependent ratio . PI , AEs and serious adverse events ( SAEs ) were recorded daily for 14 days . Primary outcome was average PI day 3 . Secondary outcomes were PI now and AEs day 3 and 14 and number of SAEs . RESULTS Twenty one patients were r and omised to each group , 16 ( SAG ) and 19 ( 3DS ) patients received methadone . The mean preswitch morphine doses were 900 mg/day in SAG and 1330 mg/day in 3DS . No differences between groups were found in mean average PI day 3 ( mean difference 0.5 ( CI -1.2 - 2.2 ) ; SAG 4.1 ( CI 2.3 - 5.9 ) and 3DS 3.6 ( CI 2.9 - 4.3 ) or in PI now . The SAG group had more dropouts and three SAEs ( two deaths and one severe sedation ) . No SAEs were observed in the 3DS group . CONCLUSION The SAG patients reported a trend of more pain , had significantly more dropouts and three SAEs , which indicate that the SAG strategy should not replace the 3DS when switching from high doses of morphine or oxycodone to methadone Background : This study was design ed to evaluate the role of epidural methadone-lidocaine in cancer pain combined or not to epidural dexamethasone . Methods : In all , 72 cancer patients , 32- to 67-year-old were r and omized to six groups ( n=12 ) and prospect ively studied to examine analgesia and adverse effects for 3 weeks . Patients received single-dose protocol epidural test drugs : Control group ( CG ) received epidural 40-mg lidocaine diluted to 10-ml volume with saline . Dexamethasone group ( DG ) 40-mg lidocaine plus 10-mg dexamethasone . The 2.5MetG 2.5-mg epidural methadone with 40-mg lidocaine ; the 5MetG , 5-mg epidural methadone plus 40-mg lidocaine , the 7.5MetG , 7.5-mg epidural methadone plus 40-mg lidocaine and finally the 7.5Met-DexG , 7.5-mg methadone with 40-mg lidocaine and 10-mg dexamethasone . Results : Groups CG , DG and 2.5MetG were similar regarding analgesia and side effects . Patients from 5MetG and 7.5MetG took 3±1 and 5±1 days , respectively , to restart oral morphine . Patients from 7.5MetDG took 14±2 to restart oral morphine  ( P<0.001 ) . Daily somnolence and appetite improved in the 7.5MetDG during 2-week evaluation ( P<0.005 ) . Fatigue improved for both DG and 7.5MetDG during 2-week evaluation ( P<0.005 ) . By the third week of evaluation , all patients were similar . Conclusions : Epidural methadone plus lidocaine result ed in dose-dependent analgesia , further improved by epidural dexamethasone , which also improved fatigue PURPOSE To compare the effectiveness and side effects of methadone and morphine as first-line treatment with opioids for cancer pain . PATIENTS AND METHODS Patients in international palliative care clinics with pain requiring initiation of strong opioids were r and omly assigned to receive methadone ( 7.5 mg orally every 12 hours and 5 mg every 4 hours as needed ) or morphine ( 15 mg sustained release every 12 hours and 5 mg every 4 hours as needed ) . The study duration was 4 weeks . RESULTS A total of 103 patients were r and omly assigned to treatment ( 49 in the  methadone  group and 54 in the  morphine  group ) . The groups had similar baseline scores for pain , sedation , nausea , confusion , and constipation . Patients receiving methadone had more opioid-related drop-outs ( 11 of 49 ; 22 % ) than those receiving morphine ( three of 54 ; 6 % ; P = .019 ) . The opioid escalation index at days 14 and 28 was similar between the two groups . More than three fourths of patients in each group reported a 20 % or more reduction in pain intensity by day 8 . The proportion of patients with a 20 % or more improvement in pain at 4 weeks in the methadone group was 0.49 ( 95 % CI , 0.34 to 0.64 ) and was similar in the morphine group ( 0.56 ; 95 % CI , 0.41 to 0.70 ) . The rates of patient-reported global benefit were nearly identical to the pain response rates and did not differ between the treatment groups . CONCLUSION Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain OBJECTIVES Neuropathic cancer pain ( NCP ) is a common manifestation of cancer and /or its treatment . Treatment following the WHO analgesic ladder provides relief for the majority of cancer pain patients ; however , concern remains that opioids may be less efficacious for neuropathic pain ( NP ) compared with nociceptive pain , often necessitating the use of higher doses . Adjuvants , such as pregabalin , have shown to be efficacious for the treatment of NP , although data come mostly from noncancer studies . The comparative efficacy and safety of opioids versus adjuvants has not been studied for NCP . The aim of this study was to directly compare pregabalin versus a strong opioid for the treatment of NCP . METHODS A total of 120 patients , diagnosed with " definite " NCP , were r and omized into two groups and received increasing doses of either oral pregabalin or transdermal fentanyl for 28 days . VAS score , patient satisfaction , need for opioid rescue , and adverse events ( AEs ) were recorded . RESULTS In the pregabalin group , a significantly higher proportion of patients achieved at least 30 % reduction in VAS compared with the fentanyl group ( 73.3 % , 95 % CI : 60.3%-83.93 vs. 36.7 % , 95 % CI : 24.5%-50.1 % , P < 0.0001 , respectively ) , while the percentage mean change from baseline was also significantly different [ 46 % ( 95 % CI : 39.5%-52.8 % ) for pregabalin and 22 % ( 95 % CI : 14.9%-29.5 % ) for fentanyl ( P < 0.0001 ) ] . Patient-reported satisfaction was more frequent with pregabalin , while AEs and treatment discontinuations were more frequent in the fentanyl group . DISCUSSION Prompt use of a neuropathic pain-specific adjuvant , such as pregabalin , in NCP may lead to better control of the neuropathic component , with opioid-sparing effects Eighteen patients suffering from cancer were entered into a study of the pharmacokinetics and efficacy of methadone and morphine in pain control .  All patients had both clinical and radiological evidence of metastatic spread of their cancer and there were no significant differences in age , weight and sites of the primary cancer between the methadone ( n = 9 ) and morphine ( n = 9 ) groups .  Blood opioid concentration , visual analogue pain scores ( VAPS ) and end-tidal percent carbon dioxide were measured before and after both an intravenous and oral dose of either methadone or morphine .  Terminal half-lives ( mean + /- S.D. ) were 30.4 + /- 16.3 h and 2.7 + /- 1.2 h respectively for methadone and morphine while the clearance values ( mean + /- S.D. ) were 0.19 + /- 0.13 l/min and 1.16 + /- 0.47 l/min . The long half-life of methadone was associated with prolonged pain relief . However , the large variation in the half-life of methadone necessitated careful adjustment of the dosing interval in individual patients . There were pronounced differences in oral bioavailability between the two opioids : methadone , 79 + /- 11.7 % , compared to morphine , 26 + /- 13 % ( mean + /- S.D. ) . Of greater clinical significance was the variability in these bioavailability estimates with a coefficient of variation of 15 % for methadone compared to 50 % for morphine . The combined effects of low and variable oral bioavailability for morphine may result in sub-therapeutic doses being administered as practitioners may be inhibited by the size of the effective oral morphine dose and may be confused by the variability in this dose compared to intramuscular doses . The initial oral dose of morphine varied from 15 mg 4 hourly to 150 mg 3 hourly , while the initial dose for methadone varied from 15 mg on alternate nights to 20 mg twice daily . There was no rapid escalation of daily opioid dose for either methadone or morphine when adequate pain control was provided rapidly at the start of treatment by the technique described in this study PURPOSE The aim of this study was to compare the analgesic and adverse effects , doses , as well as cost of opioid drugs , supportive drug therapy and other analgesic drugs in patients treated with oral sustained-release morphine , transdermal fentanyl , and oral methadone .  PATIENTS AND METHODS One hundred and eight cancer patients , no longer responsive to opioids for moderate pain , were selected to r and omly receive initial daily doses of 60 mg of oral sustained-release morphine , 15 mg of oral methadone , or 0.6 mg ( 25 microg/h ) of transdermal fentanyl . Oral morphine was used as breakthrough pain medication during opioid titration .  Opioid doses , pain intensity , adverse effects , symptomatic drugs , were recorded at week intervals for 4 weeks . Costs of opioid therapy , supportive drugs , and other analgesic drugs were also evaluated . RESULTS Seventy patients completed the 4 weeks period of study . Five , five , and four patients , treated with oral morphine , transdermal fentanyl , and oral methadone , respectively , required opioid switching . No differences in pain and symptom intensity were observed . Opioid escalation index was significantly lower in patients receiving methadone ( p<0.0001 ) , although requiring up and down changes in doses . At the doses used , methadone was significantly less expensive ( p<0.0001 ) , while the use and costs of supportive drugs and other analgesics were similar in the three groups . No relevant differences in adverse effects were observed among the groups during either the titration phase and chronic treatment . CONCLUSION All the three opioids used as first-line therapy were effective , well tolerated , and required similar amounts of symptomatic drugs or co-analgesics .  Methadone was significantly less expensive , but required more changes , up and down , of the doses , suggesting that dose titration of this drug requires major clinical expertise The analgesic effectiveness and adverse effect incidence of a daily 
    Output:
    
None of the studies reported effects on appetite .
Based on low- quality evidence , methadone is a drug that has similar analgesic benefits to morphine and has a role in the management of cancer pain in adults .
Other opioids such as morphine and fentanyl are easier to manage but may be more expensive than methadone in many economies