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Metadona para el dolor por cáncer

Appendices

Appendix 1. 2016 Search strategies

CENTRAL

  1. MESH DESCRIPTOR methadone EXPLODE ALL TREES (895)

  2. (methadone or amidine or amidone or methadone or phenadone or heptadon or physeptone or eptadone or symoron or metasedin or sedo or ketalgine or "Martindale methadone mixture DTF" or methadose or methex or dolophine):TI,AB,KY (1857)

  3. #1 or #2 (1867)

  4. MESH DESCRIPTOR neoplasms EXPLODE ALL TREES (46032)

  5. (neoplasm* or malignan* or tumour* or tumor* or cancer* or carcinoma*):TI,AB,KY (95750)

  6. #4 or #5 (100496)

  7. MESH DESCRIPTOR Pain EXPLODE ALL TREES (32221)

  8. (pain* or nocicept* or neuropath*):TI,AB,KY (87637)

  9. #7 or #8 (93445)

  10. 3 AND #6 AND #9 (48)

MEDLINE (via OVID)  

  1. exp Methadone/ (11005)

  2. (methadone or amidine or amidone or methadone or phenadone or heptadon or physeptone or eptadone or symoron or metasedin or sedo or ketalgine or "Martindale methadone mixture DTF" or methadose or methex or dolophine).mp. (14357)

  3. 1 or 2 (14357)

  4. exp Neoplasms/ (2821099)

  5. (neoplasm* or malignan* or tumour* or tumor* or cancer* or carcinoma*).mp. (3083681)

  6. 4 or 5 (3400565)

  7. exp Pain/ (328104)

  8. (pain* or nocicept* or neuropath*).mp. (636872)

  9. 7 or 8 (708138)

  10. randomized controlled trial.pt. (413578)

  11. controlled clinical trial.pt. (90546)

  12. randomized.ab. (310481)

  13. placebo.ab. (157686)

  14. drug therapy.fs. (1847843)

  15. randomly.ab. (219181)

  16. trial.ab. (320971)

  17. 10 or 11 or 12 or 13 or 14 or 15 or 16 (2482796)

  18. 3 and 6 and 9 and 17 (319)

  19. limit 18 to yr="2006 ‐Current" (130)

Embase (via OVID)

  1. exp Methadone/ (27180)

  2. (methadone or amidine or amidone or methadone or phenadone or heptadon or physeptone or eptadone or symoron or metasedin or sedo or ketalgine or "Martindale methadone mixture DTF" or methadose or methex or dolophine).mp. (32962)

  3. 1 or 2 (32962)

  4. exp Neoplasms/ (3660745)

  5. (neoplasm* or malignan* or tumour* or tumor* or cancer* or carcinoma*).mp. (4191612)

  6. 4 or 5 (4648482)

  7. exp Pain/ (974712)

  8. (pain* or nocicept* neuropath*).mp. (1203279)

  9. 7 or 8 (1448357)

  10. (random* or factorial* or crossover or "cross over" or cross‐over).tw. (1136282)

  11. (placebo* or (doubl* adj blind*) or (singl* adj blind*)).tw. (307524)

  12. (allocat* or allocat*).tw. (103527)

  13. crossover Procedure/ (46919)

  14. double‐blind procedure/ (130500)

  15. single‐blind procedure/ (22010)

  16. Randomized Controlled Trial/ (402622)

  17. 10 or 11 or 12 or 13 or 14 or 15 or 16 (1381772)

  18. 3 and 6 and 9 and 17 (195)

  19. limit 18 to yr="2006 ‐Current" (116)

CINAHL (via EBSCO)

  1. MH methadone OR TX methadone or amidine or amidone or methadone or phenadone or heptadon or physeptone or eptadone or symoron or metasedin or sedo or ketalgine or "Martindale methadone mixture DTF" or methadose or methex or dolophine (3328)

  2. MH neoplasms OR TX ( neoplasm* or malignan* or tumour* or tumor* or cancer* or carcinoma* ) (269,166)

  3. MW pain OR TX ( pain* or nocicept* or neuropath* ) (173,682)

  4. S1 AND S2 AND S3 (214)

  5. TX ( (singl* blind* ) or (doubl* blind* ) or (tripl* blind* ) or (trebl* blind* ) or (trebl* mask* ) or (tripl* mask* ) or (doubl* mask* ) or (singl* mask* ) ) OR TX randomi#ed control$ trial$ OR MH random assignment OR TX random* allocat* OR TX placebo* OR MH Quantitative Studies OR TX allocat* random* (725,719)

  6. S4 AND S5 (59)

Appendix 2. Results

Study ID

Design

Total Participants

No worse than mild pain

Results Methadone

Results control

Beaver 1967

Cross‐over

37

Not estimable

N/A

N/A

Bruera 2004

Parallel

103

Not estimable

> 20% improvement 37/49

> 20% improvement 41/54

Mercadante 1998

Parallel

40

Pain score < 4/10.
Mean values morphine 3.3 +/‐ 0.2, methadone 3.4 +/‐ 0.1

N/A

N/A

Mercadante 2008

Parallel

108

At Wweek 4 mean pain for morphine 2.5 (1.7 ‐ 3.3), fentanyl 2.4 (2 ‐ 2.8) and methadone 3.4 (2.6 ‐ 4.1) (completers only)

N/A

N/A

Twycross 1977

Parallel

46

Not reported

Survival worse on methadone

N/A

Ventafridda 1986

Parallel

54

All participants achieved no worse than mild pain based on mean pain scores (completers only)

N/A

N/A

Total

388

Appendix 3. Adverse events including appetite, consciousness and thirst

Summary of results: adverse events relating to appetite, consciousness and thirst

Study ID

No of Participants

Methadone

Control

Appetite

Consciousness

Thirst

Other adverse effects

Beaver 1967

37

Oral and IM doses to 48 mg

Morphine oral and IM doses to 32 mg

Not reported

Sedation on morphine 16/92 doses; on methadone 25/92 doses.

Hallucinations morphine 1/92

Dry mouth on methadone 4/92 doses

Vomiting on morphine 7/92 doses; on methadone 10/92 doses.

Constipation not reported

Bruera 2004

103

Oral 7.5 mg every 12 h + 5 mg 4 h as required

Morphine MR 15 mg oral every 12 h + 5 mg 4 h as required

Not reported

Sedation more severe in methadone group. Confusion similar between groups

Not reported

Nausea and constipation similar between groups

Mercadante 1998

40

Oral liquid 2‐ to 3 times a day. Dose titrated according to need

Morphine MR tablets 2‐ to 3 times a day.

Dose titrated according to need

Not reported

Drowsiness on morphine 8/20; on methadone 3/20. Confusion 1/20 in both groups.

Dry mouth on morphine 8/20; on methadone 3/20

Constipation on morphine 12/20; on methadone 6/20

Mercadante 2008

108

Oral 15 mg daily then titrated to need

Morphine MR 60 mg oral daily then titrated to need. TD fentanyl 0.6 mg daily then titrated to need

Not reported

Not reported

Not reported

Results not easy to interpret but appear low for all arms. ''No relevant differences among the groups"

Twycross 1977

46

5 to ‐20 mg daily

Diamorphine 5 to ‐40 mg + cocaine 10 mg daily

Not reported

Not reported

Not reported

Over 20 days, 17/20 died on methadone, and 21/27 died in diamorphine + cocaine group (from graph)

Ventafridda 1986

54

8 to ‐28 mg as oral liquid daily (as divided doses, 6‐hourly, then 8‐hourly)

Morphine average 4 to ‐24 mg oral (normal release) every 4 h

Not reported

Somnolence worse on morphine

Dry mouth worse on morphine

Constipation similar

between groups

Study flow diagram
Figuras y tablas -
Figure 1

Study flow diagram

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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies

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Risk of bias summary: review authors' judgements about each risk of bias item for each included study
Figuras y tablas -
Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study

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Summary of findings for the main comparison. Methadone compared to Morphine for cancer pain

Methadone compared to morphine for cancer pain

Patient or population: people with cancer pain
Intervention: methadone
Comparison: morphine

Outcomes

Assumed risk

Corresponding risk

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Morphine

Methadone

Participant‐reported pain intensity

Pain intensity scores:

One study (103 participants) reported > 20% improvement in pain scores for 76% of morphine and 75% methadone participants in those that completed

No worse than mild pain (pain score of 3/10 or less after treatment):

One study (54 participants) reported all achieved no worse than mild pain based on mean pain scores. Two studies (148 participants) reported mean pain scores very close to a score of 3

⊕⊕⊝⊝
low1,2

Downgraded two points for reasons stated

Adverse events: appetite, thirst, somnolence

Not estimable

Not estimable

Not estimable

342
(5 studies)

⊕⊝⊝⊝
very low1,2,3

Downgraded three points for reasons stated

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence

High quality: we are very confident that the true effect lies close to that of the estimate of the effect

Moderate quality: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of effect, but there is a possibility that it is substantially different

Low quality: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect

Very low quality: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: random allocation and allocation concealment unclear, all had sample size of less than 200 per treatment arm.
2 Imprecision: sample size is smaller than optimal information size; confidence interval around estimate of effect is wide and included no effect and appreciable benefit/harm.
3 Indirectness. Surrogates for appetite, thirst and somnolence such as sedation, drowsiness and dry mouth used.

Figuras y tablas -
Summary of findings for the main comparison. Methadone compared to Morphine for cancer pain
Ir a la tabla de la revisión