The Background, Methods, Results and Discussion were updated and revised to conform with current Cochrane style guidelines.

In the first update and this second update we searched a range of trial registers that were not searched in the original Cochrane Review. However, while the ISRCTN Trials Register (www.controlled‐trials.com/isrctn) was searched in the first update, it was not searched in this latest update as it is covered by WHO Portal.

We did not search the Cochrane Pain, Palliative & Supportive Care Register as its contents are captured by CENTRAL.

We added an additional 25 drugs to our search and thus database searches for these were rerun from 2012 (see Appendix 9).

We updated the Background section to include references to more recently published work.

We updated the Methods section to take into account changes in the search strategy. We thought that we should be searching for studies currently in progress, in addition to published studies, and thus undertook searches of trial registers.

We added new outcomes, and specified primary and secondary outcomes. We specified that we will report outcomes assessed at one week.

We changed the description of 'Types of participants' and 'Types of interventions' to reflect current terminology. We also added comparators of interest.

We expanded our risk of bias descriptions.

We stated that we planned to construct a 'Summary of findings' table and to assess the quality of the evidence used the GRADE approach.

The Results and Discussion sections were updated to take into account the fact that no studies were found to include in the review and to include references to more recently published work.

All sections were updated and revised to conform with current Cochrane style guidelines.