• P J Wiffen and H J McQuay.
• Churchill Hospital, Pain Research Unit, Old Road, Headington, Oxford, UK, OX3 7LJ. phil.wiffen@pru.ox.ac.uk
• Cochrane Db Syst Rev. 2007 Jan 1(4):CD003868.

BackgroundThis is an updated version of a previous Cochrane review first published in Issue 4, 2003 of The Cochrane Library. Morphine has been used for many years to relieve pain. Oral morphine in either immediate release or modified release form remains the analgesic of choice for moderate or severe cancer pain.ObjectivesTo determine the efficacy of oral morphine in relieving cancer pain and to assess the incidence and severity of adverse effects.Search StrategyThe following databases were searched: Cochrane Pain, Palliative and Supportive Care Group Trials Register (December 2006); Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 4); MEDLINE (1966 to December 2006); and EMBASE (1974 to December 2006).Selection CriteriaPublished randomised controlled trials (RCTs) reporting on the analgesic effect of oral morphine in adults and children with cancer pain. Any comparator trials were considered. Trials with fewer than ten participants were excluded.Data Collection And AnalysisOne review author extracted data, which was checked by the other review author. There were insufficient comparable data for meta-analysis to be undertaken or to produce numbers-needed-to-treat (NNT) for the analgesic effect.Main ResultsIn this update, nine new studies with 688 participants were added. Fifty-four studies (3749 participants) met the inclusion criteria. Fifteen studies compared oral modified release morphine (Mm/r) preparations with immediate release morphine (MIR). Twelve studies compared Mm/r in different strengths, five of these included 24-hour modified release products. Thirteen studies compared Mm/r with other opioids. Six studies compared MIR with other opioids. Two studies compared oral Mm/r with rectal Mm/r. Two studies compared MIR with MIR by a different route of administration. One study was found comparing each of the following: Mm/r tablet with Mm/r suspension; Mm/r with non-opioids; MIR with non-opioids; and oral morphine with epidural morphine. Morphine was shown to be an effective analgesic. Pain relief did not differ between Mm/r and MIR. Modified release versions of morphine were effective for 12 or 24-hour dosing depending on the formulation. Daily doses in studies ranged from 25 mg to 2000 mg with an average of between 100 mg and 250 mg. Dose titration were undertaken with both instant release and modified release products. Adverse effects were common but only 4% of patients discontinued treatment because of intolerable adverse effects.Authors' ConclusionsThe randomised trial literature for morphine is small given the importance of this medicine. Most trials recruited fewer than 100 participants and did not provide appropriate data for meta-analysis. Trial design was frequently based on titration of morphine or comparator to achieve adequate analgesia, then crossing participants over in crossover design studies. It was not clear if these trials are sufficiently powered to detect any clinical differences between formulations or comparator drugs. Studies added to the review reinforce the view that it is possible to use modified release morphine to titrate to analgesic effect. There is qualitative evidence for effectiveness of oral morphine which compares well to other available opioids. There is limited evidence to suggest that transmucosal fentanyl provides more rapid pain relief for breakthrough pain compared to morphine.

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