One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity. The usual criterion is at least moderate pain on a categorical pain intensity scale. When visual analogue scales (VAS) are the only pain measure in trials we need to know what point on a VAS represents moderate pain, so that these trials can be included in meta-analysis when baseline pain of at least moderate intensity is an inclusion criterion. To investigate this we used individual patient data from 1080 patients from randomised controlled trials of various analgesics. Baseline pain was measured using a 4-point categorical pain intensity scale and a pain intensity VAS under identical conditions. The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain. The VAS scores corresponding to moderate or severe pain were also examined by gender. Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain. Of the patients reporting moderate pain 85% scored over 30 mm on the corresponding VAS, with a mean score of 49 mm. For those reporting severe pain 85% scored over 54 mm with a mean score of 75 mm. There was no difference between the corresponding VAS scores of men and women. Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4-point categorical scale.

Background This review updates parts of two earlier Cochrane reviews investigating effects of gabapentin in chronic neuropathic pain (pain due to nerve damage). Antiepileptic drugs are used to manage pain, predominantly for chronic neuropathic pain, especially when the pain is lancinating or burning. Objectives To evaluate the analgesic effectiveness and adverse effects of gabapentin for chronic neuropathic pain management. Search methods We identified randomised trials of gabapentin in acute, chronic or cancer pain from MEDLINE, EMBASE, and CENTRAL. We obtained clinical trial reports and synopses of published and unpublished studies from Internet sources. The date of the most recent search was January 2011. Selection criteria Randomised, double-blind studies reporting the analgesic and adverse effects of gabapentin in neuropathic pain with assessment of pain intensity and/or pain relief, using validated scales. Participants were adults aged 18 and over. Data collection and analysis Two review authors independently extracted data. We calculated numbers needed to treat to benefit (NNTs), concentrating on IMM-PACT (Initiative on Methods, Measurement and Pain Assessment in Clinical Trials) definitions of at least moderate and substantial benefit, and to harm (NNH) for adverse effects and withdrawal. Meta-analysis was undertaken using a fixed-effect model. Main results Twenty-nine studies (3571 participants), studied gabapentin at daily doses of 1200 mg or more in 12 chronic pain conditions; 78% of participants were in studies of postherpetic neuralgia, painful diabetic neuropathy or mixed neuropathic pain. Using the IMMPACT definition of at least moderate benefit, gabapentin was superior to placebo in 14 studies with 2831 participants, 43% improving with gabapentin and 26% with placebo; the NNT was 5.8 (4.8 to 7.2). Using the IMMPACT definition of substantial benefit, gabapentin was superior to placebo in 13 studies with 2627 participants, 31% improving with gabapentin and 17% with placebo; the NNT was 6.8 (5.6 to 8.7). These estimates of efficacy are more conservative than those reported in a previous review. Data from few studies and participants were available for other painful conditions. Adverse events occurred significantly more often with gabapentin. Persons taking gabapentin can expect to have at least one adverse event (66%), withdraw because of an adverse event (12%), suffer dizziness (21%), somnolence (16%), peripheral oedema (8%), and gait disturbance (9%). Serious adverse events (4%) were no more common than with placebo. There were insufficient data for comparisons with other active treatments. Authors’ conclusions Gabapentin provides pain relief of a high level in about a third of people who take if for painful neuropathic pain. Adverse events are frequent, but mostly tolerable. More conservative estimates of efficacy resulted from using better definitions of efficacy outcome at higher, clinically important, levels, combined with a considerable increase in the numbers of studies and parti...

Background Pharmacotherapy remains an important modality for the treatment of neuropathic pain. However, as monotherapy current drugs are associated with limited e icacy and dose-related side e ects. Combining two or more di erent drugs may improve analgesic e icacy and, in some situations, reduce overall side e ects (e.g. if synergistic interactions allow for dose reductions of combined drugs). Objectives This review evaluated the e icacy, tolerability and safety of various drug combinations for the treatment of neuropathic pain. Search methods We identified randomised controlled trials (RCTs) of various drug combinations for neuropathic pain from CENTRAL, MEDLINE, EMBASE and handsearches of other reviews and trial registries. The most recent search was performed on 9 April 2012. Selection criteria Double-blind, randomised studies comparing combinations of two or more drugs (systemic or topical) to placebo and/or at least one other comparator for the treatment of neuropathic pain. Data collection and analysis Data extracted from each study included: proportion of participants a) reporting ≥ 30% pain reduction from baseline OR ≥ moderate pain relief OR ≥ moderate global improvement; b) dropping out of the trial due to treatment-emergent adverse e ects; c) reporting each specific adverse e ect (e.g. sedation, dizziness) of ≥ moderate severity. The primary comparison of interest was between study drug(s) and one or both single-agent comparators. We combined studies if they evaluated the same drug class combination at roughly similar doses and durations of treatment. We used RevMan 5 to analyse data for binary outcomes. Main results We identified 21 eligible studies: four (578 participants) evaluated the combination of an opioid with gabapentin or pregabalin; two (77 participants) evaluated an opioid with a tricyclic antidepressant; one (56 participants) of gabapentin and nortriptyline; one (120 participants) of gabapentin and alpha-lipoic acid, three (90 participants) of fluphenazine with a tricyclic antidepressant; three (90 participants) of an N-methyl-D-aspartate (NMDA) blocker with an agent from a di erent drug class; five (604 participants) of various topical medications; one (313 participants) of tramadol with acetaminophen; and another one (44 participants) of a cholecystokinin blocker (L-365,260) with morphine. The majority of combinations evaluated to date involve drugs, each of which share some element of central nervous system (CNS) depression (e.g. sedation, cognitive dysfunction). This aspect of side e ect overlap between the combined Combination pharmacotherapy for the treatment of neuropathic pain in adults (Review)

The amount and quality of evidence around the use of opioids for treating cancer pain is disappointingly low, although the evidence we have indicates that around 19 out of 20 people with moderate or severe pain who are given opioids and can tolerate them should have that pain reduced to mild or no pain within 14 days. This accords with the clinical experience in treating many people with cancer pain, but overstates to some extent the effectiveness found for the WHO pain ladder. Most people will experience adverse events, and help may be needed to manage the more common undesirable adverse effects such as constipation and nausea. Perhaps between 1 in 10 and 2 in 10 people treated with opioids will find these adverse events intolerable, leading to a change in treatment.

Of the 4 million annual births in the United States, 2.4 million involve epidural analgesia. Serious adverse events are rare but are important in young women. Robust estimates for the risk of harm are not available. Data for superficial and deep infections, hematoma, and transient and permanent neurologic injury were obtained from studies reporting adverse events with obstetric epidural analgesia, and incidence presented as individual risk for a woman, number of events per million women, and percentage incidence. A total of 1.37 million women received an epidural for childbirth, reported in 27 articles. Most information (85% of women) was in larger (> 10,000 women) studies published after 1990, with risk estimates as follows: epidural hematoma, 1 in 168,000; deep epidural infection, 1 in 145,000; persistent neurologic injury, 1 in 240,000; and transient neurologic injury, 1 in 6,700. Earlier and smaller studies produced significantly higher risk estimates for transient neurologic injury plus injury of unknown duration.

Randomised controlled trials (RCTs) alone are unlikely to provide reliable estimates of the incidence of rare events because of their limited size. Cohort, case control, and other observational studies have large numbers but are vulnerable to various kinds of bias. Wanting to estimate the risk of death from bleeding or perforated gastroduodenal ulcers with chronic usage of non-steroidal anti-inflammatory drugs (NSAIDs) with greater precision, we developed a model to quantify the frequency of rare adverse events which follow a biological progression. The model combined data from both RCTs and observational studies. We searched systematically for any report of chronic (>/=2 months) use of NSAIDs which gave information on gastroduodenal ulcer, bleed or perforation, death due to these complications, or progression from one level of harm to the next. Fifteen RCTs (19364 patients exposed to NSAIDs for 2-60 months), three cohort studies (215076 patients redeeming a NSAID prescription over a 3-12 month period), six case-control studies (2957 cases) and 20 case series (7406), and case reports (4447) were analysed. In RCTs the incidence of bleeding or perforation in 6822 patients exposed to NSAIDs was 0.69%; two deaths occurred. Of 11040 patients with bleeding or perforation with or without NSAID exposure across all reports, 6-16% (average 12%) died; the risk was lowest in RCTs and highest in case reports. Death from bleeding or perforation in all controls not exposed to NSAIDs occurred in 18 out of 849489 (0.002%). From these numbers we calculated the number-needed-to-treat for one patient to die due to gastroduodenal complications with chronic (>/=2 months) NSAIDs as 1/((0.69x¿6-16%, average 12%¿)-0.002%))=909-2500 (average 1220). On average 1 in 1200 patients taking NSAIDs for at least 2 months will die from gastroduodenal complications who would not have died had they not taken NSAIDs. This extrapolates to about 2000 deaths each year in the UK.

In the first 24 h after surgery, ketamine reduces morphine requirements. Ketamine also reduces PONV. Adverse effects are mild or absent. These data should be interpreted with caution as the retrieved studies were heterogenous and the result of the meta-analysis can not be translated into any specific administration regimen with ketamine.

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