Overview review: Comparative efficacy of oral ibuprofen and paracetamol (acetaminophen) across acute and chronic pain conditions.

BACKGROUND: Ibuprofen and paracetamol have long been used as analgesics in a range of acute, intermittent and chronic pain conditions. Paracetamol is often the first line analgesic recommended, without consensus about which is the better analgesic. METHODS: An overview review of systematic reviews and meta-analyses directly compares ibuprofen and paracetamol at standard doses in particular painful conditions, or uses indirect comparisons against placebo. Electronic searches for systematic reviews were sought published since 1995 using outcomes approximating to ≥50% pain intensity reduction. Painful conditions were acute post-operative pain, dysmenorrhoea, tension-type headache (TTH), migraine, osteoarthritis and rheumatoid arthritis, back pain, cancer and paediatric pain. There was no systematic assessment of harm. RESULTS: Sixteen systematic reviews and four individual patient data meta-analyses were included. Ibuprofen was consistently superior to paracetamol at conventional doses in a range of painful conditions. Two direct comparisons favoured ibuprofen (acute pain, osteoarthritis). Three of four indirect comparisons favoured ibuprofen (acute pain, migraine, osteoarthritis); one showed no difference (TTH), although there were methodological problems. In five pain conditions (dysmenorrhoea, paediatric pain, cancer pain, back pain and rheumatoid arthritis), there were limited data on paracetamol and ibuprofen. CONCLUSIONS: At standard doses in different painful conditions, ibuprofen was usually superior producing more patients with the degree of pain relief that patients feel worthwhile. Neither of the drugs will be effective for everyone, and both are needed. This overview questions the practice of routinely using paracetamol as a first line analgesic because there is no good evidence for efficacy of paracetamol in many pain conditions.

Validating speed of onset as a key component of good analgesic response in acute pain.

BACKGROUND: Previous analysis of a single data set in acute pain following third molar extraction demonstrated a strong relationship between the speed of reduction of pain intensity and overall pain relief, as well as need for additional analgesia. METHODS: Individual patient data analysis of a single randomized, double-blind trial of placebo, paracetamol 1000 mg, ibuprofen sodium 400 mg and ibuprofen-poloxamer 400 mg following third molar extraction. Visual analogue scale pain intensity (VASPI) and other measurements were made at baseline, every 5-45 min, and at 60, 90, 120, 180, 240, 300 and 360 min. RESULTS: Most patients produced consistent VASPI results over time. For placebo and paracetamol, few patients achieved low VASPI scores and maintained them. For both ibuprofen formulations, VASPI scores fell rapidly during the first hour and were then typically maintained until later re-medication. Analysis of all patients showed that rapid VASPI reduction in the first hour was strongly correlated with good overall pain relief (high total pain relief over 0-6 h), and with lesser need for additional analgesia within 6 h. Results for this analysis were in very good agreement with a previous analysis, validating the relationship between fast initial pain intensity reduction and overall good pain relief in this setting. CONCLUSIONS: In acute pain following third molar extraction, faster acting analgesic formulations provide earlier onset of pain relief, better overall pain relief and a less frequent need for additional analgesia, indicating longer lasting pain relief.

Challenges in design and interpretation of chronic pain trials.

The process of systematic review has shone a light on the methodology of randomized controlled trials. Notably, a range of potential biases hinders the interpretation of chronic pain trials. These include a consistent bias favouring active over placebo in trials that are small and of short duration. The use of the 'last observation carried forward' imputation method is known to inflate results, often generating statistically significance when adverse event withdrawals are high; in clinical practice terms, this is the wrong answer. Patients want outcomes of low pain scores, large reductions in pain and relief from associated symptoms, with improvements in ability to function and in quality of life. Some patients achieve this, but many do not. The distribution of benefit is skewed and the use of average pain scores, or change in pain, can be misleading compared with responder analysis in which withdrawal is regarded as non-response. Historically, chronic pain trials have had a simple classic or a crossover design. They have been small and short, and used inappropriate imputation and outcomes unconnected to the experiences of most patients. While these designs are useful for answering some questions, they may be insensitive for many interventions. Newer designs, like enriched enrolment randomized withdrawal (EERW) trials or clinical effectiveness trials, are potentially more interesting and informative.

Relative efficacy of oral analgesics after third molar extraction--a 2011 update.

This article provides a summary of the efficacy, and relative efficacy, of 38 different drugs or drug combinations tested in standard postoperative pain trials. It will help clinicians and patients make informed choices about analgesia based on pain relief, duration of action, and adverse events, which can then be put into context for the individual patient, depending on local availability. This article highlights the fact that no single drug is effective in all patients--even the best drugs fail to provide good levels of pain relief in at least 30%. These patients should try a different analgesic.

Oral morphine for cancer pain.

BACKGROUND: This 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. OBJECTIVES: To determine the efficacy of oral morphine in relieving cancer pain and to assess the incidence and severity of adverse effects. SEARCH STRATEGY: The 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 CRITERIA: Published 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 ANALYSIS: One 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 RESULTS: In 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' CONCLUSIONS: The 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.

Antidepressants for neuropathic pain.

BACKGROUND: This is an updated version of the original Cochrane review published in Issue 3, 2005 of The Cochrane Library. For many years antidepressant drugs have been used to manage neuropathic pain, and are often the first choice treatment. It is not clear, however, which antidepressant is more effective, what role the newer antidepressants can play in treating neuropathic pain, and what adverse effects are experienced by patients. OBJECTIVES: To determine the analgesic effectiveness and safety of antidepressant drugs in neuropathic pain. SEARCH STRATEGY: Randomised controlled trials (RCTs) of antidepressants in neuropathic pain were identified in MEDLINE (1966 to Oct 2005); EMBASE (1980 to Oct 2005); the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, Issue 3, 2005; and the Cochrane Pain, Palliative and Supportive Care Trials Register (May 2002). Additional reports were identified from the reference list of the retrieved papers, and by contacting investigators. SELECTION CRITERIA: RCTs reporting the analgesic effects of antidepressant drugs in adult patients, with subjective assessment of pain of neuropathic origin. Studies that included patients with chronic headache and migraine were excluded. DATA COLLECTION AND ANALYSIS: Two review authors agreed the included studies, extracted data, and assessed methodological quality independently. Sixty one trials of 20 antidepressants were considered eligible (3293 participants) for inclusion. Relative Risk (RR) and Number-Needed-to-Treat (NNTs) were calculated from dichotomous data for effectiveness and adverse effects. This update includes 11 additional studies (778 participants). MAIN RESULTS: Sixty one RCTs were included in total. Tricyclic antidepressants (TCAs) are effective and have an NNT of 3.6 (95% CI 3 to 4.5) RR 2.1 (95% CI 1.8 to 2.5) for the achievement of at least moderate pain relief. There is limited evidence for the effectiveness of the newer SSRIs but no studies of SNRIs were found. Venlafaxine (three studies) has an NNT of 3.1 (95% CI 2.2 to 5.1) RR 2.2 (95% CI 1.5 to 3.1). There were insufficient data to assess effectiveness for other antidepressants such as St Johns Wort and L-tryptophan. For diabetic neuropathy the NNT for effectiveness was 1.3 (95% CI 1.2 to 1.5) RR 12.4 (95% CI 5.2 to 29.2) (five studies); for postherpetic neuralgia 2.7 (95% CI 2 to 4.1), RR 2.2 (95% CI 1.6 to 3.1) (four studies). There was evidence that TCAs are not effective in HIV-related neuropathies. The number needed to harm (NNH) for major adverse effects defined as an event leading to withdrawal from a study was 28 (95% CI 17.6 to 68.9) for amitriptyline and 16.2 (95% CI 8 to 436) for venlafaxine. The NNH for minor adverse effects was 6 (95% CI 4.2 to 10.7) for amitriptyline and 9.6 (95% CI 3.5 to 13) for venlafaxine. AUTHORS' CONCLUSIONS: This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Lamotrigine for acute and chronic pain.

BACKGROUND: Anticonvulsant medicines have a place in the treatment of neuropathic pain (pain due to nerve damage). This review looks at the evidence for the pain relieving properties of lamotrigine. OBJECTIVES: To assess the analgesic efficacy and adverse effects of the anticonvulsant lamotrigine for acute and chronic pain. SEARCH STRATEGY: Randomised Controlled Trials (RCTs) of lamotrigine (and key brand names Lamictal, Lamictin, Neurium) in acute, chronic or cancer pain were identified from MEDLINE (1966 to August 2006), EMBASE 1994 to August 2006 and the CENTRAL register on The Cochrane Library (Issue 3, 2006). Additional reports were sought from the reference list of the retrieved papers. SELECTION CRITERIA: RCTs investigating the use of lamotrigine (any dose and by any route) for treatment of acute or chronic pain. Assessment of pain intensity or pain relief, or both, using validated scales. Participants were adults aged 18 and over. Only full journal publication articles were included. DATA COLLECTION AND ANALYSIS: Dichotomous data were used to calculate relative risk with 95% confidence intervals using a fixed effects model unless significant statistical heterogeneity was found. Continuous data was also reported where available. Meta-analysis was undertaken using a fixed effect model unless significant heterogeneity was present (I(2) >50%) in which case a random effects model was used. Numbers-needed-to-treat (NNTs) were calculated as the reciprocal of the absolute risk reduction. For unwanted effects, the NNT becomes the number-needed-to-harm (NNH) and was calculated. MAIN RESULTS: Sixteen studies were identified. Nine studies were excluded. No studies for acute pain were identified. The seven included studies involved 502 participants, all for neuropathic pain. The studies covered the following conditions: central post stroke pain (1), diabetic neuropathy (1), HIV related neuropathy (2), intractable neuropathic pain (1), spinal cord injury related pain (1) and trigeminal neuralgia (1). The studies included participants in the age range of 26 to 77 years. Only one study for HIV related neuropathy had a statistically significant result for a sub group of patients on anti-retroviral therapy; this result is unlikely to be clinically significant NNT 4.3 (95% CI 2.3 to 37). Approximately 7% of participants taking lamotrigine reported a skin rash. AUTHORS' CONCLUSIONS: Given the availability of more effective treatments including anticonvulsants and antidepressant medicines, lamotrigine does not have a significant place in therapy at present. The limited evidence currently available suggests that lamotrigine is unlikely to be of benefit for the treatment of neuropathic pain.

The ORION statement: guidelines for transparent reporting of outbreak reports and intervention studies of nosocomial infection.

The quality of research in hospital epidemiology (infection control) must be improved to be robust enough to influence policy and practice. In order to raise the standards of research and publication, a CONSORT equivalent for these largely quasi-experimental studies has been prepared by the authors of two relevant systematic reviews, following consultation with learned societies, editors of journals and researchers. It consists of a 22 item checklist, and a summary table. The emphasis is on transparency to improve the quality of reporting and on the use of appropriate statistical techniques. The statement has been endorsed by a number of professional special interest groups and societies. Like CONSORT, ORION should be considered a 'work in progress', which requires ongoing dialogue for successful promotion and dissemination. The statement is therefore offered for further public discussion. Journals and research councils are strongly recommended to incorporate it into their submission and reviewing processes. Feedback to the authors is encouraged and the statement will be revised in 2 years.

EFNS guidelines on pharmacological treatment of neuropathic pain.

Neuropathic pain treatment remains unsatisfactory despite a substantial increase in the number of trials. This EFNS Task Force aimed at evaluating the existing evidence about the pharmacological treatment of neuropathic pain. Studies were identified using first the Cochrane Database then Medline. Trials were classified according to the aetiological condition. All class I and II controlled trials (according to EFNS classification of evidence) were assessed, but lower-class studies were considered in conditions that had no top level studies. Only treatments feasible in an outpatient setting were evaluated. Effects on pain symptoms/signs, quality of life and comorbidities were particularly searched for. Most of the randomized controlled trials included patients with postherpetic neuralgia (PHN) and painful polyneuropathies (PPN) mainly caused by diabetes. These trials provide level A evidence for the efficacy of tricyclic antidepressants, gabapentin, pregabalin and opioids, with a large number of class I trials, followed by topical lidocaine (in PHN) and the newer antidepressants venlafaxine and duloxetine (in PPN). A small number of controlled trials were performed in central pain, trigeminal neuralgia, other peripheral neuropathic pain states and multiple-aetiology neuropathic pains. The main peripheral pain conditions respond similarly well to tricyclic antidepressants, gabapentin, and pregabalin, but some conditions, such as HIV-associated polyneuropathy, are more refractory. There are too few studies on central pain, combination therapy, and head-to-head comparison. For future trials, we recommend to assess quality of life and pain symptoms or signs with standardized tools.

Interventions to improve antibiotic prescribing practices for hospital inpatients.

BACKGROUND: Up to 50% of antibiotic usage in hospitals is inappropriate. In hospitals infections caused by antibiotic-resistant bacteria are associated with higher mortality, morbidity and prolonged hospital stay compared with infections caused by antibiotic-susceptible bacteria. Clostridium difficile associated diarrhoea (CDAD) is a hospital acquired infection that is caused by antibiotic prescribing. OBJECTIVES: To estimate the effectiveness of professional interventions that alone, or in combination, are effective in promoting prudent antibiotic prescribing to hospital inpatients, to evaluate the impact of these interventions on reducing the incidence of antimicrobial resistant pathogens or CDAD and their impact on clinical outcome. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care (EPOC) specialized register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE from 1980 to November 2003. Additional studies were obtained from the bibliographies of retrieved articles SELECTION CRITERIA: We included all randomised and controlled clinical trials (RCT/CCT), controlled before and after studies (CBA) and interrupted time series (ITS) studies of antibiotic prescribing to hospital inpatients. Interventions included any professional or structural interventions as defined by EPOC. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data and assessed quality. MAIN RESULTS: Sixty six studies were included and 51 (77%) showed a significant improvement in at least one outcome. Six interventions only aimed to increase treatment, 57 interventions aimed to decrease treatment and three interventions aimed to both increase and decrease treatment. The intervention target was the decision to prescribe antibiotics (one study), timing of first dose (six studies), the regimen (drug, dosing interval etc, 61 studies) or the duration of treatment (10 studies); 12 studies had more than one target. Of the six interventions that aimed to increase treatment, five reported a significant improvement in drug outcomes and one a significant improvement in clinical outcome. Of the 60 interventions that aimed to decrease treatment 47 reported drug outcomes of which 38 (81%) significantly improved, 16 reported microbiological outcomes of which 12 (75%) significantly improved and nine reported clinical outcomes of which two (22%) significantly deteriorated and 3 (33%) significantly improved. Five studies aimed to reduce CDAD. Three showed a significant reduction in CDAD. Due to differences in study design and duration of follow up it was only possible to perform meta-regression on a few studies. AUTHORS' CONCLUSIONS: The results show that interventions to improve antibiotic prescribing to hospital inpatients are successful, and can reduce antimicrobial resistance or hospital acquired infections.

Anticonvulsant drugs for acute and chronic pain.

BACKGROUND: Anticonvulsant drugs have been used in the management of pain since the 1960s. The clinical impression is that they are useful for chronic neuropathic pain, especially when the pain is lancinating or burning. Readers are referred to reviews of carbamazepine and gabapentin in the Cochrane Library which replace the information on those drugs in this review. Other drugs remain unchanged at present in this review OBJECTIVES: To evaluate the analgesic effectiveness and adverse effects of anticonvulsant drugs for pain management in clinical practice . Migraine and headache studies are excluded in this revision. SEARCH STRATEGY: Randomised trials of anticonvulsants in acute, chronic or cancer pain were identified by MEDLINE (1966-1999), EMBASE (1994-1999), SIGLE (1980-1999) and the Cochrane Controlled Trials Register (CENTRAL/CCTR) (Cochrane Library Issue 3, 1999). In addition, 41 medical journals were hand searched. Additional reports were identified from the reference list of the retrieved papers, and by contacting investigators. Date of most recent search: September 1999. SELECTION CRITERIA: Randomised trials reporting the analgesic effects of anticonvulsant drugs in patients, with subjective pain assessment as either the primary or a secondary outcome. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent reviewers, and trials were quality scored. Numbers-needed-to-treat (NNTs) were calculated from dichotomous data for effectiveness, adverse effects and drug-related study withdrawal, for individual studies and for pooled data. MAIN RESULTS: Twenty-three trials of six anticonvulsants were considered eligible (1,074 patients). The only placebo-controlled study in acute pain found no analgesic effect of sodium valproate. Three placebo-controlled studies of carbamazepine in trigeminal neuralgia had a combined NNT (95% confidence interval (CI)) for effectiveness of 2.5 (CI 2.0-3.4). A single placebo-controlled trial of gabapentin in post-herpetic neuralgia had an NNT of 3.2 (CI 2.4-5.0). For diabetic neuropathy NNTs for effectiveness were as follows: (one RCT for each drug) carbamazepine 2.3 (CI 1.6-3.8), gabapentin 3.8 (CI 2.4-8.7) and phenytoin 2.1 (CI 1.5-3.6).Numbers-needed-to-harm (NNHs) were calculated where possible by combining studies for each drug entity irrespective of the condition treated. The results were, for minor harm, carbamazepine 3.7 (CI 2.4-7.8), gabapentin 2.5 (CI 2.0-3.2), phenytoin 3.2 (CI 2.1-6.3). NNHs for major harm were not statistically significant for any drug compared with placebo. Phenytoin had no effect in irritable bowel syndrome, and carbamazepine little effect in post-stroke pain. Clonazepam was effective in one study of temporomandibular joint dysfunction. AUTHORS' CONCLUSIONS: Although anticonvulsants are used widely in chronic pain surprisingly few trials show analgesic effectiveness. Only one studied considered cancer pain. There is no evidence that anticonvulsants are effective for acute pain. In chronic pain syndromes other than trigeminal neuralgia, anticonvulsants should be withheld until other interventions have been tried. While gabapentin is increasingly being used for neuropathic pain the evidence would suggest that it is not superior to carbamazepine.

Carbamazepine for acute and chronic pain.

BACKGROUND: Anticonvulsant drugs have been used in the management of pain since the 1960s. The clinical impression is that they are useful for chronic neuropathic pain, especially when the pain is lancinating or burning. OBJECTIVES: To evaluate the analgesic effectiveness and adverse effects of the anticonvulsant medicine carbamazepine for pain management in clinical practice and to identify a clinical research agenda. Migraine and headache studies are not included in this review. SEARCH STRATEGY: Randomised trials (RCTs) of anticonvulsants in acute, chronic or cancer pain were identified by MEDLINE (1966-2004), EMBASE (1994-2004), SIGLE (1980-2004) and the Cochrane Controlled Trials Register (CENTRAL/CCTR) (Cochrane Library Issue 3, 2003). In addition, 41 medical journals were hand searched for a previous version of this review. Additional reports were identified from the reference list of the retrieved papers, and by contacting investigators. Date of most recent search: November 2004. SELECTION CRITERIA: Randomised trials reporting the analgesic effects of carbamazepine in patients, with subjective pain assessment as either the primary or a secondary outcome. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent reviewers, and trials were quality scored. Numbers-needed-to-treat (NNTs) were calculated from dichotomous data for effectiveness, adverse effects and drug-related study withdrawal, for individual studies and for pooled data. MAIN RESULTS: Twelve studies were included (404 participants). Four studies included trigeminal neuralgia patients. Two studies which provided evaluable data yielded an NNT for effectiveness of 1.8 (95%CI 1.4-2.8). For diabetic neuropathy there was insufficient data for an NNT to be calculated.Numbers-needed-to-harm (NNHs) were calculated where possible by combining studies for each drug entity irrespective of the condition treated. The results were, for minor harm, carbamazepine 3.7 (CI 2.4-7.8), NNHs for major harm were not statistically significant for carbamazepine compared with placebo. There is no evidence that carbamazepine is effective for acute pain. AUTHORS' CONCLUSIONS: There is evidence to show that carbamazepine is effective but trials are small.

Gabapentin for acute and chronic pain.

BACKGROUND: Anticonvulsant drugs have been used in the management of pain since the 1960s. The clinical impression is that they are useful for chronic neuropathic pain, especially when the pain is lancinating or burning. OBJECTIVES: To evaluate the analgesic effectiveness and adverse effects of gabapentin for pain management in clinical practice. SEARCH STRATEGY: Randomised trials of gabapentin in acute, chronic or cancer pain were identified by MEDLINE (1966-Nov 2004), EMBASE (1994-Nov 2004), SIGLE (1980-Jan 2004) and the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 4, 2004). Additional reports were identified from the reference list of the retrieved papers, and by contacting investigators. Date of most recent search: January 2004. SELECTION CRITERIA: Randomised trials reporting the analgesic effects of gabapentin in patients, with subjective pain assessment as either the primary or a secondary outcome. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent reviewers, and trials were quality scored. Numbers-needed-to-treat (NNTs) were calculated, where possible, from dichotomous data for effectiveness, adverse effects and drug-related study withdrawal. MAIN RESULTS: Fourteen reports describing 15 studies of gabapentin were considered eligible (1468 participants). One was a study of acute pain. The remainder included the following conditions: post-herpetic neuralgia (two studies), diabetic neuropathy (seven studies), a cancer related neuropathic pain (one study) phantom limb pain (one study), Guillain Barré syndrome (one study) , spinal chord injury pain (one study) and various neuropathic pains (one study). The study in acute post-operative pain (70 participants) showed no benefit for gabapentin compared to placebo for pain at rest. In chronic pain, the NNT for improvement in all trials with evaluable data is 4.3 (95%CI 3.5-5.7). Forty two percent of participants improved on gabapentin compared to 19% on placebo. The number needed to harm(NNH) for adverse events leading to withdrawal from a trial was not significant. Fourteen percent of participants withdrew from active arms compared to 10% in placebo arms. The NNH for minor harm was 3.7 (95% CI 2.4 to 5.4). The NNT for effective pain relief in diabetic neuropathy was 2.9 (95% CI 2.2 to 4.3) and for post herpetic neuralgia 3.9 (95% CI 3 to 5.7). AUTHORS' CONCLUSIONS: There is evidence to show that gabapentin is effective in neuropathic pain. There is limited evidence to show that gabapentin is ineffective in acute pain.

Antidepressants for neuropathic pain.

BACKGROUND: For many years antidepressant drugs have been used to manage neuropathic pain, and are often the first choice treatment. It is not clear, however, which antidepressant is more effective, what role the newer antidepressants can play in treating neuropathic pain, and what adverse effects are experienced by patients. OBJECTIVES: To determine the analgesic effectiveness and safety of antidepressant drugs in neuropathic pain. Migraine and headache studies were not considered. SEARCH STRATEGY: Randomised trials of antidepressants in neuropathic pain were identified in MEDLINE (1966 to Dec 2003); EMBASE (1980 to Dec 2003); the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library 2004, Issue 1; and the Cochrane Pain, Palliative and Supportive Care Trials Register (May 2002). Additional reports were identified from the reference list of the retrieved papers, and by contacting investigators. SELECTION CRITERIA: Randomised trials reporting the analgesic effects of antidepressant drugs in adult patients, with subjective assessment of pain of neuropathic origin. Studies that included patients with chronic headache and migraine were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers agreed the included studies, extracted data, and assessed methodological quality independently. Fifty trials of 19 antidepressants were considered eligible (2515 patients) for inclusion. Relative Risk (RR) estimates and Number-Needed-to-Treat (NNTs) were calculated from dichotomous data for effectiveness and adverse effects. MAIN RESULTS: Tricyclic antidepressants (TCAs) are effective treatments for the treatment of neuropathic pain. Amitriptyline has an NNT of 2 (95%CI 1.7 to 2.5) RR 4.1(95%CI 2.9-5.9) for the achievement of at least moderate pain relief. There is limited evidence for the effectiveness of the newer selective serotonin reuptake inhibitor antidepressant drugs (SSRIs). There were insufficient data for an assessment of evidence of effectiveness for other antidepressants such as St Johns Wort, venlafaxine and L-tryptophan. For diabetic neuropathy the NNT for effectiveness was 1.3 (95%CI 1.2 to 1.5) RR 12.4(95%CI 5.2-29.2) (five studies); for postherpetic neuralgia 2.2 (95%CI 1.7 to 3.1), RR 4.8(95%CI 2.5-9.5)(three studies). There was evidence that TCAs are not effective in HIV-related neuropathies. The number needed to harm(NNH) for major adverse effects defined as an event leading to withdrawal from a study was 16 (95%CI: 10-45). The NNH for minor adverse effects was 4.6 (95%CI 3.3-6.7) AUTHORS' CONCLUSIONS: Antidepressants are effective for a variety of neuropathic pains. The best evidence available is for amitriptyline. There are only limited data for the effectiveness of SSRIs. It is not possible to identify the most effective antidepressant until more studies of SSRIs are conducted.

Audit of antibiotic policies in the South East of England, 2004.

OBJECTIVES: The antibiotic policies of hospitals and primary care trusts (PCTs) in South East England were audited in the summer of 2004, to see how they had improved since 2000. METHODS: Antibiotic policies were obtained from pharmacists in NHS hospitals and PCTs, and examined for dates, formats, evidence base for policies, the type of guidance given on dosage, length of treatment, choice of antibiotics, coverage of common infections and reasons for prophylaxis. RESULTS: Twenty-three hospital and 25 primary care policies were examined. The average age of policies was 12 months, but 13 were more than 2 years old. The commonest format was an A4-sized document available in an electronic version. Primary care policies were more uniform than hospital policies. More primary care than hospitals' policies gave evidence to support their guidance. Ten policies used plain English for dosages, and 38 (79%) policies made few or no cautionary points about the drugs recommended. Respiratory and urinary infections were covered in most policies, but guidance on gastroenteritis and antibiotic prophylaxis was less frequent. There was little advice in the policies on the management of methicillin-resistant Staphylococcus aureus. CONCLUSIONS: Primary care policies have improved since 2000, using a national model for evidence and a consistent style. Hospitals could benefit from similar national guidance, especially in the evidence to support the contents of antibiotic policies.

Relative efficacy of oral analgesics after third molar extraction.

OBJECTIVES: To compare the relative efficacy of analgesics after third molar extraction from systematic reviews of randomised, double blind studies. DATA SOURCES: Dental trials from systematic reviews of randomised, double-blind studies of analgesics in acute pain. DATA SELECTION: Number of patients with moderate or severe pain achieving at least half pain relief over 4 to 6 hours after a single oral dose of analgesic. DATA EXTRACTION: Independently by two reviewers. DATA SYNTHESIS: Use of dichotomous information from active and placebo treatments, first to calculate the statistical significance using relative risk, and then to evaluate the clinical relevance using number needed to treat (NNT). Non-steroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase-2 (COX-2) inhibitors had the lowest (best) NNTs for the outcome of at least half pain relief over 4-6 hours compared with placebo. With the best performing analgesics, 50-70 patients out of 100 had good pain relief compared with about 10 out of 100 with placebo. Only paracetamol 600/650 mg plus codeine 60 mg was associated with any significant increase in any patient experiencing an adverse event. CONCLUSIONS: NSAIDs and COX-2 inhibitors have the lowest (best) NNTs. They may also have fewer adverse effects after third molar surgery, though conclusive evidence is lacking. At least 80% of analgesic prescribing by UK dentists is in line with the best available evidence on efficacy and safety.

Oral morphine for cancer pain.

BACKGROUND: Morphine has been used to relieve pain for many years. Oral morphine in either immediate release or sustained release form remains the analgesic of choice for moderate or severe cancer pain. OBJECTIVES: To determine the efficacy of oral morphine in relieving cancer pain. To assess the incidence and severity of adverse effects. SEARCH STRATEGY: The following databases were searched: The Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Library, Issue 4, 2002; the trials register of the Cochrane Pain, Palliative and Supportive Care group (February 2002); MEDLINE 1966 to December 2002; EMBASE 1988 to December 2002; and the Oxford Pain Relief database 1950 to 1994. SELECTION CRITERIA: Published randomised controlled trials (full reports) reporting on the analgesic effect of oral morphine in adults and children with cancer pain. Any comparator trials were considered. Trials with fewer than 10 subjects were excluded. DATA COLLECTION AND ANALYSIS: One reviewer extracted data, and the findings were checked by two other reviewers. There were insufficient comparable data for meta-analysis to be undertaken, or to produce numbers-needed-to-treat (NNT) for the analgesic effect. MAIN RESULTS: Forty five studies (3061 subjects) met the inclusion criteria. Fourteen studies compared oral sustained release morphine (MSR) preparations with immediate release morphine (MIR). Eight studies compared MSR and MSR in different strengths. Nine studies compared MSR with other opioids. Five studies compared MIR with other opioids. Two studies compared oral MSR with rectal MSR. One study was found comparing each of the following: MSR tablet with MSR suspension; MSR with MSR at different dose frequencies; MSR with non-opioids; MIR with non-opioids; oral morphine with epidural morphine; and MIR with MIR by a different route of administration. Morphine was shown to be an effective analgesic. Pain relief did not differ between MSR and MIR. Sustained release versions of morphine were effective for 12 or 24 hour dosing depending on the formulation. Adverse effects were common but only 4% of patients discontinued treatment because of intolerable adverse effects. REVIEWER'S CONCLUSIONS: The 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 subjects over in crossover design studies. It is not clear if these trials are sufficiently powered to detect any clinical differences between formulations or comparator drugs.