Cannabis-based medicines and medical cannabis for adults with cancer pain.

BACKGROUND: Pain is a common symptom in people with cancer; 30% to 50% of people with cancer will experience moderate-to-severe pain. This can have a major negative impact on their quality of life. Opioid (morphine-like) medications are commonly used to treat moderate or severe cancer pain, and are recommended for this purpose in the World Health Organization (WHO) pain treatment ladder. Pain is not sufficiently relieved by opioid medications in 10% to 15% of people with cancer. In people with insufficient relief of cancer pain, new analgesics are needed to effectively and safely supplement or replace opioids. OBJECTIVES: To evaluate the benefits and harms of cannabis-based medicines, including medical cannabis, for treating pain and other symptoms in adults with cancer compared to placebo or any other established analgesic for cancer pain. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 26 January 2023. SELECTION CRITERIA: We selected double-blind randomised, controlled trials (RCT) of medical cannabis, plant-derived and synthetic cannabis-based medicines against placebo or any other active treatment for cancer pain in adults, with any treatment duration and at least 10 participants per treatment arm. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. The primary outcomes were 1. proportions of participants reporting no worse than mild pain; 2. Patient Global Impression of Change (PGIC) of much improved or very much improved and 3. withdrawals due to adverse events. Secondary outcomes were 4. number of participants who reported pain relief of 30% or greater and overall opioid use reduced or stable; 5. number of participants who reported pain relief of 30% or greater, or 50% or greater; 6. pain intensity; 7. sleep problems; 8. depression and anxiety; 9. daily maintenance and breakthrough opioid dosage; 10. dropouts due to lack of efficacy; 11. all central nervous system adverse events. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We identified 14 studies involving 1823 participants. No study assessed the proportions of participants reporting no worse than mild pain on treatment by 14 days after start of treatment. We found five RCTs assessing oromucosal nabiximols (tetrahydrocannabinol (THC) and cannabidiol (CBD)) or THC alone involving 1539 participants with moderate or severe pain despite opioid therapy. The double-blind periods of the RCTs ranged between two and five weeks. Four studies with a parallel design and 1333 participants were available for meta-analysis. There was moderate-certainty evidence that there was no clinically relevant benefit for proportions of PGIC much or very much improved (risk difference (RD) 0.06, 95% confidence interval (CI) 0.01 to 0.12; number needed to treat for an additional beneficial outcome (NNTB) 16, 95% CI 8 to 100). There was moderate-certainty evidence for no clinically relevant difference in the proportion of withdrawals due to adverse events (RD 0.04, 95% CI 0 to 0.08; number needed to treat for an additional harmful outcome (NNTH) 25, 95% CI 16 to endless). There was moderate-certainty evidence for no difference between nabiximols or THC and placebo in the frequency of serious adverse events (RD 0.02, 95% CI -0.03 to 0.07). There was moderate-certainty evidence that nabiximols and THC used as add-on treatment for opioid-refractory cancer pain did not differ from placebo in reducing mean pain intensity (standardised mean difference (SMD) -0.19, 95% CI -0.40 to 0.02). There was low-certainty evidence that a synthetic THC analogue (nabilone) delivered over eight weeks was not superior to placebo in reducing pain associated with chemotherapy or radiochemotherapy in people with head and neck cancer and non-small cell lung cancer (2 studies, 89 participants, qualitative analysis). Analyses of tolerability and safety were not possible for these studies. There was low-certainty evidence that synthetic THC analogues were superior to placebo (SMD -0.98, 95% CI -1.36 to -0.60), but not superior to low-dose codeine (SMD 0.03, 95% CI -0.25 to 0.32; 5 single-dose trials; 126 participants) in reducing moderate-to-severe cancer pain after cessation of previous analgesic treatment for three to four and a half hours (2 single-dose trials; 66 participants). Analyses of tolerability and safety were not possible for these studies. There was low-certainty evidence that CBD oil did not add value to specialist palliative care alone in the reduction of pain intensity in people with advanced cancer. There was no difference in the number of dropouts due to adverse events and serious adverse events (1 study, 144 participants, qualitative analysis). We found no studies using herbal cannabis. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that oromucosal nabiximols and THC are ineffective in relieving moderate-to-severe opioid-refractory cancer pain. There is low-certainty evidence that nabilone is ineffective in reducing pain associated with (radio-) chemotherapy in people with head and neck cancer and non-small cell lung cancer. There is low-certainty evidence that a single dose of synthetic THC analogues is not superior to a single low-dose morphine equivalent in reducing moderate-to-severe cancer pain. There is low-certainty evidence that CBD does not add value to specialist palliative care alone in the reduction of pain in people with advanced cancer.

ANTECEDENTES: El dolor es un síntoma común en las personas con cáncer; entre el 30% y el 50% de las personas con cáncer experimentarán dolor de moderado a intenso. Esto puede tener un gran impacto negativo en su calidad de vida. Los fármacos opiáceos (similares a la morfina) se utilizan habitualmente para tratar el dolor por cáncer moderado o intenso, y se recomiendan para este propósito en la escala de tratamiento del dolor de la Organización Mundial de la Salud (OMS). El dolor no se alivia lo suficiente con los medicamentos opiáceos en el 10% al 15% de las personas con cáncer. En las personas con un alivio insuficiente del dolor por cáncer, se necesitan nuevos analgésicos que complementen o sustituyan de forma eficaz y segura a los opiáceos. OBJETIVOS: Evaluar los efectos beneficiosos y perjudiciales de los medicamentos con cannabis, incluido el cannabis medicinal, para tratar el dolor y otros síntomas en adultos con cáncer en comparación con placebo o cualquier otro analgésico establecido para el dolor por cáncer. MÉTODOS DE BÚSQUEDA: Se utilizaron los métodos exhaustivos estándar de búsqueda de Cochrane. La última fecha de búsqueda fue el 26 de enero de 2023. CRITERIOS DE SELECCIÓN: Se seleccionaron los ensayos controlados aleatorizados (ECA) doble ciego de cannabis medicinal, medicamentos derivados de plantas y sintéticos con cannabis versus placebo o cualquier otro tratamiento activo para el dolor por cáncer en adultos, con cualquier duración del tratamiento y al menos 10 participantes por grupo de tratamiento. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Se utilizaron los métodos estándar de Cochrane. Los desenlaces principales fueron los siguientes: 1. proporción de participantes que declararon dolor leve; 2. Patient Global Impression of Change (PGIC) de mucha o muchísima mejoría y 3. retiros debido a eventos adversos. Los desenlaces secundarios fueron 4. número de participantes que declararon un alivio del dolor del 30% o superior y un consumo general de opiáceos reducido o estable; 5. número de participantes que declararon un alivio del dolor del 30% o superior, o del 50% o superior; 6. intensidad del dolor; 7. problemas de sueño; 8. depresión y ansiedad; 9. dosis diaria de opiáceos de mantenimiento y de inicio; 10. abandonos por falta de eficacia; 11. todos los eventos adversos del sistema nervioso central. Se utilizó el método GRADE para evaluar la calidad de la evidencia de cada desenlace. RESULTADOS PRINCIPALES: Se identificaron 14 estudios con 1823 participantes. Ningún estudio evaluó las proporciones de participantes que declararon un dolor no peor que leve a los 14 días de inicio del tratamiento. Se encontraron cinco ECA que evaluaron nabiximoles oromucosos (tetrahidrocannabinol [THC] y cannabidiol [CBD]) o THC solo, con 1539 participantes con dolor moderado o intenso a pesar del tratamiento con opiáceos. Los periodos doble ciego de los ECA variaron entre dos y cinco semanas. Para el metanálisis se dispuso de cuatro estudios con un diseño paralelo y 1333 participantes. Hubo evidencia de certeza moderada de que no hubo efectos beneficiosos clínicamente relevantes en las proporciones de PGIC de mucha o muchísima mejoría (diferencia de riesgos [DR] 0,06; intervalo de confianza [IC] del 95%: 0,01 a 0,12; número necesario a tratar para lograr un resultado beneficioso adicional [NNTB] 16; IC del 95%: 8 a 100). Hubo evidencia de certeza moderada de que no hubo diferencias clínicamente relevantes en la proporción de retiros debido a eventos adversos (DR 0,04; IC del 95%: 0 a 0,08; número necesario a tratar para lograr un desenlace perjudicial adicional [NNTD] 25; IC del 95%: 16 a infinito). Hubo evidencia de certeza moderada de que no hubo diferencias entre nabiximols o THC y placebo en la frecuencia de eventos adversos graves (DR 0,02; IC del 95%: ­0,03 a 0,07). Hubo evidencia de certeza moderada de que los nabiximoles y el THC utilizados como tratamiento complementario para el dolor por cáncer refractario a los opiáceos no difirieron del placebo en cuanto a la reducción de la intensidad media del dolor (diferencia de medias estandarizada [DME] ­0,19; IC del 95%: ­0,40 a 0,02). Hubo evidencia de certeza baja de que un análogo sintético del THC (nabilona) administrado durante ocho semanas no fue superior a placebo para reducir el dolor asociado con la quimioterapia o la radioquimioterapia en personas con cáncer de cabeza y cuello y cáncer de pulmón de células no pequeñas (dos estudios, 89 participantes, análisis cualitativo). En estos estudios no fue posible realizar análisis de tolerabilidad y seguridad. Hubo evidencia de certeza baja de que los análogos sintéticos del THC fueron superiores a placebo (DME ­0,98; IC del 95%: ­1,36 a ­0,60), pero no superiores a la codeína en dosis bajas (DME 0,03; IC del 95%: ­0,25 a 0,32; cinco ensayos de dosis única; 126 participantes) en cuanto a la reducción del dolor moderado a intenso por cáncer después de la interrupción del tratamiento analgésico previo durante tres a cuatro horas y media (dos ensayos de dosis única; 66 participantes). En estos estudios no fue posible realizar análisis de tolerabilidad y seguridad. Hubo evidencia de certeza baja de que el aceite de CBD no agregó valor a los cuidados paliativos especializados solos en la reducción de la intensidad del dolor en personas con cáncer avanzado. No hubo diferencias en el número de abandonos debido a eventos adversos ni eventos adversos graves (un estudio, 144 participantes, análisis cualitativo). No se encontraron estudios que utilizaran la planta de cannabis. CONCLUSIONES DE LOS AUTORES: Existe evidencia de certeza moderada de que los nabiximoles y el THC por vía oromucosa no son efectivos para aliviar el dolor de moderado a intenso por cáncer refractario a los opiáceos. Hay evidencia de certeza baja de que la nabilona no es efectiva para reducir el dolor asociado con la radio­quimioterapia en personas con cáncer de cabeza y cuello y cáncer de pulmón de células no pequeñas. Hay evidencia de certeza baja de que una dosis única de análogos sintéticos del THC no es superior a una dosis única baja equivalente de morfina para reducir el dolor moderado a intenso por cáncer. Hay evidencia de certeza baja de que el CBD no aporta valor a los cuidados paliativos especializados solos en la reducción del dolor en personas con cáncer avanzado.

Interventions for the reduction of prescribed opioid use in chronic non-cancer pain.

BACKGROUND: This is the first update of the original Cochrane Review published in 2013. The conclusions of this review have not changed from the 2013 publication. People with chronic non-cancer pain who are prescribed and are taking opioids can have a history of long-term, high-dose opioid use without effective pain relief. In those without good pain relief, reduction of prescribed opioid dose may be the desired and shared goal of both patient and clinician. Simple, unsupervised reduction of opioid use is clinically challenging, and very difficult to achieve and maintain. OBJECTIVES: To investigate the effectiveness of different methods designed to achieve reduction or cessation of prescribed opioid use for the management of chronic non-cancer pain in adults compared to controls. SEARCH METHODS: For this update we searched CENTRAL, MEDLINE, and Embase in January 2017, as well as bibliographies and citation searches of included studies. We also searched one trial registry for ongoing trials. SELECTION CRITERIA: Included studies had to be randomised controlled trials comparing opioid users receiving an intervention with a control group receiving treatment as usual, active control, or placebo. The aim of the study had to include a treatment goal of dose reduction or cessation of opioid medication. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias. We sought data relating to prescribed opioid use, adverse events of opioid reduction, pain, and psychological and physical function. We planned to assess the certainty of the evidence using the GRADE approach, however, due to the heterogeneity of studies, we were unable to combine outcomes in a meta-analysis and therefore we did not assess the evidence with GRADE. MAIN RESULTS: Three studies are new to this update, resulting in five included studies in total (278 participants). Participants were primarily women (mean age 49.63 years, SD = 11.74) with different chronic pain conditions. We judged the studies too heterogeneous to pool data in a meta-analysis, so we have summarised the results from each study qualitatively. The studies included acupuncture, mindfulness, and cognitive behavioral therapy interventions aimed at reducing opioid consumption, misuse of opioids, or maintenance of chronic pain management treatments. We found mixed results from the studies. Three of the five studies reported opioid consumption at post-treatment and follow-up. Two studies that delivered 'Mindfulness-Oriented Recovery Enhancement' or 'Therapeutic Interactive Voice Response' found a significant difference between groups at post-treatment and follow-up in opioid consumption. The remaining study found reduction in opioid consumption in both treatment and control groups, and between-group differences were not significant. Three studies reported adverse events related to the study and two studies did not have study-related adverse events. We also found mixed findings for pain intensity and physical functioning. The interventions did not show between-group differences for psychological functioning across all studies. Overall, the risk of bias was mixed across studies. All studies included sample sizes of fewer than 100 and so we judged all studies as high risk of bias for that category. AUTHORS' CONCLUSIONS: There is no evidence for the efficacy or safety of methods for reducing prescribed opioid use in chronic pain. There is a small number of randomised controlled trials investigating opioid reduction, which means our conclusions are limited regarding the benefit of psychological, pharmacological, or other types of interventions for people with chronic pain trying to reduce their opioid consumption. The findings to date are mixed: there were reductions in opioid consumption after intervention, and often in control groups too.

Topical analgesics for acute and chronic pain in adults - an overview of Cochrane Reviews.

BACKGROUND: Topical analgesic drugs are used for a variety of painful conditions. Some are acute, typically strains or sprains, tendinopathy, or muscle aches. Others are chronic, typically osteoarthritis of hand or knee, or neuropathic pain. OBJECTIVES: To provide an overview of the analgesic efficacy and associated adverse events of topical analgesics (primarily nonsteroidal anti-inflammatory drugs (NSAIDs), salicylate rubefacients, capsaicin, and lidocaine) applied to intact skin for the treatment of acute and chronic pain in adults. METHODS: We identified systematic reviews in acute and chronic pain published to February 2017 in the Cochrane Database of Systematic Reviews (the Cochrane Library). The primary outcome was at least 50% pain relief (participant-reported) at an appropriate duration. We extracted the number needed to treat for one additional beneficial outcome (NNT) for efficacy outcomes for each topical analgesic or formulation, and the number needed to treat for one additional harmful outcome (NNH) for adverse events. We also extracted information on withdrawals due to lack of efficacy or adverse events, systemic and local adverse events, and serious adverse events. We required information from at least 200 participants, in at least two studies. We judged that there was potential for publication bias if the addition of four studies of typical size (400 participants) with zero effect increased NNT compared with placebo to 10 (minimal clinical utility). We extracted GRADE assessment in the original papers, and made our own GRADE assessment. MAIN RESULTS: Thirteen Cochrane Reviews (206 studies with around 30,700 participants) assessed the efficacy and harms from a range of topical analgesics applied to intact skin in a number of acute and chronic painful conditions. Reviews were overseen by several Review Groups, and concentrated on evidence comparing topical analgesic with topical placebo; comparisons of topical and oral analgesics were rare.For at least 50% pain relief, we considered evidence was moderate or high quality for several therapies, based on the underlying quality of studies and susceptibility to publication bias.In acute musculoskeletal pain (strains and sprains) with assessment at about seven days, therapies were diclofenac Emulgel (78% Emulgel, 20% placebo; 2 studies, 314 participants, NNT 1.8 (95% confidence interval 1.5 to 2.1)), ketoprofen gel (72% ketoprofen, 33% placebo, 5 studies, 348 participants, NNT 2.5 (2.0 to 3.4)), piroxicam gel (70% piroxicam, 47% placebo, 3 studies, 522 participants, NNT 4.4 (3.2 to 6.9)), diclofenac Flector plaster (63% Flector, 41% placebo, 4 studies, 1030 participants, NNT 4.7 (3.7 to 6.5)), and diclofenac other plaster (88% diclofenac plaster, 57% placebo, 3 studies, 474 participants, NNT 3.2 (2.6 to 4.2)).In chronic musculoskeletal pain (mainly hand and knee osteoarthritis) therapies were topical diclofenac preparations for less than six weeks (43% diclofenac, 23% placebo, 5 studies, 732 participants, NNT 5.0 (3.7 to 7.4)), ketoprofen over 6 to 12 weeks (63% ketoprofen, 48% placebo, 4 studies, 2573 participants, NNT 6.9 (5.4 to 9.3)), and topical diclofenac preparations over 6 to 12 weeks (60% diclofenac, 50% placebo, 4 studies, 2343 participants, NNT 9.8 (7.1 to 16)). In postherpetic neuralgia, topical high-concentration capsaicin had moderate-quality evidence of limited efficacy (33% capsaicin, 24% placebo, 2 studies, 571 participants, NNT 11 (6.1 to 62)).We judged evidence of efficacy for other therapies as low or very low quality. Limited evidence of efficacy, potentially subject to publication bias, existed for topical preparations of ibuprofen gels and creams, unspecified diclofenac formulations and diclofenac gel other than Emulgel, indomethacin, and ketoprofen plaster in acute pain conditions, and for salicylate rubefacients for chronic pain conditions. Evidence for other interventions (other topical NSAIDs, topical salicylate in acute pain conditions, low concentration capsaicin, lidocaine, clonidine for neuropathic pain, and herbal remedies for any condition) was very low quality and typically limited to single studies or comparisons with sparse data.We assessed the evidence on withdrawals as moderate or very low quality, because of small numbers of events. In chronic pain conditions lack of efficacy withdrawals were lower with topical diclofenac (6%) than placebo (9%) (11 studies, 3455 participants, number needed to treat to prevent (NNTp) 26, moderate-quality evidence), and topical salicylate (2% vs 7% for placebo) (5 studies, 501 participants, NNTp 21, very low-quality evidence). Adverse event withdrawals were higher with topical capsaicin low-concentration (15%) than placebo (3%) (4 studies, 477 participants, NNH 8, very low-quality evidence), topical salicylate (5% vs 1% for placebo) (7 studies, 735 participants, NNH 26, very low-quality evidence), and topical diclofenac (5% vs 4% for placebo) (12 studies, 3552 participants, NNH 51, very low-quality evidence).In acute pain, systemic or local adverse event rates with topical NSAIDs (4.3%) were no greater than with topical placebo (4.6%) (42 studies, 6740 participants, high quality evidence). In chronic pain local adverse events with topical capsaicin low concentration (63%) were higher than topical placebo (5 studies, 557 participants, number needed to treat for harm (NNH) 2.6), high quality evidence. Moderate-quality evidence indicated more local adverse events than placebo in chronic pain conditions with topical diclofenac (NNH 16) and local pain with topical capsaicin high-concentration (NNH 16). There was moderate-quality evidence of no additional local adverse events with topical ketoprofen over topical placebo in chronic pain. Serious adverse events were rare (very low-quality evidence).GRADE assessments of moderate or low quality in some of the reviews were considered by us to be very low because of small numbers of participants and events. AUTHORS' CONCLUSIONS: There is good evidence that some formulations of topical diclofenac and ketoprofen are useful in acute pain conditions such as sprains or strains, with low (good) NNT values. There is a strong message that the exact formulation used is critically important in acute conditions, and that might also apply to other pain conditions. In chronic musculoskeletal conditions with assessments over 6 to 12 weeks, topical diclofenac and ketoprofen had limited efficacy in hand and knee osteoarthritis, as did topical high-concentration capsaicin in postherpetic neuralgia. Though NNTs were higher, this still indicates that a small proportion of people had good pain relief.Use of GRADE in Cochrane Reviews with small numbers of participants and events requires attention.

Aspirin for acute treatment of episodic tension-type headache in adults.

BACKGROUND: Tension-type headache (TTH) affects about 1 person in 5 worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH (two to 14 headache days per month), and chronic TTH (15 headache days per month or more). Aspirin is one of a number of analgesics suggested for acute treatment of episodic TTH. OBJECTIVES: To assess the efficacy and safety of aspirin for acute treatment of episodic tension-type headache (TTH) in adults compared with placebo or any active comparator. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and the Oxford Pain Relief Database from inception to September 2016, and also reference lists of relevant published studies and reviews. We sought unpublished studies by asking personal contacts and searching online clinical trial registers and manufacturers' websites. SELECTION CRITERIA: We included randomised, double-blind, placebo-controlled studies (parallel-group or cross-over) using oral aspirin for symptomatic relief of an acute episode of TTH. Studies had to be prospective, with participants aged 18 years or over, and include at least 10 participants per treatment arm. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and extracted data. For various outcomes (predominantly those recommended by the International Headache Society (IHS)), we calculated the risk ratio (RR) and number needed to treat for one additional beneficial outcome (NNT), one additional harmful outcome (NNH), or to prevent one event (NNTp) for oral aspirin compared to placebo or an active intervention.We assessed the evidence using GRADE and created a 'Summary of findings' table. MAIN RESULTS: We included five studies enrolling adults with frequent episodic TTH; 1812 participants took medication, of which 767 were included in comparisons of aspirin 1000 mg with placebo, and 405 in comparisons of aspirin 500 mg or 650 mg with placebo. Not all of these participants provided data for outcomes of interest in this review. Four studies specified using IHS diagnostic criteria; one predated commonly recognised criteria, but described comparable characteristics and excluded migraine. All participants treated headaches of at least moderate pain intensity.None of the included studies were at low risk of bias across all domains considered, although for most studies and domains this was likely to be due to inadequate reporting rather than poor methods. We judged one study to be at high risk of bias due to small size.There were no data for aspirin at any dose for the IHS preferred outcome of being pain free at two hours, or for being pain free at any other time, and only one study provided data equivalent to having no or mild pain at two hours (very low quality evidence). Use of rescue medication was lower with aspirin 1000 mg than with placebo (2 studies, 397 participants); 14% of participants used rescue medication with aspirin 1000 mg compared with 31% with placebo (NNTp 6.0, 95% confidence interval (CI) 4.1 to 12) (low quality evidence). Two studies (397 participants) reported a Patient Global Evaluation at the end of the study; we combined the top two categories for both studies to determine the number of participants who were 'satisfied' with treatment. Aspirin 1000 mg produced more satisfied participants (55%) than did placebo (37%) (NNT 5.7, 95% CI 3.7 to 12) (very low quality evidence).Adverse events were not different between aspirin 1000 mg and placebo (RR 1.1, 95% CI 0.8 to 1.5), or aspirin 500 mg or 650 mg and placebo (RR 1.3, 95% CI 0.8 to 2.0) (low quality evidence). Studies reported no serious adverse events.The quality of the evidence using GRADE comparing aspirin doses between 500 mg and 1000 mg with placebo was low or very low. Evidence was downgraded because of the small number of studies and events, and because the most important measures of efficacy were not reported.There were insufficient data to compare aspirin with any active comparator (paracetamol alone, paracetamol plus codeine, peppermint oil, or metamizole) at any of the doses tested. AUTHORS' CONCLUSIONS: A single dose of aspirin between 500 mg and 1000 mg provided some benefit in terms of less frequent use of rescue medication and more participants satisfied with treatment compared with placebo in adults with frequent episodic TTH who have an acute headache of moderate or severe intensity. There was no difference between a single dose of aspirin and placebo for the number of people experiencing adverse events. The amount and quality of the evidence was very limited and should be interpreted with caution.

Non-prescription (OTC) oral analgesics for acute pain - an overview of Cochrane reviews.

BACKGROUND: Non-prescription (over-the-counter, or OTC) analgesics (painkillers) are used frequently. They are available in various brands, package sizes, formulations, and dose. They can be used for a range of different types of pain, but this overview reports on how well they work for acute pain (pain of short duration, usually with rapid onset). Thirty-nine Cochrane reviews of randomised trials have examined the analgesic efficacy of individual drug interventions in acute postoperative pain. OBJECTIVES: To examine published Cochrane reviews for information about the efficacy of pain medicines available without prescription using data from acute postoperative pain. METHODS: We identified OTC analgesics available in the UK, Australia, Canada, and the USA by examining online pharmacy websites. We also included some analgesics (diclofenac potassium, dexketoprofen, dipyrone) of importance in parts of the world, but not currently available in these jurisdictions.We identified systematic reviews by searching the Cochrane Database of Systematic Reviews (CDSR) on The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group, had a standard title, and had as their primary outcome numbers of participants with at least 50% pain relief over four to six hours compared with placebo. From individual reviews we extracted the number needed to treat for an additional beneficial outcome (NNT) for this outcome for each drug/dose combination, and also calculated the success rate to achieve at least 50% of maximum pain relief. We also examined the number of participants experiencing any adverse event, and whether the incidence was different from placebo. MAIN RESULTS: We found information on 21 different OTC analgesic drugs, doses, and formulations, using information from 10 Cochrane reviews, supplemented by information from one non-Cochrane review with additional information on ibuprofen formulations (high quality evidence). The lowest (best) NNT values were for combinations of ibuprofen plus paracetamol, with NNT values below 2. Analgesics with values close to 2 included fast acting formulations of ibuprofen 200 mg and 400 mg, ibuprofen 200 mg plus caffeine 100 mg, and diclofenac potassium 50 mg. Combinations of ibuprofen plus paracetamol had success rates of almost 70%, with dipyrone 500 mg, fast acting ibuprofen formulations 200 mg and 400 mg, ibuprofen 200 mg plus caffeine 100 mg, and diclofenac potassium 50 mg having success rates above 50%. Paracetamol and aspirin at various doses had NNT values of 3 or above, and success rates of 11% to 43%. We found no information on many of the commonly available low dose codeine combinations.The proportion of participants experiencing an adverse event were generally not different from placebo, except for aspirin 1000 mg and (barely) ibuprofen 200 mg plus caffeine 100 mg. For ibuprofen plus paracetamol, adverse event rates were lower than with placebo. AUTHORS' CONCLUSIONS: There is a body of reliable evidence about the efficacy of some of the most commonly available drugs and doses widely available without prescription. The postoperative pain model is predominantly pain after third molar extraction, which is used as the industry model for everyday pain. The proportion of people with acute pain who get good pain relief with any of them ranges from around 70% at best to less than 20% at worst; low doses of some drugs in fast acting formulations were among the best. Adverse events were generally no different from placebo. Consumers can make an informed choice based on this knowledge, together with availability and price. Headache and migraine were not included in this overview.

Vitamin D for the treatment of chronic painful conditions in adults.

BACKGROUND: This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (Issue 1, 2010) on 'Vitamin D for the treatment of chronic painful conditions in adults'.Vitamin D is produced in the skin after exposure to sunlight and can be obtained through food. Vitamin D deficiency has been linked with a range of conditions, including chronic pain. Observational and circumstantial evidence suggests that there may be a role for vitamin D deficiency in the aetiology of chronic painful conditions. OBJECTIVES: To assess the efficacy and safety of vitamin D supplementation in chronic painful conditions when tested against placebo or against active comparators. SEARCH METHODS: For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE to February 2015. This was supplemented by searching the reference lists of retrieved articles, reviews in the field, and online trial registries. SELECTION CRITERIA: We included studies if they were randomised double-blind trials of vitamin D supplementation compared with placebo or with active comparators for the treatment of chronic painful conditions in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies for inclusion, assessed methodological quality, and extracted data. We did not undertake pooled analysis due to the heterogeneity of the data. Primary outcomes of interest were pain responder outcomes, and secondary outcomes were treatment group average pain outcomes and adverse events. MAIN RESULTS: We included six new studies (517 participants) in this review update, bringing the total of included studies to 10 (811 participants). The studies were heterogeneous with regard to study quality, the chronic painful conditions that were investigated, the dose of vitamin D given, co-interventions, and the outcome measures reported. Only two studies reported responder pain outcomes; the other studies reported treatment group average outcomes only. Overall, there was no consistent pattern that vitamin D treatment was associated with greater efficacy than placebo in any chronic painful condition (low quality evidence). Adverse events and withdrawals were comparatively infrequent, with no consistent difference between vitamin D and placebo (good quality evidence). AUTHORS' CONCLUSIONS: The evidence addressing the use of vitamin D for chronic pain now contains more than twice as many studies and participants than were included in the original version of this review. Based on this evidence, a large beneficial effect of vitamin D across different chronic painful conditions is unlikely. Whether vitamin D can have beneficial effects in specific chronic painful conditions needs further investigation.

Single dose oral ibuprofen plus codeine for acute postoperative pain in adults.

BACKGROUND: This is an update of the original Cochrane review published in Issue 3, 2013. There is good evidence that combining two different analgesics in fixed doses in a single tablet can provide better pain relief in acute pain and headache than either drug alone, and that the drug-specific effects are essentially additive. This appears to be broadly true in postoperative pain and migraine headache across a range of different drug combinations and when tested in the same and different trials. Some combinations of ibuprofen and codeine are available without prescription (but usually only from a pharmacy) where the dose of codeine is lower, and with a prescription when the dose of codeine is higher.Use of combination analgesics that contain codeine has been a source of some concern because of misuse from over-the-counter preparations. OBJECTIVES: To assess the analgesic efficacy and adverse effects of a single oral dose of ibuprofen plus codeine for acute moderate-to-severe postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Relief Database, ClinicalTrials.gov, and the reference lists of articles. The date of the most recent search was 1 December 2014. SELECTION CRITERIA: Randomised, double-blind, placebo- or active-controlled clinical trials of single dose oral ibuprofen plus codeine for acute postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants prescribed ibuprofen plus codeine, placebo, or the same dose of ibuprofen alone with at least 50% pain relief over six hours, using validated equations. We calculated the risk ratio (RR) and number needed to treat to benefit (NNT). We used information on the use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse effects. Analyses were planned for different doses of ibuprofen and codeine, but especially for codeine where we set criteria for low (< 10 mg), medium (10 to 20 mg), and high (> 20 mg) doses. MAIN RESULTS: Since the last version of this review no new studies were found. Information was available from six studies with 1342 participants, using a variety of doses of ibuprofen and codeine. In four studies (443 participants) using ibuprofen 400 mg plus codeine 25.6 mg to 60 mg (high dose codeine) 64% of participants had at least 50% maximum pain relief with the combination compared to 18% with placebo. The NNT was 2.2 (95% confidence interval 1.8 to 2.6) (high quality evidence). In three studies (204 participants) ibuprofen plus codeine (any dose) was better than the same dose of ibuprofen (69% versus 55%) but the result was barely significant with a relative benefit of 1.3 (1.01 to 1.6) (moderate quality evidence). In two studies (159 participants) ibuprofen plus codeine appeared to be better than the same dose of codeine alone (69% versus 33%), but no analysis was done. There was no difference between the combination and placebo in the reporting of adverse events in these acute studies (moderate quality evidence). AUTHORS' CONCLUSIONS: The combination of ibuprofen 400 mg plus codeine 25.6 mg to 60 mg demonstrates good analgesic efficacy. Very limited data suggest that the combination is better than the same dose of either drug alone, and that similar numbers of people experience adverse events with the combination as with placebo.

Caffeine as an analgesic adjuvant for acute pain in adults.

BACKGROUND: This is an updated version of the original Cochrane review published in Issue 3, 2012. Caffeine has been added to common analgesics such as paracetamol, ibuprofen, and aspirin, in the belief that it enhances analgesic efficacy. Evidence to support this belief is limited and often based on invalid comparisons. OBJECTIVES: To assess the relative efficacy of a single dose of an analgesic plus caffeine against the same dose of the analgesic alone, without restriction on the analgesic used or the pain condition studied. We also assessed serious adverse events. SEARCH METHODS: We searched CENTRAL, MEDLINE, and EMBASE from inception to 28 August 2014, the Oxford Pain Relief Database, and also carried out Internet searches and contacted pharmaceutical companies known to have carried out trials that have not been published. SELECTION CRITERIA: We included randomised, double-blind studies that compared a single dose of analgesic plus caffeine with the same dose of the analgesic alone in the treatment of acute pain. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility and quality of studies, and extracted data. Any disagreements or uncertainties were settled by discussion with a third review author. We sought any validated measure of analgesic efficacy, but particularly the number of participants experiencing at least 50% of the maximum possible pain relief over four to six hours, participants reporting a global evaluation of treatment of very good or excellent, or headache relief after two hours. We pooled comparable data to look for a statistically significant difference, and calculated numbers needed to treat to benefit (NNT) with caffeine. We also looked for any numerical superiority associated with the addition of caffeine, and information about any serious adverse events. MAIN RESULTS: We identified no new studies with available results for this update. The earlier review included 20 studies (7238 participants) in valid comparisons, but because we used different outcomes for some headache studies, the number of participants in the analyses of the effects of caffeine is now 4262 when previously it was 5243. The studies were generally of good methodological quality, using standard designs and mostly standard scales of pain measurement, although many of those treating postoperative pain were small.Most studies used paracetamol or ibuprofen, with 100 mg to 130 mg caffeine, and the most common pain conditions studied were postoperative dental pain, postpartum pain, and headache. There was a small but statistically significant benefit with caffeine used at doses of 100 mg or more, which was not dependent on the pain condition or type of analgesic. About 5% to 10% more participants achieve a good level of pain relief (at least 50% of the maximum over four to six hours) with the addition of caffeine, giving a NNT of about 14 (high quality evidence).Most comparisons individually demonstrated numerical superiority with caffeine, but not statistical superiority. One serious adverse event was reported with caffeine, but was considered unrelated to any study medication.We know of the existence of around 25 additional studies with almost 12,500 participants for which data for analysis were not obtainable. The additional analgesic effect of caffeine remained statistically significant but clinically less important even if all the known missing data had no effect; the bulk of the unobtainable data are reported to have similar results as this review. AUTHORS' CONCLUSIONS: The addition of caffeine (≥ 100 mg) to a standard dose of commonly used analgesics provides a small but important increase in the proportion of participants who experience a good level of pain relief.

Interventions for the reduction of prescribed opioid use in chronic non-cancer pain.

BACKGROUND: Patients with chronic non-cancer pain who are prescribed and are taking opioids can have a history of long term high dose opioid use without effective pain relief. In those without good pain relief, reduction of prescribed opioid dose may be the desired and shared goal of both patient and clinician. Simple unsupervised reduction of opioid use is clinically challenging, and very difficult to achieve and maintain. OBJECTIVES: To investigate the effectiveness of different methods designed to achieve reduction or cessation of prescribed opioid use for the management of chronic non-cancer pain. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE from inception to 8th April 2013, as well as bibliographies. SELECTION CRITERIA: Included studies had to be randomised controlled trials comparing opioid users receiving an intervention with a control group receiving treatment as usual, active control, or placebo. The aim of the study had to include a treatment goal of dose reduction or cessation of opioid medication. DATA COLLECTION AND ANALYSIS: We sought data relating to prescribed opioid use, adverse events of opioid reduction, pain, and psychological and physical function. MAIN RESULTS: Two studies provided information on 86 participants. One compared electroacupuncture with sham acupuncture for 20 minutes twice a week for six weeks; there was no difference between treatments. The other followed 11 weeks of cognitive behavioural therapy with either therapeutic interactive voice response through a computer for four months or usual treatment; the active group had a significant reduction in opioid use, while the usual care group had a significant increase. AUTHORS' CONCLUSIONS: Both included studies were at significant risk of bias because of their small size, together with other important issues, including blinding. Because of this risk and the paucity of relevant studies, no conclusions can be drawn regarding the effectiveness of interventions for opioid withdrawal in chronic non-cancer pain.

Single dose oral ibuprofen plus codeine for acute postoperative pain in adults.

BACKGROUND: There is good evidence that combining two different analgesics in fixed doses in a single tablet can provide better pain relief in acute pain and headache than either drug alone, and that the drug-specific effects are essentially additive. This appears to be broadly true in postoperative pain and migraine headache across a range of different drug combinations and when tested in the same and different trials. Some combinations of ibuprofen and codeine are available without prescription (but usually only from a pharmacy) where the dose of codeine is lower, and with a prescription when the dose of codeine is higher. OBJECTIVES: To assess the analgesic efficacy and adverse effects of a single oral dose of ibuprofen plus codeine for moderate to severe postoperative pain. We compared ibuprofen plus codeine with placebo and with the same dose of ibuprofen alone. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Database, ClinicalTrials.gov, and reference lists of articles. The date of the most recent search was 30 September 2012. SELECTION CRITERIA: Randomised, double-blind, placebo- or active-controlled clinical trials of single dose oral ibuprofen plus codeine for acute postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently considered trials for inclusion in the review, assessed quality, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants prescribed ibuprofen plus codeine, placebo, or the same dose of ibuprofen alone with at least 50% pain relief over six hours, using validated equations. We calculated the relative risk (RR) and number needed to treat to benefit (NNT). We used information on the use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse effects. Analyses were planned for different doses of ibuprofen and codeine, but especially for codeine where we set criteria for low (< 10 mg), medium (10 to 20 mg), and high (> 20 mg) doses. MAIN RESULTS: Information was available from six studies with 1342 participants, with a variety of doses of ibuprofen and codeine. In four studies (443 participants) using ibuprofen 400 mg plus codeine 25.6 to 60 mg (high dose codeine) 64% of participants had at least 50% maximum pain relief with the combination compared to 18% with placebo. The NNT was 2.2 (95% CI 1.8 to 2.6). In three studies (204 participants) ibuprofen plus codeine (any dose) was better than the same dose of ibuprofen (69% versus 55%) but the result was barely significant with a relative benefit of 1.3 (95% CI 1.01 to 1.6). In two studies (159 participants) ibuprofen plus codeine appeared to be better than the same dose of codeine alone (69% versus 33%), but no analysis was done. There was no difference between the combination and placebo in the reporting of adverse events in these acute studies. AUTHORS' CONCLUSIONS: The combination of ibuprofen 400 mg plus codeine 25.6 to 60 mg demonstrates good analgesic efficacy. Very limited data suggest that the combination is better than the same dose of either drug alone. Use of combination analgesics that contain codeine has been a source of some concern because of misuse from over-the-counter preparations.

Caffeine as an analgesic adjuvant for acute pain in adults.

BACKGROUND: Caffeine has been added to common analgesics such as paracetamol, ibuprofen, and aspirin, in the belief that it enhances analgesic efficacy. Evidence to support this belief is limited and often based on invalid comparisons. OBJECTIVES: To assess the relative efficacy in acute pain of a single dose of any analgesic plus caffeine against the same dose of analgesic alone. SEARCH METHODS: We searched CENTRAL, MEDLINE, EMBASE, and the Oxford Pain Relief Database to January 2012, and also carried out Internet searches and contacted pharmaceutical companies known to have carried out trials that have not been published. SELECTION CRITERIA: We included randomised, double-blind studies that compared a single dose of analgesic plus caffeine with the same dose of the analgesic alone in the treatment of acute pain. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and quality of studies, and extracted data. Any disagreements or uncertainties were settled by discussion with a third review author. We sought any validated measure of analgesic efficacy, but particularly the number of participants experiencing at least 50% of the maximum possible pain relief over four to six hours, participants reporting a global evaluation of treatment of very good or excellent, or headache relief after two hours. We pooled comparable data to look for a statistically significant difference, and calculated numbers needed to treat to benefit (NNT) with caffeine. We also looked for any numerical superiority associated with the addition of caffeine, and information about any serious adverse events. MAIN RESULTS: We identified 19 studies (7238 participants) in valid comparisons. Most studies used paracetamol or ibuprofen, with 100 mg to 130 mg caffeine, and the most common pain conditions studied were postoperative dental pain, postpartum pain, and headache. There was a small but statistically significant benefit with caffeine used at doses of 100 mg or more, which was not dependent on the pain condition or type of analgesic. About 5% to 10% more participants achieve a good level of pain relief (at least 50% of the maximum) with the addition of caffeine, giving a NNT of about 15.Most comparisons individually demonstrated numerical superiority with caffeine, but not statistical superiority. One serious adverse event was reported with caffeine, but was considered unrelated to any study medication.We know or suspect of the existence of 20 additional studies with 9785 participants for which data for analysis were not obtainable. The additional analgesic effect of caffeine remained statistically significant but clinically less important even if all the known missing data had no effect; that is not likely to be the case. AUTHORS' CONCLUSIONS: The addition of caffeine (≥ 100 mg) to a standard dose of commonly used analgesics provides a small but important increase in the proportion of participants who experience a good level of pain relief.

Meta-analysis of efficacy and safety of intravenous ferric carboxymaltose (Ferinject) from clinical trial reports and published trial data.

BACKGROUND: Recommendations given for intravenous iron treatment are typically not supported by a high level of evidence. This meta-analysis addressed this by summarising the available date from clinical trials of ferric carboxymaltose using clinical trial reports and published reports. METHODS: Clinical trial reports were supplemented by electronic literature searches comparing ferric carboxymaltose with active comparators or placebo. Various outcomes were sought for efficacy (attainment of normal haemoglobin (Hb), increase of Hb by a defined amount, for example), together with measures of harm, including serious adverse events and deaths. RESULTS: Fourteen studies were identified with 2,348 randomised patients exposed to ferric carboxymaltose, 832 to oral iron, 762 to placebo, and 384 to intravenous iron sucrose. Additional data were available from cohort studies. Intravenous ferric carboxymaltose was given up to the calculated iron deficit (up to 1,000 mg in one week) for iron deficiency anaemia secondary to chronic kidney disease, blood loss in obstetric and gynaecological conditions, gastrointestinal disease, and other conditions like heart failure. The most common comparator was oral iron, and trials lasted 1 to 24 weeks. Intravenous ferric carboxymaltose improved mean Hb, serum ferritin, and transferrin saturation levels; the mean end-of-trial increase over oral iron was, for Hb 4.8 (95% confidence interval 3.3 to 6.3) g/L, for ferritin 163 (153 to 173) µg/L, and for transferrin saturation 5.3% (3.7 to 6.8%). Ferric carboxymaltose was significantly better than comparator in achievement of target Hb increase (number needed to treat (NNT) 6.8; 5.3 to 9.7) and target Hb NNT (5.9; 4.7 to 8.1). Serious adverse events and deaths were similar in incidence in ferric carboxymaltose and comparators; rates of constipation, diarrhoea, and nausea or vomiting were lower than with oral iron. CONCLUSIONS: This review examined the available trials of intravenous ferric carboxymaltose using details from published papers and unpublished clinical trial reports. It increases the evidence available to support recommendations given for intravenous iron treatment, but there are limited trial data comparing different intravenous iron preparations.

Triptans for acute cluster headache.

BACKGROUND: Cluster headache is an uncommon, but severely painful and disabling condition, with rapid onset. Validated treatment options are limited, and first-line therapy includes inhaled oxygen. Alternative therapies such as intranasal lignocaine and ergotamine are not as commonly used and are less well studied. Triptans are successfully used to treat migraine attacks and, because of this, they may also be useful for cluster headache. OBJECTIVES: To determine the efficacy and tolerability of triptans for the acute treatment of cluster headaches. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE and EMBASE for studies through 22 January 2010. SELECTION CRITERIA: Randomised, double-blind, placebo-controlled studies of triptans for acute treatment of cluster headache episodes. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study quality and extracted data. Numbers of participants with different levels of pain relief, requiring rescue medication and experiencing adverse events and headache-associated symptoms in treatment and control groups were used to calculate relative risk and numbers needed to treat (NNT) and harm (NNH). MAIN RESULTS: All six included studies used a single dose of triptan to treat an attack of moderate to severe pain intensity. In total 231 participants received zolmitriptan 5 mg, 223 received zolmitriptan 10 mg, 131 received sumatriptan 6 mg, 88 received sumatriptan 12 mg, and 326 received placebo. Zolmitriptan was administered either orally or intranasally, and sumatriptan either subcutaneously or intranasally.Overall, the triptans studied were better than placebo for headache relief and pain-free responses, with an NNT of 2.4 for 15 minute pain relief with subcutaneous sumatriptan 6 mg (75% with sumatriptan and 32% with placebo), and 2.8 for 30 minute pain relief with intranasal zolmitriptan 10 mg (62% with zolmitriptan and 26% with placebo). Fewer participants need rescue medication with triptan than with placebo, but more experienced adverse events. AUTHORS' CONCLUSIONS: Zolmitriptan and sumatriptan are effective in the acute treatment of cluster headaches and may provide a useful treatment option, potentially offering convenience over oxygen therapy and a better safety and tolerability profile than ergotamine. Non-oral routes of administration are likely to provide better and more rapid responses.

Vitamin D for the treatment of chronic painful conditions in adults.

BACKGROUND: Vitamin D is produced in the skin after sun-light exposure and can also be obtained through food. Vitamin D deficiency has recently been linked with a range of diseases including chronic pain. Observational and circumstantial evidence suggests that there may be a role for vitamin D deficiency in the aetiology of chronic pain conditions. OBJECTIVES: To assess the efficacy and adverse events of vitamin D supplementation in chronic painful conditions. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to September 2009. This was supplemented by searching the reference lists of retrieved articles, textbooks and reviews. SELECTION CRITERIA: Studies were included if they were randomised double blind trials of vitamin D supplementation compared with placebo or with active comparators for the treatment of chronic pain conditions in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies for inclusion, assessed methodological quality, and extracted data. Pooled analysis was not undertaken due to paucity and heterogeneity of data. MAIN RESULTS: Four studies, with a total of 294 participants, were included. The studies were heterogeneous with regard to study quality, the chronic painful conditions that were investigated, and the outcome measures reported. Only one study reported a beneficial effect, the others found no benefit of vitamin D over placebo in treating chronic pain. AUTHORS' CONCLUSIONS: The evidence base for the use of vitamin D for chronic pain in adults is poor at present. This is due to low quality and insufficient randomised controlled trials in this area of research.

Topical agents in the treatment of rheumatic pain.

In rheumatic pain there is good evidence that topical nonsteroidal anti-inflammatory drugs are about as effective as oral nonsteroidal anti-inflammatory drugs, but are probably safer and more tolerable because of much less systemic absorption and lower plasma concentrations. The best information is for topical diclofenac. For topical capsaicin, evidence of efficacy is trivial. For topical rubefacients there is no evidence of efficacy.

Faecal blood loss with aspirin, nonsteroidal anti-inflammatory drugs and cyclo-oxygenase-2 selective inhibitors: systematic review of randomized trials using autologous chromium-labelled erythrocytes.

INTRODUCTION: Faecal blood loss has been measured using autologous erythrocytes labelled with radioactive chromium for several decades, using generally similar methods. We conducted a systematic review of studies employing this technology to determine the degree of blood loss associated with use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase-2 selective inhibitors (coxibs). METHODS: A systematic search of PubMed and the Cochrane Library (to December 2006) was conducted to identify randomized trials in which treatment with aspirin, NSAIDs, or coxibs was continued for at least 7 days, and with at least 7 days of washout for crossover trials. Rates of faecal blood loss associated with these agents were determined in the randomized trials identified. Comparators were placebo, active, or no treatment. Outcomes of interest were mean daily faecal blood loss, and the number or proportion of individuals recording faecal blood above 5 ml/day and above 10 ml/day. RESULTS: Forty-five reports of 47 trials were included, including 1,162 individuals, mostly healthy volunteers and predominantly young men. Only 136 patients (as opposed to healthy volunteers; 12%) were included, and these were mostly older people with an arthritic condition. Most NSAIDs and low-dose (325 mg) aspirin resulted in a small average increase in faecal blood loss of 1 to 2 ml/day from about 0.5 ml/day at baseline. Aspirin at full anti-inflammatory doses resulted in much higher average levels of blood loss of about 5 ml/day. Some individuals lost much more blood than average, at least for some of the time, with 5% of those taking NSAIDs having daily blood loss of 5 ml or more and 1% having daily blood loss of 10 ml or more; rates of daily blood loss of 5 ml/day or 10 ml/day were 31% and 10%, respectively, for aspirin at daily doses of 1,800 mg or greater. CONCLUSION: At baseline, or with placebo, faecal blood loss is measured at 1 ml/day or below. With low-dose aspirin and some NSAIDs, average values may be two to four times this, and anti-inflammatory doses of aspirin result in much higher average losses. A small proportion of individuals respond to aspirin or NSAIDs with much higher faecal blood loss of above 5 ml/day or 10 ml/day. There are significant limitations regarding the quality and validity of reporting of these studies, such as limited size and inclusion of inappropriate participants. The potential for blood loss and consequent anaemia requires more study.

Systematic review of topical capsaicin for the treatment of chronic pain.

OBJECTIVE: To determine the efficacy and safety of topically applied capsaicin for chronic pain from neuropathic or musculoskeletal disorders. DATA SOURCES: Cochrane Library, Medline, Embase, PubMed, an in-house database, and contact with manufacturers of topical capsaicin. STUDY SELECTION: Randomised controlled trials comparing topically applied capsaicin with placebo or another treatment in adults with chronic pain. DATA EXTRACTION: Primary outcome was dichotomous information for the number of patients with about a 50% reduction in pain. Outcomes were extracted at four weeks for musculoskeletal conditions and eight weeks for neuropathic conditions. Secondary outcomes were adverse events and withdrawals due to adverse events. DATA SYNTHESIS: Six double blind placebo controlled trials (656 patients) were pooled for analysis of neuropathic conditions. The relative benefit from topical capsaicin 0.075% compared with placebo was 1.4 (95% confidence interval 1.2 to 1.7) and the number needed to treat was 5.7 (4.0 to 10.0). Three double blind placebo controlled trials (368 patients) were pooled for analysis of musculoskeletal conditions. The relative benefit from topical capsaicin 0.025% or plaster compared with placebo was 1.5 (1.1 to 2.0) and the number needed to treat was 8.1 (4.6 to 34). Around one third of patients experienced local adverse events with capsaicin, which would not have been the case with placebo. CONCLUSIONS: Although topically applied capsaicin has moderate to poor efficacy in the treatment of chronic musculoskeletal or neuropathic pain, it may be useful as an adjunct or sole therapy for a small number of patients who are unresponsive to, or intolerant of, other treatments.