BACKGROUND: Chronic pain is common in adults, and often has a detrimental impact upon physical ability, well-being, and quality of life. Previous reviews have shown that certain antidepressants may be effective in reducing pain with some benefit in improving patients' global impression of change for certain chronic pain conditions. However, there has not been a network meta-analysis (NMA) examining all antidepressants across all chronic pain conditions.
OBJECTIVES: To assess the comparative efficacy and safety of antidepressants for adults with chronic pain (except headache).
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, AMED and PsycINFO databases, and clinical trials registries, for randomised controlled trials (RCTs) of antidepressants for chronic pain conditions in January 2022.
SELECTION CRITERIA: We included RCTs that examined antidepressants for chronic pain against any comparator. If the comparator was placebo, another medication, another antidepressant, or the same antidepressant at different doses, then we required the study to be double-blind. We included RCTs with active comparators that were unable to be double-blinded (e.g. psychotherapy) but rated them as high risk of bias. We excluded RCTs where the follow-up was less than two weeks and those with fewer than 10 participants in each arm. DATA COLLECTION AND ANALYSIS: Two review authors separately screened, data extracted, and judged risk of bias. We synthesised the data using Bayesian NMA and pairwise meta-analyses for each outcome and ranked the antidepressants in terms of their effectiveness using the surface under the cumulative ranking curve (SUCRA). We primarily used Confidence in Meta-Analysis (CINeMA) and Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) to assess the certainty of the evidence. Where it was not possible to use CINeMA and ROB-MEN due to the complexity of the networks, we used GRADE to assess the certainty of the evidence. Our primary outcomes were substantial (50%) pain relief, pain intensity, mood, and adverse events. Our secondary outcomes were moderate pain relief (30%), physical function, sleep, quality of life, Patient Global Impression of Change (PGIC), serious adverse events, and withdrawal.
MAIN RESULTS: This review and NMA included 176 studies with a total of 28,664 participants. The majority of studies were placebo-controlled (83), and parallel-armed (141). The most common pain conditions examined were fibromyalgia (59 studies); neuropathic pain (49 studies) and musculoskeletal pain (40 studies). The average length of RCTs was 10 weeks. Seven studies provided no useable data and were omitted from the NMA. The majority of studies measured short-term outcomes only and excluded people with low mood and other mental health conditions. Across efficacy outcomes, duloxetine was consistently the highest-ranked antidepressant with moderate- to high-certainty evidence. In duloxetine studies, standard dose was equally efficacious as high dose for the majority of outcomes. Milnacipran was often ranked as the next most efficacious antidepressant, although the certainty of evidence was lower than that of duloxetine. There was insufficient evidence to draw robust conclusions for the efficacy and safety of any other antidepressant for chronic pain. Primary efficacy outcomes Duloxetine standard dose (60 mg) showed a small to moderate effect for substantial pain relief (odds ratio (OR) 1.91, 95% confidence interval (CI) 1.69 to 2.17; 16 studies, 4490 participants; moderate-certainty evidence) and continuous pain intensity (standardised mean difference (SMD) -0.31, 95% CI -0.39 to -0.24; 18 studies, 4959 participants; moderate-certainty evidence). For pain intensity, milnacipran standard dose (100 mg) also showed a small effect (SMD -0.22, 95% CI -0.39 to 0.06; 4 studies, 1866 participants; moderate-certainty evidence). Mirtazapine (30 mg) had a moderate effect on mood (SMD -0.5, 95% CI -0.78 to -0.22; 1 study, 406 participants; low-certainty evidence), while duloxetine showed a small effect (SMD -0.16, 95% CI -0.22 to -0.1; 26 studies, 7952 participants; moderate-certainty evidence); however it is important to note that most studies excluded participants with mental health conditions, and so average anxiety and depression scores tended to be in the 'normal' or 'subclinical' ranges at baseline already. Secondary efficacy outcomes Across all secondary efficacy outcomes (moderate pain relief, physical function, sleep, quality of life, and PGIC), duloxetine and milnacipran were the highest-ranked antidepressants with moderate-certainty evidence, although effects were small. For both duloxetine and milnacipran, standard doses were as efficacious as high doses. Safety There was very low-certainty evidence for all safety outcomes (adverse events, serious adverse events, and withdrawal) across all antidepressants. We cannot draw any reliable conclusions from the NMAs for these outcomes.
AUTHORS' CONCLUSIONS: Our review and NMAs show that despite studies investigating 25 different antidepressants, the only antidepressant we are certain about for the treatment of chronic pain is duloxetine. Duloxetine was moderately efficacious across all outcomes at standard dose. There is also promising evidence for milnacipran, although further high-quality research is needed to be confident in these conclusions. Evidence for all other antidepressants was low certainty. As RCTs excluded people with low mood, we were unable to establish the effects of antidepressants for people with chronic pain and depression. There is currently no reliable evidence for the long-term efficacy of any antidepressant, and no reliable evidence for the safety of antidepressants for chronic pain at any time point.
OBJECTIVES: Irritable bowel syndrome (IBS) is a chronic functional bowel disorder that is thought to be due to a disorder of brain-gut function. Drugs acting centrally, such as antidepressants, and psychological therapies may, therefore, be effective.
METHODS: We updated a previous systematic review and meta-analysis of randomized controlled trials (RCTs). MEDLINE, EMBASE, PsychINFO, and the Cochrane Controlled Trials Register were searched (up to July 2017). Trials recruiting adults with IBS, which compared antidepressants versus placebo, or psychological therapies versus control therapy or "usual management" were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI).
RESULTS: The search strategy identified 5316 citations. Fifty-three RCTs, reported in 51 separate articles, were eligible for inclusion: 17 compared antidepressants with placebo, 35 compared psychological therapies with control therapy or "usual management", and one compared both psychological therapy and antidepressants with placebo. Four of the trials of psychological therapies, and one of the RCTs of antidepressants, were identified since our previous meta-analysis. The RR of IBS symptoms not improving with antidepressants versus placebo was 0.66 (95% CI 0.57-0.76), with similar treatment effects for both tricyclic antidepressants and SSRIs, although with heterogeneity between RCTs of the latter (I2 = 49%, P = 0.07). The RR of symptoms not improving with psychological therapies was 0.69 (95% CI 0.62-0.76). Cognitive behavioral therapy, relaxation therapy, multi-component psychological therapy, hypnotherapy, and dynamic psychotherapy were all beneficial when data from two or more RCTs were pooled. There was significant heterogeneity between studies (I2 = 69%, P < 0.001) and significant funnel plot asymmetry. There were also issues regarding trial design, including lack of blinding.
CONCLUSIONS: Antidepressants are efficacious in reducing symptoms in IBS patients. Psychological therapies also appear to be effective treatments for IBS, although there are limitations in the quality of the evidence, and treatment effects may be overestimated as a result.
Background. The objective of this study was to compare the efficacy and side effects of acupuncture, sham acupuncture, and drugs in the treatment of diarrhoea-predominant irritable bowel syndrome. Methods. Randomized controlled trials (RCTs) assessing the effects of acupuncture and drugs were comprehensively retrieved from electronic databases (such as PubMed, Cochrane Library, Embase, CNKI, Wanfang Database, VIP Database, and CBM) up to December 2017. Additional references were obtained from review articles. With document quality evaluations and data extraction, Network Meta-Analysis was performed using a random-effects model under a frequentist framework. Results. A total of 29 studies (n = 9369) were included; 19 were high-quality studies, and 10 were low-quality studies. NMA showed the following: (1) the ranking of treatments in terms of efficacy in diarrhoea-predominant irritable bowel syndrome is acupuncture, sham acupuncture, pinaverium bromide, alosetron = eluxadoline, ramosetron, and rifaximin; (2) the ranking of treatments in terms of severity of side effects in diarrhoea-predominant irritable bowel syndrome is rifaximin, alosetron, ramosetron = pinaverium bromide, sham acupuncture, and acupuncture; and (3) the treatment of diarrhoea-predominant irritable bowel syndrome includes common acupoints such as ST25, ST36, ST37, SP6, GV20, and EX-HN3. Conclusion. Acupuncture may improve diarrhoea-predominant irritable bowel syndrome better than drugs and has the fewest side effects. Sham acupuncture may have curative effect except for placebo effect. In the future, it is necessary to perform highly qualified research to prove this result. Pinaverium bromide also has good curative effects with fewer side effects than other drugs.
BACKGROUND: According to the multifactorial etiology of Irritable bowel syndrome (IBS), psychological factors play an important role. It is possible that antidepressant therapy may be more effective for patients with IBS. The aim of this study was a systematic review of the best available antidepressant therapies for IBS.
METHODS: The databases Medline, PubMed, EMBASE, and the Cochrane Controlled Trials Register for randomized controlled trials were searched for studies published before September 2016. Meta-analyses, randomized controlled trials, controlled trials, uncontrolled trials, cohort studies, and open-label studies were analyzed.
RESULTS: Of 513 articles, 29 fulfilled the inclusion criteria: 6 meta-analyses, 18 randomized controlled trials, and 5 studies without randomization. In these studies, the efficacy of tricyclics, selective serotonin reuptake inhibitors or serotonin-noradrenaline reuptake inhibitors, were analyzed in IBS. Different interventions were used, though in most studies their effect on global symptom relief in IBS as a primary outcome was investigated. Generally, patients' tolerance of the therapies was good. Only severe adverse events were observed as a result of the nature of the drug.
CONCLUSIONS: Generally, antidepressants improved IBS symptoms. In comparison with placebo, tricyclic therapy for IBS was more effective than selective serotonin reuptake inhibitors. Antidepressants might be an alternative therapy for patients suffering from IBS, especially diarrhea-predominant IBS.
OBJETIVES: It has been suggested that some placebo interventions might be associated with larger clinical effects than others. In a systematic review, we investigated whether there is evidence from direct comparisons in randomized clinical trials including two or more placebo groups supporting this hypothesis.
STUDY DESIGN AND SETTING: Eligible trials were identified through electronic database searches and citation tracking up to February 2013. Placebo interventions in a trial were categorized into a more intense and a less intense intervention based on complexity, invasiveness, or route of administration and time needed for application. RESULTS: Twelve studies with 1,059 patients receiving placebo met the eligibility criteria. Studies were highly heterogeneous regarding patients, interventions, outcomes, and risk of bias. Seven studies did not find any significant differences between the more intense and the less intense placebo intervention, four studies found differences for single outcomes, and one study consistently reported significantly larger effects of the more intense placebo. An explorative meta-analysis yielded a standardized mean difference -0.22 (95% confidence interval: -0.46, 0.02; P = 0.07; I2 = 68%). CONCLUSION: In the studies included in this review, more intense placebos were not consistently associated with larger effects than less intense placebos.
AIM: The aim of this meta-analysis was to analyze the efficacy and safety of antidepressants for the treatment of irritable bowel syndrome.
METHODS: We searched MEDLINE, EMBASE, Scopus and The Cochrane Library for randomized controlled trials investigating the efficacy and safety of antidepressants in the treatment of irritable bowel syndrome. Article quality was evaluated by Jadad score. RevMan 5.0 and Stata 12.0 were used for the meta-analysis.
RESULTS: Twelve randomized controlled trials were included in this study and most of these trials were of high quality (Jadad score ≥4). Five articles focused on tricyclic antidepressants, six articles involved selective serotonin reuptake inhibitors, and one article investigated both types of treatment. The pooled risk ratio showed antidepressant treatment can improve global symptoms (RR = 1.38, 95% CI 1.08, 1.77). In the subgroup analysis, treatment with tricyclic antidepressants showed an improvement in global symptoms (RR = 1.36, 95% CI 1.07, 1.71), while treatment with selective serotonin reuptake inhibitors showed no statistically significant difference in global symptoms compared with the control groups (RR = 1.38, 95% CI 0.83, 2.28). The pooled risk ratio of dropout due to side effects following antidepressant treatment was 1.71 with 95% CI (0.98, 2.99). The subgroup analysis showed the pooled risk ratio of dropout in the tricyclic antidepressants group was 1.92 with 95% CI (0.89, 4.17). In the selective serotonin reuptake inhibitors group, the pooled risk ratio of dropout was 1.5 with 95% CI (0.67, 3.37). Selective serotonin reuptake inhibitors showed no benefit in alleviating abdominal pain and improving quality of life. There was no difference in the incidence of common adverse events between treatment and control groups.
CONCLUSIONS: TCAs can improve global symptoms of irritable bowel syndrome, while there was no strong evidence to confirm the effectiveness of SSRIs for the treatment of IBS.
ObjectiveThis méta-analyse systématiquement examiné l'association de traumatisme psychologique signalé et le trouble de stress post-traumatique (SSPT) des syndromes somatiques fonctionnels y compris la fibromyalgie, la douleur chronique généralisée, syndrome de fatigue chronique, troubles temporo-mandibulaire, et le syndrome du côlon irritable. Nos objectifs étaient de déterminer la taille de l'effet global de l'association et d'examiner les modérateurs de la relation.recherches de MethodsLiterature identifié 71 études avec un groupe témoin ou de comparaison et ont examiné l'association des syndromes avec des événements traumatiques, y compris l'abus de nature psychologique, émotionnelle, sexuelle, physique ou subis pendant l'enfance ou l'âge adulte, l'exposition au combat, ou SSPT. Un modèle à effets aléatoires a été utilisé pour estimer le rapport de cotes commun et l'intervalle de confiance de 95%. Analyses sous-groupe prévue et méta-régression a examiné modérateurs potentiels.ResultsIndividuals qui ont déclaré une exposition à un traumatisme étaient de 2,7 (intervalle de confiance à 95% = 2.27 à 3.10) fois plus susceptibles d'avoir un syndrome somatique fonctionnel. Cette association a été soutenue à la fois contre le biais de publication et la qualité généralement médiocre de la littérature. L'ampleur de la liaison avec le SSPT était significativement plus grande que celle de la violence sexuelle ou physique. Syndrome de fatigue chronique a une association plus grande avec un traumatisme rapporté que ne soit le syndrome du côlon irritable ou la fibromyalgie. Des études utilisant des questionnaires non validés ou d'auto-évaluation des traumatismes signalés grandes associations, que ceux utilisant des questionnaires validés.ConclusionsFindings mettent en évidence les limites de la littérature existante et soulignent l'importance de mener des études prospectives, examiner plus avant les similitudes et les différences de ces conditions possibles et poursuivre des études guidés par les hypothèses sur les mécanismes qui sous-tendent le lien entre le traumatisme, stress post-traumatique, et syndromes somatiques fonctionnels.
OBJECTIF: Evaluer les preuves portant sur l'utilisation des inhibiteurs de recapture de la sérotonine (ISRS) pour le traitement du syndrome du côlon irritable (IBS).
SOURCES DE DONNÉES: Une recherche documentaire a été réalisée en utilisant PubMed (1950 à Février 2014) pour les termes MeSH sérotonine inhibiteur de la recapture et le syndrome du côlon irritable; sous-termes de termes MeSH identifiés (c.-à-explosion) ont également été évalués. EMBASE (1947 à Février 2014) a été recherché en utilisant des termes de recherche similaires. Les références des articles identifiés ont été vérifiés et un examen mis à jour la base de données Cochrane a été réalisée.
SÉLECTION DES ÉTUDES ET DE L'INFORMATION: Tous identifié en langue anglaise des publications évaluées par les pairs ont été évalués. Articles (à l'exclusion des résumés de réunion) portant spécifiquement sur les ISRS pour le traitement de l'IBS ont été examinés. La revue de la littérature a été limitée à des essais contrôlés randomisés (ECR) menées chez des sujets humains.
SYNTHÈSE DES DONNÉES: fluoxétine, le citalopram, et la paroxétine ont été étudiés pour le traitement des symptômes de l'IBS. Fluoxétine améliore significativement la douleur abdominale, des ballonnements et des selles consistance après 12 semaines de traitement, mais ces données contredisent les résultats d'une autre étude de 6 semaines. Citalopram diminue la gêne abdominale après 6 à 12 semaines de traitement, mais plusieurs études ont pas démontré une amélioration de soulagement adéquat de la plupart des symptômes de l'IBS. Dans l'ensemble du bien-être a été améliorée après 12 semaines d'utilisation de la paroxétine; symptômes cependant, IBS liés et le fonctionnement social / travail ne sont pas améliorées.
CONCLUSIONS: Les données disponibles évaluant l'utilisation des ISRS dans le traitement des symptômes du SCI-liés sont contradictoires. D'autres grands ECR durant plus de 12 semaines sont nécessaires pour déterminer la place dans le traitement des ISRS dans le traitement des symptômes IBS liés.
OBJECTIFS: le syndrome du côlon irritable (IBS) est un trouble gastro-intestinal fonctionnel chronique. La preuve relative au traitement de cette condition avec des antidépresseurs et des thérapies psychologiques continue d'accumuler.
Méthodes: Nous avons effectué une revue systématique mise à jour et une méta-analyse d'essais contrôlés randomisés (ECR). MEDLINE, EMBASE, et le Cochrane Controlled Trials Register ont été fouillés (jusqu'à Décembre 2013). Essais de recrutement des adultes atteints du SCI, qui a comparé les antidépresseurs avec un placebo, ou thérapies psychologiques avec la thérapie de contrôle ou «gestion habituelle» étaient admissibles. données sur les symptômes dichotomiques ont été regroupées pour obtenir un risque relatif (RR) de rester symptomatique après le traitement, avec un intervalle de confiance de 95% (IC).
RÉSULTATS: La stratégie de recherche identifiés 3,788 citations. Quarante-huit ECR étaient admissibles pour l'inclusion: trente et un des thérapies psychologiques par rapport à la thérapie de contrôle ou «gestion habituelle," seize antidépresseurs par rapport au placebo, et un rapport à la fois la thérapie psychologique et les antidépresseurs avec placebo. Dix des essais de thérapies psychologiques, et quatre des ECR des antidépresseurs, avait été publié depuis notre précédente méta-analyse. Le RR de l'IBS symptômes ne pas améliorer avec des antidépresseurs par rapport au placebo était de 0,67 (IC à 95% = 0,58 au 0,77), avec des effets de traitement similaires pour les deux antidépresseurs tricycliques et les inhibiteurs de recapture de la sérotonine. Le RR de symptômes non amélioration des thérapies psychologiques était de 0,68 (IC à 95% = 0,61 à 0,76). La thérapie cognitivo-comportementale, hypnothérapie, thérapie psychologique multicomposant, et la psychothérapie dynamique étaient tous bénéfiques.
CONCLUSIONS: Les antidépresseurs et certaines thérapies psychologiques sont des traitements efficaces pour IBS. Malgré le nombre considérable d'études publiées dans les intermédiaires de 5 ans depuis notre dernière a examiné cette question, les estimations globales de synthèse de l'effet du traitement sont restées remarquablement stables.
Chronic pain is common in adults, and often has a detrimental impact upon physical ability, well-being, and quality of life. Previous reviews have shown that certain antidepressants may be effective in reducing pain with some benefit in improving patients' global impression of change for certain chronic pain conditions. However, there has not been a network meta-analysis (NMA) examining all antidepressants across all chronic pain conditions.
OBJECTIVES:
To assess the comparative efficacy and safety of antidepressants for adults with chronic pain (except headache).
SEARCH METHODS:
We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, AMED and PsycINFO databases, and clinical trials registries, for randomised controlled trials (RCTs) of antidepressants for chronic pain conditions in January 2022.
SELECTION CRITERIA:
We included RCTs that examined antidepressants for chronic pain against any comparator. If the comparator was placebo, another medication, another antidepressant, or the same antidepressant at different doses, then we required the study to be double-blind. We included RCTs with active comparators that were unable to be double-blinded (e.g. psychotherapy) but rated them as high risk of bias. We excluded RCTs where the follow-up was less than two weeks and those with fewer than 10 participants in each arm.
DATA COLLECTION AND ANALYSIS:
Two review authors separately screened, data extracted, and judged risk of bias. We synthesised the data using Bayesian NMA and pairwise meta-analyses for each outcome and ranked the antidepressants in terms of their effectiveness using the surface under the cumulative ranking curve (SUCRA). We primarily used Confidence in Meta-Analysis (CINeMA) and Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) to assess the certainty of the evidence. Where it was not possible to use CINeMA and ROB-MEN due to the complexity of the networks, we used GRADE to assess the certainty of the evidence. Our primary outcomes were substantial (50%) pain relief, pain intensity, mood, and adverse events. Our secondary outcomes were moderate pain relief (30%), physical function, sleep, quality of life, Patient Global Impression of Change (PGIC), serious adverse events, and withdrawal.
MAIN RESULTS:
This review and NMA included 176 studies with a total of 28,664 participants. The majority of studies were placebo-controlled (83), and parallel-armed (141). The most common pain conditions examined were fibromyalgia (59 studies); neuropathic pain (49 studies) and musculoskeletal pain (40 studies). The average length of RCTs was 10 weeks. Seven studies provided no useable data and were omitted from the NMA. The majority of studies measured short-term outcomes only and excluded people with low mood and other mental health conditions. Across efficacy outcomes, duloxetine was consistently the highest-ranked antidepressant with moderate- to high-certainty evidence. In duloxetine studies, standard dose was equally efficacious as high dose for the majority of outcomes. Milnacipran was often ranked as the next most efficacious antidepressant, although the certainty of evidence was lower than that of duloxetine. There was insufficient evidence to draw robust conclusions for the efficacy and safety of any other antidepressant for chronic pain. Primary efficacy outcomes Duloxetine standard dose (60 mg) showed a small to moderate effect for substantial pain relief (odds ratio (OR) 1.91, 95% confidence interval (CI) 1.69 to 2.17; 16 studies, 4490 participants; moderate-certainty evidence) and continuous pain intensity (standardised mean difference (SMD) -0.31, 95% CI -0.39 to -0.24; 18 studies, 4959 participants; moderate-certainty evidence). For pain intensity, milnacipran standard dose (100 mg) also showed a small effect (SMD -0.22, 95% CI -0.39 to 0.06; 4 studies, 1866 participants; moderate-certainty evidence). Mirtazapine (30 mg) had a moderate effect on mood (SMD -0.5, 95% CI -0.78 to -0.22; 1 study, 406 participants; low-certainty evidence), while duloxetine showed a small effect (SMD -0.16, 95% CI -0.22 to -0.1; 26 studies, 7952 participants; moderate-certainty evidence); however it is important to note that most studies excluded participants with mental health conditions, and so average anxiety and depression scores tended to be in the 'normal' or 'subclinical' ranges at baseline already. Secondary efficacy outcomes Across all secondary efficacy outcomes (moderate pain relief, physical function, sleep, quality of life, and PGIC), duloxetine and milnacipran were the highest-ranked antidepressants with moderate-certainty evidence, although effects were small. For both duloxetine and milnacipran, standard doses were as efficacious as high doses. Safety There was very low-certainty evidence for all safety outcomes (adverse events, serious adverse events, and withdrawal) across all antidepressants. We cannot draw any reliable conclusions from the NMAs for these outcomes.
AUTHORS' CONCLUSIONS:
Our review and NMAs show that despite studies investigating 25 different antidepressants, the only antidepressant we are certain about for the treatment of chronic pain is duloxetine. Duloxetine was moderately efficacious across all outcomes at standard dose. There is also promising evidence for milnacipran, although further high-quality research is needed to be confident in these conclusions. Evidence for all other antidepressants was low certainty. As RCTs excluded people with low mood, we were unable to establish the effects of antidepressants for people with chronic pain and depression. There is currently no reliable evidence for the long-term efficacy of any antidepressant, and no reliable evidence for the safety of antidepressants for chronic pain at any time point.
