Pharmaceutical Company Websites Research Articles

Comparative effects of drug interventions for the acute management of migraine episodes in adults: systematic review and network meta-analysis

ObjectiveTo compare all licensed drug interventions as oral monotherapy for the acute treatment of migraine episodes in adults.DesignSystematic review and network meta-analysis.Data sourcesCochrane Central Register of Controlled Trials, Medline, Embase,...

Harnessing policy to promote inclusive medical product evidence: development of a reference standard and structured audit of clinical trial diversity policies

ObjectiveTo develop a reference standard based on US Food and Drug Administration and stakeholder guidance for pharmaceutical companies' policies on diversity in clinical trials and to assess these policies.DesignDevelopment of...

Struktur Biomolekul dan Mekanisme Aksi Vaksin Sars-Cov-2 Efektif dalam Melawan Covid-19

Abstract: Purpose: The aim of this study is to deepen understanding of the structure of the vaccine against SARS-CoV-2 infection and the underlying mechanism so that its efficacy and effectiveness can be assessed. Method: used in this journal is a systematic literature review. References for this review were identified through searches of PubMed, Google Scholar, BioRxiv, MedRxiv, drug regulatory agencies, and pharmaceutical company websites. Results: Overall, all COVID-19 vaccines had high efficacy against the SARS-CoV-2 strain and were well tolerated. All vaccines appear to be a safe and effective strategy to prevent COVID-19 from getting worse. Limitations: Further research is needed to assess the magnitude of the risks of using the vaccine against its benefits in preventing SARS-CoV-2 infection. Contribution: By understanding the structure of the vaccine and its mechanism of action, it is hoped that the selection of the right vaccine can effectively suppress the pandemic. Keywords: 1. antibody 2. efficacy 3. effectiveness 4. COVID-19 5. SARS-CoV-2 6. vaccine

National patient groups in Canada and their disclosure of relationships with pharmaceutical companies: a cross-sectional study

ObjectivesThis study investigates the information and policies that Canadian patient groups post on their publicly available websites about their relationships with pharmaceutical companies.DesignCross-sectional study.SettingCanadian national patient groups.ParticipantsNinety-seven patient groups with...

WORLD PHARMACEUTICAL MARKET: TRENDWATCHING

At present, the importance of the pharmaceutical sector of the economy has increased significantly in public perception. This review provides up-to-date information at the beginning of 2022 on the main trends in the global pharmaceutical market. Among the current trends are: the key role of pharmaceuticals in the fight against the SARS-Covid-19 pandemic, the problems of a latent pandemic of drug-resistant infections, the high cost of new drugs and an increase in the market share of cheap biosimilars, the expansion of cooperation between developers of new drugs and vaccines, features in changes in the structure pharmaceutical companies, expanding opportunities in the retail pharmaceutical market, analysts՚ opinions on market prospects for the next 5 years. Materials from open sources were used: industry and business media, websites of pharmaceutical companies and non-profit organizations, WHO publications and scientific publications.

Metabolic side effects of antipsychotic drugs in individuals with schizophrenia during medium- to long-term treatment: protocol for a systematic review and network meta-analysis of randomized controlled trials

BackgroundAntipsychotic drugs and especially the newer compounds are known to cause metabolic side effects. However, a comprehensive comparison of the different substances regarding their propensity to cause metabolic side effects in medium- to long-term treatment of schizophrenia is lacking.MethodsWe will conduct a systematic review and network meta-analysis (NMA). We will include randomized controlled trials (RCTs) in which participants received either placebo or an antipsychotic (i.e. placebo-controlled trials and head-to-head comparisons of drugs). We will include studies in individuals with schizophrenia or related disorders (such as schizophreniform or schizoaffective disorders) at any stage of the disease (acute episode; maintenance phase). We will include studies with a duration of more than 3 months (medium- to long-term treatment). The primary outcome will be the change in body weight. Secondary outcomes will be the further metabolic parameters: fastening glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides. We will search for eligible studies (independent of the publication status) in Cochrane Schizophrenia Group’s Study-Based Register of Trials, which is compiled by regular searches in trial registries and multiple electronic databases from their inception onwards including MEDLINE, EMBASE and PsycINFO. Additionally, we will search previously published systematic reviews and websites of pharmaceutical companies for eligible studies. At least two reviewers will independently conduct the process of study selection and data extraction. We will use the Cochrane Risk of Bias 2 tool to evaluate the risk of bias in studies. We will conduct random-effects NMA within a Bayesian framework to synthesize all evidence for each outcome. We will conduct sensitivity and subgroup analyses to assess the robustness of the findings and to explore heterogeneity. The confidence in the results will be evaluated using the Confidence in Network Meta-Analysis (CINeMA) framework.DiscussionThis systematic review and network meta-analysis will provide a synthesis of the existing evidence from RCTs how antipsychotic drugs differ in terms of metabolic side effects during medium- to long-term treatment. The findings have the potential to influence the choice of antipsychotic medication made by individuals with schizophrenia and their physicians.Systematic review registrationPROSPERO CRD42020175414

Safe and Effective Treatment for Anemic Patients With Chronic Kidney Disease: An Updated Systematic Review and Meta-Analysis on Roxadustat

Background: Roxadustat is a new oral drug for anemia in chronic kidney disease (CKD). This study aimed to synthesize the evidence from randomized controlled trial (RCT)-based studies that estimated the efficacy and safety of roxadustat in anemia patients with non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD. Methods: We searched the PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases for related published studies. Moreover, we manually searched relevant pharmaceutical company websites and two international clinical trial registers to search for published and unpublished RCTs comparing roxadustat with erythropoietin-stimulating agents (ESAs) or placebo. Results: Fifteen RCTs (seven for DD-CKD patients, eight for NDD-CKD patients) were included in the meta-analysis, with 10,189 patients, 4,810 DD-CKD patients, and 5,379 NDD-CKD patients enrolled. Compared with ESAs (epoetin alfa or darbepoetin alfa) and placebo, roxadustat raised the hemoglobin level [weighted mean difference (WMD): 0.82 g/dL; 95% confidence interval (CI): 0.43–1.21], transferrin level (WMD: 0.5 g/L; 95% CI: 0.34–0.65), and TIBC level (WMD: 41.79 μg/dL; 95% CI: 38.67–44.92) and lowered the hepcidin level (WMD: −37.38 ng/ml; 95% CI: −46.63– −28.12) in both the DD-CKD and NDD-CKD patients with renal anemia. Roxadustat improved hemoglobin response and lowered the ferritin and TAST levels in the NDD-CKD patients but not in the DD-CKD patients. Furthermore, there was no difference between the treatment-emergent adverse events (TEAEs) of roxadustat and that of ESAs or placebo. But the incidence of serious TEAEs in the roxadustat group was significantly higher with NDD-CKD patients (OR: 1.15; 95% CI: 1.02–1.29). Conclusion: This study confirmed that roxadustat therapy could alleviate the anemia of DD-CKD and NDD-CKD patients by raising the hemoglobin level and regulating iron metabolism, but increased serious incidences of treatment-emergent adverse events (TEAEs) in NDD-CKD patients.

Indian contribution toward biomedical research and development in COVID-19: A systematic review.

COVID-19 pandemic led to an unprecedented collaborative effort among industry, academia, regulatory bodies, and governments with huge financial investments. Scientists and researchers from India also left no stone unturned to find therapeutic and preventive measures against COVID-19. Indian pharmaceutical companies are one of the leading manufacturers of vaccine in the world, are utilizing its capacity to its maximum, and are one among the forerunners in vaccine research against COVID-19 across the globe. In this systematic review, the information regarding contribution of Indian scientists toward COVID-19 research has been gathered from various news articles across Google platform apart from searching PubMed, WHO site, COVID-19 vaccine tracker, CTRI, clinicaltrials.gov, and websites of pharmaceutical companies. The article summarizes and highlights the various therapeutic and vaccine candidates, diagnostic kits, treatment agents, and technology being developed and tested by Indian researcher community against COVID-19.

Study of deviant use of international non-proprietary name of medicines in India

Introduction: International Nonproprietary Names (INNs) are internationally documented names for medicines recommended by the World Health Organization (WHO) and provide a standardized system of nomenclature. Objective: To analyse the current pattern of use of INNs by different pharmaceuticals companies in India. Methodology: The relevant material was systemically collated and analysed after collecting material from websites of WHO, pharmaceutical companies, MIMS and CIMS. We then analysed what is the severity of misuse of INNs in India and categorize the gaps and loopholes at the different level. Results: It has been found that for implementation of INN, most important problem lies in the policy regime along with and deficient coordination in between drug authorities in India. Both big and small pharmaceutical companies were involved in the misuse (10-40%) of INNs. Number of INN stems have been exploited by different companies. Most commonly used INN were by “-grel”, followed by “-pril “-pride” and “gli-”. A great number of cases of misuse of INNs in our country involve drugs for cardiac, renal diseases, and diabetes. Although drug authority has issued INN protection letter by WHO to few pharmaceutical companies but in spite of that number of brand names are still derived from INN. Conclusion: Many lacunae exist in the INN implementation in India. It is essential to develop improved coordination, specific mandate and suitable policy to safeguard INNs in India. Keywords: Brand name, Generic, Propriety name.

Relevance between Methods of Obtaining Drug Information and the Utilization of the Information in Community Pharmacies -Research on Awareness of Drug Information of "Increased Risk of Developing Diabetes in Patients Treated with HMG-CoA Reductase Inhibitors" in Community Pharmacies

Lipid lowering therapy using statins prevents the risk of cardiovascular events. However, since the year 2000, there have been some reports that statins increased the risk of developing diabetes (SIRDD). It is socially demanded that pharmacists must apply pharmacotherapy to patients by utilizing drug information like the above, such as selecting appropriate drugs and providing correct drug information. Accordingly, pharmacists must correct drug information, and they should analyze and evaluate such information. Therefore, we conducted a questionnaire survey for pharmacists in community pharmacies with an aim to verify relevance between methods of obtaining drug information and the utilization of the information of "SIRDD" as a subject. We sent a questionnaire by letter to 1522 pharmacists in Fukushima and Mie prefecture, and received the results of the questionnaire from them using "Google forms" that is software to make web questionnaire and letters. We obtained responses from 356 (23.4%) pharmacists out of 1522. The number of responses from the pharmacists that "know" the information of "SIRDD" was 135 (37.9%). We found that these pharmacists obtained the information by websites of pharmaceutical companies, m3, Inc. (Portal site for medical professionals), and Pharmaceuticals and Medical Devices Agency (PMDA), as the sources of information. Our results suggested that pharmacists responded that they "know" "SIRDD" utilized websites as a quick information tool. The difference in network environments will relate to the difference of providable medical quality. So, it is very important to maintain appropriate network environment in cooperation with medical institutions, professional associations and the government.

Pharmaceutical Benefit-Risk Perception and Age Differences in the USA and Germany.

Understanding how patients of all ages perceive the benefits and risks of medical treatments is vitally important. Yet, the role of older age on pharmaceutical benefit-risk perceptions has hardly been empirically investigated as a central focus of study. This study tested the generalizability of recent pilot findings to explore benefit-risk perception age differences between adults aged 65years old and over (older group) and those aged 18-64years old (younger group). An online survey representative for age, sex, and education was conducted in Ohio, USA (N = 1520) and Germany (N = 1536). A combination of benefit, risk, and affect questions measured respondents' perceptions of 18 medicines, tests, vaccines, and procedures. Further questions investigated general perceptions of side effects and effectiveness, as well as respondents' reliance on different sources of medicines information. Clear age differences were found that strongly support recent pilot findings. Older adults perceived prescription medicines significantly more positively than their younger counterparts. They had significantly higher benefit and lower risk perceptions for most, but not all, medical treatments investigated. Older adults' benefit-risk perceptions were more strongly correlated with positive/negative affect, that is, their positive/negative experiences and feelings of "goodness" or "badness" they associated with each medical treatment investigated. They also perceived doctors and pharmacists as more competent and trustworthy. Contrary to popular belief, both age groups ranked their reliance on 15 different medical (e.g. doctors), societal (e.g. social media), industry (e.g. pharmaceutical company websites), and governmental (e.g. regulatory agencies) sources of medicines information remarkably similarly. Age has an important role in patients' pharmaceutical benefit-risk perceptions. Findings show that, when designing messages, benefit-risk communicators should incorporate age differences. This includes older patients' positive perceptions of pharmaceuticals, greater reliance on affect, and information seeking versus scanning behaviour. Field experiments are now needed to test the effectiveness of such changes for improving benefit-risk communication practice.

Predicting the treatment response of certolizumab for individual adult patients with rheumatoid arthritis: protocol for an individual participant data meta-analysis

BackgroundA model that can predict treatment response for a patient with specific baseline characteristics would help decision-making in personalized medicine. The aim of the study is to develop such a model in the treatment of rheumatoid arthritis (RA) patients who receive certolizumab (CTZ) plus methotrexate (MTX) therapy, using individual participant data meta-analysis (IPD-MA).MethodsWe will search Cochrane CENTRAL, PubMed, and Scopus as well as clinical trial registries, drug regulatory agency reports, and the pharmaceutical company websites from their inception onwards to obtain randomized controlled trials (RCTs) investigating CTZ plus MTX compared with MTX alone in treating RA. We will request the individual-level data of these trials from an independent platform (http://vivli.org). The primary outcome is efficacy defined as achieving either remission (based on ACR-EULAR Boolean or index-based remission definition) or low disease activity (based on either of the validated composite disease activity measures). The secondary outcomes include ACR50 (50% improvement based on ACR core set variables) and adverse events. We will use a two-stage approach to develop the prediction model. First, we will construct a risk model for the outcomes via logistic regression to estimate the baseline risk scores. We will include baseline demographic, clinical, and biochemical features as covariates for this model. Next, we will develop a meta-regression model for treatment effects, in which the stage 1 risk score will be used both as a prognostic factor and as an effect modifier. We will calculate the probability of having the outcome for a new patient based on the model, which will allow estimation of the absolute and relative treatment effect. We will use R for our analyses, except for the second stage which will be performed in a Bayesian setting using R2Jags.DiscussionThis is a study protocol for developing a model to predict treatment response for RA patients receiving CTZ plus MTX in comparison with MTX alone, using a two-stage approach based on IPD-MA. The study will use a new modeling approach, which aims at retaining the statistical power. The model may help clinicians individualize treatment for particular patients.Systematic review registrationPROSPERO registration number pending (ID#157595).

Comparisons of exacerbations and mortality among regular inhaled therapies for patients with stable chronic obstructive pulmonary disease: Systematic review and Bayesian network meta-analysis.

BackgroundAlthough exacerbation and mortality are the most important clinical outcomes of stable chronic obstructive pulmonary disease (COPD), the drug classes that are the most efficacious in reducing exacerbation and mortality among all possible inhaled drugs have not been determined.Methods and findingsWe performed a systematic review (SR) and Bayesian network meta-analysis (NMA). We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the European Union Clinical Trials Register, and the official websites of pharmaceutical companies (from inception to July 9, 2019). The eligibility criteria were as follows: (1) parallel-design randomized controlled trials (RCTs); (2) adults with stable COPD; (3) comparisons among long-acting muscarinic antagonists (LAMAs), long-acting beta-agonists (LABAs), inhaled corticosteroids (ICSs), combined treatment (ICS/LAMA/LABA, LAMA/LABA, or ICS/LABA), or a placebo; and (4) study duration ≥ 12 weeks. This study was prospectively registered in International Prospective Register of Systematic Reviews (PROSPERO; CRD42017069087). In total, 219 trials involving 228,710 patients were included. Compared with placebo, all drug classes significantly reduced the total exacerbations and moderate to severe exacerbations. ICS/LAMA/LABA was the most efficacious treatment for reducing the exacerbation risk (odds ratio [OR] = 0.57; 95% credible interval [CrI] 0.50–0.64; posterior probability of OR > 1 [P(OR > 1)] < 0.001). In addition, in contrast to the other drug classes, ICS/LAMA/LABA and ICS/LABA were associated with a significantly higher probability of reducing mortality than placebo (OR = 0.74, 95% CrI 0.59–0.93, P[OR > 1] = 0.004; and OR = 0.86, 95% CrI 0.76–0.98, P[OR > 1] = 0.015, respectively). The results minimally changed, even in various sensitivity and covariate-adjusted meta-regression analyses. ICS/LAMA/LABA tended to lower the risk of cardiovascular mortality but did not show significant results. ICS/LAMA/LABA increased the probability of pneumonia (OR for triple therapy = 1.56; 95% CrI 1.19–2.03; P[OR > 1] = 1.000). The main limitation is that there were few RCTs including only less symptomatic patients or patients at a low risk.ConclusionsThese findings suggest that triple therapy can potentially be the best option for stable COPD patients in terms of reducing exacerbation and all-cause mortality.

Optimal dose of selective serotonin reuptake inhibitors, venlafaxine, and mirtazapine in major depression: a systematic review and dose-response meta-analysis

SummaryBackgroundDepression is the single largest contributor to non-fatal health loss worldwide. Second-generation antidepressants are the first-line option for pharmacological management of depression. Optimising their use is crucial in reducing the burden of depression; however, debate about their dose dependency and their optimal target dose is ongoing. We have aimed to summarise the currently available best evidence to inform this clinical question.MethodsWe did a systematic review and dose-response meta-analysis of double-blind, randomised controlled trials that examined fixed doses of five selective serotonin reuptake inhibitors (SSRIs; citalopram, escitalopram, fluoxetine, paroxetine, and sertraline), venlafaxine, or mirtazapine in the acute treatment of adults (aged 18 years or older) with major depression, identified from the Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS, MEDLINE, PsycINFO, AMED, PSYNDEX, websites of drug licensing agencies and pharmaceutical companies, and trial registries. We imposed no language restrictions, and the search was updated until Jan 8, 2016. Doses of SSRIs were converted to fluoxetine equivalents. Trials of antidepressants for patients with depression and a serious concomitant physical illness were excluded. The main outcomes were efficacy (treatment response defined as 50% or greater reduction in depression severity), tolerability (dropouts due to adverse effects), and acceptability (dropouts for any reasons), all after a median of 8 weeks of treatment (range 4–12 weeks). We used a random-effects, dose-response meta-analysis model with flexible splines for SSRIs, venlafaxine, and mirtazapine.Findings28 554 records were identified through our search (24 524 published and 4030 unpublished records). 561 published and 121 unpublished full-text records were assessed for eligibility, and 77 studies were included (19 364 participants; mean age 42·5 years, SD 11·0; 7156 [60·9%] of 11 749 reported were women). For SSRIs (99 treatment groups), the dose-efficacy curve showed a gradual increase up to doses between 20 mg and 40 mg fluoxetine equivalents, and a flat to decreasing trend through the higher licensed doses up to 80 mg fluoxetine equivalents. Dropouts due to adverse effects increased steeply through the examined range. The relationship between the dose and dropouts for any reason indicated optimal acceptability for the SSRIs in the lower licensed range between 20 mg and 40 mg fluoxetine equivalents. Venlafaxine (16 treatment groups) had an initially increasing dose-efficacy relationship up to around 75–150 mg, followed by a more modest increase, whereas for mirtazapine (11 treatment groups) efficacy increased up to a dose of about 30 mg and then decreased. Both venlafaxine and mirtazapine showed optimal acceptability in the lower range of their licensed dose. These results were robust to several sensitivity analyses.InterpretationFor the most commonly used second-generation antidepressants, the lower range of the licensed dose achieves the optimal balance between efficacy, tolerability, and acceptability in the acute treatment of major depression.FundingJapan Society for the Promotion of Science, Swiss National Science Foundation, and National Institute for Health Research.

User Perception of the Usability and Usefulness of Pharmaceutical Company Websites in Finding Drug Information

User Perception of the Usability and Usefulness of Pharmaceutical Company Websites in Finding Drug Information

PP105 Applying Horizon Scanning To Decision Making: The Case of Tafamidis

Introduction:Horizon scanning (HS) is an important tool for guiding health policy formulation and the decision-making process in Brazil. In 2016, the Ministry of Health started to draft Brazilian clinical practice guidelines for transthyretin familial amyloid polyneuropathy (TTR-FAP), which is a rare disease caused by a mutation of the transthyretin gene. An initial HS report was conducted that provided information about new and emerging technologies for TTR-FAP. The HS identified five drugs that were based on two mechanisms of action: transthyretin stabilization (diflunisal, tafamidis, and tolcapone) and gene silencing (ALN-TTR02 and ISIS-TTR-Rx). At that time in Brazil there were no drugs registered for the treatment of TTR-FAP. However, a few months later tafamidis was licensed in Brazil. In early 2017 the manufacturer submitted an application to the National Committee for Health Technology Incorporation (CONITEC), with the aim of incorporating tafamidis into the Brazilian health system. As a result the HS report was updated to support the assessment by CONITEC. This study aims to show how HS is being used to support CONITEC in this issue.Methods:As per the EuroScan toolkit, we performed a reassessment of the technologies included in the initial HS report. We searched clinical trial registers, the websites of pharmaceutical companies, conference proceedings, scientific journals, HS databases, and regulatory websites for further information. The data were synthesized and a reformulated landscape of the technological environment for TTR-FAP therapy was presented to the CONITEC Plenary.Results:The main difference between the initial and final HS output was that tafamidis was approved for use in Brazil, making it the only registered drug for TTR-FAP. Another difference was related to the start of a new clinical trial with diflunisal for TTR-FAP, indicating that this drug could be a potential competitor for tafamidis. It was also possible to add published positive results from a clinical trial with ISIS-TTR-Rx, which were unavailable when the first report was written. Beyond that, it appears that there are two promising gene silencers on the horizon that could represent potential competitors for tafamidis.Conclusions:The analysis of tafamidis for incorporation into the Brazilian health system is ongoing, but HS was able to deliver strategic information that could affect the final recommendation of CONITEC.

Current Advances in Pharmacotherapy and Technology for Diabetic Retinopathy: A Systematic Review

Diabetic retinopathy (DR) is classically defined by its vascular lesions and damage in the neurons of the retina. The cellular and clinical elements of DR have many features of chronic inflammation. Understanding the individual cell-specific inflammatory changes in the retina may lead to novel therapeutic approaches to prevent vision loss. The systematic use of available pharmacotherapy has been reported as a useful adjunct tool to laser photocoagulation, a gold standard therapy for DR. Direct injections or intravitreal anti-inflammatory and antiangiogenesis agents are widely used pharmacotherapy to effectively treat DR and diabetic macular edema (DME). However, their effectiveness is short term, and the delivery system is often associated with adverse effects, such as cataract and increased intraocular pressure. Further, systemic agents (particularly hypoglycemic, hypolipidemic, and antihypertensive agents) and plants-based drugs have also provided promising treatment in the progression of DR. Recently, advancements in pluripotent stem cells technology enable restoration of retinal functionalities after transplantation of these cells into animals with retinal degeneration. This review paper summarizes the developments in the current and potential pharmacotherapy and therapeutic technology of DR. Literature search was done on online databases, PubMed, Google Scholar, clinitrials.gov, and browsing through individual ophthalmology journals and leading pharmaceutical company websites.

Drug-eluting stents versus bare-metal stents for acute coronary syndrome.

Drug-eluting stents versus bare-metal stents for acute coronary syndrome.

Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis

BackgroundThe evidence on selective serotonin reuptake inhibitors (SSRIs) for major depressive disorder is unclear.MethodsOur objective was to conduct a systematic review assessing the effects of SSRIs versus placebo, ‘active’ placebo, or no intervention in adult participants with major depressive disorder. We searched for eligible randomised clinical trials in The Cochrane Library’s CENTRAL, PubMed, EMBASE, PsycLIT, PsycINFO, Science Citation Index Expanded, clinical trial registers of Europe and USA, websites of pharmaceutical companies, the U.S. Food and Drug Administration (FDA), and the European Medicines Agency until January 2016. All data were extracted by at least two independent investigators. We used Cochrane systematic review methodology, Trial Sequential Analysis, and calculation of Bayes factor. An eight-step procedure was followed to assess if thresholds for statistical and clinical significance were crossed. Primary outcomes were reduction of depressive symptoms, remission, and adverse events. Secondary outcomes were suicides, suicide attempts, suicide ideation, and quality of life.ResultsA total of 131 randomised placebo-controlled trials enrolling a total of 27,422 participants were included. None of the trials used ‘active’ placebo or no intervention as control intervention. All trials had high risk of bias. SSRIs significantly reduced the Hamilton Depression Rating Scale (HDRS) at end of treatment (mean difference −1.94 HDRS points; 95% CI −2.50 to −1.37; P < 0.00001; 49 trials; Trial Sequential Analysis-adjusted CI −2.70 to −1.18); Bayes factor below predefined threshold (2.01*10−23). The effect estimate, however, was below our predefined threshold for clinical significance of 3 HDRS points. SSRIs significantly decreased the risk of no remission (RR 0.88; 95% CI 0.84 to 0.91; P < 0.00001; 34 trials; Trial Sequential Analysis adjusted CI 0.83 to 0.92); Bayes factor (1426.81) did not confirm the effect). SSRIs significantly increased the risks of serious adverse events (OR 1.37; 95% CI 1.08 to 1.75; P = 0.009; 44 trials; Trial Sequential Analysis-adjusted CI 1.03 to 1.89). This corresponds to 31/1000 SSRI participants will experience a serious adverse event compared with 22/1000 control participants. SSRIs also significantly increased the number of non-serious adverse events. There were almost no data on suicidal behaviour, quality of life, and long-term effects.ConclusionsSSRIs might have statistically significant effects on depressive symptoms, but all trials were at high risk of bias and the clinical significance seems questionable. SSRIs significantly increase the risk of both serious and non-serious adverse events. The potential small beneficial effects seem to be outweighed by harmful effects.Systematic review registrationPROSPERO CRD42013004420.

Topical capsaicin (high concentration) for chronic neuropathic pain in adults.

Topical creams with capsaicin are used to treat pain from a wide range of chronic conditions including neuropathic pain. Following application to the skin capsaicin causes enhanced sensitivity to noxious stimuli, followed by a period with reduced sensitivity and, after repeated applications, persistent desensitisation. There is uncertainty about the efficacy and tolerability of capsaicin for treating painful chronic neuropathies. This is an update of an earlier review of topical capsaicin for chronic neuropathic pain in adults that looked at all doses and formulations of capsaicin. The original review has now been split: here we consider only formulations using a low concentration of capsaicin (< 1%) applied several times daily over several weeks, while another review will consider a single application of capsaicin at a high concentration.To review the evidence from controlled trials on the efficacy and tolerability of topically applied low-concentration (< 1%) capsaicin in chronic neuropathic pain in adults.Cochrane CENTRAL, MEDLINE, EMBASE and Oxford Pain Relief Database, searched to July 2012.Randomised, double-blind, placebo-controlled studies of at least six weeks' duration, using low-concentration (< 1%) topical capsaicin to treat neuropathic pain.Two review authors independently assessed study quality and validity, and extracted data. Information was extracted on numbers of participants with pain relief (clinical improvement) after at least six weeks, and with local skin reactions, and used to calculate relative risk (or risk ratio, RR) and numbers needed to treat to benefit (NNT) and harm (NNH). Details of definition of pain relief and specific adverse events were sought.No additional studies were identified for this update of low concentration capsaicin. Included studies were published before 1996. Six studies (389 participants in total) compared regular application of low dose (0.075%) capsaicin cream with placebo cream. There was substantial heterogeneity in results, probably as a result of the small number of studies each with small numbers of participants, as well as the different pain conditions studied and different definitions of "clinical success" reported. Only two studies reported data for the preferred primary outcome of at least 50% pain relief, and there were too few data for pooled analysis. Local skin reactions were more common with capsaicin, usually tolerable, and attenuated with time; the NNH for repeated low-dose application was 2.5 (95% confidence interval (CI) 2.1 to 3.1). All studies satisfied minimum criteria for quality and validity, but maintenance of blinding remains a potential problem.There were insufficient data to draw any conclusions about the efficacy of low-concentration capsaicin cream in the treatment of neuropathic pain. The information we have suggests that low-concentration topical capsaicin is without meaningful effect beyond that found in placebo creams; given the potential for bias from small study size, this makes it unlikely that low-concentration topical capsaicin has any meaningful use in clinical practice. Local skin irritation, which was often mild and transient but may lead to withdrawal, was common. Systemic adverse effects were rare.