scholarly journals Efficacy and safety of antidepressants for the treatment of back pain and osteoarthritis: systematic review and meta-analysis

BMJ ◽  
2021 ◽  
pp. m4825 ◽  
Author(s):  
Giovanni E Ferreira ◽  
Andrew J McLachlan ◽  
Chung-Wei Christine Lin ◽  
Joshua R Zadro ◽  
Christina Abdel-Shaheed ◽  
...  

Abstract Objective To investigate the efficacy and safety of antidepressants for back and osteoarthritis pain compared with placebo. Design Systematic review and meta-analysis. Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, CINAHL, International Pharmaceutical Abstracts, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform from inception to 15 November and updated on 12 May 2020. Eligibility criteria for study selection Randomised controlled trials comparing the efficacy or safety, or both of any antidepressant drug with placebo (active or inert) in participants with low back or neck pain, sciatica, or hip or knee osteoarthritis. Data extraction and synthesis Two independent reviewers extracted data. Pain and disability were primary outcomes. Pain and disability scores were converted to a scale of 0 (no pain or disability) to 100 (worst pain or disability). A random effects model was used to calculate weighted mean differences and 95% confidence intervals. Safety (any adverse event, serious adverse events, and proportion of participants who withdrew from trials owing to adverse events) was a secondary outcome. Risk of bias was assessed with the Cochrane Collaboration’s tool and certainty of evidence with the grading of recommendations assessment, development and evaluation (GRADE) framework. Results 33 trials (5318 participants) were included. Moderate certainty evidence showed that serotonin-noradrenaline reuptake inhibitors (SNRIs) reduced back pain (mean difference −5.30, 95% confidence interval −7.31 to −3.30) at 3-13 weeks and low certainty evidence that SNRIs reduced osteoarthritis pain (−9.72, −12.75 to −6.69) at 3-13 weeks. Very low certainty evidence showed that SNRIs reduced sciatica at two weeks or less (−18.60, −31.87 to −5.33) but not at 3-13 weeks (−17.50, −42.90 to 7.89). Low to very low certainty evidence showed that tricyclic antidepressants (TCAs) did not reduce sciatica at two weeks or less (−7.55, −18.25 to 3.15) but did at 3-13 weeks (−15.95, −31.52 to −0.39) and 3-12 months (−27.0, −36.11 to −17.89). Moderate certainty evidence showed that SNRIs reduced disability from back pain at 3-13 weeks (−3.55, −5.22 to −1.88) and disability due to osteoarthritis at two weeks or less (−5.10, −7.31 to −2.89), with low certainty evidence at 3-13 weeks (−6.07, −8.13 to −4.02). TCAs and other antidepressants did not reduce pain or disability from back pain. Conclusion Moderate certainty evidence shows that the effect of SNRIs on pain and disability scores is small and not clinically important for back pain, but a clinically important effect cannot be excluded for osteoarthritis. TCAs and SNRIs might be effective for sciatica, but the certainty of evidence ranged from low to very low. Systematic review registration PROSPERO CRD42020158521.

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
James D. Millard ◽  
Elizabeth A. Mackay ◽  
Laura J. Bonnett ◽  
Geraint R. Davies

Abstract Background Pyrazinamide (PZA) is a key component of current and future regimens for tuberculosis (TB). Inclusion of PZA at higher doses and for longer durations may improve efficacy outcomes but must be balanced against the potential for worse safety outcomes. Methods We will search for randomised and quasi-randomised clinical trials in adult participants with and without the inclusion of PZA in TB treatment regimens in the Cochrane infectious diseases group’s trials register, Cochrane central register of controlled trials (CENTRAL), MEDLINE, EMBASE, LILACS, the metaRegister of Controlled Trials (mRCT) and the World Health Organization (WHO) international clinical trials registry platform. One author will screen abstracts and remove ineligible studies (10% of which will be double-screened by a second author). Two authors will review full texts for inclusion. Safety and efficacy data will be extracted to pre-piloted forms by one author (10% of which will be double-extracted by a second author). The Cochrane risk of bias tool will be used to assess study quality. The study has three objectives: the association of (1) inclusion, (2) dose and (3) duration of PZA with efficacy and safety outcomes. Risk ratios as relative measures of effect for direct comparisons within trials (all objectives) and proportions as absolute measures of effect for indirect comparisons across trials (for objectives 2 and 3) will be calculated. If there is insufficient data for direct comparisons within trials for objective 1, indirect comparisons between trials will be performed. Measures of effect will be pooled, with corresponding 95% confidence intervals and p values. Meta-analysis will be performed using the generalised inverse variance method for fixed effects models (FEM) or the DerSimonian-Laird method for random effects models (REM). For indirect comparisons, meta-regression for absolute measures against dose and duration data will be performed. Heterogeneity will be quantified through the I2-statistic for direct comparisons and the τ2 statistic for indirect comparisons using meta-regression. Discussion The current use of PZA for TB is based on over 60 years of clinical trial data, but this has never been synthesised to guide rationale use in future regimens and clinical trials. Systematic review registration: International Prospective Register of Systematic Reviews (PROSPERO) CRD42019138735


2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Xi-qian Yang ◽  
Ling Liu ◽  
Shu-ping Ming ◽  
Jie Fang ◽  
Dong-nan Wu

Background. The Traditional Chinese Medicine (TCM) Tian Wang Bu Xin Dan (TWBXD) has been used widely for treating insomnia in China. The purpose of this meta-analysis was to evaluate the efficacy and safety of TWBXD in the treatment of insomnia. Objective. This study evaluated the efficacy and safety of TWBXD for insomnia. Methods. We searched seven main databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese Biomedicine Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wan-fang. We identified randomized-controlled trials (RCTs) for insomnia treatment involving TWBXD, TWBXD combined with conventional Western medicine, and conventional Western medicine from their inception to May 2018. The quality of literature was evaluated by Cochrane assessing tool to reduce the risk of bias. Meta-analysis and heterogeneity of results across the trials were performed. RevMan 5.3 was used to synthesize the results. Results. 14 studies involving 1,256 participants were identified in this systematic review. Methodological deficiencies existed in most of the included trials. Few studies described the generation of a random sequence in detail, the concealment of allocation, and the methods of blinding. No placebo was used in treatment. 12 trials compared TWBXD with conventional Western medicine and 2 trials compared TWBXD combined with conventional Western medicine. The results of our meta-analysis showed relative benefits in effective rates in favor of TWBXD (Odds Ratio [OR] 2.71, 95% confidence interval [CI] 1.67 to 4.39, P < 0.00001) and TWBXD combined with conventional Western medicine (OR 5.05, 95% CI 1.58 to 16.12, P=0.006). The Pittsburgh Sleep Quality Index (PSQI) scores showed similar results, which favored TWBXD (Weighted Mean Difference [WMD] -1.82, 95% CI -3.00 to -0.64, P=0.003). Only 5 trials reported adverse events, whereas the other 9 trials did not provide the safety information. Conclusion. This review demonstrates that although the effects of TWBXD on insomnia were promising, they need to be interpreted with caution, due to the poor methodological quality and the small number of trials of the included studies. TWBXD seems to be generally safe, but there is insufficient evidence to make conclusions on the safety because fewer studies reported the adverse events. Further studies on a larger scale with more rigorous designs are required to evaluate the role of TWBXD in the insomnia treatment.


BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e040906
Author(s):  
Xinyu Zhao ◽  
Lihui Meng ◽  
Youxin Chen

ObjectiveTo give a comprehensive efficacy and safety ranking of different therapeutic regimens of ranibizumab for neovascular age-related macular degeneration (nAMD).DesignA systematic review and network meta-analysis.MethodsThe PubMed, Embase, Cochrane Central Register of Controlled Trials, and other clinical trial registries were searched up to 1 October 2019 to identify related randomised controlled trials (RCT) of different regimens of ranibizumab for nAMD. The primary efficacy outcome was the changes of best-corrected visual acuity (BCVA) at 1 year, the primary safety outcome was the incidence of severe ocular adverse events. Secondary outcomes such as changes of central retinal thickness (CRT) were evaluated. We estimated the standardised mean difference (SMD), ORs, 95% CIs, the surface under the cumulative ranking curves and the mean ranks for each outcome using network meta-analyses with random effects by Stata 14.0.ResultsWe identified 26 RCTs involving 10 821 patients with nAMD randomly assigned to 21 different therapeutic regimens of ranibizumab or sham treatment. Ranibizumab 0.5 mg (treat and extend, T&E) is most effective in terms of changes of BCVA (letters, SMD=21.41, 95% CI 19.86 to 22.95) and three or more lines of BCVA improvement (OR=2.83, 95% CI 1.27 to 4.38). However, it could not significantly reduce retreatment times compared with monthly injection (SMD=−0.94, 95% CI −2.26 to 0.39). Ranibizumab 0.5 mg (3+pro re nata)+non-steroidal anti-inflammatory drugs (NSAIDs) is most effective in reducing CRT and port delivery system of ranibizumab (100 mg/mL) could reduce the number of retreatment most significantly. All regimes have no more risk of severe ocular complications (including vitreous haemorrhage, rhegmatogenous retinal detachment, endophthalmitis, retinal tear and retinal pigment epithelium tear) or cardiocerebral vascular complications.ConclusionsRanibizumab 0.5 mg (T&E) is most effective in improving the visual outcome. The administration of topical NSAIDs could achieve additional efficacy in CRT reduction and visual improvement. Both interventions had acceptable risks of adverse events.


2021 ◽  
pp. 10.1212/CPJ.0000000000001143
Author(s):  
Glenardi Glenardi ◽  
Tutwuri Handayani ◽  
Jimmy Barus ◽  
Ghea Mangkuliguna

ABSTRACTPurposeof Review: To investigate the efficacy and safety of CVT-301 for motor fluctuation in Parkinson’s disease (PD).Recent Findings:This study demonstrated that the CVT-301 group had a higher proportion of patients achieving an ON state than the placebo group (OR=2.68; 95% CI: 1.86-3.86; p<0.00001). Moreover, CVT-301 had also shown to improve motor function by UPDRS-III score (SMD=3.83; 95% CI: 2.44-5.23; p<0.00001) and promote an overall improvement of PD by PGIC self-rating (OR=2.95; 95% CI: 1.78-4.9; p<0.00001). The most common adverse events encountered were respiratory symptoms (OR=12.18; 95% CI: 5.01-29.62; p<0.00001) and nausea (OR=3.95; 95% CI: 1.01-15.41; p=0.05).Summary:CVT-301 had the potential to be an alternative or even a preferred treatment for motor fluctuation in PD patients.


BMJ Open ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. e047344
Author(s):  
Qingwu Wu ◽  
Lianxiong Yuan ◽  
Huijun Qiu ◽  
Xinyue Wang ◽  
Xuekun Huang ◽  
...  

ObjectivesTo assess the efficacy and safety of omalizumab for chronic rhinosinusitis with nasal polyps (CRSwNP) and to identify evidence gaps that will guide future research on omalizumab for CRSwNP.DesignSystematic review and meta-analysis.Data sourcesA comprehensive search was performed in PubMed, Embase, Web of Science and the Cochrane Library on 13 October 2020.Eligibility criteriaRandomised controlled trials (RCTs) comparing omalizumab with placebo, given for at least 16 weeks in adult patients with CRSwNP.Data extraction and synthesisTwo independent authors screened search results, extracted data and assessed studies using the Cochrane risk of bias tool. Data were pooled using the inverse-variance method and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed by the χ2 test and the I2 statistic.ResultsA total of four RCTs involving 303 participants were identified. When comparing omalizumab to placebo, there was a significant difference in Nasal Polyps Score (MD=−1.20; 95% CI −1.48 to −0.92), Nasal Congestion Score (MD=−0.67; 95% CI −0.86 to −0.48), Sino-Nasal Outcome Test-22 (MD=−15.62; 95% CI −19.79 to −11.45), Total Nasal Symptom Score (MD=−1.84; 95% CI −2.43 to −1.25) and reduced need for surgery (risk ratio (RR)=5.61; 95% CI 1.99 to 15.81). Furthermore, there was no difference in the risk of serious adverse events ((RR=1.40; 95% CI 0.29 to 6.80), adverse events (RR=0.83; 95% CI 0.60 to 1.15) and rescue systemic corticosteroid (RR=0.52; 95% CI 0.17 to 1.61).ConclusionsThis was the first meta-analysis that identified omalizumab significantly improved endoscopic, clinical and patient-reported outcomes in adults with moderate to severe CRSwNP and it was safe and well tolerated.PROSPERO registration numberCRD42020207639.


BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e050004
Author(s):  
Wenjuan Wu ◽  
Lingxiao Qiu ◽  
Jizhen Wu ◽  
Xueya Liu ◽  
Guojun Zhang

ObjectivesIdiopathic pulmonary fibrosis (IPF) has been defined as a distinctive type of chronic fibrotic disease, characterised by a progressive decline in lung function and a common histological pattern of interstitial pneumonia. To analyse the efficacy and safety of pirfenidone in the treatment of IPF, a systematic review and meta-analysis was performed.DesignThis is a meta-analysis study.ParticipantsPatients were diagnosed as IPF.InterventionsUse of pirfenidone.Primary and secondary outcomeProgression-free survival (PFS), acute exacerbation and worsening of IPF and Impact on adverse events.MeasuresThe inverse variance method for the random-effects model was used to summarise the dichotomous outcomes, risk ratios and 95% CIs.ResultsA total of 9 randomised controlled trials with 1011 participants receiving pirfenidone and 912 controls receiving placebo were summarised. The pooled result suggested a statistically significant difference inall-cause mortality after pirfenidone use, with a summarised relative ratio of 0.51 (p<0.01). Longer PFS was observed in patients receiving pirfenidone compared with those who were given placebo (p<0.01). The IPF groups presented a high incidence of adverse events with a pooled relative ratio of 3.89 (p<0.01).ConclusionsPirfenidone can provide survival benefit for patients with IPF. Pirfenidone treatment was also associated with a longer PFS, a lower incidence of acute exacerbation and worsening of IPF.


Author(s):  
Afsaneh Noormandi ◽  
Mohammad Fathalipour ◽  
Reza Daryabeygi-Khotbehsara ◽  
Soheil Hassanipour

Background and objective: COVID-19 has since been declared a global pandemic by the World Health Organization (WHO), infecting millions worldwide. The use of Interferon (INF) subtypes previously examined in the treatment of SARS and MERS is also being initiated in some clinical trials. Although different clinical trials were evaluated IFNs in the treatment of COVID-19, their efficacy and safety remain unknown. Therefore, this study aims to systematically assess IFNs efficacy and safety in treating patients with COVID-19. Methods: The protocol has been registered in the PROSPERO International Prospective Register (CRD42020200643) on 24 July 2020. This protocol has been arranged according to the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) 2015 checklist. Discussion: Due to lack of approved medication for the covid-19 treatment and also various mutations of this virus, evaluated the efficacy and safety of medications by various studies could help for finding treatments with high effectiveness. IFNs are one of the medications that have been administered in covid-19 infection.  Moreover, the best time of administration and dose of this medication was unknown. Although meta-analysis is a potent source for assessing the accuracy of subjects, heterogeneity of articles is a potent limitation of our work.


BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e034996
Author(s):  
Emma Ho ◽  
Manuela Ferreira ◽  
Lingxiao Chen ◽  
Milena Simic ◽  
Claire Ashton-James ◽  
...  

IntroductionPsychological factors such as fear avoidance beliefs, depression, anxiety, catastrophic thinking and familial and social stress, have been associated with high disability levels in people with chronic low back pain (LBP). Guidelines endorse the integration of psychological interventions in the management of chronic LBP. However, uncertainty surrounds the comparative effectiveness of different psychological approaches. Network meta-analysis (NMA) allows comparison and ranking of numerous competing interventions for a given outcome of interest. Therefore, we will perform a systematic review with a NMA to determine which type of psychological intervention is most effective for adults with chronic non-specific LBP.Methods and analysisWe will search electronic databases (MEDLINE, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, Web of Science, SCOPUS and CINAHL) from inception until 22 August 2019 for randomised controlled trials comparing psychological interventions to any comparison interventions in adults with chronic non-specific LBP. There will be no restriction on language. The primary outcomes will include physical function and pain intensity, and secondary outcomes will include health-related quality of life, fear avoidance, intervention compliance and safety. Risk of bias will be assessed using the Revised Cochrane risk-of-bias tool for randomised trials (RoB 2) tool and confidence in the evidence will be assessed using the Confidence in NMA (CINeMA) framework. We will conduct a random-effects NMA using a frequentist approach to estimate relative effects for all comparisons between treatments and rank treatments according to the mean rank and surface under the cumulative ranking curve values. All analyses will be performed in Stata.Ethics and disseminationNo ethical approval is required. The research will be published in a peer-reviewed journal.PROSPERO registration numberCRD42019138074.


BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e030713 ◽  
Author(s):  
Dacheng Li ◽  
Li Zhu ◽  
Daming Liu

IntroductionRefractory gastro-oesophageal reflux disease (rGORD) is a common disease, affecting patients’ quality of life. Since conventional medicines have limitations, like low effective rates and adverse events, acupuncture may be a promising therapy for rGORD. While no related systematic review has been published, the present study is designed to evaluate the efficacy and safety of acupuncture for rGORD.Methods and analysisPubMed, the Cochrane Central Register of Controlled Trials and Chinese electronic databases, including China National Knowledge Infrastructure, Wan Fang database, VIP, SinoMed and the Chinese Clinical Trial Registry, will be searched from establishment of the database to 31 August 2019. There will be no limitations on language, and all articles will be screened and collected by two reviewers independently. RevMan V.5.3.5 software will be used for meta-analysis, and the conduction of study will refer to the Cochrane Handbook for Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol guidelines. The efficacy and safety of acupuncture for rGORD will be evaluated based on outcomes, including global symptom improvement, oesophageal sphincter function test measured by high-resolution manometry, quality of life, recurrence rate and adverse events.Ethics and disseminationThere is no necessity for this study to acquire an ethical approval, and this review will be disseminated in a peer-reviewed journal or conference presentation.Trial registration numberCRD42018111912.


2017 ◽  
Vol 05 (01) ◽  
pp. E67-E75 ◽  
Author(s):  
Ashok Shiani ◽  
Seth Lipka ◽  
Andrew Lai ◽  
Andrea Rodriguez ◽  
Christian Andrade ◽  
...  

Abstract Background and study aims Carbon dioxide (CO2) insufflation has been suggested to be an ideal alternative to room air insufflation to reduce trapped air within the bowel lumen after balloon assisted enteroscopy (BAE). We performed a systematic review and meta-analysis to assess the safety and efficacy of utilizing CO2 insufflation as compared to room air during BAE. Patients and methods The primary outcome is mean change in visual analog scale (VAS; 10 cm) at 1, 3, and 6 hours to assess pain. Secondary outcomes include insertion depth (anterograde or retrograde), adverse events, total enteroscopy rate, diagnostic yield, mean anesthetic dosage, and PaCO2 at procedure completion. We searched MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception until May 2015. Multiple independent extractions were performed, the process was executed as per the standards of the Cochrane collaboration. Results Four randomized controlled trials (RCTs) were included in the meta-analysis. VAS at 6 hours favored CO2 over room air (MD 0.13; 95 % CI 0.01, 0.25; p = 0.03). Anterograde insertion depth (cm) was improved in the CO2 group (MD, 58.2; 95 % CI 17.17, 99.23; p = 0.005), with an improvement in total enteroscopy rate in the CO2 group (RR 1.91; 95 % CI 1.20, 3.06; p = 0.007). Mean dose of propofol (mg) favored CO2 compared to air (MD, – 70.53; 95 % CI – 115.07, – 25.98; P = 0.002). There were no differences in adverse events in either group. Conclusions Despite the ability of CO2 to improve insertion depth and decrease amount of anesthesia required, further randomized control trials are needed to determine the agent of choice for insufflation in balloon assisted enteroscopy.


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