Discontinuation rates of SSRIs and tricyclic antidepressants: a meta-analysis and investigation of heterogeneity

1997 ◽  
Vol 170 (2) ◽  
pp. 120-127 ◽  
Author(s):  
Matthew Hotopf ◽  
Rebecca Hardy ◽  
Glyn Lewis

BackgroundPrevious meta-analyses suggest that individuals treated with serotonin-specific reuptake inhibitors (SSRIs) in randomised controlled trials (RCTs) are less likely to discontinue treatment than those on tricyclic antidepressants. This metaanalysis investigates whether this is due to the frequent use in RCTs of older reference tricyclics (imipramine and amitriptyline), which may have worse side-effects than more recent compounds.MethodsA meta-analysis of RCTs comparing tricyclic and heterocyclic antidepressants with SSRIs in the treatment of depression.ResultsThe overall odds ratio of discontinuation on tricyclic/heterocyclic antidepressants compared with SSRIs was 0.86 (95% CI 0.78–0.94). The odds ratio for reference tricyclics was 0.82 95% CI 0.72–0.23), newer tricyclics 0.89 (95% CI 0.74–1.06), and heterocyclics 1.02 (95% CI 0.78–1.35). The pooled advantage of SSRIs over tricyclics was maintained whether the population studied consisted of younger adults or only the elderly. No differences in discontinuation rates were detected between the SSRIs.ConclusionsThe lower rate of discontinuation in patients on SSRIs may be due to the use of old tricyclics (which have worse side-effects) as reference compounds. The SSRIs do not show a statistically significant difference in discontinuation rates when compared with newer tricyclics or heterocyclics.

2016 ◽  
Vol 40 (6) ◽  
pp. E13 ◽  
Author(s):  
Karthik Madhavan ◽  
Lee Onn Chieng ◽  
Hanyao Foong ◽  
Michael Y. Wang

OBJECTIVE Cervical spondylotic myelopathy usually presents in the 5th decade of life or later but can also present earlier in patients with congenital spinal stenosis. As life expectancy continues to increase in the United States, the preconceived reluctance toward operating on the elderly population based on older publications must be rethought. It is a known fact that outcomes in the elderly cannot be as robust as those in the younger population. There are no publications with detailed meta-analyses to determine an acceptable level of outcome in this population. In this review, the authors compare elderly patients older than 75 years to a nonelderly population, and they discuss some of the relevant strategies to minimize complications. METHODS In accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, the authors performed a PubMed database search to identify English-language literature published between 1995 and 2015. Combinations of the following phrases that describe the age group (“elderly,” “non-elderly,” “old,” “age”) and the disease of interest as well as management (“surgical outcome,” “surgery,” “cervical spondylotic myelopathy,” “cervical degenerative myelopathy”) were constructed when searching for relevant articles. Two reviewers independently assessed the outcomes, and any disagreement was discussed with the first author until it was resolved. A random-effects model was applied to assess pooled data due to high heterogeneity between studies. The mean difference (MD) and odds ratio were calculated for continuous and dichromatic parameters, respectively. RESULTS Eighteen studies comprising elderly (n = 1169) and nonelderly (n = 1699) patients who received surgical treatment for cervical spondylotic myelopathy were included in this meta-analysis. Of these studies, 5 were prospective and 13 were retrospective. Intraoperatively, both groups required a similar amount of operation time (p = 0.35). The elderly group had lower Japanese Orthopaedic Association (JOA) scores (MD −1.36, 95% CI −1.62 to −1.09; p < 0.00001) to begin with compared with the nonelderly group. The nonelderly group also had a higher postoperative JOA score (MD −1.11, 95% CI −1.44 to −0.79; p < 0.00001), therefore demonstrating a higher recovery rate from surgeries (MD −11.98, 95% CI −16.16 to −7.79; p < 0.00001). The length of stay (MD 4.14, 95% CI 3.54–4.73; p < 0.00001) was slightly longer in the elderly group. In terms of radiological outcomes, the elderly group had a smaller postoperative Cobb angle but a greater increase in spinal canal diameter compared with the nonelderly group. The complication rates were not significant. CONCLUSIONS Cervical myelopathy is a disease of the elderly, and age is an independent factor for recovery from surgery. Postoperative and long-term outcomes have been remarkable in terms of improvement in mobility and independence requiring reduced nursing care. There is definitely a higher potential risk while operating on the elderly population, but no significant difference in the incidence of postoperative complications was noted. Withholding surgery from the elderly population can lead to increased morbidity due to rapid progression of symptoms in addition to deconditioning from lack of mobility and independence. Reduction in operative time under anesthesia, lower blood loss, and perioperative fluid management have been shown to minimize the complication rate. The authors request that neurosurgeons weigh the potential benefit against the risks for every patient before withholding surgery from elderly patients.


2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S168-S168
Author(s):  
Dan Siskind ◽  
Brian Wu ◽  
Tommy Wong ◽  
Steve Kisely

Abstract Background People living with schizophrenia are 3 times more likely to smoke than the general population, and have fewer and less successful quitting attempts. In concert with psychosocial quit interventions, there is a need for evidence based pharmacological interventions to assist people living with schizophrenia achieve smoking abstinence. Methods We systematically searched PubMed, PsycInfo, EMBASE and Cochrane for randomised controlled trials of pharmacological interventions for reducing smoking among people living with schizophrenia. We conducted pairwise and network meta-analyses of effectiveness of interventions for achieving abstinence and reduction in smoking. We also examined psychiatric and physical adverse events of interventions. Results Nineteen studies were included in the systematic review. Data was available for buproprion, varenicline and nicotine replacement therapy (NRT). Buproprion (RR 3.4, 95%CI 1.6–7.3, p=0.002), varenicline (RR 3.8, 95%CI 2.0–7.2, p&lt;0.001) and NRT (RR 4.3, 95%CI 1.7–10.7, p=0.002) were all associated with increased rates of abstinence in pairwise meta-analyses. In a network meta-analysis varenicline was superior to buproprion (RR 2.0, 95%CI 1.0–3.9), however there was no statistically significant difference between varenicline and NRT or buproprion and NRT. Varenicline was associated with higher rates of nausea than placebo. Discussion Buproprion, varenicline and NRT were all superior to placebo for achieving abstinence. Varenicline appears to be superior to buproprion for achieving abstinence, however varenicline is associated with higher rates of nausea.


Open Heart ◽  
2018 ◽  
Vol 5 (2) ◽  
pp. e000706
Author(s):  
Ik Hur Teoh ◽  
Moulinath Banerjee

BackgroundRanolazine is an antianginal drug reported to have hypoglycaemic effects.ObjectivesTo assess the effect of ranolazine versus placebo on glycaemic control for adults with and without diabetes.MethodsA systematic search of seven databases was conducted to identify all randomised controlled trials that compared the effect of ranolazine versus placebo on haemoglobin A1c (HbA1c) and/or fasting plasma glucose (FPG) and/or incidence of hypoglycaemia. We used mean differences in HbA1c and FPG to express intervention effect estimates and analysed the data with random-effects model for meta-analyses using Revman 5.3.ResultsWe identified seven trials including 6543 subjects to assess the effect of ranolazine on HbA1c and/or FPG. A separate trial that included 944 subjects was included to assess the effect of ranolazine on hypoglycaemia. The change in HbA1c for all patients was −0.36% (95% CI −0.57% to −0.15%; p=0.0004, I2=78%). In patients with diabetes, the change in HbA1c was −0.41% (95% CI −0.58% to −0.25%; p<0.00001, I2=65%). There was no significant difference in FPG between ranolazine and placebo groups (−2.58 mmol/L, 95% CI −7.02 to 1.85; p=0.25; I2=49%) or incidence of hypoglycaemia between ranolazine and placebo groups (OR 1.70, 95% CI 0.89 to 3.26; p=0.61, I2=0%).ConclusionsOur meta-analytic findings support the fact that ranolazine improves HbA1c without increasing the risk of hypoglycaemia. It therefore has a potential of having an additional benefit of improving glycaemic control in patients with chronic stable angina and diabetes.


1998 ◽  
Vol 172 (3) ◽  
pp. 227-231 ◽  
Author(s):  
Joanna Moncrieff ◽  
Simon Wessely ◽  
Rebecca Hardy

BackgroundUnblinding effects may-introduce bias into clinical trials. The use of active placebos to mimic side-effects of medication may therefore produce more rigorous evidence on the efficacy of antidepressants.MethodTrials comparing antidepressants with active placebos were located. A standard measure of effect was calculated for each trial and weighted pooled estimates obtained. Heterogeneity was examined and sensitivity analyses performed. A subgroup analysis of in-patient and out-patient trials was conducted.ResultsOnly two of the nine studies examined produced effect sizes which showed a consistent significant difference in favour of the active drug. Combining all studies produced pooled effect size estimates of between 0.41 (0.27–0.56) and 0.46 (0.31–0.60) with high heterogeneity due to one strongly positive trial. Sensitivity analyses excluding this and one other trial reduced the pooled effect to between 0.21 (0.03–0.38) and 0.27 (0.10–0.45).ConclusionsMeta-analysis is very sensitive to decisions about exclusions. Previous general meta-analyses have found combined effect sizes in the range 0.4–0.8. The more conservative estimates produced here suggest that unblinding effects may inflate the efficacy of antidepressants in trials using inert placebos.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
James Patrick Finnerty ◽  
Aravind Ponnuswamy ◽  
Prosjenjit Dutta ◽  
Ammar Abdelaziz ◽  
Hafiz Kamil

Abstract Background Research questions To compare the efficacy of nintedanib and pirfenidone in the treatment of progressive pulmonary fibrosis; and to compare the efficacy of anti-fibrotic therapy (grouping nintedanib and pirfenidone together) in patients with IPF versus patients with progressive lung fibrosis not classified as IPF. Study design and methods A search of databases including MEDLINE, EMBASE, PubMed, and clinicaltrials.gov was conducted. Studies were included if they were randomised controlled trials of pirfenidone or nintedanib in adult patients with IPF or non-IPF patients, and with extractable data on mortality or decline in forced vital capacity (FVC). Random effects meta-analyses were performed on changes in FVC and where possible on mortality in the selected studies. Results 13 trials of antifibrotic therapy were pooled in a meta-analysis (with pirfenidone and nintedanib considered together as anti-fibrotic therapy). The change in FVC was expressed as a standardised difference to allow pooling of percentage and absolute changes. The mean effect size in the IPF studies was − 0.305 (SE 0.043) (p < 0.001) and in the non-IPF studies the figures were − 0.307 (SE 0.063) (p < 0.001). There was no evidence of any difference between the two groups for standardised rate of FVC decline (p = 0.979). Pooling IPF and non-IPF showed a significant reduction in mortality, with mean risk ratio of 07.01 in favour of antifibrotic therapy (p = 0.008). A separate analysis restricted to non-IPF did not show a significant reduction in mortality (risk ratio 0.908 (0.547 to 1.508), p = 0.71. Interpretation Anti-fibrotic therapy offers protection against the rate of decline in FVC in progressive lung fibrosis, with similar efficacy shown between the two anti-fibrotic agents currently in clinical use. There was no significant difference in efficacy of antifibrotic therapy whether the underlying condition was IPF or non-IPF with progressive fibrosis, supporting the hypothesis of a common pathogenesis. The data in this analysis was insufficient to be confident about a reduction in mortality in non-IPF with anti-fibrotic therapy. Trial Registration PROSPERO, registration number CRD42021266046.


2000 ◽  
Vol 176 (5) ◽  
pp. 421-428 ◽  
Author(s):  
P. Bech ◽  
P. Cialdella ◽  
M. C. Haugh ◽  
M. A. Birkett ◽  
A. Hours ◽  
...  

BackgroundPrevious meta-analyses of fluoxetine as an antidepressant have many methodological problems, including diagnosis of major depression, validity of outcome measures and lack of intention-to-treat analyses.AimsTo provide an estimate of the effect of fluoxetine compared with placebo and tricyclic antidepressants (TCAs), and to investigate reasons for early discontinuation from acute treatment.MethodRandomised trials were analysed using both intention-to-treat, efficacy and end-point.ResultsFluoxetine was superior to placebo but effect size was low. In trials comparing fluoxetine v. TCA, the results for all trials and for the USA trials showed a trend in favour of fluoxetine. Those for the non-USA trials showed a trend in favour of TCA. When combined, the results showed that significantly fewer patients on fluoxetine discontinued treatment because of adverse events.ConclusionFluoxetine is superior to placebo, irrespective of the analytical approach use, whereas the results obtained v. TCAs depend on the approach used. Hence, the results should be interpreted in this light.


BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e044356
Author(s):  
Benjamin Ng ◽  
Magnus Fugger ◽  
Igho Jovwoke Onakpoya ◽  
Andrew Macdonald ◽  
Carl Heneghan

IntroductionPatients with end-stage renal disease may require arteriovenous (AV) access in the form of arteriovenous fistulae (AVFs) or arteriovenous grafts (AVGs) for haemodialysis. AV access dysfunction requires intervention such as plain balloon angioplasty or covered stents to regain patency.AimTo systematically review and meta-analyse the patency outcomes of covered stents in failing haemodialysis AV access, compared with balloon angioplasty.MethodsThe review was first registered on the International Prospective Register of Systematic Reviews (CRD42018069955) before data collection. We searched six electronic databases to identify relevant randomised controlled trials (RCTs) up until August 2020, without language restriction. Two reviewers assessed the suitability and quality of studies for inclusion using the Consolidated Standards of Reporting Trials guidelines. We meta-analysed data using a random-effects model.ResultsWe included seven studies including 1147 patients in the systematic review, of which 867 had AVGs and 280 had AVFs. One study was an ongoing RCT. In the meta-analyses, we assessed patients with failing AVGs only. Overall risk of bias was moderate. Covered stents were associated with lower loss of patency versus angioplasty alone at 6, 12 and 24 months (OR 4.48, 95% CI 1.98 to 10.14, p<0.001; OR 4.07, 95% CI 1.74 to 9.54, p=0.001; OR 2.24, 95% CI 1.17 to 4.29, p=0.01, respectively). Covered stents afforded superior access circuit primary patency compared with angioplasty alone at 6 and 12 months (OR 1.91, 95% CI 1.31 to 2.80, p<0.001; OR 1.97, 95% CI 1.14 to 3.41, p=0.02, respectively). This was not significant at 24 months. There was no significant difference in loss of secondary patency between groups at 12 or 24 months (OR 0.74, 95% CI 0.45 to 1.23, p=0.25; OR 0.67, 95% CI 0.29 to 0.154, p=0.34, respectively).ConclusionOur results support use of covered stents over angioplasty alone, at 6, 12 and 24 months in failing AVGs. Further clinical trials are warranted.


2020 ◽  
pp. 000486742093116 ◽  
Author(s):  
Matthew Large ◽  
Amy Corderoy ◽  
Catherine McHugh

Objective: Suicidal ideation and suicidal behaviour are both regarded as important risk factors for suicide, but it is usually believed that suicidal ideation is less strongly linked to suicide than suicidal behaviours. In this study, we assessed and compared the strengths of the associations that suicidal ideation and suicidal behaviour have with later suicide using meta-analysis of primary studies reporting both these independent variables and the dependent variable of suicide. Methods: A total of 51 English language publications describing cohort or controlled studies that reported on both the association between suicidal ideation and suicide and the association between suicidal behaviours and suicide were located using searches for titles in PubMed containing variants of the word suicide (suicid*). Suicides were considered to include reported suicides and open verdicts from mortality registers. The strengths of the two associations were examined in separate random effects meta-analyses and were then compared using mixed effects meta-regression. Subgroups were examined according to study characteristics including the definitions of suicidal ideation or behaviour used, setting (psychiatric or non-psychiatric), diagnostic mix of the study population, study design (cohort or control) and study quality. Results: Suicidal ideation (odds ratio = 3.11, 95% confidence interval = 2.51, 3.86) and suicidal behaviours (odds ratio = 4.09, 95% confidence interval = 3.05, 5.49) were both significantly associated with suicide but there was no significant difference in the strengths of association ( p = 0.14). Nor were there significant differences in the strengths of the two associations in multiple subgroup analyses. Conclusion: Suicidal ideation and suicidal behaviour are both moderately associated with suicide. Existing data cannot conclusively demonstrate that suicidal behaviours are more strongly associated with suicide than suicidal ideation. Clinicians should not strongly prioritise suicidal behaviour over suicidal ideation when considering suicide risk.


2022 ◽  
Vol 16 ◽  
pp. 263235242110705
Author(s):  
Carol Chunfeng Wang ◽  
Ellen Yichun Han ◽  
Mark Jenkins ◽  
Xuepei Hong ◽  
Shuqin Pang ◽  
...  

Introduction: This study aimed to synthesise the best available evidence on the safety and efficacy of using moxibustion and/or acupuncture to manage cancer-related insomnia (CRI). Methods: The PRISMA framework guided the review. Nine databases were searched from its inception to July 2020, published in English or Chinese. Randomised clinical trials (RCTs) of moxibustion and or acupuncture for the treatment of CRI were selected for inclusion. Methodological quality was assessed using the method suggested by the Cochrane collaboration. The Cochrane Review Manager was used to conduct a meta-analysis. Results: Fourteen RCTs met the eligibility criteria. Twelve RCTs used the Pittsburgh Sleep Quality Index (PSQI) score as continuous data and a meta-analysis showed positive effects of moxibustion and or acupuncture ( n = 997, mean difference (MD) = −1.84, 95% confidence interval (CI) = −2.75 to −0.94, p < 0.01). Five RCTs using continuous data and a meta-analysis in these studies also showed significant difference between two groups ( n = 358, risk ratio (RR) = 0.45, 95% CI = 0.26–0.80, I2 = 39%). Conclusion: The meta-analyses demonstrated that moxibustion and or acupuncture showed a positive effect in managing CRI. Such modalities could be considered an add-on option in the current CRI management regimen.


2020 ◽  
Vol 45 (6) ◽  
pp. 589-597
Author(s):  
BGS Casado ◽  
EP Pellizzer ◽  
JR Souto Maior ◽  
CAA Lemos ◽  
BCE Vasconcelos ◽  
...  

Clinical Relevance The use of laser light during bleaching will not reduce the incidence or severity of sensitivity and will not increase the degree of color change compared with nonlaser light sources. SUMMARY Objective: To evaluate whether the use of laser during in-office bleaching promotes a reduction in dental sensitivity after bleaching compared with other light sources. Methods: The present review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and is registered with PROSPERO (CDR42018096591). Searches were conducted in the PubMed/Medline, Web of Science, and Cochrane Library databases for relevant articles published up to August 2018. Only randomized clinical trials among adults that compared the use of laser during in-office whitening and other light sources were considered eligible. Results: After analysis of the texts retrieved during the database search, six articles met the eligibility criteria and were selected for the present review. For the outcome dental sensitivity, no significant difference was found favoring any type of light either for intensity (mean difference [MD]: −1.60; confidence interval [CI]: −3.42 to 0.22; p=0.09) or incidence (MD: 1.00; CI: 0.755 to 1.33; p=1.00). Regarding change in tooth color, no significant differences were found between the use of the laser and other light sources (MD: −2.22; CI: −6.36 to 1.93; p=0.29). Conclusions: Within the limitations of the present study, laser exerts no influence on tooth sensitivity compared with other light sources when used during in-office bleaching. The included studies demonstrated that laser use during in-office bleaching may have no influence on tooth color change.


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