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Why has the antidepressant-placebo difference in antidepressant clinical trials diminished over the past three decades?

ABSTRACT: The increasing rate of failure of antidepressant clinical trials has led to the assertion that antidepressants do not have meaningful clinical benefits. Our hypothesis was that the decrease in antidepressant-placebo differences in antidepressant clinical trials over the past three decades could be explained by changes in research design features rather than a lack of potency of the antidepressants being tested. We collected data from 130 double blind placebo controlled antidepressant clinical trials conducted between 1981 and 2008 that included 35,122 depressed patients with 23,157 patients assigned to antidepressants and 11,965 assigned to placebo. We conducted a hierarchical regression analysis of change in HAM-D scores in antidepressant and placebo groups separately with year of publication, and research design features as independent variables. We found that antidepressant-placebo differences in antidepressant clinical trials have declined markedly over the past three decades. Decline in change scores in the antidepressant group was related to mean total baseline HAM-D scores in the trial, the version of HAM-D used, and duration of trial. Similarly, decline in change scores in the placebo group was related to mean total baseline HAM-D scores, duration of trial, and year of publication. Overall, we found that antidepressant-placebo differences were statistically significantly higher in trials that used HAM-D 21 rather than HAM-D 17 and in trials that lasted 6 weeks or less. These data suggest that, apart from the efficacy of the antidepressant being tested, factors such as baseline HAM-D scores, version of HAM-D used and duration of trial have a significant impact on outcome. As such a clinician's assessment of the usefulness of antidepressants should not be based solely on the results of such clinical trials. In the meantime there is a need for continuing research to improve the methodology of antidepressant clinical trials. These data suggest that many aspects of the design of antidepressant trials have a significant impact on outcome. Further, these data suggest that the results of more recent placebo controlled trials do not adequately inform clinicians about the potential utility of antidepressants.

SUBMITTER: Khan A

PROVIDER: S-EPMC6493812 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Why has the antidepressant-placebo difference in antidepressant clinical trials diminished over the past three decades?

Khan Arif A Bhat Amritha A Kolts Russell R Thase Michael E ME Brown Walter W

CNS neuroscience & therapeutics 20100416 4

The increasing rate of failure of antidepressant clinical trials has led to the assertion that antidepressants do not have meaningful clinical benefits. Our hypothesis was that the decrease in antidepressant-placebo differences in antidepressant clinical trials over the past three decades could be explained by changes in research design features rather than a lack of potency of the antidepressants being tested. We collected data from 130 double blind placebo controlled antidepressant clinical tr ...[more]

PMID: 20406269

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Project description:AimThe prevalence and mortality of abdominal aortic aneurysms (AAA) has been reported to decline. The aim of this study is to compare survival, prevalence, and repair rate of AAA in Denmark in the 1990s, the 2000s and the 2010s - and to examine any change in factors known to influence the prevalence.MethodsBaseline status and up to 5-year outcomes of 34,079 general population men aged 65-74 were obtained from three RCTs; the Viborg study (1994-1998, n=4,860), the Viborg Vascular (VIVA) trial (2008-2011, n=18,748), and the Danish Cardiovascular (DANCAVAS) trial (2015-2018, n=10,471). After the millennium (VIVA and DANCAVAS) men with AAA were further offered low dose aspirin and statins. Follow-up data were not available for the DANCAVAS trial yet.ResultsAcross the three decades, the AAA prevalence was 3.8% (Reference), 3.3% (p<0.001) and 4.2% (p=0.882), the proportion of smokers were 62%, 42% and 34% (p<0.001) amongst men with AAA, but AAA risk associations with smoking increased during the decades suggesting increased tobacco consumption of smokers. In addition, the proportions of attenders with ischemic heart disease or stroke increased significantly. The aneurysmal progression rate in the 1990s was 2.90 vs 2.98 mm/year in the 2000s (p=0.91). The need for preventive AAA repair increased insignificantly in the 2000s (Age adj. HR= 1.29, 95% C.I.: 0.95; 1.71, p=0.10), and mortality of men with screen-detected AAA was lower in the 2000s compared to the 1990s (Age-adj. HR= 0.28, 95% C.I.: 0.22; 0.36, p<0.001).ConclusionThe Danish prevalence of AAA today compares to the nineties. Unchanged aneurysmal progression rates combined with improved survival of men at risk of AAA leave them in longer time to develop an AAA, be diagnosed and to need later aneurysmal repair or experience rupture.Clinical trial registrationsViborg study: No possibility of registration in the nineties. VIVA: NCT00662480, URL: https://clinicaltrials.gov/show/NCT00662480, DANCAVAS: ISRCTN12157806, URL: http://www.isrctn.com/ISRCTN12157806.

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Project description:BackgroundTuberculosis, as a communicable disease, is an ongoing global epidemic that accounts for high burden of global mortality and morbidity. Globally, with an estimated 10 million new cases and around 1.4 million deaths, TB has emerged as one of the top 10 causes of morbidity and mortality in 2019. Worst hit 8 countries account for two thirds of the new TB cases in 2019, with India leading the count. Despite India's engagement in various TB control activities since its first recognition through the resolution passed in the All-India Sanitary Conference in 1912 and launch of first National Tuberculosis Control Programme in 1962, it has remained a major public health challenge to overcome. To accelerate progress towards the goal of ending TB by 2025, 5 years ahead of the global SDG target, it is imperative to outline the incidence and mortality trends of tuberculosis in India. This study aims to provide deep insights into the recent trends of TB incidence and mortality in India from 1990 to 2019.MethodsThis is an observational study based on the most recent data from the Global Burden of Disease (GBD) Study 2019. We extracted numbers, age-specific and age-standardized incidence and mortality rates of Tuberculosis for the period 1990-2019 from the Global Health Data Exchange. The average annual percent change (AAPC) along with 95% Confidence Interval (CI) in incidence and mortality were derived by joinpoint regression analysis; the net age, period, and cohort effects on the incidence and mortality rates were estimated by using Age-Period-Cohort model.ResultsDuring the study period, age-standardized incidence and mortality rates of TB in India declines from 390.22 to 223.01 and from 121.72 to 36.11 per 100,000 population respectively. The Joinpoint regression analysis showed a significant decreasing pattern in incidence rates in India between 1990 and 2019 for both male and female; but larger decline was observed in case of females (AAPC: - 2.21; 95% CI: - 2.29 to - 2.12; p < 0.001) as compared to males (AAPC: - 1.63; 95% CI: - 1.71 to - 1.54; p < 0.001). Similar pattern was observed for mortality where the declining trend was sharper for females (AAPC: - 4.35; 95% CI: - 5.12 to - 3.57; p < 0.001) as compared to males (AAPC: - 3.88; 95% CI: - 4.63 to - 3.11; p < 0.001). For age-specific rates, incidence and mortality rates of TB decreased for both male and female across all ages during this period. The age effect showed that both incidence and mortality significantly increased with advancing age; period effect showed that both incidence and mortality decreased with advancing time period; cohort effect on TB incidence and mortality also decreased from earlier birth cohorts to more recent birth cohorts.ConclusionMortality and Incidence of TB decreased across all age groups for both male and female over the period 1990-2019. The incidence as well as mortality was higher among males as compared to females. The net age effect showed an unfavourable trend while the net period effect and cohort effect presented a favourable trend. Aging was likely to drive a continued increase in the mortality of TB. Though the incidence and mortality of tuberculosis significantly decreased from 1990 to 2019, the annual rate of reduction is not sufficient enough to achieve the aim of India's National Strategic plan 2017-2025. Approximately six decades since the launch of the National Tuberculosis Control Programme, TB still remains a major public health problem in India. Government needs to strengthen four strategic pillars "Detect-Treat-Prevent-Build" (DTPB) in order to achieve TB free India as envisaged in the National Tuberculosis Elimination Programme (2020).

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Why has the antidepressant-placebo difference in antidepressant clinical trials diminished over the past three decades?

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Why has the antidepressant-placebo difference in antidepressant clinical trials diminished over the past three decades?

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