Multisite international collaborative clinical trials in mania

Vázquez, Gustavo; Baldessarini, Ross J.; Yıldız, Ayşegül; Tamayo, Jorge M.; Tondo, Leonardo; Salvatore, Paola

doi:10.1017/s1461145711000447

Cited by 12 publications

(11 citation statements)

References 25 publications

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“…This trend probably has encouraged increased reliance on larger trials (more subjects and collaborating sites) in order to maintain statistical power. Moreover, increasing reliance on complex trials carried out in varied geographic locations and cultures may tend to limit the reliability of research findings (Vázquez et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…It is increasingly clear that drug-placebo differences in trials of antidepressants and other psychotropic agents have been declining (Gartlehner et al, 2008;Ioannidis, 2008;Kirsch et al, 2008;Tsapakis et al, 2008;Turner et al, 2008;Bridge et al, 2009;Masi et al, 2010;Khin et al, 2011;Vázquez et al, 2011;Yildiz et al, 2011a, b). In accord with recent findings in controlled treatment trials for mania (Yildiz et al, 2011a, b), a secular increase in sites and participants per trial was associated, selectively, with rising placeboassociated response rates, resulting in declining drugplacebo contrasts or effect-size (Figure 2; Table 3).…”

Section: Discussionmentioning

confidence: 99%

“…In accord with recent findings in controlled treatment trials for mania (Yildiz et al, 2011a, b), a secular increase in sites and participants per trial was associated, selectively, with rising placeboassociated response rates, resulting in declining drugplacebo contrasts or effect-size (Figure 2; Table 3). We propose that this tendency may, at least in part, reflect declining quality-control and greater heterogeneity of diagnostic and clinical assessments in large, complex, multi-site trials, particularly when dissimilar cultures are involved and local standardization of assessment methods is limited (Yildiz et al, 2011a, b;Vázquez et al, 2011). We propose that selective increases in response rates associated with randomized placebo-treatment might reflect 'regression-to-mean' effects (Anderson, 1990;Bland and Altman, 1994) or random outcomes.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Randomized, Placebo-Controlled Trials of Antidepressants for Acute Major Depression: Thirty-Year Meta-Analytic Review

Undurraga

Baldessarini

2011

Neuropsychopharmacol

218

168

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Antidepressant-placebo response-differences (RDs) in controlled trials have been declining, potentially confounding comparisons among older and newer drugs. For clinically employed antidepressants, we carried out a meta-analytic review of placebo-controlled trials in acute, unipolar, major depressive episodes reported over the past three decades to compare efficacy (drug-placebo RDs) of individual antidepressants and classes, and to consider factors associated with year-of-reporting by bivariate and multivariate regression modeling. Observed drug-placebo differences were moderate and generally similar among specific drugs, but larger among older antidepressants, notably tricyclics, than most newer agents. This outcome parallels selective increases in placebo-associated responses as trial-size has increased in recent years. Study findings generally support moderate efficacy of clinically employed antidepressants for acute major depression, but underscore limitations of meta-analyses of controlled trials for ranking drugs by efficacy. We suggest that efficiency and drug-placebo differences may be improved with fewer sites and subjects, and better quality-control of diagnostic and clinical assessments.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Randomized, Placebo-Controlled Trials of Antidepressants for Acute Major Depression: Thirty-Year Meta-Analytic Review

Undurraga

Baldessarini

2011

Neuropsychopharmacol

218

168

View full text Add to dashboard Cite

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“…To compensate, some investigators seek ever-larger samples and pool data across multiple, often culturally and clinically heterogeneous, sites. This option can provide larger numbers of subjects seemingly more ef fi ciently, but standards of diagnosis, clinical assessment, and staff-training may be compromised, and greater variance in outcomes introduced from variance in local, cultural differences in the interpretation of diagnostic and symptomatic concepts [ 215 ] . Such efforts to increase numbers may be able to force statistical signi fi cance from modest drug-placebo differences, but may well increase risk of misleading fi ndings.…”

Section: Comparative Ef Fi Cacy Among Antipsychotic Drugsmentioning

confidence: 99%

Antipsychotic Agents

Baldessarini

2012

Chemotherapy in Psychiatry

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“…It is also likely that heterogeneity and compromised control of the conduct of trials have contributed to a noteworthy trend in recent years toward falling drug-placebo contrasts in trials of various types of psychotropic drugs [ 77,83 ] . In turn, it is tempting to combat this trend by use of ever-larger and more complex multisite trials in order to increase statistical power ( N ) as effect-size (drug-placebo contrast) diminishes, in a basically circular process [ 77,78 ] .…”

Section: Effects Of Trial Sizementioning

confidence: 99%

Modern Psychopharmacology and Psychiatric Treatment

Baldessarini

2012

Chemotherapy in Psychiatry

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In the fi elds of observation chance favors only the prepared mind Louis PasteurThe need for effective treatments of psychiatric disorders is indicated by the high prevalence of many of these disorders [ 47 ] , particularly substance-use, anxiety, and mood disorders, as well as their high burden of direct and indirect costs to society (Tables 1.1 and 1.2 ). Psychiatric, substance-abuse, and primary brain disorders account for approximately 13% of the global disease burden (years of healthy life lost due to early death or disability). Depression alone, even excluding bipolar disorders, is the third leading contributor to the worldwide disability. Associated suicides number 1.5 million/year, and attempts are estimated at over 20 million/year [ 24 ] . Throughout the recorded history of medicine, efforts have been made to utilize chemical or medicinal means to modify abnormal behavior and emotional pain. Alcohol and opiates have been used for centuries not only by physicians and healers but also spontaneously for their soothing or mind-altering effects. Stimulant and hallucinogenic plant products also have been a part of folk practices for centuries. More recently, man has applied modern technology, fi rst to "rediscovering" and purifying many natural products, later to synthesizing and manufacturing their active principles or structural variants with desired properties. Throughout the discussion that follows, the classes of chemicals used for their psychotropic effects (altering feelings, thinking, or behavior) are referred to by the somewhat arbitrary terms antipsychoti c, antimanic or mood-stabilizing , antidepressant , and antianxiety agents. This system of terminology grows out of the allopathic tradition of modern scienti fi c medicine, which treats with drugs producing effects opposite, or antagonistic to the signs and symptoms of a given illness.The modern era of psychopharmacology can be dated from 1949, when the antimanic effects of the lithium ion were discovered, or 1952, when the psychotropic and antiadrenergic effects of reserpine were investigated, and when the special properties of chlorpromazine began to be recognized. The antidepressant monoamineoxidase (MAO) inhibitor iproniazid also was introduced in the early 1950s, and in the

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Multisite international collaborative clinical trials in mania

Cited by 12 publications

References 25 publications

Randomized, Placebo-Controlled Trials of Antidepressants for Acute Major Depression: Thirty-Year Meta-Analytic Review

Randomized, Placebo-Controlled Trials of Antidepressants for Acute Major Depression: Thirty-Year Meta-Analytic Review

Antipsychotic Agents

Modern Psychopharmacology and Psychiatric Treatment

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