Antidepressants versus placebo in major depression: an overview (Khan & Brown) Flashcards
Although the early antidepressant trials which included severely ill and hospitalized patients showed substantial drug-placebo differences,
these robust differences have not held up in the trials of the past couple of decades, whether sponsored by pharmaceutical companies or
non-profit agencies.
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wat voor redenen werden gegeven voor dat er minder drug-placebo differences werden gevonden
- DSM-III aanpassingen, bredere diagnose criteria voor MDD (dus inclusie mild/moderate patients into antidepressant trials) -> deze patienten gevoelig voor placebo-effect
- drug development regulators hebben een grote rol, wilden geen vals positieven en daardoor slechte, lastige trials gemaakt. en nu vinden ze geen goede resultaten meer
wat geloofden we 20 jaar geleden over antidepressants and placebo
Twenty years ago we believed that antidepressants worked in 70% of depressed patients and placebo in 30% of them
A considerable body of research subsequently
exploredwhich depressed patients
responded to select antidepressants
such as …. compared to ….
imipramine and phenelzine compared to electroconvulsive therapy (ECT)
what did Klerman and Cole find regarding the trials evaluating the effectiveness of imipramine
they reported that hospitalized depressed patients with a melancholic pattern of symptoms were most likely to respond to the drug
Much of the wisdom about the magnitude of antidepressant and placebo response was based on these early clinical trials of tricyclic antidepressants, and these data carried well into the early 1990s (6).
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wat was de belangrijkste psychiatrische verandering in de 1970s en 1980s
the advent of DSM 3
waarom had de advent van de dsm 3 zo’n grote impact op de antidepressant industry
Using an atheoretical approach, this diagnostic system minimized differences between subtypes of depression and conceptualized a broad syndrome called major depressive disorder, characterized by a single or recurrent bouts named major depressive episodes. Such a “uniform” diagnosis now included millions of patients and became an attractive target for the pharmaceutical industry. Thus, the American PsychiatricAssociation, sponsor of the DSM-III, unintentionally expanded the market for antidepressants.
wat gebeurde er na de advent van de dsm met clinical trials
die includeerden allerlei soorten patienten, vaak gewoon met generalised mdd, soms met subtypes zoals melancholic maar lang niet altijd.
wat was toen de symptom reduction van deze antidepressants (na dsm3)
40% antidepressants, 30% placebo
wat vonden walsh et al
the magnitude of symptom reduction with placebo had been increasing in the past three decades
the effectiveness of modern antidepressants was not only questioned by placebo controlled trials…
but also by trials based on non placebo trials
wat liet het STAR*D project zien
dat alleen 4 uit 10 depressed outpatients een therapeutic response kregen
wat is nog meer een kritiekpunt op de antidepressiva
dat het heel duidelijk een commerciele venture is. vooral kritiek op integriteit van de data, die gegenereerd wordt door de industrie zelf
wat was een belangrijke beviding over placebos in dit onderzoek
the magnitude of reduction due to placebo pills was larger in non-industry trials than FDA depression trials (dus het placebo effect is groter in non-industry dan FDA depression trial data)
wat laten de gestreepte bars zien en de zwarte
striped: the magnitude of depressive syptom reduction in trials where the investigators and their staff were aware of the design and expectations of the study
black: the magnitude of symptom reduction when the investigators and raters were blinded to the design and execution of the study
dus wat laat het verschil in deze bars zien
expectation bias!