Antidepressant–placebo differences in 16 clinical trials over 10 years at a single site: role of baseline severity

Khan, Arif; Bhat, Amritha; Faucett, James; Kolts, Russell L.; Brown, Walter A.

doi:10.1007/s00213-010-2107-1

Cited by 11 publications

(11 citation statements)

References 13 publications

(14 reference statements)

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“…Specifically, our analysis was based on a drugplacebo difference on the HAM-D 17 that is on the high end of what has been detected in contemporary placebocontrolled antidepressant trials. The average drugplacebo difference on the HAM-D 17 for a number of effective antidepressants is approximately 2.0 (Khan et al, 2011), which is consistent with the mean difference observed for desvenlafaxine in the studies in this analysis. We chose to use the more stringent cutoff of 3.0 rather than 2.0 to effectively 'raise the bar,' as we try to better define 'clinically significant' improvements in functional outcomes.…”

Section: Discussionsupporting

confidence: 82%

Assessing the relationship between functional impairment/recovery and depression severity

Guico-Pabia

Fayyad

Soares

2012

International Clinical Psychopharmacology

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The objective of this study was to explore the relationship between assessments of functional impairment, emotional well-being, and depression symptoms. Data were pooled from 3530 outpatients with major depressive disorder enrolled in 10 desvenlafaxine clinical trials. The primary outcome measures included (a) the 17-item Hamilton Rating Scale for Depression (HAM-D17) as a measure of depressive symptom severity and (b) the Sheehan Disability Scale (SDS) and five-item World Health Organization Well-Being Index (WHO-5) as measures of functional impairment and well-being. A linear regression model was used to identify the SDS and WHO-5 values that equate to the predetermined clinically relevant three-point difference between active treatment and placebo on the HAM-D17. A receiver operating characteristic analysis was conducted to determine the SDS score that equates to a remission of depression symptoms (i.e. HAM-D17≤7). An approximate three-point difference between active treatment and placebo on the SDS (2.8) and WHO-5 (2.5) was determined to be clinically relevant in relation to improvements in depressive symptoms. An SDS of less than or equal to 7 was equivalent to a remission of depression symptoms, providing a definition of functional remission. A better understanding of the relationship between depressive symptoms and functional impairment and well-being may provide clinicians with a more comprehensive means of assessing treatment effects in major depressive disorder.

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Section: Discussionsupporting

confidence: 82%

Assessing the relationship between functional impairment/recovery and depression severity

Guico-Pabia

Fayyad

Soares

2012

International Clinical Psychopharmacology

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“…The finding that antidepressants have modest symptom reducing effects relative to placebo has been replicated in several other studies (Khan et al, 2002, 2005, 2011; Fournier et al, 2010). The British consider the difference between placebo and antidepressant to be small enough to recommend that antidepressants not be used except in cases of severe depression (Bonin, 2012).…”

Section: Modest Efficacy Of Antidepressants During Treatmentmentioning

confidence: 65%

Primum Non Nocere: An Evolutionary Analysis of Whether Antidepressants Do More Harm than Good

Andrews¹,

Thomson²,

Amstadter³

et al. 2012

Front. Psychology

106

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Antidepressant medications are the first-line treatment for people meeting current diagnostic criteria for major depressive disorder. Most antidepressants are designed to perturb the mechanisms that regulate the neurotransmitter serotonin – an evolutionarily ancient biochemical found in plants, animals, and fungi. Many adaptive processes evolved to be regulated by serotonin, including emotion, development, neuronal growth and death, platelet activation and the clotting process, attention, electrolyte balance, and reproduction. It is a principle of evolutionary medicine that the disruption of evolved adaptations will degrade biological functioning. Because serotonin regulates many adaptive processes, antidepressants could have many adverse health effects. For instance, while antidepressants are modestly effective in reducing depressive symptoms, they increase the brain’s susceptibility to future episodes after they have been discontinued. Contrary to a widely held belief in psychiatry, studies that purport to show that antidepressants promote neurogenesis are flawed because they all use a method that cannot, by itself, distinguish between neurogenesis and neuronal death. In fact, antidepressants cause neuronal damage and mature neurons to revert to an immature state, both of which may explain why antidepressants also cause neurons to undergo apoptosis (programmed death). Antidepressants can also cause developmental problems, they have adverse effects on sexual and romantic life, and they increase the risk of hyponatremia (low sodium in the blood plasma), bleeding, stroke, and death in the elderly. Our review supports the conclusion that antidepressants generally do more harm than good by disrupting a number of adaptive processes regulated by serotonin. However, there may be specific conditions for which their use is warranted (e.g., cancer, recovery from stroke). We conclude that altered informed consent practices and greater caution in the prescription of antidepressants are warranted.

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“…However, research in MDD has suggested that antidepressant efficacy may depend upon initial symptom severity. Both trial‐level (Khan, Leventhal, Khan, & Brown, ; Kirsch et al., ) and individual patient data (IPD) meta‐analyses (Fournier et al., ; Khan, Bhat, Faucett, Kolts, & Brown, ; Khan, Brodhead, Kolts, & Brown, ) have found that antidepressants are more effective for patients with high initial severity, with some of these analyses suggesting that efficacy is minimal for patients with mild depression (Fournier et al., ; Kirsch et al., ). Consequently, many guidelines no longer recommend antidepressants for mild depression (National Institute for Health and Care Excellence, ; Spijker et al., ).…”

Section: Introductionmentioning

confidence: 99%

Initial severity and antidepressant efficacy for anxiety disorders, obsessive‐compulsive disorder, and posttraumatic stress disorder: An individual patient data meta‐analysis

et al. 2018

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Antidepressant–placebo differences in 16 clinical trials over 10 years at a single site: role of baseline severity

Abstract: Our results show that no diminution of drug-placebo difference occurs over time when baseline severity remains constant. As such, they support the importance of depression severity as a determinant of antidepressant-placebo difference.

Cited by 11 publications

References 13 publications

Assessing the relationship between functional impairment/recovery and depression severity

Assessing the relationship between functional impairment/recovery and depression severity

Primum Non Nocere: An Evolutionary Analysis of Whether Antidepressants Do More Harm than Good

Initial severity and antidepressant efficacy for anxiety disorders, obsessive‐compulsive disorder, and posttraumatic stress disorder: An individual patient data meta‐analysis

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