A regulatory Apologia — A review of placebo-controlled studies in regulatory submissions of new-generation antidepressants

Melander, Hans; Salmonson, Tomas; Abadie, Eric; Zwieten-Boot, Barbara van

doi:10.1016/j.euroneuro.2008.06.003

Cited by 108 publications

(70 citation statements)

References 6 publications

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“…A difference between active treatment and placebo response rates of 10% may be regarded as indicative of a clinically relevant advantage (Montgomery and Moller, 2009). Furthermore, a published analysis of several SSRI and SNRI trials reported an average difference in response rates between antidepressant and placebo of 16% (Melander et al, 2008). Thus, by either of these two markers, the mean response rates for quetiapine XR reported here suggest a clinically relevant effect.…”

Section: Discussionmentioning

confidence: 50%

Efficacy of extended release quetiapine fumarate monotherapy in patients with major depressive disorder

Weisler

Montgomery

Earley

et al. 2012

International Clinical Psychopharmacology

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Prospectively planned pooled analysis evaluating the efficacy of quetiapine extended release (XR) monotherapy in major depressive disorder (MDD). Data were pooled from two 6-week, randomized, double-blind, placebo-controlled studies of quetiapine XR in outpatients with MDD. The primary endpoint was Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from randomization at week 6. Other evaluations were MADRS response/remission, Hamilton Rating Scale for Anxiety, and subgroup analyses. A total of 968 patients were randomized to quetiapine XR, 150 mg/day (n=315), 300 mg/day (n=323), or placebo (n=330). The mean MADRS total score reductions from randomization were significant at week 6 with quetiapine XR, 150 mg/day (-14.7; P<0.001) and 300 mg/day (-14.7; P<0.001) versus placebo (-11.1), with significant reductions versus placebo from week 1 onward. Response rates (week 6): 52.7% (P<0.001) quetiapine XR 150 mg/day and 49.5% (P<0.001) quetiapine XR 300 mg/day versus placebo (33.0%). MADRS remission (score≤8; week 6): 23.5% (P=0.208) quetiapine XR 150 mg/day and 28.8% (P<0.01) quetiapine XR 300 mg/day versus placebo (19.4%). Quetiapine XR (both doses) significantly improved eight of 10 MADRS items versus placebo at week 6. The therapeutic effect of quetiapine XR was neither limited to nor driven by factors such as sex, age, or severity of depression. In patients with MDD, quetiapine XR (150 and 300 mg/day) monotherapy reduced depressive symptoms, with significant improvements compared with placebo from week 1 onward.

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Section: Discussionmentioning

confidence: 50%

Efficacy of extended release quetiapine fumarate monotherapy in patients with major depressive disorder

Weisler

Montgomery

Earley

et al. 2012

International Clinical Psychopharmacology

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“…First, perhaps the best-known issue in trials of depression and schizophrenia is the increasing difficulty of separating drug from placebo which, in the context of a modern clinical trial, resembles a form of "psychotherapy" with multifarious neurobiological effects (Alphs et al, 2012;Enck et al, 2013;Melander et al, 2008;Benedetti, 2014). Ironically, this advantage will not usually be available in the real-world of treatment (Enck et al, 2013).…”

Section: Lack Of Clinical Efficacy In Clinical Trials: Possible Explamentioning

confidence: 98%

Learning from the past and looking to the future: Emerging perspectives for improving the treatment of psychiatric disorders

Millan¹,

Goodwin²,

Meyer‐Lindenberg³

et al. 2015

European Neuropsychopharmacology

113

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“…Placebo-controlled studies in depression face a variety of challenges. A recent review of all the data submitted to the European Medicines Agency [1] demonstrated that the average treatment benefit when comparing rates of response of actively treated patients with those treated with placebo was approximately 17%. In other words, the bench mark against which any new compound should be compared is relatively modest and there is substantial variation around that figure in the total sample of clinical trials conducted.…”

Section: Clinical Trials In Major Depressionmentioning

confidence: 98%

Clinical Studies on the Efficacy of Agomelatine on Depressive Symptoms

Goodwin

2009

CNS Drugs

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The novel mechanism of action of agomelatine, with affinity for melatonergic and 5-HT(2C) receptors, offers the prospect of efficacy in major depression and anxiety with minimal adverse effects. The challenge of performing acute placebo-controlled treatment trials in a relevant sample of patients with moderate to severe major depression is considerable. The efficacy of active treatment may be obscured by excessive responses in placebo and active treatment arms. The agomelatine programme has successfully introduced methodological innovation to overcome this risk and ensure that cases of major depression display adequate severity on both ratings of symptoms and measures of functional impairment. The efficacy of agomelatine in major depression has thus been demonstrated at doses of 25-50 mg against the full range of symptoms that make up the depressive syndrome in patients with moderate to severe major depression.

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A regulatory Apologia — A review of placebo-controlled studies in regulatory submissions of new-generation antidepressants

Cited by 108 publications

References 6 publications

Efficacy of extended release quetiapine fumarate monotherapy in patients with major depressive disorder

Efficacy of extended release quetiapine fumarate monotherapy in patients with major depressive disorder

Learning from the past and looking to the future: Emerging perspectives for improving the treatment of psychiatric disorders

Clinical Studies on the Efficacy of Agomelatine on Depressive Symptoms

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