Severity of depressive symptoms and response to antidepressants and placebo in antidepressant trials

Khan, Arif; Brodhead, Amy E.; Kolts, Russell L.; Brown, Walter A.

doi:10.1016/j.jpsychires.2004.06.005

Cited by 107 publications

(66 citation statements)

References 16 publications

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“…41 The large effect size we observed reflects the small and transient placebo response shown by these samples (as expected given the severity and chronicity of illness) 42 and the robustness of the antidepressant effect. The latter is highlighted by the proportion of the sample achieving remission with scopolamine vs placebo (56%), which compares with 10% to 20% with antidepressant agents that lack anticholinergic effects compared with placebo.…”

Section: Commentsupporting

confidence: 51%

Antidepressant Efficacy of the Antimuscarinic Drug Scopolamine

Furey¹,

Drevets²

2006

Arch Gen Psychiatry

390

292

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Context-The need for improved therapeutic agents that more quickly and effectively treat depression is critical. In a pilot study we evaluated the role of the cholinergic system in cognitive symptoms of depression and unexpectedly observed rapid reductions in depression severity following the administration of the antimuscarinic drug scopolamine hydrobromide (4 μg/kg intravenously) compared with placebo (P=.002). Subsequently a clinical trial was designed to assess more specifically the antidepressant efficacy of scopolamine.Objective-To evaluate scopolamine as a potential antidepressant agent.Design-Two studies were conducted: a double-blind, placebo-controlled, dose-finding study followed by a double-blind, placebo-controlled, crossover clinical trial. Setting-The National Institute of Mental Health.Patients-Currently depressed outpatients aged 18 to 50 years meeting DSM-IV criteria for recurrent major depressive disorder or bipolar disorder. Of 39 eligible patients, 19 were randomized and 18 completed the trial.Interventions-Multiple sessions including intravenous infusions of placebo or scopolamine hydrobromide (4 μg/kg). Individuals were randomized to a placebo/ scopolamine or scopolamine/ placebo sequence (series of 3 placebo sessions and series of 3 scopolamine sessions). Sessions occurred 3 to 5 days apart.Main Outcome Measures-Psychiatric evaluations using the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale were performed to assess antidepressant and antianxiety responses to scopolamine.Results-The placebo/scopolamine group showed no significant change during placebo infusion vs baseline; reductions in depression and anxiety rating scale scores (P<.001 for both) were observed after the administration of scopolamine compared with placebo. The scopolamine/ placebo group also showed reductions in depression and anxiety rating scale scores (P<.001 for both) after the administration of scopolamine, relative to baseline, and these effects persisted as they received placebo. In both groups, improvement was significant at the first evaluation after scopolamine administration (P≤.002).Conclusion-Rapid, robust antidepressant responses to the antimuscarinic scopolamine occurred in currently depressed patients who predominantly had poor prognoses.Correspondence: Maura L. Furey, PhD, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, 15K North Dr, Bldg 15K, Room 115B, Bethesda, MD 20892 (mfurey@mail.nih.gov). Additional Information: A use-patent application for the use of scopolamine as an antidepressant agent has been filed. NIH Public Access Author ManuscriptArch Gen Psychiatry. Author manuscript; available in PMC 2012 January 3. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMajor depression is the leading cause of years lived with disability. 1 A range of antidepressant agents is available, but 30% to 40% of patients with major depressive disorder (MDD) do not respond to initial treatment, 2 an...

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Section: Commentsupporting

confidence: 51%

Antidepressant Efficacy of the Antimuscarinic Drug Scopolamine

Furey¹,

Drevets²

2006

Arch Gen Psychiatry

390

292

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“…Elkin et al [44] found that, among patients with an RDC diagnosis of major depressive disorder, those with an initial score of less than 20 on the HRSD-17 did not recover more frequently with imipramine, cognitive behavioural therapy or interpersonal therapy than with placebo plus clinical management, whereas patients with an initial score of 20 or more did significantly better with imipramine and interpersonal therapy than with placebo. Similarly, in an analysis of 15 placebo-controlled trials of new antidepressants, patients with an initial score of 29 or higher on the HRSD-17 had an effect size of 1.09, whereas the effect size was 0.51 in those with an initial score of 13–22 [45]. …”

Section: Validation Of the Concept Of Major Depressionmentioning

confidence: 99%

Development and Validation of the Current Concept of Major Depression

Maj¹

2012

Psychopathology

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The operational diagnostic criteria for major depression have remained more or less the same in the past 40 years. However, the threshold for the diagnosis fixed by operational definitions has been criticized for either being too high, excluding many depressive states which do not differ from currently defined major depression on several variables, or too low, so that the milder cases receiving the diagnosis do not respond to antidepressants better than to placebo. Furthermore, it has been stated that current operational criteria do not convey anymore the gestalt of the depressive syndrome, and that they lead to the inclusion under the heading of depression of several homeostatic responses to adverse life events. This paper reviews the development and validation of the current concept of major depression and identifies priorities for future research.

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“…The response to antidepressant therapy is greater for patients that are severely depressed at baseline measurement as compared to patients with less severe depression (Elkin et al 1989;Fournier et al 2010;Khan et al 2002b;Khan et al 2005;Kirsch et al 2008;Klerman & Cole 1965). Less is known about the response of more severely depressed patients assigned to the placebo trial arm, although there is an assumption that placebo treatment is more effective for patients with less severe depression.…”

Section: Introductionmentioning

confidence: 99%