The Efficacy of Paroxetine and Placebo in Treating Anxiety and Depression: A Meta-Analysis of Change on the Hamilton Rating Scales

Abstract

BackgroundPrevious meta-analyses of published and unpublished trials indicate that antidepressants provide modest benefits compared to placebo in the treatment of depression; some have argued that these benefits are not clinically significant. However, these meta-analyses were based only on trials submitted for the initial FDA approval of the medication and were limited to those aimed at treating depression. Here, for the first time, we assess the efficacy of a selective serotonin reuptake inhibitor (SSRI) in the treatment of both anxiety and depression, using a complete data set of all published and unpublished trials sponsored by the manufacturer.Methods and FindingsGlaxoSmithKline has been required to post the results for all sponsored clinical trials online, providing an opportunity to assess the efficacy of an SSRI (paroxetine) with a complete data set of all trials conducted. We examined the data from all placebo-controlled, double-blind trials of paroxetine that included change scores on the Hamilton Rating Scale for Anxiety (HRSA) and/or the Hamilton Rating Scale for Depression (HRSD). For the treatment of anxiety (k = 12), the efficacy difference between paroxetine and placebo was modest (d = 0.27), and independent of baseline severity of anxiety. Overall change in placebo-treated individuals replicated 79% of the magnitude of paroxetine response. Efficacy was superior for the treatment of panic disorder (d = 0.36) than for generalized anxiety disorder (d = 0.20). Published trials showed significantly larger drug-placebo differences than unpublished trials (d’s = 0.32 and 0.17, respectively). In depression trials (k = 27), the benefit of paroxetine over placebo was consistent with previous meta-analyses of antidepressant efficacy (d = 0.32).ConclusionsThe available empirical evidence indicates that paroxetine provides only a modest advantage over placebo in treatment of anxiety and depression. Treatment implications are discussed.

Efficacy and Safety of Selective Serotonin Reuptake Inhibitors, Serotonin-Norepinephrine Reuptake Inhibitors, and Placebo for Common Psychiatric Disorders Among Children and Adolescents

“…While in line with older reviews in children 69 , this is in contrast to adult studies that found no significant differences in placebo effect size between depression and anxiety 70 . This contrast is not unique: placebo responses between children and adults differ significantly for binary outcomes across a wide variety of diseases 71 .…”

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

“…Antidepressants are also commonly used for anxiety disorders, OCD, and PTSD (Wong et al., ), but comparatively little evidence regarding the influence of severity is available for these disorders. Trial‐level meta‐analyses have found no evidence that antidepressant efficacy increases with increasing severity (Ackerman & Greenland, ; Curtiss, Andrews, Davis, Smits, & Hofmann, ; Davis, Smits, & Hofmann, ; de Vries, de Jonge, van den Heuvel, Turner, & Roest, ; Sugarman, Loree, Baltes, Grekin, & Kirsch, ). However, such trial‐level analyses may be prone to the ecological fallacy (Thompson & Higgins, ), in which a trial‐level relationship can be found that does not exist at the participant level, or vice versa.…”

Is the Efficacy of “Antidepressant” Medications Overrated?

“…For instance, haloperidol was the most common typical antipsychotic to which atypical antipsychotics were compared (Leucht, Kissling, & Davis,, 2009). In the realm of anxiety treatment, publication bias has been demonstrated for paroxetine (Sugarman, Loree, Baltes, Grekin, & Kirsch, 2014). Further, haloperidol was often given in unnecessarily high doses, leading to increased adverse events and likely reduced efficacy, making the atypical antipsychotics appear safer and a bit more efficacious in comparison (Leucht et al, 2009).…”