Antidepressant trials depression rating scales

Throughout the rest of this chapter, response and remission rates are used. Therefore, these concepts are briefly discussed here. Response is most often defined as a 50% or greater reduction in symptom severity as measured by a standardized rating assessment such as the Hamilton Depression Rating Scale (HDRS). The drawback to this approach is that response does not differentiate between partial and complete response, particularly when the initial symptom severity is high. Thus, a patient could be classified as a responder and still be quite symptomatic. In some instances, a patient could be classified as responder and still meet entry requirements for an antidepressant clinical trial based on their persistent symptom severity. 

Beck Depression Inventory. The Beck Depression Inventory (Beck) test may be used to measure the depth of depression as a rapid screen for depressed patients. It is a self-rating scale of 21 items (13 in a shortened form), with each item rated on a four-point scale. It measures the immediate present and has been used in antidepressant medicine trials. The original 21-item scale can be completed in about 10 minutes and the test is able to discriminate between anxiety and depression. No subtests are present in the Beck. 

Venlafaxine is not FDA approved for use in children below the age of 18 however, it has been used in this population as an antidepressant as well as treatment for ADHD. In 1997, a placebo-controlled trial for children and adolescents (n = 32) diagnosed with major depression failed to show a difference between the control and venlafaxine groups (Mandoki, et al., 1997), possibly because of subtherapeutic doses of venlafaxine. A 5-week open trial of venlafaxine (n = 14) in children and adolescents (ages 8-14) with ADHD yielded significant improvements in parent ratings of hyperactivity and impulsivity on the Conners Parent rating scales (Olvera et ah, 1996). 

Another meta-analysis of placebo-controlled trials in depression published between 1980 and 2000 showed an increase in the response rates in the placebo arms of trials with a variety of antidepressants (Walsh et al.y 2002). Responses to placebo increased significantly in recent years, as shown by the high positive correlation with the year of publication. The association between response rate and year of publication was more statistically robust for placebo than for active medication. The change in placebo response rate did not appear to be explained directly by changes in study characteristics such as patient age, placebo lead-in or minimum required Hamilton Rating Scale for Depression score. A potential explanation could be the changing awareness of patients and the fact that many patients in recent clinical trials had been exposed to several previous treatments and thus expected to improve (see Box 5.4). 

In contrast a large trial of a naturally occurring biological compound called Substance P found no detectable difference from placebo. However the fact that substance P was associated with almost no side effects means that it was probably not distinguishable from an inert placebo. Paroxetine was used as the active comparator in these trials and the published paper suggests that its antidepressant effects were confirmed. In fact the difference between paroxetine and placebo was a miniscule 2-3 points on the Hamilton Rating Scale for Depression (Keller et al. 2006). 

Most efficacy trials with reboxetine have so far only been published in review articles ( 178). Most of these articles did not have peer review and do not contain the full details concerning methodology or results. This fact limits the ability to accurately determine its relative efficacy and tolerability. In short-term (4 to 8 weeks), placebo-controlled clinical trials, reboxetine produced a response (defined as at least a 50% reduction in severity scores) in 56% to 74% of patients. These results were statistically superior to placebo in most studies. Reboxetine was also found to be as effective as imipramine and desipramine in four double-blind, randomized, active-controlled (but not placebo-controlled) studies involving more than 800 outpatients or inpatients with major depression. Reboxetine produced equivalent antidepressant response rates compared with fluoxetine in two clinical trials, one of which was also placebo-controlled. However, reboxetine was reported to have improved social motivation and behavior more than fluoxetine as assessed by the newly developed Social Adaptation Self-Evaluation Scale. In all of the studies, reboxetine had a similar time (i.e., 2 to 3 weeks) to onset of the antidepressant efficacy as do other antidepressants. 

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