Abstract
The Hamilton Depression Rating Scale (HDRS-17) measures symptoms that may overlap with common antidepressant side effects (e.g., sexual dysfunction), thus making it possible that side effects of antidepressant treatment are erroneously rated as symptoms of depression, and vice versa. This study uses patient-level data from previously conducted antidepressant treatment trials to assess whether side effect ratings co-vary with HDRS-17 ratings. Data from all HDRS-17-rated, industry-sponsored pre- and post-marketing trials (n = 4647) comparing the serotonin and noradrenaline reuptake inhibitor, duloxetine, to placebo and/or to a selective serotonin reuptake inhibitor were pooled; three studies, which utilised sub-therapeutic doses, did not have symptom-level ratings available and could not be included. Severity was assessed for side effects related to sleep, somatic anxiety, gastrointestinal function, and sexual dysfunction. Analysis of covariance was used to assess the relation between these side effects and ratings of relevant HDRS-17-derived outcome parameters. Side effects related to sleep, somatic anxiety and sexual dysfunction significantly and exclusively associated with higher scores on HDRS-17 items measuring the corresponding domains. Side effects related to gastrointestinal function associated with higher HDRS-17 item scores on all assessed domains. Treatment outcome was significantly related to side effect severity when assessed using HDRS-17-sum (beta 0.32 (0.074), p < 0.001), but not when the HDRS-6-sum-score (beta 0.035 (0.043), p = 0.415) or the depressed mood item (beta 0.007 (0.012), p = .527) were used as effect parameters. That some HDRS-17 items co-vary with common antidepressant side effects suggests some of these adverse events are counted twice, potentially leading to an underestimation of antidepressant efficacy.
Highlights
It is desirable that a rating scale accurately reflects the underlying severity of the condition it aims to depict, as well as how this severity is influenced by treatment[1,2]
The primary finding of this study is that the HDRS-17 sum-score associates with side effects (SEs) commonly occurring in patients treated with sum as a measureSelective serotonin reuptake inhibitors (SSRIs) or serotonin and noradrenaline reuptake inhibitors (SNRIs), and that this impact is primarily mediated by the HDRS items that show content overlap with the corresponding SEs
As a follow-up analysis, we looked at the association between SEs and outcome measured by the sum of the HDRS items not included in the HDRS-6 subscale (Fig. 3 and Supplementary Fig. 3)
Summary
It is desirable that a rating scale accurately reflects the underlying severity of the condition it aims to depict, as well as how this severity is influenced by treatment[1,2]. This has since long been suggested not to be the case for the effect parameter most widely used in trials of antidepressants, namely the sum of the 17 items of the Hamilton Depression Rating Scale (HDRS-17-sum)[3,4,5,6]. It is possible that the antidepressant efficacy of compounds with sedative or appetite increasing effects may be erroneously overestimated due to reduced ratings of sleep disturbance or weight loss[15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
