A critical evaluation of QIDS-SR-16 using data from a trial of psilocybin therapy versus escitalopram treatment for depression

Abstract

Background: In a recent clinical trial examining the comparative efficacy of psilocybin therapy (PT) versus escitalopram treatment (ET) for major depressive disorder, 14 of 16 major efficacy outcome measures yielded results that favored PT, but the Quick Inventory of Depressive Symptomatology, Self-Report, 16 items (QIDS-SR16) did not. Aims: The present study aims to (1) rationally and psychometrically account for discrepant results between outcome measures and (2) to overcome psychometric problems particular to individual measures by re-examining between-condition differences in depressive response using all outcome measures at item-, facet-, and factor-levels of analysis. Method: Four depression measures were compared on the basis of their validity for examining differences in depressive response between PT and ET conditions. Results/Outcomes: Possible reasons for discrepant findings on the QIDS-SR16 include its higher variance, imprecision due to compound items and whole-scale and unidimensional sum-scoring, vagueness in the phrasing of scoring options for items, and its lack of focus on a core depression factor. Reanalyzing the trial data at item-, facet-, and factor-levels yielded results suggestive of PT’s superior efficacy in reducing depressed mood, anhedonia, and a core depression factor, along with specific symptoms such as sexual dysfunction. Conclusion/Interpretation: Our results raise concerns about the adequacy of the QIDS-SR16 for measuring depression, as well as the practice of relying on individual scales that tend not to capture the multidimensional structure or core of depression. Using an alternative approach that captures depression more granularly and comprehensively yielded specific insight into areas where PT therapy may be particularly useful to patients and clinicians.

Psychedelics and sexual functioning: a mixed-methods study

“…With regard to sexual dysfunction, patients treated with escitalopram were more likely to retrospectively report higher levels of sexual dysfunction after treatment compared with the individuals treated with psilocybin. These observations are consistent with recent findings from the same trial that explicit symptoms of depression related to SD (i.e., Hamilton Rating Scale for Depression-17 Libido 50 , Beck Depression Inventory-Reduced Sexual Interest 51 ), as well as amotivation, anhedonia and energy levels were among the most differentially responsive to psilocybin versus escitalopram 52 . The results constitute the first empirical evidence that psychedelics might exert beneficial effects on sexual functioning and sexual wellbeing after acute use of the drug itself, consistent with previous qualitative reports indicating such an effect 30 – 35 .…”

Effects of discontinuation of serotonergic antidepressants prior to psilocybin therapy versus escitalopram for major depression

“…These results provide a more nuanced interpretation of the results presented in ( Carhart-Harris et al, 2021 ), which reported an absence of evidence for an effect of treatment condition in the primary outcome QIDS-SR-16 (despite there being between-subjects differences in other measures of depression, possibly linked to the presence of compound imprecise items in the primary outcome ( Weiss et al, 2023 )). The analysis presented in this work reveals that this was the case only for discontinuers, suggesting that a discontinuation confound may have contributed to a dampening of true differences between treatment condition – that is, a superior efficacy of psilocybin.…”

Psychedelics and the ‘inner healer’: Myth or mechanism?

“…The BDI was chosen to assess the predictive validity of the inner healer item due to its apparent mechanistic sensitivity and validity in relation to psilocybin ( Daws et al, 2022 ). We chose not to use the Quick Inventory for Depressive Symptomatology - Self Rated assessment 16 (QIDS-SR16) due to problems that have been identified with the scale, as described in detail here ( Weiss et al, 2023 ).…”