Parsing the heterogeneity of depression: An exploratory factor analysis across commonly used depression rating scales

Abstract

Background: Due to the heterogeneity of depressive symptoms-which can include depressed mood, anhedonia, negative cognitive biases, and altered activity levels-researchers often use a combination of depression rating scales to assess symptoms. This study sought to identify unidimensional constructs measured across rating scales for depression and to evaluate these constructs across clinical trials of a rapid-acting antidepressant (ketamine).

Methods: Exploratory factor analysis (EFA) was conducted on baseline ratings from the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Snaith-Hamilton Pleasure Rating Scale (SHAPS). Inpatients with major depressive disorder (n = 76) or bipolar depression (n = 43) were participating in clinical ketamine trials. The trajectories of the resulting unidimensional scores were evaluated in 41 subjects with bipolar depression who participated in clinical ketamine trials.

Results: The best solution, which exhibited excellent fit to the data, comprised eight factors: Depressed Mood, Tension, Negative Cognition, Impaired Sleep, Suicidal Thoughts, Reduced Appetite, Anhedonia, and Amotivation. Various response patterns were observed across the clinical trial data, both in treatment effect (ketamine versus placebo) and in degree of placebo response, suggesting that use of these unidimensional constructs may reveal patterns not observed with traditional scoring of individual instruments.

Limitations: Limitations include: 1) small sample (and related inability to confirm measurement invariance); 2) absence of an independent sample for confirmation of factor structure; and 3) the treatment-resistant nature of the population, which may limit generalizability.

Conclusions: The empirical identification of unidimensional constructs creates more refined scores that may elucidate the connection between specific symptoms and underlying pathophysiology.

Trial registration: ClinicalTrials.gov NCT00088699.

Keywords: Clinical trials; Depression; Factor analysis; Ketamine; Psychometrics.

Conflict of interest statement

Declaration of Interest

Dr. Zarate is listed as a coinventor on a patent for the use of ketamine and its metabolites in major depression and suicidal ideation. Dr. Zarate is listed as a co-inventor on a patent for the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereoisomeric dehydro and hydroxylated metabolites of (R,S)-ketamine metabolites in the treatment of depression and neuropathic pain. Dr. Zarate is listed as co-inventor on a patent application for the use of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders; he has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. All other authors have no conflict of interest to disclose, financial or otherwise.

Published by Elsevier B.V.

Figures

Figure 1. Results of mixed models in Bipolar Depression analysis (n=41)

Item-mean scores reflect the average proportion of points endorsed to points available across items on the subscale. For all constructs except Tension, Impaired Sleep, and Reduced Appetite, the difference between ketamine and placebo was statistically significant (p<.05) at all post-baseline assessments. The effect of drug on Tension was significant except at Day 3. The effect of drug on Impaired Sleep was not significant until 230 minutes. The effect of drug on Reduced Appetite was significant (in favour of placebo) until 230, after which it was not significant. BDI: Beck Depression Inventory; HAM-D: Hamilton Rating Scale for Depression; MADRS: Montgomery-Asberg Depression Rating Scale; SHAPS: Snaith Hamilton Pleasure Scale.

Figure 2. Effect sizes (ketamine versus placebo) at Day 1 in the Bipolar Depression analysis (n=41)

Effect sizes were calculated using least square mean estimates at Day 1 from the mixed model. BDI: Beck Depression Inventory; HAM-D: Hamilton Rating Scale for Depression; MADRS: Montgomery-Asberg Depression Rating Scale; SHAPS: Snaith Hamilton Pleasure Scale.