Features of Dissociation Differentially Predict Antidepressant Response to Ketamine in Treatment-Resistant Depression
Mark J. Niciu, Bridget J. Shovestul, Brittany A. Jaso, Cristan A Farmer, D. Luckenbaugh, Nancy E. Brutsché, Lawrence T. Park, Elizabeth D. Ballard, Carlos A. Zarate
Journal of Affective Disorders February 17, 2018 DOI: 10.1016/j.jad.2018.02.049 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Follow-up study with confirmatory factor analysis and general linear model Peer reviewed |
|---|---|
| Sample size | 126 |
| Population | Treatment-resistant patients with major depressive disorder or bipolar disorder |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg |
| Measures | Clinician-Administered Dissociative States Scale (CADSS), 17-item Hamilton Depression Rating Scale (HAM-D) |
| Topics | Depression Esketamine Ketamine |
| Citations | 134 |
| Key points | Depersonalization was positively related to antidepressant response across all studies and timepoints, while derealization showed a significant effect at only one timepoint in one study, and amnesia was unrelated. |
Abstract
Background: Ketamine induces rapid and robust antidepressant effects, and many patients also describe dissociation, which is associated with antidepressant response. This follow-up study investigated whether antidepressant efficacy is uniquely related to dissociative symptom clusters.
Methods: Treatment-resistant patients with major depressive disorder (MDD) or bipolar disorder (BD) (n=126) drawn from three studies received a single subanesthetic (0.5mg/kg) ketamine infusion. Dissociative effects were measured using the Clinician-Administered Dissociative States Scale (CADSS). Antidepressant response was measured using the 17-item Hamilton Depression Rating Scale (HAM-D). A confirmatory factor analysis established the validity of CADSS subscales (derealization, depersonalization, amnesia), and a general linear model with repeated measures was fitted to test whether subscale scores were associated with antidepressant response.
Results: Factor validity was supported, with a root mean square error of approximation of .06, a comparative fit index of .97, and a Tucker-Lewis index of .96. Across all studies and timepoints, the depersonalization subscale was positively related to HAM-D percent change. A significant effect of derealization on HAM-D percent change was observed at one timepoint (Day7) in one study. The amnesia subscale was unrelated to HAM-D percent change.
Limitations: Possible inadequate blinding; combined MDD/BD datasets might have underrepresented ketamine’s antidepressant efficacy; the possibility of Type I errors in secondary analyses.
Conclusions: From a psychometric perspective, researchers may elect to administer only the CADSS depersonalization subscale, given that it was most closely related to antidepressant response. From a neurobiological perspective, mechanistic similarities may exist between ketamine-induced depersonalization and antidepressant response, although off-target effects cannot be excluded.