Major Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Bipolar DisorderDepressive DisordersChronic PainSuicidalityPublic Health, Prevention & Behaviour ChangeKetamine

Prospective association of psychological pain and hopelessness with suicidal thoughts

This study (n=108) used the data from three clinical trials where ketamine was used to treat treatment-resistant depression (TRD) or bipolar disorder (BD) to assess the interaction between hopelessness and psychological pain was associated with future suicidal ideation (SI). Psychological pain and hopelessness were not associated with SI in short-term or long-term analyses yet long-term analyses found that SI was associated with later psychological pain and hopelessness.

Authors

  • Carlos Zarate

Published

Journal of Affective Disorders
meta Study

Abstract

Background

Early markers preceding suicide ideation (SI) may provide valuable information for both assessment and treatment. The glutamatergic modulator ketamine has rapid, transient effects on SI, creating an opportunity to observe potential antecedents of the re-emergence of SI. This analysis evaluated whether the interaction between two suicide risk factors-psychological pain and hopelessness-were prospectively associated with SI post-ketamine administration.

Methods

Data were drawn from three ketamine clinical trials of participants with treatment-resistant major depressive disorder or bipolar disorder (n = 108) with short- and/or long-term follow-up (three or 11 days). A random intercept cross-lagged panel model evaluated the longitudinal relationship between the correlated concepts, specifically whether the interaction between hopelessness and psychological pain was associated with future SI.

Results

Psychological pain and hopelessness were not prospectively associated with SI in short-term or long-term analyses; rather, long-term analyses found that SI was associated with later psychological pain and hopelessness. Similarly, no relationship was observed for other suicide risk factors, including anhedonia, depressed mood, and impaired sleep.

Limitations

Secondary analysis of clinical trial data not collected for this purpose; hopelessness and psychological pain were assessed via proxy measures from existing depression rating scales; the small sample size required a restricted statistical model.

Conclusions

Psychological pain and hopelessness were not associated with the re-emergence of SI post-ketamine. These results may be due to limited variability in the data. The re-emergence of SI post-ketamine may also not follow patterns typically seen in non-pharmacologic contexts. Individuals with a history of SI warrant careful monitoring post-ketamine administration.

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Research Summary of 'Prospective association of psychological pain and hopelessness with suicidal thoughts'

Introduction

Suicidal thoughts and behaviours remain a major public health problem, and earlier research has shown limited improvement in predicting suicidal behaviour despite repeated evaluation of similar risk factors. Contemporary suicide theories adopt an "ideation-to-action" framework that treats suicide ideation (SI) as distinct from suicidal behaviour and emphasise the need to identify short-term antecedents that precipitate transitions into states of heightened suicidal thinking. Identifying reliably predictive short-term markers is challenging because SI fluctuates and it is difficult to prospectively observe who will experience re-emergent SI over brief intervals. Ballard and colleagues used clinical trials of the glutamatergic agent ketamine as a model system to study short-term antecedents of SI, because ketamine often produces rapid but transient reductions in SI that then reappear within days. The study tested whether the interaction of two psychological constructs strongly linked to suicide risk—hopelessness (negative expectations about the future) and psychological pain (also termed psychache)—would prospectively predict re-emergence of SI after ketamine. As a secondary aim, the investigators examined whether other depressive symptom clusters (anhedonia, depressed mood, impaired sleep) showed similar prospective relationships with SI.

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Study Details

References (6)

Papers cited by this study that are also in Blossom

Improvement in suicidal ideation after ketamine infusion: Relationship to reductions in depression and anxiety

Ionescu, D. F., Vande Voort, J. L., Niciu, M. J. et al. · Journal of Psychiatric Research (2014)

Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial

Grunebaum, M. F., Galfalvy, H. C., Choo, T. H. et al. · American Journal of Psychiatry (2018)

371 cited
Ketamine has distinct electrophysiological and behavioral effects in depressed and healthy subjects

Nugent, A. C., Ballard, E. D., Gould, T. D. et al. · Molecular Psychiatry (2018)

223 cited
The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis

Wilkinson, S. T., Ballard, E. D., Bloch, M. H. et al. · American Journal of Psychiatry (2017)

Replication of Ketamine’s Antidepressant Efficacy in Bipolar Depression: A Randomized Controlled Add-On Trial

Zarate, C. A., Brutsche, N. E., Ibrahim, L. et al. · Biological Psychiatry (2012)

757 cited

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