Pain mediates the improvement of social functions of repeated intravenous ketamine in patients with unipolar and bipolar depression
This re-analysis of an open-label study (n=103) investigated the effects of ketamine (35mg/70kg, 6x) on pain, depression, and social function in patients with bipolar or unipolar depressive disorder. The results showed that ketamine treatment significantly improved psychosocial functioning and reduced pain index. Mediation analysis revealed that the severity of depressive symptoms and the affective index of pain partially mediated the association between ketamine treatment and improvements in subjective and objective social functioning.
Authors
- Yuping Ning
- Chengyu Wang
Published
Abstract
Objective
Previous research has shown that ketamine can improve social functions. In addition, evidence also suggests that ketamine can alleviate pain. Herein, we propose that ketamine-induced improvements in pain and depression are partially mediated by a reduction in pain. We aimed to determine whether improvements in pain-mediated changes in psychological function were associated with ketamine treatment.
Method
This trial included unipolar or bipolar patients (n = 103) who received 6 intravenous infusions (0.5 mg/kg) of ketamine over 2 weeks. The severity of current depressive symptoms and social function were evaluated by the Montgomery-Åsberg Depression Scale (MADRS), Self-Rating Depression Scale (SDS) and Global Assessment Function (GAF), respectively, at baseline and on day 13 and day 26. At the same time points, the three dimensions of pain, including the sensory index, affective index and present pain intensity (PPI), were measured by the Simple McGill Pain Scale (SF-MPQ).
Results
The mixed model results showed that ketamine plays an important role in improving the psychosocial functioning of patients. There was a significant decrease from baseline to the day 13 and day 26, indicating that the pain index of the patient improved significantly. Mediation analysis showed that for SDS score (coef = −5.171, 95 % CI[−6.317, −4.025]) and GAF score (coef = 1.021, 95 % CI[0.848, 1.194]), the overall effect of ketamine was observable. The overall indirect and direct effects of ketamine on social functioning were significant (SDS: direct: coef = −1949 to −2114; total indirect: from 0.594 to 0.664; GAF: from 0.399 to 0.427; total indirect: coef = 0.593 to 0.664). The MADRS total score and emotional index were important mediators of the association between ketamine treatment and improvements in subjective and objective social functioning.
Conclusion
Depressive symptom severity and the affective index of pain partially mediated improvements in social function after six repeated ketamine treatments among patients with bipolar or unipolar depressive disorder.
Research Summary of 'Pain mediates the improvement of social functions of repeated intravenous ketamine in patients with unipolar and bipolar depression'
Introduction
Depressive disorders, including major depressive disorder (MDD) and bipolar depression, cause marked impairments in psychosocial functioning and are a major contributor to global disease burden. A substantial proportion of patients are treatment resistant and conventional antidepressants can be slow to act; chronic pain is common in depressive disorders and is associated with worse psychosocial outcomes. Over the past two decades, subanaesthetic doses of the NMDA receptor antagonist ketamine have shown rapid antidepressant effects and preliminary evidence suggests ketamine may also relieve pain and improve functional outcomes, but the pathways linking symptom change to functional recovery are unclear. Wu and colleagues set out to test whether improvements in psychosocial functioning following a course of repeated intravenous ketamine are mediated by changes in depressive symptoms and/or by reductions in pain. Specifically, the authors hypothesised that total depressive symptom severity (MADRS) and the affective component of pain would act as important mediators of improvements in both subjective (SDS) and objective (GAF) measures of social functioning after six ketamine infusions.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Wu, Z., Gan, Y., Li, N., Lan, X., Wang, C., Zhang, F., Liu, H., Li, W., Ye, Y., Hu, Z., Ning, Y., & Zhou, Y. (2023). Pain mediates the improvement of social functions of repeated intravenous ketamine in patients with unipolar and bipolar depression. Journal of Affective Disorders, 334, 152-158. https://doi.org/10.1016/j.jad.2023.04.122
References (5)
Papers cited by this study that are also in Blossom
Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)
Hashimoto, K. · Psychiatry and Clinical Neurosciences (2019)
Singh, J. B., Fedgchin, M., Daly, E. J. et al. · American Journal of Psychiatry (2016)
Zheng, W., Zhou, Y-L., Liu, W. et al. · Journal of Psychiatric Research (2018)
Liu, W., Wang, C., Zhan, Y. et al. · Journal of Psychopharmacology (2018)
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