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Y. Yang

Repeated ketamine injections in synergy with antidepressants for treating refractory depression: A case showing 6-month improvement.

August 30, 2019 / Depression, Ketamine, Papers, Psychiatry, Psychology, Publications / By / , , , , , ,

Abstract

WHAT IS KNOWN AND OBJECTIVE:
Some patients with refractory depression who fail to respond to rapid injection of standard-dose ketamine are injected with high doses, but the safety and efficacy of this practice are unclear.
CASE DESCRIPTION:
A 57-year-old woman with refractory depression whose symptoms did not improve after 20-seconds intravenous injection of 0.5 mg/kg ketamine went into remission following eight, 1-minute intravenous injections of 1 mg/kg ketamine delivered over a 4-week period. By 6-month follow-up, no significant adverse events had occurred and cognitive function had improved.
WHAT IS NEW AND CONCLUSION:
High-dose intravenous injections of ketamine may stably improve depressive symptoms and cognitive function in patients with refractory depression who do not respond to rapid intravenous injection of standard-dose ketamine. The high-dose treatment appears to be associated with only mild side effects.
Wang, M., Xiong, Z., Su, B., Wang, L., Li, Z., Yang, Y., & Fang, J. (2019). Repeated ketamine injections in synergy with antidepressants for treating refractory depression: A case showing 6-month improvement. Journal of clinical pharmacy and therapeutics., https://doi.org/10.1111/jcpt.13041
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Ketamine blocks bursting in the lateral habenula to rapidly relieve depression

February 14, 2018 / Depression, Ketamine, Neuroscience, Papers, Psychology, Psychopharmacology, Publications / By / , , , , , ,

Abstract

The N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine has attracted enormous interest in mental health research owing to its rapid antidepressant actions, but its mechanism of action has remained elusive. Here we show that blockade of NMDAR-dependent bursting activity in the ‘anti-reward center’, the lateral habenula (LHb), mediates the rapid antidepressant actions of ketamine in rat and mouse models of depression. LHb neurons show a significant increase in burst activity and theta-band synchronization in depressive-like animals, which is reversed by ketamine. Burst-evoking photostimulation of LHb drives behavioural despair and anhedonia. Pharmacology and modelling experiments reveal that LHb bursting requires both NMDARs and low-voltage-sensitive T-type calcium channels (T-VSCCs). Furthermore, local blockade of NMDAR or T-VSCCs in the LHb is sufficient to induce rapid antidepressant effects. Our results suggest a simple model whereby ketamine quickly elevates mood by blocking NMDAR-dependent bursting activity of LHb neurons to disinhibit downstream monoaminergic reward centres, and provide a framework for developing new rapid-acting antidepressants.
Yang, Y., Cui, Y., Sang, K., Dong, Y., Ni, Z., Ma, S., & Hu, H. (2018). Ketamine blocks bursting in the lateral habenula to rapidly relieve depression. Nature, 554(7692), 317. 10.1038/nature25509
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30 April - Q&A with Rick Strassman

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