A Novel Application of Ketamine for 
Improving Perioperative Sleep 
Disturbances [Letter]

Dear Editor We have read a review article captioned as “A Novel Application of Ketamine for Improving Perioperative Sleep Disturbances” by Bijia Song and Junchao Zhu published in Nature and Science of Sleep (1). We praise the authors on successful publication of this descriptive review article and would like to add up some elements. The article elaborated the role of Ketamine for ameliorating sleep disturbance in Perioperative patients. The article provided detailed information on risk factors for perioperative sleep disturbances and discussed circadian rhythm in wide aspect. Authors described antidepressant mechanisms of action of Ketamine. Whilst article explained several antidepressant mechanisms of action, authors didn’t focus much on the protein called glycogen synthase kinase-3 (GSK- 3) a master switch serine-threonine kinase. Adjunct GSK- 3β inhibitors, can augment ketamine’s efficacy by promoting and prolonging its antidepressants effects such as lithium (2). The authors narrated treatment of major depressive disorder (MDD) with ketamine efficiently but didn’t mention ketamine role in the treatment of bipolar disorders (BD). Lisa Scheuing et al in their mini-review explained knock-in mouse model providing both forms of GSK-3 maximally active, by removing the inhibitory phosphorylation sites of serine-21 and -9 for GSK-3 and GSK-3β respectively. GSK-3 inhibition is compulsory for ketamine’s rapid antidepressant like effects. Two studies elaborated that lithium a GSK-inhibitor combined with low-dose ketamine augmented and prolonged the molecular and behavioral effects of ketamine (2). Authors didn’t discuss the issues with ketamine treatment and its solutions. Usage of Ketamine at sub-anesthetic dose may induce schizophrenia like behaviors in humans for up to one week (2). In the ketamine treatment, addition of mood stabilizers like lithium can modify the side effects (2). Animal preclinical studies showed gender difference in the sub-anesthetic dosage of ketamine (3). Chadi.G. Abdullah et al n their review article also discussed the synaptogenesis and anti-depressant like effects of sub-therapeutic dosage of ketamine were saved when given together with sub-therapeutic dosage of lithium or other GSK-3 inhibitors (3). So, mood stabilizers are necessary with ketamine treatment to subside the possible psychiatric side effects which occur after the treatment of psychiatric disorders.

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