Relationship of Ketamines Plasma Metabolites with Response, Diagnosis, and Side Effects in Major Depression
Biological Psychiatry, 04/24/2012Zarate CA et al.
A diagnostic difference was observed in the metabolism and disposition of ketamine. Concentrations of (2S,5S;2R,5R)–hydroxynorketamine metabolites were related to nonresponse to ketamine in bipolar depression. Some hydroxylated metabolites of ketamine correlated with psychotic and dissociative symptoms.
Following a 40-minute ketamine infusion (.5 mg/kg), plasma samples were collected at 40, 80, 110, and 230 minutes and day 1 postinfusion in 67 patients currently experiencing a major depressive episode (MDD, n = 45; BD, n = 22).
Concentrations of ketamine, norketamine (NK), dehydronorketamine (DHNK), six hydroxynorketamine metabolites (HNK), and hydroxyketamine (HK) were measured.
Plasma concentrations were analyzed by diagnostic group and correlated with patients' depressive, psychotic, and dissociative symptoms.
The relationship between cytochrome P450 gene polymorphisms and metabolites, response, and diagnosis was also examined.
Ketamine, NK, DHNK, four of six HNKs, and HK were present during the first 230 minutes postinfusion.
Patients with BD had higher plasma concentrations of DHNK, (2S,6S;2R,6R)-HNK, (2S,6R;2R,6S)-HNK, and (2S,5S;2R,5R)-HNK than patients with MDD, who, in turn, had higher concentrations of (2S,6S;2R,6R)-HK.
Higher (2S,5S;2R,5R)-HNK concentrations were associated with nonresponse to ketamine in BD patients.
Dehydronorketamine, HNK4c, and HNK4f levels were significantly negatively correlated with psychotic and dissociative symptoms at 40 minutes.
No relationship was found between cytochrome P450 genes and any of the parameters examined.
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