Intranasal antidepressant? Biol Psych. 2014 (Ahead of print)


Evidence suggest that only one-third of patients with depression receiving antidepressants  achieve remission. The delay to achieve this is also considerable. Focus of research in this area is moving beyond mono amines. IV ketamine is showing great promise. Intranasal ketamine would reduce many difficulties around IV administration. Intranasal ketamine is used in ambulatory patients for other indications.

Mount Sinai  team lead by Kyle A.B. Lapidus report the results of the proof-of-concept clinical trial  testing the rapid antidepressant effect of a single 50-mg of ketamine via an intranasal route in patients with MDD who had failed to respond to at least one prior antidepressant trial. Participants continued with their current medications.20 patients were randomly allocated to receive   intranasal ketamine and placebo at least 7 days apart in a  double-bind crossover design. Patients were monitored for at least 4 hours . Primary outcome measure was change in depression severity (=MADRS score) at 24 hours.


Intranasal Ketamine group showed significant mood improvement.Mean difference in MADRS score between ketamine and placebo groups was 7.6  3.7 (95% CI, 3.9–11.3).   8 of 18 subjects (44%) met response criteria at 24 hours after ketamine administration compared with 1 of 18 (6%) after placebo giving an NNT of  3. Repeated measures showed that ketamine group showed greater improvement at 7 days also. There was a small increase in psychosis and dissociation measures (from BPRS), but this was not related to antidepressant effect. Small increase in BP was observed in ketamine group, but none required any intervention for that and all such changes were resolved in 4 hours. Feeling strange or unreal/ poor memory/ weakness or fatigue were more seen in ketamine group, but all resolved by 4 hours. Compared with IV ketamine, the  proportion of treatment responders in this study are lower; may be because of lower plasma ketamine levels achieved with intrnasal route compared with IV.

Limitations: ongoing treatment with antidepressant make it difficult to distinguish an intrinsic effect of ketamine from benefits of combination of ketamine with such agents.

Conclusion: Intranasal ketamine is safe, well tolerated, and effective for rapid reduction of depressive symptoms

Comments: Results support the idea that intransal ketamine is generally safe. Conclusions on efficacy could not be made from short lasting effects observed in the study.

Summary of the article:

Randomized Controlled Trial of Intranasal Ketamine in Major Depressive Disorder.

Lapidus KA, Levitch CF, Perez AM, Brallier JW, Parides MK, Soleimani L, Feder A, Iosifescu DV, Charney DS, Murrough JW.

Biol Psychiatry. 2014 Apr 3. ( ahead of print)

one interesting and exciting area is glutamate system.progressing to look at

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