Martin M. Katz:  Onset of clinical action of antidepressants


Carlos Morra’s response to Donald F. Klein’s reply to his comment

Ketamine and the onset of antidepressant effect


My intention with my comment was to bring to attention that current findings in this area of research are in favor of Marty Katz’s contention that one can detect antidepressant effect after one week of treatment, or even sooner. Whether one can do it on the basis of his data, I don’t know.

 I agree with Dr. Klein that the hypothesis or belief that a drug–induced increase of a neurotransmitter in the synaptic gap is responsible for antidepressant effects has not paid off in terms of drug development. But, then the hypothesis or belief that postsynaptic changes (“cascade”) are responsible for antidepressant effects, has not paid off either. In recent years, ketamine administration, allegedly by its effect on ion channels, resulted in improvement of depression within 110 minutes (Maeng and Zarate 2007; Zarate et al 2003, 2006).   

Nothing of this has, of course, anything to do with whether one can predict antidepressant effects from Dr. Katz’s data after one week of treatment and that is at the heart of this exchange. But, to repeat: my intention with my comment was to bring to attention that some current findings are in favor of the contention that, in general, one can predict whether a patient will respond to antidepressant treatment within the time frame Marty Katz suggests, even if Dr. Klein’s argument is correct that the substantial response to treatment takes place later.

Maeng S, Zarate CA Jr. The role of glutamate in mood disorders: results from the ketamine in major depression study and the presumed cellular mechanism underlying its antidepressant effects. Curr Psychiatry Rep 2007; 9:467-74.

Zarate CA Jr, Du J, Quiroz J, Gray NA, Denicoff KD, Singh J, Charney DS, Manji HK. Regulation of cellular plasticity cascades in the pathophysiology and treatment of mood disorders: role of the glutamatergic system. Ann N Y Acad Sci. 2003;1003: 273-91.

Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006; 63: 856-64.


Carlos Morra

April 14, 2016