Martin M. Katz:  Onset of clinical action of antidepressants

Martin M. Katz’s response to Carlos Morra’s response to Donald F. Klein’s reply to Morra’s comment

Carlos Morra agrees that reported findings from several well-controlled studies firmly support significant clinical actions of antidepressant drugs as occurring within the first two weeks of treatment. He agrees with D. Klein that the hypothesis linking the drug effective actions to inhibition of reuptake of neurotransmitters at synapses, is dubious, thus, disappointing in its implications for new drug development. He cites findings, however, with ketamine of rapid antidepressant action that indicate the drug effect probably due to another cellular mechanism.

This does not invalidate the main issue of whether clinical response at outcome can be predicted from patient reactivity to treatment during the first two weeks. In essence, he supports the main thesis of the onset controversy. Thus, he takes seriously, as we do, that adopting this finding that outcome can be predicted from two-week’s response, should lead to shorter trials, and prevent long suffering patients from being exposed to unnecessary, additional weeks of ineffective treatments. Adopting this procedure will, as in the case of ketamine, help open pathways to the discovery of new, more effective and more rapidly acting drugs.

Martin M. Katz

May 26, 2016