Martin M. Katz’s reply to Donald F. Klein’s 6^th Comment (Antidepressants are not stimulants).

D. Klein refers to my characterization in the book of the relationship of the functioning of the central monoamine neurotransmitter systems to the regulation of specific behaviors and mood, and then cites the limitations of those relationships. My analysis was based on a network of findings in basic laboratory research assembled over the past several decades that show an increase in availability of serotonin in the central nervous system to be associated with impulsive aggression and with level of anxiety and an increase of norepinephrine associated with “arousal”. I did not, however, view these relationships as rheostatic in quality. We agree that there are limitations to these relationships of neural and behavioral functioning based on our knowledge that the antidepressants clearly decrease the aggressive impulse, anxiety and stimulate motor activity in a large number of patients suffering from a depressive or anxiety disorder, but apparently, do not function in the same manner in normal people. The antidepressants are more likely, as he states, to have little but adverse effects in their actions in healthy controls.

I, therefore, have no quarrel with his statement that the antidepressants, although having a stimulant-effect in many depressed patients, are not “stimulants”.  It is clear that the still unsolved issue is the basis for this uneven relationship of neurotransmitter and behavioral functioning, i.e., the antidepressants’ “normalizing” actions in most categorically depressed or anxious patients against a background of the drugs’ producing relatively neutral or adverse actions in healthy normal controls.  The issue is central to understanding the neurobehavioral mechanisms underlying the efficacy of the antidepressants and remains unresolved. If it can be solved, it offers great promise for important advances in this field. I strongly agree with Klein that this issue deserves greater discussion from our colleagues.

Martin M Katz                                                                                                                             

May 7, 2015