Martin M. Katz: Component-Specific vs. Diagnosis-Specific Clinical Trial in Depression
Donald F. Klein’s comment
Katz’s central point is, “Antidepressant drugs have been found to be equally effective for anxiety, phobic and obsessive-compulsive disorders. Thus, their therapeutic effects in depression are more likely based on the changes they effect in the components of anxiety, hostility and motor functioning, components not necessarily in the “core” pathology of depression.”
We attempt to clarify the logical structure and factual merits supporting this conclusion.
“Basic research links serotonin with impulsive aggression and anxiety, norepinephrine with “arousal” and motor activity (Katz and Maas 1994).
Certain neurotransmitters are “linked” to distinctive pharmacologic effects (SET NT), each specific pharmacologic effect supporting specific emotional behaviors (SET SS). Therefore, SET NT correlates with SET SS
The distinctive, depression relevant, pharmacologic effects of anti-depressants (SET AP) benefit other clinical syndromes, e.g., anxiety, phobia and obsessive-compulsive disorders (SET OD.)
Therefore, SET AP correlates with SET OD.
SET SS is the causal basis for SET AP (implying SET SS correlates with SET AP.)
The skeleton is:
NT Correlate SS
AP Correlate OD
SS Correlate AP
This is far from logical.
Substantively, does basic research support that specific neurotransmitters yield specific SS? That the neurotransmitter serotonin causes a particular effect does not fit well with its fourteen differing receptors. Norepinephrine stimulates the superior cervical ganglion, limbic lobes, prefrontal areas, etc. yielding an array of distinctive effects. Therefore, Premise 1 is not factually sound.
Premise 2 asserts that “antidepressants” as a class benefit depression and also, anxiety, phobia and obsessive-compulsive disorders. This is an erroneous overgeneralization. Examples: electroconvulsive therapy, bupropion and sleep deprivation do not benefit panic disorder. Desipramine does not benefit obsessive compulsive disorder. Imipramine does not benefit specific phobia and early onset atypical depression. Therefore, Premise 2 is not factually sound.
The conclusion is an incorrect deduction from erroneous premises, with no factual basis.
Also noted, is the belief that certain neurotransmitters systems are causally relevant to depression, stems from the initial effects of some antidepressants on such systems. This does not prove these neurotransmitters are causally related to depression pathophysiology. An outstanding contradiction is the lack of mood effects when “antidepressants” are given to normal subjects, despite neurotransmitter effects. Both Katz and Klein agree this salient fact is worth substantive research, although Katz does not see that this finding invalidates his premises. Further, other agents with similar NT effects fail to act as antidepressants.
Donald F. Klein
November 10, 2016