Vegetative Symptoms Of Depression, Endogenous Versus Exogenous: Still Not The Issue
Q: Many readers may recall a time during the early 1980s when it was
believed to be important to classify depression as either endogenous or
exogenous. The idea was that there was a difference between depression
precipitated by life events, called exogenous depression, and depression
that was inherent to the patients' physiology, referred to as endogenous
depression. The theory was that patients with exogenous depression did
not respond to antidepressants -- ie, tricyclic antidepressants or
monoamine oxidase inhibitors (MAOIs) -- because, presumably, their
depression was not a function of their physiology but rather a reaction
to their life situation. As such, they required treatment with some form
of talking therapy. This theory, as it was promoted at the time, not
only made the distinction between endogenous and exogenous depression
based on symptoms (ie, did they or did they not have vegetative symptoms
of depression), but also by assumed etiology. Thus, it was believed that
depression precipitated by the loss of a loved one or any other
grief-inducing event would not respond to antidepressants because it was
exogenous, ie, not physiological.
A:In retrospect, this rather dualist approach to depression seemed to
imply that only some behaviors had anything to do with the chemistry of
the brain, but other behaviors were somehow exempt. All of this thinking
came, to a certain extent, from the discovery of monoamine
neurotransmitters and their role in depression. Since antidepressants
seemed to increase the amount of norepinephrine, serotonin, and perhaps
dopamine by making more neurotransmitters seemingly available, it made
sense at the time to understand depression as a deficit of these
neurotransmitters. Ignoring the fact that the effect of these drugs on
the neurotransmitters was virtually immediate, their effect on the
patient took considerably longer. The assumption was that the depressed
patients clearly needed more of something, and the neurotransmitters
were the best candidate at the time. It was hard to believe, then, that
life events could change fundamental biochemistry. We now are fairly
certain -- armed with new knowledge from various studies about dietary
manipulation, blood and CSF level monitoring, and other sophisticated
methodology -- that the deficit model of neurotransmitters is
considerably more simplistic than whatever the reality of the
pathophysiology of depression is.
Much more recently, we came up with a new application of the semantic
distinction between endogenous and exogenous. In spite of the data that
question the validity of a deficit paradigm, we continue to think of
psychopharmacology as somehow having an effect on some sort of balance.
One often hears patients parroting this idea by referring to themselves
as having a chemical imbalance. As we strive to somehow rebalance that
imbalance, we struggle to conceive of exactly what it is that is out of
balance. Throughout most of the history of the treatment of depression,
we have done this with reuptake blockers, which ostensibly increase the
amount of neurotransmitter available to the outside of the neuron by
blocking reuptake. These drugs, by the semantic distinction described
above, would be exogenous, ie, they are not something that the body
naturally produces but are ingested to achieve an impact on the balance
of neurotransmitters.
More recently, we have begun to get interested in the use of endogenous
compounds, ie, hormones or other substances that are naturally produced
by the body, in the treatment of depression. The idea is that if we
administer substances that the body already has, but perhaps doesn't
have enough of, this may treat the depression. Recent studies have shown
that estrogen supplementation, growth hormone, and even secretin, which
is used in the treatment of autism, may have beneficial effects in