STEROIDS
STEROIDS AND DEPRESSION
Glucocorticoids are important in the pathogenesis of depression,
but this potentially serious effect is often overlooked
in clinical practice.
Placebo controlled studies have reported that a third of
patients taking glucocorticoids experience significant mood
disturbance and sleep disruption. Up to 20% of patients
on high dose glucocorticoids report psychiatric disorders
including depression, mania, psychosis, or a mixed affective
state. A recent double blind placebo controlled trial of
corticosteroid administration in healthy individuals showed
that 75% of subjects developed disturbances in mood and
cognition, which reversed when steroids were stopped.
Dysregulation of the hypothalamo-pituitary axis in depression
is one of the oldest and most consistent findings in biological
psychiatry. A large scale meta-analysis of over 140 studies
using the low dose dexamethasone test illustrated that persistent
adrenocortical hyperactivity is a robust indicator of poor
prognosis and a weaker predictor of suicide in depression.
From the physician’s point of view medical disorders
which feature sustained overdrive of the hypothalamo-pituitary
axis carry an unexpectedly high risk of mood disorders.
Patients with Cushing’s disease, stroke, or chronic
alcoholism, and those taking long term steroid treatment
have a reported prevalence of depression above 50%.
Underactivity of the axis may also be associated with a
range of psychiatric disorders, the most expensively investigated
being post-traumatic stress disorder.
Overall, data from conditions of both exogenous and endogenous
steroid excess provide support for a glucocorticoid theory
of depression. Several vexing questions remain however.
The therapeutic potential of antiglucocorticoid drugs has
recently been explored in patients with mood disorders.
Encouraging results with steroid synthesis inhibitors used
in the treatment of depression in patients with Cushing’s
disease led to several successful controlled trials in primary
depressive disorder. Furthermore, a re-examination of the
actions of conventional antidepressants hints at a mechanism
which involves reduction in activity of the hypothalamo-pituitary
axis.
BMJ no. 7127 pp244-5
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