Glucocorticoid dependence and withdrawal (Case study 3, box 3)
Glucocorticoid withdrawal syndrome is defined by symptoms that develop
as glucocorticoid therapy is withdrawn, despite normal HPA function.
These symptoms can be similar to those of adrenal insufficiency, which
makes it difficult to tell the two conditions apart (table 3). One
distinguishing feature is that glucocorticoid withdrawal syndrome can be
symptomatic even at supraphysiological glucocorticoid doses, whereas
adrenal insufficiency is controlled by physiological doses.
Inherent in the description of glucocorticoid withdrawal syndrome is the
implication that patients become dependent on or ‘addicted to’
glucocorticoids, accounting for both physiological and psychological
discomfort when treatment is withdrawn [32]. Glucocorticoids have
pleiotropic effects, altering many different pathways and mediators,
which could contribute to development of dependence. Candidates include
CRH, vasopressin, pro-opiomelanocortin and the adrenergic system
[33]. In the brain, exogenous glucocorticoids may alter
neurotransmitters [32] and impair recovery from neuronal damage
[7]. It is well recognised that patients taking glucocorticoids can
develop neuropsychiatric effects including psychotic reactions, as well
as changes in mood, cognition, memory and/or behaviour [7].
Neuropsychiatric effects including depression, delirium, confusion or
disorientation, non-psychotic mania and panic disorder have also been
reported during dose reduction [34] and may complicate treatment
withdrawal. Glucocorticoids have been implicated as a driver of
addictive behaviour [35] and occasionally are used as drugs of abuse
[36]. Anfinson and colleagues identified 22 cases of glucocorticoid
dependence on a MEDLINE search that met criteria for DSM I-IV substance
dependence [36]. They commented that glucocorticoids may induce
dependence through their propensity to induce euphoria and by directly
influencing reward circuitry, as well as through physical dependence.