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Glucocorticoid withdrawal syndrome is defined by symptoms that develop as glucocorticoid therapy is withdrawn, despite normal HPA function.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on or ‘addicted to’ glucocorticoids, accounting for both physiological and psychological discomfort when treatment is withdrawn [32].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.