When possible, initial treatment should include discontinuing or tapering corticosteroids to <40 mg/d of prednisone-equivalent.1,4,10,18 Most studies have reported rapid reversal of deficits in declarative memory and of hippocampal volume loss once corticosteroids were tapered and discontinued.1,18 One study reported that >90% of patients recovered within 6 weeks, with patients with delirium recovering more quickly (mean: 5.4 days) than those with depression, mania, or psychosis (mean: 19.3 days).3 Another found that the vast majority (92%) of patients treated only with a steroid taper achieved clinical recovery, and 84% recovered with administration of antipsychotics without a steroid taper.3 In this study, all patients who received electroconvulsive therapy (ECT) recovered, as did those who received a steroid taper plus lithium or antipsychotics. Steroid tapering regimens are especially important for patients who have received long-term glucocorticoid treatment. Patients need to be closely monitored for signs of new or increased depression, delirium, or confusion during the taper. If these symptoms occur, the patient should be checked for adrenocortical insufficiency, which can be resolved by re-administering or increasing the dosage of the glucocorticoid.10
Mania. The treatment of mania/hypomania includes mood stabilizers (valproate, lithium, lamotrigine) and antipsychotics (quetiapine, olanzapine, haloperidol).2,4,5,10,14,18 Valproate has been reported to be an effective prophylactic of corticosteroid-induced mania,2 perhaps because it dampens neuronal hyperexcitability by attenuating NMDA receptors, blocking voltage-dependent sodium channels, and inhibiting the synthesis of cortical GABAergic steroids. Starting valproate while continuing corticosteroids (if necessary) may help lessen mania.2 Benzodiazepines also may be useful on a short-term basis.
Depression. Steroid-induced depression may be treated with sertraline or other first-line antidepressants.5,14 Consider ECT for patients with severe depression. Support for the use of antipsychotic medications stems from studies that reported steroids’ role in disrupting dopamine and 5HT2 activity. Lithium also has been used successfully to manage and prevent glucocorticoid-associated affective disorder.10,18 It can be used alone or in combination with selective serotonin reuptake inhibitors to alleviate depressive symptoms.10 Tricyclic antidepressants are generally avoided because their anticholinergic effects can exacerbate or worsen delirium.18 In general, ECT is an effective treatment for persistent and/or unresponsive steroid-induced depression,2,10 but may be difficult to use in patients with serious medical illnesses.
Agitation. Medications that have been proposed for treating steroid-induced agitation include benzodiazepines, haloperidol, and second-generation antipsychotics.5,17
Other considerations. Clinicians, patients, and families should discuss in detail the risks of steroid-induced psychiatric symptoms so an early diagnosis and appropriate intervention can be implemented. Before starting steroids, it is important to review the patient’s current medication list to ensure that steroid treatment is indicated, and to check for potential drug–drug interactions. In addition, the medical condition that is being treated with steroids also needs to be carefully reviewed, because certain illnesses are associated with the development of psychiatric symptoms. 5,10
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