Elsevier

Mayo Clinic Proceedings

Volume 81, Issue 10, October 2006, Pages 1361-1367
Mayo Clinic Proceedings

REVIEW
Psychiatric Adverse Effects of Corticosteroids

https://doi.org/10.4065/81.10.1361Get rights and content

Psychiatric adverse effects during systemic corticosteroid therapy are common. Two large meta-analyses found that severe reactions occurred in nearly 6% of patients, and mild to moderate reactions occurred in about 28%. Although disturbances of mood, cognition, sleep, and behavior as well as frank delirium or even psychosis are possible, the most common adverse effects of short-term corticosteroid therapy are euphoria and hypomania. Conversely, long-term therapy tends to induce depressive symptoms. Dosage is directly related to the incidence of adverse effects but is not related to the timing, severity, or duration of these effects. Neither the presence nor the absence of previous reactions predicts adverse responses to subsequent courses of corticosteroids. Corticosteroid-induced symptoms frequently present early in a treatment cycle and typically resolve with dosage reduction or discontinuation of corticosteroids. In severe cases or situations in which the dose cannot be reduced, antipsychotics or mood stabilizers may be required. This review offers an approach to identifying and managing corticosteroid-induced psychiatric syndromes based on the type of symptoms and anticipated duration of corticosteroid treatment.,

Section snippets

Psychiatric Disturbances

Long-discounted mid 20th-century studies by Rome and Braceland5 and Garner and Falk6 suggested that the occurrence of corticosteroid-induced psychiatric reactions depended on the patient's premorbid personality organizations. Brody7 also suggested that these reactions reflected an extreme version of a patient's usual stress reaction. Morerecent studies show that corticosteroids universally induce central nervous system effects, some dramatic enough to attract clinical attention. In our

INCIDENCE

Studies reporting the incidence of corticosteroid-associated adverse psychiatric reactions have cited rates ranging from 1.8% to 57% of patients. The substantial variability in reported incidence reflects the unpredictability of these reactions, the large variations in researchers' definitions of reactions, the wide range of doses, and the diverse patient groups.

In a meta-analysis of 11 uncontrolled studies involving 935 adult patients, Lewis and Smith11 found incidences of psychiatric

RISK FACTORS

The corticosteroid dosage is the most important risk factor for the development of psychiatric symptoms. Hydrocortisone equivalents for 6 commonly prescribed corticosteroids are shown in Table 2. The Boston Collaborative Drug Surveillance Program3 monitored 676 consecutive hospitalized patients who received prednisone therapy and recorded a 1.3% (6/463) incidence of psychiatric disturbances in patients receiving 40 mg/d or less, a 4.6% (8/175) incidence in patients receiving 41 to 80 mg/d, and

TIMING OF ADVERSE REACTIONS

Psychiatric disturbances can occur at any point during corticosteroid treatment, including almost immediately after initiation and even after cessation of treatment. However, most occur early in the therapeutic course. In a prospective case series of 14 patients, Hall et al19 found that 86% (12/ 14) of patients developed psychiatric adverse effects within the first week of treatment. In a review of 70 case reports, Lewis and Smith11 found a median time to onset of 11.5 days, with 39% of

CORTICOSTEROID ABUSE

Several case reports describe corticosteroid abuse or dependence driven by the euphoria these medications can induce. These cases typically involve high-dose oral or intravenous formulations, but at least 1 case of dexamethasone nasal spray abuse has been reported.33 Most cases of corticosteroid abuse have been described in patients with a premorbid history of either psychiatric illness or drug or alcohol dependence.34

MANAGEMENT

Management strategies for corticosteroid-induced psychiatric disturbances are based almost entirely on case reports, anecdotal evidence, and a few small case series. Understanding of this topic has grown only slightly during the past 50 years.

Several open-label studies have evaluated prophylactic regimens for prevention of adverse psychiatric effects associated with long-term corticosteroid treatment and reported successful use of lithium carbonate,35 chlorpromazine,36 valproic acid,37

CORTICOSTEROID WITHDRAWAL

Although reduction or cessation of corticosteroids is the mainstay of treatment for corticosteroid-induced psychiatric reactions, caution is advised when making substantial or rapid reductions in corticosteroid doses, particularly for patients receiving long-term and high-dose treatments. For these patients, a taper is advised to prevent both physiologic and psychiatric corticosteroid withdrawal phenomena.66 An inappropriate taper can result in 3 types of difficulties67: (1) suppression of the

CONCLUSION

Corticosteroid-induced psychiatric disturbances are common and include mania, depression, psychotic or mixed affective states, cognitive deficits, and minor psychiatric disturbances (irritability, insomnia, anxiety, labile mood). In children, these effects commonly manifest as behavioral changes.

Which patients will experience corticosteroid-induced psychiatric disturbances cannot be predicted. Dosage is the most important risk factor for the development of adverse effects, with patients

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    Dr Warrington is now with the University of Oregon School of Health Sciences, Portland

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