Preliminary communication
An open-label trial of olanzapine for corticosteroid-induced mood symptoms

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Abstract

Background

Prescription corticosteroids are given for a variety of common medical conditions. Psychiatric symptoms including depression, psychosis, and especially mania are common side effects of corticosteroid therapy. However, minimal data are available on the treatment of corticosteroid-induced psychiatric symptoms.

Method

In this study, 12 outpatients with manic or mixed symptoms secondary to corticosteroids were enrolled in a 5-week prospective, open-label trial of olanzapine. Psychiatric symptom measures included the Hamilton Rating Scale for Depression (HRSD), Young Mania Rating Scale (YMRS), and Brief Psychiatric Rating Scale (BPRS). Side effects were monitored with the Simpson Angus Scale (SAS), Abnormal Involuntary Movement Scale (AIMS), and Barnes Akathisia Scale (BAS). Weight and blood glucose were obtained at baseline and exit. Olanzapine dosing was flexible beginning at 2.5 mg/day and titrated upward as necessary to a maximum dose of 20 mg/day. Data were analyzed with Wilcoxon signed rank tests using baseline and exit data on all 12 participants.

Results

Participants showed significant reductions in YMRS (primary outcome measure), HRSD, and BPRS scores with no significant change in the SAS, AIMS, BAS, weight, or blood glucose levels. One participant discontinued early due to lack of efficacy.

Conclusion

These data suggest that olanzapine is well tolerated and appears to be useful for mood disturbances associated with corticosteroid therapy. Controlled trials seem warranted to confirm these observations.

Introduction

Since their introduction in the 1950s, corticosteroids have been widely prescribed for a variety of medical conditions such as asthma, rheumatic illnesses, transplant rejection, and dermatological disorders. Case reports of psychiatric side effects including mania, depression, mood lability, or even psychosis during corticosteroid therapy are numerous (Brown and Suppes, 1998, Brown et al., 1999a, Kaufmann, 1982, Wada et al., 2000, Wada et al., 2001a). The psychiatric effects of long-term corticosteroid therapy are not well investigated; however, short-term therapy appears to be primarily associated with manic or hypomanic, rather than depressive, symptoms or psychosis (Brown et al., 2002).

From the time of these first case reports, various classes of psychotropic medications have been used in an effort to prevent or treat corticosteroid-induced psychiatric syndromes. Only one controlled clinical trial has been conducted in patients with psychiatric symptoms secondary to corticosteroids. In this study, Falk et al. (1979) reported that lithium pretreatment might prevent corticosteroid-induced mood symptoms. While 14% of patients receiving corticotropin therapy suffered from mood symptoms, none of the patients receiving corticotropin following lithium pretreatment had a mood disturbance. Case reports suggest that lithium and other mood stabilizers including lamotrigine, carbamazepine, gabapentin, and valproic acid may effectively treat or prevent corticosteroid-induced mood symptoms after their development (Brown, 2003, Brown et al., 2003, Ginsberg and Sussman, 2001, Kahn et al., 1988, Preda et al., 1999, Wada et al., 2001b). Another class of medications that may effectively treat psychiatric symptoms associated with corticosteroids is antipsychotics, including both traditional neuroleptics (Ahmad and Rasul, 1999) and the newer atypical agents (Brown et al., 1999b, DeSilva et al., 2002, Goldman and Goveas, 2002, Kramer and Cottingham, 1999). Our group reported a case wherein a patient with depressed mood, insomnia, and suicidal ideation—all attributed to chronic corticosteroid therapy—responded with almost complete amelioration of these symptoms following the initiation of olanzapine therapy at 2.5 mg/day (Brown et al., 1999b). Recently, Goldman and Goveas (2002) reported a case series of five patients with a variety of symptoms including psychosis, anxiety, and mood disturbance, who responded at 2.5–15 mg/day. As symptoms associated with corticosteroids frequently include manic/hypomanic or mixed symptoms and because olanzapine is Food and Drug Administration (FDA)-approved for mania, we wanted to explore the efficacy of olanzapine in a larger sample of patients with prednisone-induced manic symptoms. In the study reported here, we provide data from an open-label trial of olanzapine in 12 patients with corticosteroid-induced manic or mixed symptoms.

Section snippets

Methods

Twelve outpatients between the ages of 18 and 65 years from University of Texas Southwestern Medical Center-affiliated clinics, or recruited from offsite flyer postings, who were receiving corticosteroids and experiencing clinically significant manic or mixed symptoms (defined as a Young Mania Rating Scale (YMRS) (Young et al., 1978) score≥10) related to corticosteroid use were included. This YMRS cutoff was selected to include people with clinically significant manic or hypomanic symptoms

Results

Demographic characteristics of the participants are provided in Table 1. All the patients met diagnostic criteria based on the SCID for a prednisone-induced mood disorder, with five having manic features and seven having mixed features. Eleven of 12 participants completed the study. One participant discontinued from the study on the third visit while receiving olanzapine at 7.5 mg/day due to minimal improvement in irritability and insomnia.

Patients were receiving corticosteroids for the

Discussion

These findings demonstrate significant decreases in YMRS, HRSD, and BPRS scores during olanzapine treatment in patients with corticosteroid-induced manic or mixed symptoms. The results are consistent with anecdotal reports on the efficacy of olanzapine for mood symptoms with corticosteroids (Brown et al., 1999b, Goldman and Goveas, 2002).

Olanzapine was also well tolerated in this sample. As expected, measures of extrapyramidal symptom severity did not significantly change (Leucht et al., 1999).

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