Psychosomatics 43:495-497, December 2002
© 2002 The Academy of Psychosomatic Medicine
Olanzapine Treatment of Corticosteroid-Induced Mood Disorders
Larry S. Goldman, M.D., and
Joseph Goveas, M.D.
Received March 6, 2002; accepted March 26, 2002. From the Department of Psychiatry, University of Chicago. Address correspondence and reprint requests to Dr. Goldman, Department of Psychiatry, University of Chicago, 5841 S. Maryland Ave., MC3077, Chicago, IL 60637; l-goldman{at}uchicago.edu (e-mail).
Psychiatric consultants working in general medical settings are occasionally asked to assess and manage mood disturbances caused by corticosteroid treatment. This problem is seen in settings where corticosteroids, particularly in higher doses, are more commonly used, such as in transplantation, oncology, pulmonary, rheumatology, and gastroenterology practices. Patients may present with delirium or a schizophreniform psychosis, but mood disorders—including manic, depressed, and mixed states—are far more common. Most reports of the treatment of steroid-induced mood disorders have emphasized the use of typical antipsychotics, and we found only a single case report1 in which an atypical antipsychotic, olanzapine, was used.
Olanzapine is an atypical antipsychotic with high affinity for serotonin subtype 2A (5-HT2A) and muscarinic subtype 1 (M1) receptors and less affinity for dopamine subtypes 1 and 2 (D1 and D2), histamine subtype 1 (H1), and adrenergic  1 receptors. In addition to being an effective antipsychotic, it has been approved for use as a treatment for acute mania and is being studied for its mood-stabilizing properties.2 We reasoned that this agent might be especially useful for treating corticosteroid-induced mood disturbances, and we report five cases in which this treatment was used with good results.
Case Reports
Case 1. Mr. A was a 38-year-old man who underwent a kidney-pancreas transplant. He was seen by a psychiatric consultant 2 weeks after the operation, when he reported a 4-day history of mood lability, irritability, insomnia, restlessness, visual hallucinations (of "murders being done"), and feelings of agitation. He had a past history of panic attacks and long-standing depression for which he had not been treated. He was taking prednisone, tacrolimus, and metoclopramide. He was thought to have an immunosuppressant-induced mood disturbance and possible akathisia related to treatment with metoclopramide. Treatment with 2.5 mg b.i.d. of olanzapine was begun. His symptoms improved considerably over the next couple of days. His initial symptoms—along with tremulousness and some nightmares—recurred several times over the subsequent few weeks at points when his serum level of tacrolimus became supratherapeutic. Increased doses of olanzapine and addition of clonazepam helped alleviate symptoms as his tacrolimus level was adjusted. He nonetheless remained somewhat dysphoric and anxious, expressing misgivings about having agreed to the transplant and about being away from home for so long. Individual and conjoint therapy with his fiancée after discharge were recommended.
Case 2. Mr. B was a 38-year-old man who had undergone a kidney-pancreas transplant 2 weeks before an inpatient psychiatric consultation. He had marked anxiety, feelings of restlessness and increased energy, insomnia, diminished interest in activities, diminished social interactions, and difficulty concentrating, and he reported that these symptoms had begun immediately after surgery. He had no previous psychiatric history. He was taking tacrolimus and 15 mg/day of prednisone for immunosuppression. He had noticed some improvement in his symptoms when his prednisone dose had been lowered. Buspirone had been started several days after surgery, but he reported no benefit from this medication. He was thought to be experiencing steroid-induced mood changes (mixed state). After the psychiatric evaluation, buspirone was discontinued and treatment with 2.5 mg of olanzapine in the evening was begun. He reported dramatic improvement in symptoms after the first dose. When he was seen 2 weeks later as an outpatient, he had remained asymptomatic while taking the same dose of olanzapine despite continuing his immunosuppressant regimen.
Case 3. Ms. C was a 19-year-old woman who had suffered from multiple sclerosis for several years. She was admitted 3 weeks before the psychiatric evaluation for an acute exacerbation of multiple sclerosis. She received high-dose steroids parenterally and was discharged after a few days with a medication regimen of prednisone. Beginning shortly after discharge, she developed increased energy, elevated mood, increased motor activity, racing thoughts, and diminished need for sleep. She subsequently developed grandiose and persecutory ideation and then feared she was going to die. She was readmitted to address the behavioral problems. The findings of a general neurological examination were unchanged from those during her first admission, and the workup revealed no evidence of further exacerbation of her multiple sclerosis. Her mother noted that she had become "hyper" in the past when she received steroids administered with pulsed dosing, but the most recent episode was by far the worst. Olanzapine 5 mg q.h.s. was begun for presumed steroid-induced mood disorder, and the patient became calmer and much less guarded over the next 2–3 days, allowing her to return home.
Case 4. Mr. D was a 58-year-old man who underwent orthotopic liver transplantation for hepatitis C. About 6 weeks posttransplant he was readmitted after a 2-week history of increased talkativeness, increased activity, decreased sleep, new religious preoccupations, elevated mood, increased spending, and racing thoughts. There was no personal or family history of mania. The patient had had a mild depressive adjustment disorder while he was waiting for the liver transplant, and it had not been treated. He was taking 20 mg/day of prednisone and 6 mg/day of tacrolimus. His serum tacrolimus level was 9 ng/ml. The results of a neuropsychiatric workup for central nervous system causes of secondary mania were negative. He was treated with olanzapine, with the dose eventually reaching 15 mg/day after his transfer to the inpatient psychiatry service. He became euthymic over the subsequent week. He developed diabetes mellitus for the first time, so risperidone was substituted for olanzapine; he remained euthymic for the next 3 months.
Case 5. Mr. E was a 50-year-old man who underwent cardiac transplantation for idiopathic cardiomyopathy. Beginning shortly after surgery he noticed mood lability, irritability, and insomnia. He requested a psychiatric consultation when he found himself tempted to strike one of his physicians for no reason. He noted that his symptoms had increased when his prednisone dose was increased after a rejection episode; he was also taking cyclosporine. Previously he had been treated for posttraumatic stress disorder (PTSD) associated with his combat experiences in Southeast Asia. He had been stable for many years while taking fluoxetine and divalproex, and he experienced his postoperative symptoms as different from his PTSD experiences in the past. He was treated with 5 mg of olanzapine q.h.s. When he was seen the next day after one dose of olanzapine he reported such an improvement of his symptoms that he referred to the consultant as "the John Wayne of psychiatrists." His symptoms did not return throughout the remainder of his hospitalization.
Discussion
The frequency of corticosteroid-induced mood reactions has been difficult to establish clearly. A review by Brown and Suppes3 highlighted this difficulty. They found only four controlled studies that compared adverse effects in corticosteroid-treated medical patients with those in comparable patients who did not receive steroids, and none of these studies specified the psychiatric assessment methods that were used. They identified 13 (mostly older) studies that more specifically examined psychiatric symptoms occurring during steroid treatment, but these reports tended to be smaller series, most of which used neither clearly defined diagnostic criteria nor clinical rating scales.
Thirty years ago, the Boston Collaborative Drug Surveillance Program4 identified 21 patients with severe psychiatric reactions in a study of 718 patients who received prednisone (2.9%). These 21 patients included eight with "euphoria" and 13 with psychosis, six of whom may have been acutely manic. Lewis and Smith5 reviewed 79 cases from the medical literature, 14 of their own previously unreported cases, and 29 studies of the use of corticosteroids in treating various medical conditions and concluded that about 5% of steroid-treated patients developed severe psychiatric reactions and that many patients experienced mood symptoms. Both articles concluded that risks are dose-related and that higher corticosteroid doses are associated with higher percentages of affected patients.
Although the earlier studies did not use the DSM syndromal criteria, Naber and colleagues6 used the DSM-III-R criteria to evaluate 50 patients who received high-dose corticosteroids for ocular disease. Thirteen patients developed hypomania or mania, and five developed a major depressive syndrome. More recently, Wada and colleagues7 identified 18 corticosteroid-treated patients who experienced mood disorders (N=15) or psychosis (N=3). All three patients with psychosis had schizophreniform psychoses. Among the 15 patients with mood disorder, 10 patients initially had mania or hypomania and five had depression. Seven patients developed a recurrent mood disorder, and all of them demonstrated bipolarity. Another approach to clarifying the frequency of mood reactions was undertaken by Brown and colleagues.8 They followed 32 patients in an asthma clinic longitudinally and administered several rating scales at the time the patients received bursts (>40 mg/day) of prednisone for exacerbations. They found significant increases in ratings on two different mania scales during the first 3–7 days of treatment, no increase in depression ratings, and no correlation between the enhanced mood and improvements in asthma symptoms.
Treatment of steroid-induced mood disorders has received even less study. Lewis and Smith's review5 suggested that steroid taper could have led to clinical recovery in more than 90% of patients who could be treated in that fashion. More than 80% could have also responded to phenothiazine neuroleptics or haloperidol (with or without steroid taper or the inclusion of lithium) and ECT. Brown et al.1 reported the case of a young woman who developed an agitated depression during prednisolone therapy for asthma. She responded well to 2.5 mg of olanzapine at night over the subsequent 3 weeks.
Hall et al.9 described five cases and Blazer et al.10 described two other cases of depressed patients who did not respond or actually worsened when treated with tricyclic antidepressants. These findings have led some to be wary of using antidepressants at all for these patients. Possible explanations for this phenomenon have included tricyclic antidepressant anticholinergic worsening of delirium, mixed mood states, or bipolar diathesis (and thus induction of a mixed state) caused by steroids. However Beshay and Pumariega11 successfully used sertraline to treat a child who developed prednisone-induced depression. Wada et al.7 treated seven manic patients acutely with antipsychotics ("butyrophenones" or zotepine), three with valproate, and one with carbamazepine, all with successful outcomes after 1–3 months. Of the depressed patients described in their report, four each were treated with tricyclic and nontricyclic antidepressants with good results. The authors did not note the specific agents except in the cases of two patients who received intravenous clomipramine.
Our series demonstrates that olanzapine may have a role in the acute management of mood disturbances associated with corticosteroid treatment. The five patients all had good responses to the addition of olanzapine to their medical regimens, generally within the first few days after the start of olanzapine treatment. Olanzapine was generally well-tolerated, although the patient in Case 4 developed diabetes mellitus, an adverse effect known to be associated with olanzapine, as well as with corticosteroids. Because of the potential for this adverse effect, the duration of olanzapine use should be kept fairly short and patients should be monitored for problems with weight gain or glycemic control if olanzapine is continued.
Although we used the DSM-IV criteria in assessing the patients described here, these patients, like many with steroid reactions we have seen, did not necessarily meet the full syndromal criteria for a mood disorder. Another limitation of this series is that we did not use standardized rating scales to establish the patients' baseline condition and response to treatment. More rigorous examination of various interventions (steroid taper, various psychopharmacological agents, ECT) for the treatment of corticosteroid-induced mood disturbances in a controlled fashion would be highly desirable, but the logistics of doing such studies may be daunting. We encourage other centers to report their experiences with various treatment modalities.
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- Brown ES, Khan DA, Suppes T: Treatment of corticosteroid-induced mood changes with olanzapine (letter). Am J Psychiatry 1999; 156:968[Free Full Text]
- Tandon R, Milner K, Jibson MD: Antipsychotics from theory to practice: integrating clinical and basic data. J Clin Psychiatry 1999; 60(suppl 8):21-28
- Brown ES, Suppes T: Mood symptoms during corticosteroid therapy: a review. Harv Rev Psychiatry 1998; 5:239-246[Medline]
- Boston Collaborative Drug Surveillance Program: Acute adverse reactions to prednisone in relation to dosage. Clin Pharmacother 1972; 13:694-697
- Lewis DA, Smith RE: Steroid-induced psychiatric syndromes: a report of 14 cases and a review of the literature. J Affect Disord 1983; 5:319-332[CrossRef][Medline]
- Naber D, Sand P, Heigl B: Psychopathological and neuropsychological effects of 8-days' corticosteroid treatment: a prospective study. Psychoneuroendocrinology 1996; 21:25-31[CrossRef][Medline]
- Wada K, Yamada N, Sato T, Suzuki H, Miki M, Lee Y, Akiyama K, Kuroda S: Corticosteroid-induced psychotic and mood disorders: diagnosis defined by DSM-IV and clinical pictures. Psychosomatics 2001; 42:461-466[Abstract/Free Full Text]
- Brown ES, Suppes T, Khan DA, Carmody TJ: Mood changes during prednisone bursts in outpatients with asthma. J Clin Psychopharmacol 2002; 22:55-61[CrossRef][Medline]
- Hall RCW, Popkin MK, Stickney SK, Gardner ER: Presentation of the steroid psychoses. J Nerv Ment Dis 1979; 167:229-236[Medline]
- Blazer DG, Petrie WM, Wilson WP: Affective psychoses following renal transplant. Dis Nerv Syst 1976; 37:663-667[Medline]
- Beshay H, Pumariega AJ: Sertraline treatment of mood disorder associated with prednisone: a case report. J Child Adolesc Psychopharmacol 1998; 8:187-193[Medline]
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K. Budur and L. Pozuelo
Olanzapine for Corticosteroid-Induced Mood Disorders
Psychosomatics,
August 1, 2003;
44(4):
353 - 353.
[Full Text]
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