Steroid-induced mania treated with aripiprazole

2012 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved. Steroid-Induced Mania Treated with Aripiprazole Ryan J. Kimmel, M.D., Heidi Combs, M.D.
Brown and Chandler reviewed the literature on signif- One month prior to her ED presentation, Ms. A was icant psychiatric side effects of corticosteroids, not- treated with whole brain radiotherapy (WBRT) and a ing presentations of depression, mania, psychosis, and dexamethasone taper was initiated at 4 mg PO BID. Per memory deficits.Naber et al. followed a prospective, her family, her psychiatric symptoms began in the first few uncontrolled cohort of 50 patients on methylprednisolone days after the dexamethasone was started. At time of her or fluocortolone, at initial doses of 119 Ϯ 41 mg/d, and ED presentation, Ms. A was down to 2 mg of dexameth- tapered to 75 Ϯ 22 mg/d over 8 days. They found that asone every other day. Her other medications had been “manic-type” symptoms were reported by 26% of the par- stable, but included a chemotherapy regimen of weekly ticipants, most of which began in the first 3 days of treat- vinorelbine and trastuzumab. Her most recent brain MRI, ment and continued, despite the taper, over the 8 days of done 1 week prior to the ED presentation, showed numer- ous bilateral lesions throughout her cerebral hemispheres, If possible, removing the offending steroid is desir- cerebellum, and brainstem. The largest lesion in this right- able when patients present with psychiatric side effects.
handed woman was in the left medial temporal lobe and However, if the steroid-induced behavior puts the patient at significant risk of morbidity and mortality, adjunctive Ms. A’s family noted that she had mild insomnia and use of an anti-manic medication may also be warranted.
racing thoughts during a prior chemotherapy regimen that The data for pharmacologic intervention in steroid-in- had included prednisone. Otherwise, her family noted that duced mania is limited in scope and study design. Among Ms. A had no lifetime psychiatric symptoms or treatment.
the classic mood stabilizers, lithium has the most evidence Ms. A, on longer-term follow-up, subsequently confirmed in steroid-induced mania, with a 71-patient, retrospective There is a positive case report regarding the use of In the ED, blood work and urine toxicology were valproic acid.Amongst the antipsychotics, the use of normal. A head CT showed no acute changes. She was phenothiazines is supported by a 14-patient case admitted for two nights to psychiatry, wherein dexameth- Haloperidoland quetiapinehave positive case reports.
asone was discontinued. Olanzapine 5 mg daily and loraz- Olanzapine use is supported by an open-label trial in 12 epam 1 mg PRN were initiated. Her behavior was still patients.Risperidone has recent pediatric case reports.
manic, but her paranoia had improved when she leftagainst medical advice (AMA) with her family. At homethat night, she refused olanzapine. On the day after dis- charge, she was brought to an outpatient psychiatrist at hercancer clinic. At this appointment, she was loud, pres- Ms. A, a 55-year-old woman with breast cancer and brain Received February 28, 2011; revised March 3, 2011; accepted March 3, metastases was brought to the emergency department (ED) 2011. From University of Washington, Department of Psychiatry, Uni- by her family for 4 weeks of psychomotor agitation, tan- versity of Washington Medical Center, Seattle, Washington (RJK); Uni-versity of Washington, Department of Psychiatry, Harborview Medical gential thought processes, decreased need for sleep, and Center, Seattle, Washington (HK). Send correspondence and reprint re- irritability. Ms. A’s paranoia had worsened to the point quests to Ryan J. Kimmel, M.D., University of Washington, Department that she thought her cancer was the result of family mem- of Psychiatry, University of Washington Medical Center, 1959 NE Pa-cific, Box 356073, Seattle, WA 98195-6073. e-mail: bers poisoning her food and she had waved a knife at her 2012 The Academy of Psychosomatic Medicine. Published by sured, expansive, tangential, stood for most of the appoint- Given the significant renal risks associated with her ment, and refused to eat at home. She was promptly sent chemotherapy regimen, the treating team did not wish back to the ED where labs were again unremarkable and to introduce lithium. Similarly, her chemotherapy reg- an MRI showed no acute changes. She was hospitalized, imen can cause myelosuppression, and we did not want involuntarily this time, on the psychiatric unit. On this to introduce a confounder by using valproic acid. A admission, Ms. A refused olanzapine, citing the side effect phenothiazine, such as chlorpromazine, would have of sedation. However, she agreed to try a different anti- psychotic, so long as it was less likely to cause sedation.
Ours is a single case report and there are significant The treating team agreed to prescribe aripiprazole 10 mg potential confounders that stand in the way of a conclusion PO daily. Clonazepam 0.5 mg PO BID was also initiated.
regarding the diagnosis and treatment. Evidence arguing On the first evening of psychiatric admission, Ms. A for a steroid component to her presentation includes her was described as grandiose, euphoric, refusing food, and history of mild insomnia and racing thoughts when on too disorganized to answer questions. By the third day of prednisone. The onset of her symptoms were shortly after admission, she was eating and sleeping better, but still dexamethasone initiation, though the psychiatric symp- disorganized and paranoid regarding her family. By the toms continued during dexamethasone dose reduction and fifth day of admission, her mental status was normal, save for a week after complete cessation. A large review of the some mild disorganization. She was then transferred to the case reports of steroid-induced psychiatric symptoms sug- oncology service for inpatient chemotherapy. She was dis- gested that 8% of patients did not respond to steroid taper charged from the hospital after a total of 12 days.
None of her other medications, including the che- Three weeks after hospital discharge, and 5 weeks motherapy agents, have been reported to be associated after her last dexamethasone dose, she tapered off arip- with mania, and their dosing did not correlate with the iprazole. Until the time of her death, 1 year after psychi- onset or resolution of her symptoms.
atric hospitalization, Ms. A was not on psychiatric medi- It is possible that Ms. A’s manic symptoms would have cation, was not given steroids, and had no mood or improved after a week by virtue of being completely off dexamethasone, though a taper had not shown rapid benefitand the severity of the psychotic symptoms necessitated morepro-active treatment. The treating team included a benzodi-azepine as an augmentation strategy to target her physical agitation. The benzodiazepine could have hastened her im-provement, but her refusal to eat due to active psychosis Ms. A’s paranoia was causing her to refuse to eat and to merited, in our mind, the use of an antipsychotic.
physically threaten her family. This behavior motivated It is also possible that the etiology behind her psychi- the treating team to consider not only stopping the dexa- atric symptoms was not the steroid, but rather related to methasone, but the addition of an antipsychotic to hasten her metastases, transient cerebral edema, or structural her improvement. When she was admitted involuntarily, damage caused by WBRT. Ms. A’s metastatic lesions Washington state law would have allowed the treating worsened during her last year of life and she had no further team, with the consent of two attendings, to pursue a psychiatric symptoms, despite being off aripiprazole.
compel order to give intramuscular olanzapine when she Though her metastases may have contributed to vulnera- refused oral olanzapine. Unlike olanzapine and quetiapine, bility, her durable euthymia argues against the lesions aripiprazole has no prior case reports for steroid-induced being the primary etiology behind her mania.
mania. However, aripiprazole does not bind the H recep- Steroid-withdrawal mania is also a possible explana- tor (associated with sedation) as strongly as olanzapine or tion for her presentation, and this has been previously However, Ms. A did not have any other symp- would increase agitation, but the medication is FDA- toms of steroid withdrawal, such as body aches, weakness, approved for bipolar mania and continues to demonstrate efficacy in meta-analyses.Thus, the treatment team felt An agitated, psychotic delirium from another etiology that a compromise with Ms. A wherein she would be given could have resulted in a similar presentation and cannot be oral aripiprazole in order to preclude the need for com- wholly ruled out. However, Ms. A’s symptoms did not pelled IM medications, was appropriate.
wax and wane, and she was oriented. Her blood work, toxicology screen, brain imaging, lumbar puncture, clini- to be a useful medication for steroid-induced psychosis cal course, and vitals did not suggest other acute delirium etiologies. An EEG was not done in the setting of herinitial, significant agitation, and her symptomatology im-proved steadily after admission.
Disclosure: The authors disclosed no proprietary or Further research is indicated, but when circum- commercial interest in any product mentioned or concept stances and side effects warrant, aripiprazole may prove References
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