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Withdrawal Acute Psychosis After

Corticosteroid Discontinuation
ARTICLE in JOURNAL OF PAIN AND SYMPTOM MANAGEMENT SEPTEMBER 2007
Impact Factor: 2.8 DOI: 10.1016/j.jpainsymman.2007.03.005 Source: PubMed

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Sebastiano Mercadante
La Maddalena Cancer Center
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118

modification or cessation of medications for

comorbid diseases. Patients are at risk for substantial drug-drug or drug-disease interactions.
Our group recently presented data from
a prospective consecutive cohort study of a palliative care population that followed people
for a mean of 3.5 months (median of 3
months) and confirmed that patients take
greater numbers of medications as death approaches.2 Symptom controlling medications
were added to those being taken for long-term
comorbidities. Although we saw a small reduction in the latter group, this usually only occurred in the days to weeks before death and
was outweighed by drugs added for symptom
control. Other recent papers have also focused
on management of comorbid illnesses in the
last days of life.1,3 The study by Currow et al.2
suggests that management should begin at
the time it is recognized the person has
a life-limiting illness.
Two recent contributions have proposed
frameworks to allow clinicians to individualize
treatment in this setting. The first considers
the initial therapeutic intent (primary, secondary, or tertiary prevention) along with the time
frame required for net benefit or burden compared to the individuals prognosis.4 The second similarly considers the goals of care and
treatment targets.5 If the benefit is measured
for patients over many years, then effectively
the number needed to treat will rise for patients whose prognosis is measured in months.
For some comorbidities, it is probable that the
medication load could be reduced during the
months before death without risking adverse
outcomes. By contrast, ongoing medication
of some long-term comorbid conditions will
be necessary right up to the hours before
death.
A structured evidence base is needed for
managing comorbid conditions at the end of
life. Previously published literature includes
research in drug elimination, and this methodology could be used as a foundation for further study in this area.6 Participation in such
research should focus on those receiving medications as secondary prevention strategies.
James P. Stevenson, FRACP, FAChPM
Southern Adelaide Palliative Services
Repatriation General Hospital
Daw Park, South Australia
Australia

Letters

Vol. 34 No. 2 August 2007

David C. Currow, MPH, FRACP

Department of Palliative and
Supportive Services
Flinders University
Bedford Park, South Australia
Australia
Amy P. Abernethy, MD
Division of Medical Oncology
Department of Medicine
Duke University Medical Center
Durham, North Carolina, USA
doi:10.1016/j.jpainsymman.2007.04.013

References
1. Quinn K, Hudson P, Dunning T. Diabetes management in patients receiving palliative care. J Pain
Symptom Manage 2006;32:275e286.
2. Currow D, Stevenson J, Abernethy A, Plummer J,
Shelby-James T. Prescribing in palliative care as
death approaches. J Am Geriatr Soc 2007;55:
590e595.
3. Ford-Dunn S, Smith A, Quin J. Management of
diabetes during the last days of life: attitudes of consultant diabetologists and consultant palliative care
physicians in the UK. Palliat Med 2006;20:197e203.
4. Stevenson J, Miller C, Abernethy A, Currow D.
Management of long-term comorbidities in the setting of end stage disease. BMJ 2004;329:909e912.
5. Holmes HM, Cox-Hayley D, Alexander GC,
Sachs GA. Reconsidering medication appropriateness for patients late in life. Arch Intern Med
2006;166:605e609.
6. Uretsky BF, Young JB, Shahidi FE, et al. Randomized study assessing the effect of digoxin withdrawal
in patients with mild to moderate chronic congestive heart failure: results of the PROVED trial.
PROVED investigation group. J Am Coll Cardiol
1993;22(4):955e962.

Withdrawal Acute Psychosis After

Corticosteroid Discontinuation
To the Editor:
Recently, the occurrence of fever has been
described as a sign of corticosteroid withdrawal
in three patients.1 Several theories have been
suggested, including the disruption of the
hypothalamus-pituitary-adrenal axis and the
possible exacerbation of inflammatory factors
after abrupt corticosteroid discontinuation.
Since their introduction as therapeutic agents,
corticosteroids also have been associated with

Vol. 34 No. 2 August 2007

psychiatric symptoms, ranging from mood

disturbances to florid psychosis. Euphoria
and depression are the major presentations
of steroid psychosis, but mania, paranoid reactions, schizophrenia, and various other toxic
syndromes also have been reported, with an incidence widely ranging from 13% to 62%; the
vast majority of events are mild to moderate.2
We describe an unusual case in which the
abrupt discontinuation of dexamethasone in
a patient who was receiving radiotherapy
produced an acute psychotic disorder.
The patient was a 48-year-old man, diagnosed
with myeloma IgG, lambda, Stage IIIA. He had
received several oncologic treatments and was
admitted for a course of radiotherapy to treat
vertebral pain due to tumor involvement of
the lower dorsal vertebral bodies. After admission, he developed a state of hyperexcitability,
clearly perceived and reported by the patient.
This progressed to increased irritability, lability
of mood, a profound dysphoria, and pressured
speech. As he was a painter and used to take
painting material everywhere with him, he
painted the white sheets in his room with
pictures of staff. He described these scenes with
trivial sentences. A bolus of intravenous midazolam (2 mg) followed by a continuous infusion
(22 mg/day) was started to control the state of
agitation. A cerebral MNR (magnetic nuclear
resonance) scan was negative, and laboratory
data were within the normal ranges.
From the review of documentation, it was
noted that dexamethasone at a dose of
8 mg/day that had been administered for several weeks had been stopped at admission.
Dexamethasone 4 mg was started and slowly tapered in the next three days. Within one day,
the agitation declined, and the midazolam

Letters

119

was stopped. He progressively recovered and

continued the course of radiotherapy in the
following days. No other relevant events
occurred. During the next 18 months, he remained at his baseline and did not have any
memory of what happened at that time.
This report is the first describing a case of
acute psychosis after corticosteroid discontinuation. Although there is consensus in the literature that corticosteroids may induce psychotic
disorders, published evidence documenting
this is scant, consisting only of case reports.
This case suggests that the development of
a similar pattern of symptoms may appear after
discontinuation of these drugs, possibly as
a consequence of a previous sensitization.3
Psychotic reactions after sudden withdrawal
of corticosteroid therapy should be considered
a rare risk of these drugs.
Sebastiano Mercadante, MD
Patrizia Villari, MD
Giuseppe Intravaia, RN
Anesthesia and Intensive Care Unit &
Pain Relief and Palliative Care Unit
La Maddalena Cancer Center
University of Palermo, Palermo, Italy
doi:10.1016/j.jpainsymman.2007.03.005

References
1. Margolin L, Cope DK, Bakst-Sisser R,
Greenspan J. The steroid withdrawal syndrome: a review of the implications, etiology, and treatments.
J Pain Symptom Manage 2007;33:224e228.
2. Lewis DA, Smith RE. Steroid-induced psychiatric
syndromes. A report of 14 cases and a review of the
literature. J Affect Disord 1983;5:319e332.
3. Sirois F. Steroid psychosis: a review. Gen Hosp
Psychiatry 2003;25:27e33.