2. Discussion
As per MSA classification, the present case was
categorized as having SND. Clinically, parkinsonian symp-
toms are dominant in SND, and SND often manifests with
gait disturbance [4]. Orthostatic hypotension and neurogenic
bladder are found in some cases. Before treatment, our
patient had these symptoms. The hallmarks of SND include
marked atrophy and gliosis of the striatum, particularly the
putamen, and degeneration of the substantia nigra. There-
fore, head MRI facilitates differentiation between SND and
Parkinson’s disease. SND is reportedly characterized by a
slit-like high-signal region on the outer side of the putamen
on T2-weighted MRI of the head [5]. These findings were
also present in our case. Levodopa effectiveness on
parkinsonism was minimal in our case, and her depressive
state was severe. Therefore, we performed ECT, which was
effective for both psychiatric and neurological symptoms.
Although the effectiveness of ECT for treatment of the
depressive state associated with Parkinson’s disease is well
established [6], there have been only three reports on five
patients with MSA and comorbid depression receiving ECT.
Ruxin and Ruedrick [7] reported that ECT alleviated
depression but did not improve the neurological symptoms
of their patient. Hooten et al. [8] performed ECT on an MSA
patient with depression and found improvement not only in
depression but also in rigidity and tremor. Roane et al. [9]
reported ECT to improve neurological symptoms in all three
of their MSA cases with depression, though none showed
improved ability of ambulate. The mechanism by which
ECT exerts its effect in the treatment of MSA is unknown.
Fochtmann [10] proposed a mechanism by which ECT may
work in Parkinson’s disease. She hypothesized that ECT has
an effect on postsynapses in the striatal dopamine system.
ECT also affects other neurotransmitter systems. The striatal
efferent system of the globus pallidus, containing cells that
release g-aminobutyric acid (GABA), was reported to be
histochemically preserved in levodopa-responsive patients
[11]. Roane et al. [9] speculated that, after ECT, the
increased GABA concentration in the striatum might be
related to the improvement of neurological symptoms in
MSA patients.
Our patient had been confined to bed due to MSA and
comorbid depression. The symptoms of parkinsonism
were assessed as Yahr 5, and she had pressure ulcerations.
Antiparkinsonian drugs had virtually no effect, and she
seemed unlikely to be discharged from the hospital.
However, after ECT, not only depression but also the
neurological symptoms, including rigidity, akinesia, dys-
phagia, dysarthria and forced crying, showed improve-
ment. Although the patient regained the ability to get into
a wheelchair by herself, she could not walk independent-
ly. It appears that ECT has limited effects on neurological
symptoms of MSA. However, the previously reported
cases and our present patient demonstrate that ECT may
be reasonably effective in treating depression associated
with MSA.
Katsutoshi Shioda, M.D.
Koichi Nisijima, M.D.
Satoshi Kato, M.D.
Department of Psychiatry
Jichi Medical School, Minamikawachi-Machi
Kawachi-Gun, Tochigi-Ken, 329-0498, Japan
E-mail address: [email protected]
doi:10.1016/j.genhosppsych.2005.08.003
References
[1] Wenning GK, Quinn NP. Parkinsonism Multiple system atrophy.
Baillieres Clin Neurol 1997;6:187–204.
[2] Costa C, Duyckaerts C. Oligodendroglial and neuronal inclusions in
multiple system atrophy. Curr Opin Neurol 1993;6:865–71.
[3] Hoehn MH, Yahr MD. Parkinsonism: onset, progression, and
mortality. Neurology 1967;17:427–42.
[4] Gouider-Khouya N, Vidaihet M, Bonnet AM, Pichon J, Agid Y.
bPureQ striatonigral degeneration and Parkinson’s disease: a compar-
ative clinical study. Mov Disord 1995;10:288–94.
[5] Horimoto Y, Aiba I, Yasuda T, et al. Longitudinal MRI study of
multiple system atrophy — when do the findings appear, and what is
the course? J Neurol 2002;249:847–54.
[6] Kennedy R, Mittal D, O’Jile J. Electroconvulsive therapy in
movement disorders: an update. J Neuropsychiatry Clin Neurosci
2003;15:407–21.
[7] Ruxin RJ, Ruedrich S. ECT in combined multiple system atrophy and
major depression. Convuls Ther 1994;10:298–300.
[8] Hooten WM, Melin G, Richardson JW. Response of the parkinsonian
syndromes of multiple system atrophy to ECT. Am J Psychiatry 1998;
155:1628.
[9] Roane DM, Rogers JD, Helew L, Zarate J. Electroconvulsive therapy
for elderly patients with multiple system atrophy. Am J Geriatr
Psychiatry 2000;8:171–4.
[10] Fochtmann L. A mechanism for the efficacy of ECT in Parkinson’s
disease. Convuls Ther 1988;4:321–7.
[11] Ito H, Kusaka H, Matsumoto S, Imai T. Striatal efferent involvement
and its correlation to levodopa efficacy in patients with multiple system
atrophy. Neurology 1996;47:1291–9.
Ziprasidone-related agranulocytosis following
olanzapine-induced neutropenia
To the Editor,
1. Introduction
Reversible leukopenia is relatively common in patients
treated with antipsychotics [1]. Agranulocytosis is a much
less common event, occurring in approximately 0.05% of
patients treated with first generation antipsychotics [2].
Although clozapine is the second generation antipsychotic
agent most commonly associated with agranulocytosis
(0.5–2.0% risk), severe neutropenia and agranulocytosis
have also been associated with risperidone and olanzapine
[3–9]. The time course of antipsychotic-induced neutrope-
nia can be highly variable, but there have been peaks
demonstrated between days 40 and 50 in clozapine-induced
neutropenia and between days 20 and 30 in other
psychotropic agents [9].
Letters to the Editor / General Hospital Psychiatry 28 (2006) 78–87 83
Although macrocytic anemia has been associated with
the use of ziprasidone in one published case, there have
been no published reports of neutropenia (less than 1500
neutrophils/mm3) or agranulocytosis (less than 500 neutro-
phils/mm3) associated with the second generation antipsy-
chotic ziprasidone [10]. We present the case of a clozapine-
naive patient who developed severe neutropenia secondary
to olanzapine and agranulocytosis related to ziprasidone, in
consecutive trials.
2. Case report
A 19-year-old African American woman with schizo-
phreniform disorder presented to a state psychiatric hospital
primarily with poverty of thought, elective mutism, auditory
hallucinations and poor hygiene. While awaiting transfer for
our facility, she had been prescribed olanzapine 20 mg/day
for 8 days at a local private psychiatric hospital.
Upon admission to our facility, her WBC was 2.78�103
and her absolute neutrophil count (ANC) was 731 neutro-
phils/mm3. Other laboratory tests were unremarkable,
including HIV screen and antinuclear antibody. Results
from a brain CT scan without contrast revealed no evidence
of masses, lesions or other structural abnormalities, and an
electroencephalogram revealed no abnormal wave activity
or signs of encephalopathy.
The complete blood count was repeated on hospital day
(HD) 3, revealing an ANC of 811 neutrophils/mm3.
Olanzapine was discontinued on HD 7 and 5 days later;
her ANC had normalized at 2910 neutrophils/mm3.
On HD 18, ziprasidone was started and rapidly titrated to
120 mg/day. On HD 19, the patient was started on
mirtazapine 15 mg/day and rapidly titrated to 30 mg/day
to address her negative symptoms and possible depression.
Over the subsequent 6 weeks, the patient’s ANCs ranged
from 879 to 2269 neutrophils/mm3. On HD 64, the patient’s
ANC dropped to 695 neutrophils/mm3, and by HD 76, her
ANC was 499 neutrophils/mm3 (WBC, 2.63�103). The
ziprasidone was stopped immediately, and 8 days later, her
ANC had normalized (2046 neutrophils/mm3).
One month later, the patient was started on lithium
carbonate, both to address her treatment-resistant symptoms
and to augment leukocyte production in order to increase
her chances of tolerating another antipsychotic agent. On
HD 149, aripiperazole 15 mg/day was added to her regimen.
Over the next 5 weeks, the patient’s ANC’s ranged from
1785 to 4309 neutrophils/mm3.
Although rechallenging the patient with ziprasidone was
considered to confirm her sensitivity to the agent, this was
ultimately deemed not to be in her best interest, since little
clinical improvement was evident during her 6-week trial
of ziprasidone.
3. Discussion
The lack of reported ziprasidone-induced neutropenia,
both in the published literature and the drug manufacturer,
suggest that this is a rare adverse drug reaction. However,
there were potentially confounding factors that could have
contributed to the patient’s blood dyscrasia.
Mirtazapine has been shown in premarketing studies to
induce agranulocytosis in up to 0.1% of patients, and could
have contributed to this patient’s severe neutropenia [11].
However, the patient continued to receive mirtazapine for
over 1 week after the removal of ziprasidone and subsequent
normalization of her WBC. Also, in a review of the patient’s
adverse drug reaction, the hospital’s pharmacy and thera-
peutics committee concluded that there was a high likelihood
that ziprasidone, rather than mirtazapine, was the causative
agent. Albeit, it remains possible that mirtazapine and
ziprasidone shared a dual role in this case of agranulocytosis.
Substantial diurnal variation of circulating neutrophils
(i.e., bmorning pseudoneutropeniaQ) has been described
during treatment with clozapine and risperidone [12,13].
In these cases, the neutrophil count normalized by the time
the afternoon blood sample was taken. Although we did not
measure diurnal blood counts for this patient, on HD 64, the
patient’s blood was drawn at 4:00 p.m., and her ANC was
still low (879 neutrophils/mm3).
Another potentially contributing factor to this patient’s
blood dyscrasia is her race. It has been suggested that
African Americans have lower baseline neutrophil ranges
than Caucasians [14]. Unfortunately, no baseline WBC
values were available for this patient, given her lack of
previous treatment history.
This case warrants further investigation into the risk of
blood dyscrasias related to ziprasidone therapy. As sug-
gested in previous reports, where individuals whom
experienced agranulocytosis during clozapine therapy went
on to develop neutropenia secondary to olanzapine, there
may be a cross-reactivity between certain second-generation
antipsychotics with respect to blood dyscrasias [5–7].
John Montgomery, D.O.
Female Receiving Unit
Mississippi State Hospital
Whitfield, MS 39193, USA
Department of Psychiatry and Human Behavior
University of MS Medical Center
Jackson, MS 39216, USA
E-mail address: [email protected]
doi:10.1016/j.genhosppsych.2005.08.005
References
[1] Kane JM, Lieberman JA. Adverse effects of psychotropic drugs. New
York7 Guilford; 1992. p. 378–83.
[2] Meltzer HY, Fatemi SH. Treatment of schizophrenia. In: Schatzberg
CB, Nemeroff CB, editors. Textbook of psychopharmacology, 2nd ed.
Washington (DC)7 American Psychiatric Press; 1998. p. 762–3.
[3] Gajwani P, Tesar GE. Olanzapine-induced neutropenia. Psychosomatics
2000;41(2):150–1.
[4] Finkel B, Lerner AG, Oyffe I, Sigal M. Risperidone-associated
agranulocytosis. (letter)Am J Psychiatry 1998;155(6):855–6.
Letters to the Editor / General Hospital Psychiatry 28 (2006) 78–8784
[5] Godleski LS, Sernyak MJ. Agranulocytosis after addition of
risperidone to clozapine treatment. (letter)Am J Psychiatry 1996;
153(5): 735–6.
[6] Teter CJ, Early JJ, Frachtling RJ. Olanzapine-induced neutropenia in
patients with history of clozapine treatment: two case reports from a
state psychiatric institution. (letter)J Clin Psychiatry 2000;11(61):
872–3.
[7] Benedetti F, Cavallaro R, Smeraldi E. Olanzapine-induced neutro-
penia after clozapine-induced neutropenia. (letter)Lancet 1999;
354(9178):567.
[8] Duggal HS, Gates C, Pathak PC. Olanzapine-induced neutropenia:
mechanism and treatment. (letter)J Clin Psychopharmacol 2004;
24(2):234–5.
[9] Stubner S, Grohman R, Engel R, Bandelow B, LudwigWD,Wagner G,
et al. Blood dyscrasias induced by psychotropic drugs. Pharmacop-
sychiatry 2004;37(Suppl 1):S70–8.
[10] Nair P, Lippmann S. Blood dyscrasia with quetiapine and ziprasidone.
Psychosomatics 2005;46:89–90.
[11] Nelson JC. Safety and tolerability of the new antidepressants. J Clin
Psychiatry 1997;58(Suppl 6):26–3158.
[12] Esposito D, Corruble E, Hardy P, Chouinard G. Risperidone-induced
morning pseudoneutropenia. Am J Psychiatry 2005;162(2):397.
[13] Esposito D, Aouille J, Rouillion F, Limosin F. Two year follow-up of a
patient with successful continuation of clozapine treatment despite
morning pseudoneutropenia. J Clin Psychiatry 2004;65(9):1281–2.
[14] Reed WW, Diehl LF. Leukopenia, neutropenia and reduced hemo-
globin levels in healthy American blacks. Arch Intern Med
1992;152(6):1329.
Delusional parasitosis or Ekbom syndrome: a case series
To the Editor,
1. Introduction
Delusional parasitosis (DP) is a neuropsychiatric syn-
drome in which the patient has the fixed delusion of
infestation by parasites such as lice and mites [1]. Although
several cases have been recorded since the end of the 19th
century, it was the Swedish psychiatrist Karl-Axel Ekbom
who first studied systematically the presenile syndrome of
delusional dermatozoid parasitic infestation in 1938 [2].
After a multitude of different names being used over the
years such as acarophobia or parasitophobic neurodermatitis,
Ekbom’s name has become the eponym attached to the
condition referred to later as DP [2–4]. One reason for this
nomenclature change was the recognition that DP is not a
phobia, i.e., an irrational fear of being infested by parasites,
but rather a delusional condition. Some still debate whether
the primary disorder in DP is a tactile or cenestesic
hallucination precipitating a secondary delusion [3–6].
Delusional parasitosis is considered a rare condition in
neuropsychiatric settings. It has been mainly described in
case reports or small case series [6–8]. Delusional parasit-
osis patients usually seek dermatological care since the
presenting symptoms include several skin lesions such as
excoriations from scratching. Thus, some surveys performed
with dermatologists suggested that DP may be more
common than previous thought [9,10].
In this study, we report a Brazilian series of DP derived
from a psychiatric clinic.
2. Methods
All patients with DP seen by the authors since 1995
were carefully reviewed. The diagnosis of DP was based
on a detailed clinical history. The psychiatric classification
was done according to the structured clinical interview
Mini International Neuropsychiatric Interview [11,12]. The
Mini-Mental Status Examination (MMSE) was also
applied to all patients [13]. In order to exclude secondary
causes of DP, an extensive laboratory evaluation was
performed, including complete blood cell count; liver,
renal and thyroid function tests; serum electrolytes and
glucose levels; vitamin B12, folate and iron studies;
urinalysis; serological study for syphilis. Neuroimaging
studies were available for all subjects. Demographic data
were also obtained.
3. Results
Ten patients with DP were identified. The demographic
and clinical characteristics of the patients are depicted in
Table 1. Of the 10 patients, seven were female, resulting
in a female-to-male ratio of 2.3:1. The age at first clinical
evaluation ranged from 67 to 81 years (mean ageFS.D.,
72.4F5.2). Duration of symptoms ranged from 6 months
to 3 years, with a mean (FS.D.) of 18.0 (F9.4) months.
The mean (FS.D.) time of follow-up of patients was 9.9
(F2.8) months.
The presenting dermatological signs were considerably
variable, including excoriations from scratching, lichen-
ification, contact dermatitis to different topical products
applied. The bmatchbox sign,Q defined as the behavior of
bringing samples of the alleged parasites inside small
containers, was observed in just one patient (Case 9). The
phenomenon of folie a deux, i.e., shared delusion of
infestation by a partner, was not found in the present series.
Most patients were unmarried (widow, six; single, two)
or living alone (five). All had some clinical comorbidity,
mainly diabetes (four), hypertension (four) and thyroid
disease (three). None of the clinical illnesses could be
etiologically related to the diagnosis of DP. Five subjects
(50%) were diagnosed with a delusional disorder, a
primary psychotic category that cannot be attributed to
another major psychiatric disorder or physical illness
[14,15]. Two patients were diagnosed with major depres-
sion with psychotic symptoms, while another two with
dementia. One patient had a psychiatric background of
schizophrenia. The score in the MMSE was below the
expected value in three subjects (dementia, two; schizo-
phrenia, three). Of note, three patients exhibited patholog-
ical findings on neuroimaging studies, marked cortical
atrophy (Cases 8 and 10) and multiple small infarctions of
subcortical white matter (Case 7), which were compatible
with their diagnosis.
All patients used some antipsychotic medication in low
dose: half typical (haloperidol or pimozide) and half atypical
Letters to the Editor / General Hospital Psychiatry 28 (2006) 78–87 85