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: psychiat@jichi.ac.jp

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: jmontgo651@yahoo.com

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