Taiwanese Journal of Psychiatry (Taipei) Vol. 25 No.

2 2011 • 115 •
Case Report

Decreased White Blood Cell Count Related to

Haloperidol Add-on Treatment to Olanzapine
Wei-Lieh Huang, M.D., Chao-Cheng Lin, M.D., Ph.D.,
Shih-Cheng Liao, M.D.

Abstract

Background: Leukopenia is a potentially severe side effect of antipsychotic

drugs. Clozapine, olanzapine, and chlorpromazine are found to induce leukopenia.
Haloperidol-induced leukopenia is occasionally reported. Research are limited to
explore hematologic side effects related to the combined use of olanzapine and
haloperidol. Case Report: We present a case of a patient with schizophrenia,
whose white blood cell count was decreased following receiving a combination of
haloperidol and olanzapine, and increased rapidly after discontinuing haloperidol.
Conclusion: This case reminds us paying attention to the leukopenic effect of the
use of haloperidol or combined antipsychotic drugs. Encountering a patient with
a suspected antipsychotics-induced hematologic problem, clinicians need to con-
sider those frequently mentioned offending agents, and to observe its relation with
other antipsychotic drugs.

Key words: leukopenia, neutropenia, haloperidol, olanzapine

(Taiwanese Journal of Psychiatry [Taipei] 2011; 25: 115-8)

one of the most commonly used first-generation

Introduction antipsychotic drugs, has only sporadic reports of
hematologic side effects. Some research find the
Leukopenia is a potentially serious side ef- combined use of antipsychotic drugs may increase
fect of antipsychotic drugs. Low absolute neutro- the risk of leukopenia [4]. The literature of dealing
phil count (ANC) can easily cause a common bac- with the issue of drug interaction between olan-
terial infection to become a catastrophic clinical zapine and haloperidol is scarce.
condition. Among all antipsychotic drugs, clozap- Here we report a case of a female patient
ine has the highest rate to induce neutropenia with with schizophrenia, whose white blood cell
the incidence of 2.6%-2.9% [1]. Olanzapine and (WBC) count was decreased after adding halo-
chlorpromazine have also been frequently men- peridol to existing olanzapine treatment. Her
tioned to cause leukopenia [2, 3]. Haloperidol, WBC count was increased soon after haloperidol

Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan

Received: September 3, 2010; revised: October 8, 2010; accepted: October 12, 2010
Address correspondent to: Dr. Chao-Cheng Lin, Department of Psychiatry, National Taiwan University Hospital, No.7. Chung San
South Road, Taipei 100, Taiwan
• 116 • Grief-related Major Depression

was discontinued. We will discuss the relation be- dL, total-bilirubin 0.55 mg/dL , aspartate amino-
tween the combination use of antipsychotic drugs transferase (AST) 15 U/L, blood urea nitrogen
and hematologic problems based on findings of (BUN) 10.9 mg/dL, creatinine 0.8 mg/dL, sodium
this case and the reports in the literature. 141 mmol/L, and potassium 4.4 mmol/L. Because
she still had delusions, we increased her olanzap-
Case Report ine to 25 mg/day on day 25. On day 27, we re-
checked the WBC count and found that it had
Miss L, a 44-year-old Taiwanese woman pa- fallen to 3,370 cells/µL, and ANC was 1,830
tient, was hospitalized on the psychiatric ward due cells/µL. Other profiles of CBC on day 27 includ-
to her aggravated persecutory delusion. She was ed RBC 4.26 M/µL , Hb 12.0 g/dL , MCV 85.2 fL,
diagnosed to have paranoid schizophrenia eight and Plt 242.0 K/µL. Except for the low WBC
years before admission. She was prescribed ris- count, other data were all within normal limits.
peridone 3-4.5 mg/day but she had not taken it She received concurrent medications of thyroxine
regularly. She had no history of physical illnesses 50 µg/day, bromazepam 9 mg/day, and zopiclone
except for hypothyroidism, which was clinically 7.5 mg/day. Those agents are not known to induce
well controlled with thyroxine 50 µg/day. leukopenia, and the dosage was not adjusted from
Reviewing her past medical history, we did not day 18 to day 27. She did not have any infection,
find any medical record of a low WBC count. Six immune disorder, or other etiology of causing de-
months before admission, her persecutory delu- creased WBC count. The influence of antipsy-
sions were worsened. One month before admis- chotic drugs was suspected. Due to the relatively
sion, her antipsychotic drug was shifted to olan- low dosage of haloperidol, we discontinued halo-
zapine 10 mg/day, but the improvement was peridol on day 27 and kept olanzapine at 25 mg/
limited. Thus, she was admitted for inpatient day. On day 29, patient’s WBC count was in-
treatment. creased to 4,440 cells/µL, and ANC 2,550 cells/
The results of physical and laboratory exami- µL. On day 31, the WBC count was reached 5,320
nations showed no abnormality on admission. The cells/µL, and ANC 3,460 cells/L. Under decreased
WBC count on day 1 of the hospitalization was severity of the persecutory delusions and stable
5,220 cells/µL, ANC was 3,330 cells/µL, free thy- physical condition, Miss L was discharged on day
roxine (T4) serum level 1.15 ng/dL, and high-sen- 36.
sitivity thyroid-stimulating hormone (hsTSH) se-
rum level 2.21 µIU/mL. All those findings were Discussion
within normal limits. We increased the dosage of
olanzapine from 10mg/day to 20 mg/day within In the view of time sequence, Miss L’s WBC
three weeks. But she still had delusions of count curve was matching temporarily to her hal-
reference. operidol administration (Figure 1). On admission,
We added haloperidol 5 mg/day on hospital- olanzapine had been used for one month, and pa-
ization day 22 for augmentation. On day 24, we tient’s leukopenia was not found. Her WBC count
incidentally found that patient’s WBC count was was fallen two days after adding haloperidol, and
decreased to 3,860 cells/µL. Serum examinations was elevated two days after discontinuing halo-
on day 24 revealed that serum albumin was 4.2 g/ peridol. Maintaining olanzapine at 25 mg/day af-
 Kuo J, Lin SK • 117 •

ter discontinuing haloperidol did not cause leuko- pendent and can be influenced by drug-drug inter-
penia. The Naranjo score of this case is 6, and the action [4, 9]. Haloperidol and olanzapine are both
likelihood of adverse drug reaction is “probable” metabolized through cytochrome P450 2D6 (CYP
[5]. We need to consider that the decreased WBC 2D6). It is possible that the add-on of haloperidol
count caused by haloperidol, or that this finding increases serum concentration of olanzapine, re-
was strengthened under the haloperidol add-on to sulting in elevated risk of olanzapine-induced he-
olanzapine. matologic adverse reaction.
Few case reports have mentioned haloperi- If psychotic symptoms are not relieved with
dol-induced leukopenia. Only one report describes a high dosage of second-generation antipsychotic
that patient has neutropenia under a combined use drug, augmenting with a first-generation antipsy-
of haloperidol and olanzapine [6]. In that case, chotic is a common treatment strategy [10]. When
haloperidol and olanzapine were discontinued at combining olanzapine and haloperidol, most cli-
the same time, making it hard to determine wheth- nicians may assume that leukopenia is related to
er the hematologic problem was caused by the olanzapine, and consider to discontinue it first.
combination of the two agents. Another study re- Haloperidol may be continued or increased to
veals that haloperidol causes decreased mean lobe control psychotic symptoms. But in this case, pa-
numbers of neutrophils, impling immatured neu- tient’s decreased WBC count was relieved with-
trophils and an increased risk of neutropenia [7]. out removing olanzapine.
Antipsychotic drugs cause blood dyscrasias This case report has three major limitations.
by ways of bone marrow suppression, through First, the WBC count was not checked regularly in
mechanisms of direct toxicity to blood cells, or the first weeks of admission. It is possible that her
immune-mediated destruction [8]. If the mecha- WBC count had decreased before giving haloperi-
nism is direct toxicity, the risk may be positively dol. Some reports reveal that increased olanzapine
related to the serum concentration of antipsychot- dosage increases the risk of leucopenia [9], but the
ic agents. Some reports support that leukopenia WBC count maintaining within a normal range
induced by clozapine and olanzapine is dose-de- under olanzapine 25 mg/day may exclude olan-

30 10
Dose of antipsychotics

WBC count (K/uL)

Dose of
8 olanzapine ■
20 6 Dose of
(mg/day)

haloperidol ◆
4
10 WBC count
2
0 0
1 4 7 10 13 16 19 22 25 28 31 34
Days of admission

During the admission, the dose of olanzapine kept increasing. Haloperidol was added for augmentation on day 22.
Decreased WBC count was noted on day 24 and day 27. After haloperidol was discontinued on day 27, the WBC count
increased gradually despite olanzapine was kept at high dosage of 25 mg/day.

Figure 1. WBC count and dosage of antipsychotics during admission of Miss L

• 118 • Grief-related Major Depression

zapine as a single cause. Second, Miss L’s blood

cell count did not reach leukopenia or neutrope- References
nia, which are often defined as WBC count less
than 3,000 cells/µL and ANC less than 1,500 1. Copolov D, Bell W, Benson W, et al.: Clozapine
cells/µL, respectively. The possibility of a physi- treatment in Australia: a review of haematological
ologic fluctuation can not be totally ruled out, monitoring. Med J Aust 1998; 168: 495-7.
though the history of low WBC count is negative. 2. Gajwani P, Tesar G: Olanzapine-induced neutrope-
We think that it is somewhat meaningful for ob- nia. Psychosomatics 2000; 41: 150-1.
3. Flanagan RJ, Dunk L: Haematological toxicity of
serving the trend of WBC count and its relation to
drugs used in psychiatry. Hum Psychopharmacol
medication. Third, we did not re-challenge the pa-
2008; 23: 27-41.
tient with the possible offending drug because she
4. Ghaznavi S, Nakic M, Rao P, et al.: Rechallenging
did not want to expose herself to haloperidol any
with clozapine following neutropenia: treatment op-
more. tions for refractory schizophrenia. Am J Psychiatry
This is the first report of a decreased WBC 2008; 165: 813-8.
count relieved after discontinuing haloperidol 5. Naranjo CA, Busto U, Sellers EM: Difficulties in as-
alone in a patient of receiving both olanzapine and sessing adverse drug reactions in clinical trials. Prog
haloperidol. Our report suggests that a decreased Neuropsychopharmacol Biol Psychiatry 1982; 6:
WBC count may be induced by the add-on of hal- 651-7.
operidol. The possible mechanisms include the 6. Abdullah N, Voronovitch L, Taylor S, et al.:
leukopenic effect of haloperidol, synergetic leu- Olanzapine and haloperidol: potential for neutrope-
kopenic effect of haloperidol and olanzapine, and nia? Psychosomatics 2003; 44: 83-4.
the increased risk of olanzapine-induced leukope- 7. Delieu J, Horobin R, Duguid J: Formation of imma-
ture neutrophil leucocytes in schizophrenic patients
nia due to drug-drug interaction. This case serves
treated with various antipsychotic drugs: compari-
to remind us considering hematologic adverse re-
sons and predictions. J Psychopharmacol 2006; 20:
actions influenced by antipsychotic drugs other
824-8.
than the frequently mentioned agents. When en-
8. Hall R, Smith A, Edwards JG: Haematological safety
countering leukopenia in a patient using combina- of antipsychotic drugs. Expert Opin Drug Saf 2003;
tion of antipsychotic drugs, we suggest that clini- 2: 395-9.
cians need to consider the relationship between 9. Kodesh A, Finkel B, Lerner A, et al.: Dose-dependent
the blood cell count and each antipsychotic drug olanzapine-associated leukopenia: three case reports.
carefully. Int Clin Psychopharmacol 2001; 16: 117-9.
10. Gardos G: Antipsychotic polypharmacy or mono-
therapy? Neuropsychopharmacol Hung 2005; 7:
72-7.