Schwartz and Masand

Treatment of Delirium With Quetiapine

Thomas L. Schwartz, M.D., and Prakash S. Masand, M.D.

Introduction: Delirium, an organic psychiatric

syndrome, occurs in 10% of hospitalized patients
and is characterized by fluctuating consciousness
and impaired cognition, perception, and behavior.
Method: Charts of 11 consecutive patients
with delirium were retrospectively reviewed.
These patients were given quetiapine fumarate,
a novel antipsychotic, as first-line treatment for
their symptoms. The charts of a control group of
11 patients treated with haloperidol, the standard
treatment for delirium, during the same time period were also evaluated. The Delirium Rating
Scale (DRS) was used to evaluate the efficacy of
each treatment.
Results: Ten of 11 patients in both groups had
> 50% improvement in DRS scores. There was no
difference in onset of symptom resolution, duration of treatment, and overall clinical improvement. Quetiapine was better tolerated in these
medically ill patients.
Conclusion: Quetiapine appears to be an efficacious and well-tolerated treatment for delirium.
Further prospective studies are warranted.
(Primary Care Companion J Clin Psychiatry 2000;2:1012)

Co

py

rig

ht

Received Dec. 1, 1999; accepted Dec. 23, 1999. From the Department
of Psychiatry, SUNY Upstate Medical University, Syracuse, N.Y.
Supported in part by AstraZeneca.
Reprint requests to: Thomas L. Schwartz, M.D., Department of
Psychiatry, SUNY Upstate Medical University, 750 E. Adams St., Syracuse,
NY 13210 (e-mail: thomas_schwartz@yahoo.com).

The State University of New York Upstate Medical

Universitys hospital is a 350-bed tertiary care general
hospital that treats both indigent and privately insured patients. The Psychiatric Consultation Service of University
Hospital comprises 2 psychiatrists, 2 psychiatric residents, and 1 psychiatric nurse specialist. This service is
often asked to evaluate and provide treatment recommendations for delirious patients.
On review of patient care statistics, it was noted that 11
patients with delirium had been treated with quetiapine
from 1997 to 1999. The authors retrospectively reviewed
those charts and collected data with regard to age, sex,
medical diagnoses, maximum dose of quetiapine, time to
peak response with quetiapine, total duration of treatment,
and Delirium Rating Scale (DRS)11 scores prior to and after treatment. DRS is a validated scale and is a usual part

s,

es

c.
In

10

METHOD

Pr

elirium is an organic psychiatric syndrome characterized by fluctuating consciousness and impairment in cognition, perception, and behavior. It is generally
short-lived and has symptoms similar to longer duration
psychosis seen in patients suffering from schizophrenia,
major depression with psychosis, or bipolar disorder with
psychosis. Psychiatric patients with these disorders will
often experience hallucinations and delusions, such as
paranoia. Medically delirious patients may suffer from
hallucinations and delusions, as well as from confusion
and disorientation. Delirium occurs in approximately 10%
of hospitalized medical and surgical patients and in up to
80% of patients with terminal illness. 13 It is associated
with increased mortality and longer hospitalization. 46
Antipsychotic medications are generally efficacious in
treating psychotic features regardless of etiology, and outside of treating the underlying medical cause of delirium,

te

a
du
ra ted
stgprin
Po be
ns ay
ia y m
ic op
ys nal c
Pherso
00 ne p

20

they are the pharmacologic treatment of choice for these

patients.2 Haloperidol is considered the gold standard
because it has few anticholinergic side effects, few active
metabolites, and minimal propensity to cause sedation
and hypotension. Haloperidol can be administered orally,
intramuscularly, or intravenously, causing the fewest
extrapyramidal side effects when administered intravenously.7 Conventional, high-potency antipsychotics such
as haloperidol tend to produce higher rates of neurologic
side effects, such as parkinsonism and dystonia, whereas
lower potency drugs such as chlorpromazine can exacerbate delirium owing to anticholinergic effects.
Newer antipsychotics have much lower risk of causing
serious neurologic side effects. This more favorable side
effect profile occurs because these agents produce a
blockade of dopamine and serotonin receptors, whereas
the older, conventional antipsychotics only block dopamine. This favorable side effect profile has prompted use
of these newer antipsychotics in the medically ill, and
specifically in delirious patients. Risperidone8,9 and olanzapine10 were found to be effective, well-tolerated treatments for delirium. In similar fashion, we evaluated the
use of the novel antipsychotic quetiapine fumarate to treat
delirium in a general hospital setting. We hypothesized
that quetiapine, which has safety and efficacy profiles
similar to those of risperidone and olanzapine in psychotic disorders, would be at least as efficacious as haloperidol in treating delirium and would be better tolerated.

Primary Care Companion J Clin Psychiatry 2:1, February 2000

Treatment of Delirium With Quetiapine

Table 1. Mean Dose and Response Rates for Patients Taking Quetiapine or Haloperidola
Quetiapine
Variable
(N = 11)
Dose, mg/d
211.4
Peak response, d
6.5
Duration of treatment, d
13.0
DRS score prior to treatment
20.9
DRS score after treatment
2.7
a
Abbreviation: DRS = Delirium Rating Scale.

Haloperidol
(N = 11)
3.4
7.6
10.4
18.5
3.1

t Test
p Value
.0029
.6587
.4375
.1765
.7886

or concomitant medications of
other sources. Descriptive statistics, chi-square analyses, and t
tests were used to compare these
groups to determine dosing, efficacy, and tolerability profiles.
RESULTS

The mean age for the

quetiapine-treated
patients was
Table 2. Characteristics of Quetiapine-Treated Patients
57.6
years
(range,
1991
years)
Day
Duration of DRS Score Change
Age
Dose
at Peak Treatment Before/After in DRS
and for the haloperidol-treated
Patient (y) Gender Medical Diagnoses (mg/d) Response
(d)
Treatment
Score
patients, 53.7 years (range, 21
1
58
F
Multiple sclerosis
100
4
13
20/0
20
74 years). No significant base2
19
M
Brain contusion
200
7
13
21/4
17
line differences were found be3
77
M
Hypoxic brain injury
25
2
15
25/0
25
4
74
M
Stroke
400
9
17
27/6
21
tween the haloperidol- and the
5
37
M
HIV, breast abscess
100
3
6
15/8
7
quetiapine-treated population of
6
75
F
Diabetes, hypertension 200
20
25
21/6
15
b
delirious patients in regard to
7
91
M
Parkinsons disease
150
7
7
18/5
13
8
61
F
Valproate toxicity
750
3
7
22/1
21
age, sex, DRS scores, or efficacy
9c
51
F
Renal failure
100
11
18
15/0
15
measures. All but the latter sug10
45
F
Multiple sclerosis
200
3
9
22/0
22
gest that the haloperidol control
11
46
F
Renal cancer
100
3
3
24/0
24
a
group was evenly matched to the
Abbreviation: HIV = human immunodeficiency virus.
b
Quetiapine stopped owing to sedation.
quetiapine group demographic
Marked sedation reported (quetiapine continued).
cally and in regard to symptom
severity. The mean dose of quetiapine was 211.4 mg/day and of
Table 3. Characteristics of Haloperidol-Treated Patients
haloperidol, 3.4 mg/day. These
Day
Duration of DRS Score Change
doses tend to be lower than those
Age
Dose
at Peak Treatment Before/After in DRS
used in schizophrenia, but are
Patient (y) Gender Medical Diagnoses (mg/d) Response
(d)
Treatment
Score
1a
64
F
Diabetes, hypertension
2
3
4
24/0
24
consistent with the literature and
2
76
M
Dehydration, congestive 4
5
13
14/4
10
clinical practice in regard to
heart failure
delirium, which requires lower
3
44
M
Subdural hematoma
2
4
4
12/0
12
4
71
F
Third-degree heart block 2
3
3
24/7
17
doses. Ten of 11 patients on
5
41
M
HIV encephalitis
1
6
13
21/4
17
haloperidol treatment had > 50%
6a
74
M
Brain metastasis
1.5
24
24
14/10
4
improvement in DRS scores, and
7
55
M
Severe burns
3
8
12
14/2
12
8
49
M
Renal/hepatic failure
4
4
5
17/4
13
10 of 11 quetiapine-treated pa9
70
F
Chronic obstructive
4
7
7
21/1
20
tients had a similar improvepulmonary disease
ment. DRS improvement is a
10
21
M
Cerebral contusion
10
8
10
20/2
18
11
26
M
Spine fracture
4
12
19
22/0
22
global score that incorporates
a
Haloperidol discontinued owing to parkinsonism.
orientation, agitation, perceptual
disturbance, sleep-wake disturbance, and course-of-illness subof the consultation workup. Scores were derived pretreatscales. Time to peak response, total duration of treatment,
ment and posttreatment. When available, these scores
and change in DRS scores were not significantly different
were taken directly from clinicians notes. If no score was
(Table 1). Demographics of patients taking quetiapine and
available, the chart was reviewed by an independent psyhaloperidol are described in Tables 2 and 3, respectively.
chiatrist and a score retrospectively assigned on the basis
Two patients on haloperidol treatment developed exof chart-listed symptoms. Clinicians documentation of
trapyramidal symptoms (EPS) leading to discontinuation
symptoms was felt to be adequate in all charts studied. A
of the drug. None of the patients on quetiapine treatment
random selection of patients with haloperidol-treated de(including 1 with Parkinsons disease) developed EPS.
lirium were evaluated similarly and acted as controls.
Quetiapine led to mild-to-moderate sedation in 2 patients
Patients were excluded if they were taking any other con(1 had to discontinue the drug). These side effect rates are
comitant antipsychotic medication. Patients were not exsimilar in the psychiatric population in regard to quetiacluded on the basis of type or severity of medical illness
pine and haloperidol.

Co

py

rig

ht

a
du
ra ted
stgprin
Po be
ns ay
ia y m
ic op
ys nal c
Pherso
00 ne p

20

te

s,

es

Pr

c.
In

Primary Care Companion J Clin Psychiatry 2:1, February 2000

11

Schwartz and Masand

DISCUSSION

Ours is the first report of quetiapine in the treatment

of delirium. Traditionally, high-potency antipsychotics,
particularly haloperidol, are used as first-line treatment
for delirious patients. Unfortunately, haloperidol is frequently associated with extrapyramidal neurologic side
effects, including akathisia. This was evident in 2 of our
patients who developed significant EPS. Often, clinicians
will use antiparkinsonian agents that possess antimuscarinic effects to treat EPS. These agents are particularly
problematic in delirious patients since they may exacerbate anticholinergic delirium. Quetiapine is a novel antipsychotic agent whose mechanism of action is similar to
that of risperidone and olanzapine in that it blocks the
serotonin-2A receptors preferentially compared with
dopamine-2 receptors. It has a low propensity to cause
EPS and is also devoid of antimuscarinic blockade. Quetiapine was as efficacious as haloperidol and may be better tolerated, since haloperidol needed to be discontinued
more frequently.
Sipahimalani et al.8 treated 11 consecutive patients who
had delirium of multifactorial etiology with risperidone
(mean SD dose = 1.59 0.8 mg/day). The mean SD
duration of treatment with risperidone was 8.9 5.2 days.
Maximum response was seen at 5.1 4.3 days. Eight of
11 patients showed some improvement with risperidone.
The drug was very well tolerated in these patients with delirium. In another study, Sipahimalani and Masand10 used
olanzapine (mean dose = 8.2 3.4 mg at bedtime) to treat
11 delirious patients and compared them with a control
group of 11 patients who were treated with haloperidol
(mean dose = 5.1 3.5 mg at bedtime). Peak response time
was similar in both groups. Five of 11 olanzapine-treated
patients and 6 of 11 haloperidol-treated patients showed a
greater than 50% improvement on the DRS. Five of the
haloperidol-treated patients had EPS (parkinsonism, dystonia) or excessive sedation.
The above reports point to the efficacy and tolerability
of the newer antipsychotics in the treatment of delirium of
multifactorial etiology. These newer antipsychotics are
more efficacious than conventional antipsychotics in

Co

py

treating negative and mood symptoms and are less likely

to cause neurologic side effects and tardive dyskinesia.
They offer viable alternatives to the conventional antipsychotics for the treatment of not only schizophrenia but
nonschizophrenic conditions such as delirium as well.12
The purpose of this article is to provide the primary care
or hospital-based physician with up-to-date information
about these newer and potentially safer treatments for
their medically ill patients.
Finally, this pilot study has several limitations, including a small sample size, lack of randomization, and clinical ratings that were based on retrospective chart review.
Larger controlled studies in patients with delirium are
warranted to explore these preliminary observations and
conclusions.

rig

ht

Drug names: chlorpromazine (Thorazine and others), haloperidol (Haldol and others), olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal).

a
du
ra ted
stgprin
Po be
ns ay
ia y m
ic op
ys nal c
Pherso
00 ne p

20

REFERENCES

te

1. Lipowski ZJ. Delirium (acute confusional states). JAMA 1987;258:

17891792
2. Practice Guideline for the Treatment of Patients With Delirium. Am
J Psychiatry 1999;156(5 suppl):120
3. Massie MJ, Holland J, Glass E. Delirium in terminally ill cancer patients.
Am J Psychiatry 1983;140:10481050
4. Van Hemert AM, Van Der Mast RC, Hengeveld MW, et al. Excess mortality in general hospital patients with delirium: a five year follow up of 519
patients seen in psychiatric consultation. J Psychosom Res 1994;38:
339346
5. Trzepacz PT, Teague GB, Lipowski ZJ. Delirium and other organic mental
disorders in a general hospital. Gen Hosp Psychiatry 1985;7(2):101106
6. Weddington WW. The mortality of delirium: an underappreciated problem. Psychosomatics 1982;3:12321235
7. Tesar GE, Murray GB, Cassem NH. Use of high-dose intravenous
haloperidol in the treatment of agitated cardiac patients. J Clin Psychopharmacol 1985;5:344347
8. Sipahimalani A, Sime RM, Masand PS. Treatment of delirium with risperidone. Int J Geriatr Psychopharmacol 1997;1:2426
9. Ravona-Springer R, Dolbert OT, Hirschmann S, et al. Delirium in elderly
patients treated with risperidone: a report of three cases [letter]. J Clin
Psychopharmacol 1998;18:171172
10. Sipahimalani A, Masand PS. Olanzapine in the treatment of delirium. Psychosomatics 1998;39:422430
11. Trzepacz PT, Baker RW, Greenhouse J. A symptom rating scale for delirium. Psychiatry Res 1988;23:8997
12. Masand PS. Using newer antipsychotic agents in primary care. Primary
Psychiatry 1997;58:6468

s,

es

Pr

c.
In

12

Primary Care Companion J Clin Psychiatry 2:1, February 2000