ORIGINAL ARTICLE
Quetiapine for Insomnia in Parkinson Disease
Results From an Open-Label Trial
Carlos Juri, MD,*† Pedro Chaná, MD,* John Tapia,*‡
Carolina Kunstmann,* and Teresa Parrao*
Abstract: Quetiapine is an atypical antipsychotic with sedative
properties frequently used to treat hallucinations and psychosis in
Parkinson disease (PD). The objective of this trial is to evaluate
quetiapine for insomnia in nonpsychotic PD patients. Fourteen con-
secutive PD patients with frequent insomnia and without psychotic
symptoms were treated openly for 12 weeks with a single evening
dose of quetiapine. The dose was adjusted according to clinical im-
provement and tolerance. The severity of insomnia was assessed using
the Pittsburgh Sleep Quality Index (PSQI), daytime sleepiness was
evaluated with the Epworth Sleep Scale (ESS), and motor perfor-
mance was evaluated using the motor section of the Unified Parkinson’s
Disease Rating Scale (UPDRS). All evaluations were done before and
1, 2, and 3 months after initiation of treatment. Total PSQI basal scores
were 13.6 6 3.7 points. The PSQI score improved in 11 patients and
was reduced by 3.8 6 3.9 points by the end of the study (P , 0.01).
The ESS score was reduced by 4.3 6 3.7 points (P , 0.01). The
mean quetiapine dose was 31.9 mg/day. No significant change was
observed in the motor scale. Two patients were discontinued due to
nonserious adverse effects. These results suggest that quetiapine may
be a safe and effective treatment of insomnia in PD patients. Double-
blind studies will probably confirm these findings.
Key Words: Parkinson disease, sleep disorders, quetiapine
(Clin Neuropharmacol 2005;28:185–187)
I nsomnia is a frequent sleep disorder in Parkinson disease
(PD).1,2 Etiologies for insomnia in PD include sleep frag-
mentation, nocturnal immobility, nocturia, REM sleep behav-
ior disorder, restless legs symptoms, pharmacologic adverse
effects, and psychiatric comorbidity.2,3 Pharmacologic treat-
ment of insomnia is needed in some of these patients. Few
studies, however, evaluate drugs for insomnia in the PD popu-
lation. The use of drugs for insomnia in PD is complex, because
cognitive and motor side effects are frequent.4 Quetiapine is an
atypical antipsychotic with hypnotic effects, even in healthy
subjects, and it does not worsen the motor aspects of PD.5–8 No
From the *Movement Disorders Center (CETRAM); the †Department of
Neurology, Catholic University of Chile; University of Santiago of Chile.
Reprints: Dr. Carlos Juri, Movement Disorders Center (CETRAM), Belisario
Prats 1597, Independencia, Santiago, Chile (e-mail: cjuri@puc.cl).
Presented as a poster at the Eighth Movement Disorders Congress, Rome,
Italy, 2004.
Copyright Ó 2005 by Lippincott Williams & Wilkins
Clin Neuropharmacol  Volume 28, Number 4, July - August 2005
study on the use of quetiapine in the nonpsychotic PD popu-
lation has been published. The purpose of this study has been
the evaluation of the use of quetiapine to improve sleep in a PD
patient population, which frequently is affected by insomnia
and has no clinically significant psychiatric comorbidity.
METHOD
Consecutive PD patients according to established criteria9
seen in an outpatient care center for movement disorders were
interviewed. If they affirmed that they had experienced insom-
nia at least 3 nights per week during the last 3 months, they
were invited to participate in the study. A sleep-directed in-
terview and a psychiatric interview were carried out with all
subjects.
Exclusion criteria included dementia as defined by
DSM-IV criteria;10 depression as defined by a Yesavage De-
pression Scale11 score (.10 points); hallucinations or psychotic
symptoms; sleep apnea symptoms; previous treatment with
neuroleptics, modafinil, or stimulants; and renal, hepatic, or
cardiac disease.
Patients were evaluated according to the Pittsburgh Sleep
Quality Index (PSQI)12 to assess the severity of their insomnia
and related sleep behavior. Also, the Epworth Sleepiness Scale
(ESS)13 and the motor scale of the Unified Parkinson’s Disease
Rating Scale (UPDRS)14 were applied. These evaluations were
done at baseline and 1, 2, and 3 months from initiation of treat-
ment. The complete study lasted 3 months.
Patients were treated at the start with a single evening
dose of quetiapine, beginning with 12.5 mg. This dose was
adjusted after the first week and then monthly according to
response and tolerance. A maximum dose of 100 mg was pro-
posed. PD medications were not modified during the study.
Blood pressure was measured at each visit with the
patient in supine and standing positions. The local ethics com-
mittee approved the study, and all patients were informed of
the study details and signed a consent before participation.
STATISTICAL ANALYSIS
Statistical analyses were performed using SPSS version
10.0 for Windows. Nonparametric tests were used. The exact
P values (2 tailed) were computed. The significance level was
set at P , 0.05. For patients who withdrew from the trial (n = 2),
the last available observation was carried forward and used as
data for the final visit.
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Juri et al
FIGURE 1. Pittsburgh Sleep Quality Index median total scores at
baseline and with treatment at 4, 8, and 12 weeks. The hollow
boxes represent median values; the bars show median typical
errors.
RESULTS
Fourteen patients (11 men) were recruited. Their average
age was 67.6 6 8.4 years, average symptomatic PD duration
was 13.2 6 4.9 years, and the medium UPDRS value was
28.3 6 11.4 points. The average dose of equivalent levodopa
was 1325 6 334 mg. Dopamine agonists were used in 10
patients, always combined with levodopa.
Sleep fragmentation was the main etiology of insomnia
in our population (10 patients), in 2 cases nocturia was diag-
nosed, and in 2 other patients sleep fragmentation plus restless
legs symptoms were apparent. No patient had symptoms of
REM behavior disorder.
Subjective Sleep Parameters
The baseline and posttreatment sleep scales scores are
shown in Table 1. The total PSQI score and all subscales
improved significantly from baseline between the initiation of
treatment and the third month. The sleep onset (sleep latency)
period showed the greatest improvement. It was reduced from
82 6 65.4 minutes on the first visit to 28.6 6 22.7 minutes
in the last control (P , 0.05). Improvement was apparent from
the first month on and remained stable until the last visit
during the third month (Fig. 1). Additionally the ESS scores
improved substantially in the same period. There was no rela-
tion between sleep response and the dose of levodopa or
dopamine agonist.
Medication and Side Effects
The mean dose of quetiapine was 31.9 mg at week 12
(range, 12.5–50 mg). Two patients were discontinued due to
a worsening of their sleep disorder, caused mainly by restless
legs symptoms that rapidly increased since the beginning of
treatment. Symptom remission occurred after drug with-
drawal. Two subjects reported increased diurnal sleepiness. No
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Clin Neuropharmacol  Volume 28, Number 4, July - August 2005
TABLE 1. Change from Baseline to Week 12 (last observation
carried forward) for Primary Efficacy End Points
Baseline Change from Baseline
Efficacy Mean Mean
End Point n (SD) n (SD) Median P Value*
PSQI total, pt 14 13.6 (3.4) 14 23.8 (3.9) 24.0 0.005
ESS total, pt 14 10.9 (5.1) 14 24.3 (3.7) 24.0 0.003
UPDRS motor, pt 14 29.1 (12.6) 14 +0.8 (4.1) +1.0 0.599
*Wilcoxon signed-rank test.
significant changes occurred in the motor scale UPDRS
scores. No orthostatic symptoms were reported and no signif-
icant changes occurred in blood pressure.
DISCUSSION
This study was the first to investigate the effect of the
atypical antipsychotic quetiapine on insomnia in patients with
PD. This trial shows the efficacy of low, single evening dose of
quetiapine to treat insomnia in PD patients, without worsening
of motor symptoms.
Insomnia is frequently present in PD; however, there are
only few studies evaluating pharmacotherapy to release the PD
population from this complaint. Our results offer a potential
alternative for this population with few side effects. In con-
trast, the use of benzodiazepines or tricyclic antidepressants,
the 2 most commonly used hypnotics in this population, has
frequent cognitive4 and anticholinergic side effects.
The way quetiapine works on sleep disorders is not yet
fully understood. Cohrs et al7 have recently published a study
on healthy subjects that shows significant changes in several
sleep parameters through the use of quetiapine, especially reduc-
tion of sleep latency, increase of total sleep time, and en-
hancement of sleep efficiency, with a simultaneous reduction
of the time spent awake. The reason for these changes is not
known. It has been assumed that selective dopaminergic block-
ade of atypical antipsychotics could affect sleep organization.15
Also remarkable in the current study was the significant
reduction of daytime sleepiness as reflected in the decrease of
the ESS score. Some studies have shown a direct relation be-
tween insomnia and the occurrence of daytime hypersomnia,16
and even the reduction of daytime sleepiness has been docu-
mented with improvement in nocturnal sleep. We think that, at
least in part, daytime sleepiness in PD patients reflects poor
sleep quality and that the improvement of this quality may be
a way to release a number of patients from this complaint, as
shown by our results.
Also interesting in our study was the exacerbation of
symptoms of restless legs through the use of quetiapine, prob-
ably a secondary effect to dopaminergic blockade.17 Such a
finding has been reported in connection with other neuro-
leptics as well, especially older ones, and more recently with
regard to risperidone18 and olanzapine.19
The Food and Drug Administration has recently pub-
lished a public health advisory20 on the mortality risks related
to the use of antipsychotics in older patients with behavioral
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Clin Neuropharmacol  Volume 28, Number 4, July - August 2005
disturbances. This also includes quetiapine and should be taken
into account when using this drug.
Our study has some deficiencies, such as the small
number of patients and the absence of a placebo control group.
The lack of a neurophysiologic sleep study has not permitted
the precise etiologic diagnosis, such as the definition of the
electrophysiologic pattern of improvement of sleep, in these
subjects. The good results of this pilot trial justify double-blind
studies.
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