Movement Disorders

Vol. 23, No. 2, 2008, pp. 183–189

© 2007 Movement Disorder Society CME

A Systematic Review of Prevalence Studies of Depression in

Parkinson’s Disease

Jennifer S.A.M. Reijnders, MA,1 Uwe Ehrt, MD,2 Wim E.J. Weber, MD, PhD,3
Dag Aarsland, MD, PhD,2,4 and Albert F.G. Leentjens, MD, PhD1*
1
Department of Psychiatry, Maastricht University Hospital, Maastricht, The Netherlands
2
Section of Geriatric Psychiatry, Stavanger University Hospital, Stavanger, Norway
3
Department of Neurology, Maastricht University Hospital, Maastricht, The Netherlands
4
School of Medicine, University of Bergen, Bergen, Norway

Abstract: Prevalence rates of depressive disorders in Parkin- presence of a DSM defined depressive disorder, were present in
son’s disease (PD) vary widely across studies, ranging from 35%. In studies using a (semi) structured interview to establish
2.7% to more than 90%. The aim of this systematic review was DSM criteria, the reported prevalence of major depressive
to calculate average prevalences of depressive disorders taking disorder was 19%, while in studies using DSM criteria without
into account the different settings and different diagnostic a structured interview, the reported prevalence of major depres-
approaches of studies. Using Medline on Pubmed, a systematic sive disorder was 7%. Population studies report lower preva-
literature search was carried out for studies of depression in lence rates for both major depressive disorder and the clinically
Parkinson’s disease. A total of 104 articles were included and significant depressive symptoms than studies in other settings.
assessed for quality; 51 articles fulfilled the quality criteria. This systematic review suggests that the average prevalence of
Multiple publications from the same database were not in-
major depressive disorder in PD is substantial, but lower than
cluded in the meta-analysis. In the remaining 36 articles, the
generally assumed. © 2007 Movement Disorder Society
weighted prevalence of major depressive disorder was 17% of
PD patients, that of minor depression 22% and dysthymia 13%. Key words: Parkinson’s disease; depressive disorder; dys-
Clinically significant depressive symptoms, irrespective of the thymia; prevalence; systematic review.

INTRODUCTION a major impact on the prognosis of PD: depressed PD

Parkinson’s disease (PD) is a neurodegenerative dis- patients score lower on scales assessing motor function
order characterized by tremor, bradykinesia, rigidity, and and activities of daily living (ADL), exhibit more cog-
postural instability. In addition, a high prevalence of nitive symptoms, and report a lower quality of life.1–3
psychopathological syndromes is reported, including af- Despite this, depression in PD is underdiagnosed and
fective disorders, cognitive deterioration, and perceptual under-treated.4,5
and behavioral symptoms. Depression is known to have Prevalence rates of depressive syndromes in PD that are
reported in the literature vary widely, ranging from 2.7% to
more than 90%.6 – 8 Possible reasons for this variation in-
This article is part of the journal’s CME program. The CME form clude the nature of the population studied, the way the
can be found on page 313 and is available online at http://www.move- diagnosis is established, the types of depressive disorder
mentdisorders.org/education/activities.html included in the study, and the statistical measures used. In
This article contains supplementary material available via the Inter-
net at http://www.interscience.wiley.com/jpages/0885–3185/suppmat. studies assessing the presence of depressive disorders in
*Correspondence to: A.F.G. Leentjens, Department of Psychiatry, patients with physical comorbidity in general, the lowest
Maastricht University Hospital, P.O. Box 5800, 6202 AZ Maastricht,
The Netherlands. E-mail: a.leentjens@np.unimaas.nl prevalences are reported in population studies, whereas
Received 3 May 2007; Revised 2 August 2007; Accepted 2 October studies in outpatient and inpatient settings tend to report
2007 higher prevalence rates. Studies measuring depressive
Published online 6 November 2007 in Wiley InterScience (www.
interscience.wiley.com). DOI: 10.1002/mds.21803 symptoms on a rating scale may yield higher prevalences

183
184 J.S.A.M. REIJNDERS ET AL.

than studies using diagnostic criteria for depression, such as cluded. Further articles were identified from the refer-
those of the Diagnostic and Statistical Manual for Mental ence lists of the selected articles as well as from previous
Disorders (DSM) of the American Psychiatric Association review studies. Articles in languages other than English,
(APA) or the International Classification of Diseases (ICD) German, French, and Dutch were excluded (5). A total of
of the World Health Organization (WHO).9,10 Studies using 165 articles were read in full. After reading these articles,
a structured or semistructured interview probably yield the another 61 articles were excluded because of the follow-
most conservative estimates.11 Even if diagnostic criteria ing reasons: there was no reference to the prevalence of
are used, the approach to these criteria may influence prev- depression (49), patients with depression were excluded
alence rates: an “inclusive” approach yields a higher prev- (5), the population did not include PD patients (2), de-
alence than an “exclusive” approach.12 When rating scales pression was only related to “off ” periods (1), and case
are used, self-report instruments tend to give higher preva- reports or reviews (4). The remaining 104 articles were
lences than observer-rated instruments. Prevalences are in- included and underwent quality assessment.
fluenced by the syndromes included in the study: major
depressive disorder only, or less severe syndromes such as Quality Assessment
dysthymia and minor depression. Finally, some studies use The included articles were read in full and quality
point-prevalences, whereas others use monthly prevalences, rated by three of the authors (J.R., U.E., D.A.). For three
which may give rise to different prevalence rates. studies, a lack of clarity in one of the domains was
All these factors make it difficult to estimate the extent checked with the first author of the study. In case of
to which depression complicates PD. The aim of this discrepancies between the raters, consensus was
systematic review was to calculate average prevalences achieved after discussion. If consensus was not reached,
of depressive disorders taking the different settings and articles were reassessed by the last author (A.L.), who
the different approaches to diagnosis of studies into made a final decision. The quality assessment used cri-
account. teria adapted from Aarsland et al. 13 as shown in Table 1.
METHODS In order to ensure a minimum quality of studies included
in the review, only studies that scored at least 1 point on
Search Strategy all three criteria, case identification, diagnostic criteria
A systematic literature search was carried out in Med- for PD, and diagnostic criteria for depression, were in-
line using Pubmed. The entire time scale was used up to cluded. The full list of assessed studies is provided as
February 2007 (included). The following key words were supplementary information.
used to carry out multiple searches: “Parkinson,” “de-
pression,” “prevalence,” and “incidence.” In total 272 Selection of Studies
articles were retrieved. The abstracts of these 272 articles During the assessment phase it became clear that sev-
were read. All articles with potential reference to the eral publications stemmed from the same databases. In-
prevalence of depression were included (122). If no clusion of multiple publications from the same study
abstract was available, the article was nevertheless in- population would lead to a disproportional influence of

TABLE 1. Quality assessment criteria as adapted from Aarsland et al.*13

Score Case identification Diagnostic criteria for PD Diagnostic criteria for depression
3 Door-to-door survey, or questionnaire Clinical diagnosis using accepted Use of a (semi) structured interview to establish
survey of total/random sample criteria and autopsy a diagnosis based on standardized and widely
verification used criteria (DSM, ICD or RDC)14
2 Multiple sources used to identify Established and accepted Standardized and widely used criteria (DSM,
cases (GP registration, nursing diagnostic criteria such as ICD or RDC) without a (semi) structured
homes registration, private United Kingdom Parkinson’s clinical interview
specialists records, hospital Disease Society Brain Bank
records, patient support groups, Diagnostic Criteria
drug prescriptions database, etc.)
1 Single source of patients (GP Limited description of clinical Cut-off score on a depression rating scale
registration, hospital files, or inclusion and exclusion
convenience sample of outpatients criteria
0 No information No or very limited information No or inadequate criteria (e.g., subjective
clinical impression)

*Studies are scored from 0 to 3 in three different domains, yielding a maximum score of 9.

Movement Disorders, Vol. 23, No. 2, 2008

 THE PREVALENCE OF DEPRESSION IN PD 185

these studies on the calculated prevalence rates. The used patients from a combination of different settings:
authors therefore contacted the first author of those stud- population and outpatient samples (4), outpatient and
ies to check whether they were indeed based on the same inpatient samples (2), and outpatient and nursing home
sample. In all but one case the authors received an samples (1). In some of the studies in outpatient settings,
answer. They decided to follow the following strategy: if the population was restricted to a specific subgroup:
studies were based on the same sample, only the first patients screened for possible DBS-screening (3), pa-
publication was included in the meta-analysis. If for tients on long-term levodopa treatment (3), de novo
some reason, studies based on the same sample had patients (3) and patients with concurrent dementia (1).
varying numbers of patients included, the study with the Different diagnostic criteria for depression were used: 31
highest number of patients was included. For studies studies used a (semi) structured interview to establish
based on cumulative databases, only the most recent DSM criteria, 20 studies used DSM criteria without a
publication with the highest number of patients was (semi) structured interview, 38 studies used a cut-off
included. Some publications were based on joint data- score on a depression rating scale, and 15 studies used no
bases from within a single group or between several or inadequate criteria to diagnose depression.
research groups, and in this case only the publication Quality was assessed of all 104 studies according to
stemming from the combined database was included in the criteria shown in Table 1. The maximum score for
the meta-analysis. The set of studies that we received no quality according to these criteria is 9. The actual scores
information on were presumed to come from the same ranged from 1 to 7, with a mean of 3.77 (SD: 1.73). The
database. quality of depression studies in PD increases over time,
as shown in Figure 1. Of the 104 studies, 51 fulfilled the
Statistics quality criteria. After excluding studies based on the
Data are presented as numbers and proportions. De- same, cumulative or joint databases, 36 studies were
scriptive data are presented as mean with 95% confi- included in the review.
dence intervals (95% CI). For studies that assessed spe- The prevalences of major depressive disorder, minor
cific depressive disorders, the prevalences were depression, and dysthymia, as well as clinically signifi-
recorded. In addition, the percentage of patients with cant depressive symptoms are shown in Table 2. Overall,
“clinically relevant depressive symptoms” was scored. major depressive disorder was present in 17% of pa-
For studies that assessed one or more depressive disor- tients, minor depression in 22%, and dysthymia in 13%.
ders either separately or combined, this percentage
equals the combined prevalences of all depressive disor-
ders. For studies using cut-off scores on rating scales,
where no DSM diagnoses are available, this percentage
represents the presence of depressive symptoms in a
clinically relevant severity, as reflected by the number of
patients scoring above the set cut-off was taken as the
“overall prevalence” of “depression.”
Prevalence rates across studies were calculated as
weighted means. The prevalence rate per study was
multiplied by the corresponding sample size and divided
by the total sample size of all studies. Comparison of
proportions was done with ␹2 tests. SPSS version 12.0
(SPSS, Chicago) was used for statistical calculations.

RESULTS
Of a total of 104 studies, 22 studies focused on the
prevalence of depression in PD as a primary study ob-
jective; the remaining 82 studies had other primary ob-
jectives but also reported on the prevalence of depression
in the study sample. There were 16 population-based
studies, 3 studies in general practices, 71 studies in FIG. 1. Increment of the quality score over time. Scatterplot of
quality scores of the included studies from 1965 onwards, showing an
outpatient settings, 5 studies in hospital inpatient set- increase in quality over time. The regression line indicates average
tings, and 2 studies in nursing homes. Another 7 studies quality scores over time.

Movement Disorders, Vol. 23, No. 2, 2008

186 J.S.A.M. REIJNDERS ET AL.

TABLE 2. Reported prevalences (%) of major depressive disorder, minor depression, dysthymia, and clinically relevant
depressive symptoms
Clinically
Major relevant
Sample Quality depressive Minor depressive
Study Sample size score disorder depression Dysthymia symptoms
Structured clinical interview
Starkstein et al. (1990)15 Outpatient clinic 105 5 21 20 41
Starkstein et al. (1992)16a Outpatient clinic 92 5 20 21 41
Hantz et al. (1994)7 Population 73 7 2.7 2.7
Starkstein et al. (1996)17 Outpatient clinic/dementia 33 6 30 27 57
Liu et al. (1997)18 Outpatient clinic 109 5 16.5 25.7 42.2
De Rijk and Bijl (1998)19 Population 384 5 2.3 4.7 7.0
Starkstein et al. (1998)20 Outpatient clinic 112 6 22 31.3 53.3
Leentjens et al. (2000)21a Outpatient clinic 63 6 25 25
Leentjens et al. (2000)22a Outpatient clinic 53 6 23 23
Anguenot et al. (2002)23 Outpatient clinic 135 6 55.6 2.2 57.8
Naarding et al. (2002)24a Outpatient clinic 85 6 23.5 23.5
Weintraub et al. (2003)5 Outpatient clinic 77 6 20.8 13 33.8
Lauterbach et al. (2004)25 Outpatient clinic 28 5 14.3 3.6 17.9
Nuti et al. (2004)26 Outpatient clinic 90 6 21.1 18.8 39.9
Ertan et al. (2005)27 Outpatient clinic 109 6 22.9 28.4 51.4
Papapetropoulos et al. (2005)28 Brain bank data 67 7 43.3
Costa et al. (2006)29a Inpatient clinic 58 5 20.7 34.5 55.2
Costa et al. (2006)30 Inpatient clinic 83 6 21.7 25.3 47
Visser et al. (2006)31a Outpatient clinic 92 6 19 19
Wichowicz et al. (2006)32 Population 100 6 35 35
Clinical interview
Santamaria et al. (1986)33 Outpatient clinic /recent onset 34 4 2.9 29.4 32.3
Mayeux et al. (1988)34 Outpatient and inpatient clinic 339 4 47
Brown and MacCarthy (1990)35 Outpatient clinic 40 6 25
Aarsland et al. (1996)36a Population 235 6 7.7 7.7
Tandberg et al. (1996)37 Population 245 6 7.7 7.7
Tandberg et al. (1997)38a Population 245 6 7.7 7.7
Tandberg et al. (1998)39a Population 239 6 7.8 7.8
Aarsland et al. (1999)40a Population 235 5 7.2 7.2
Karlsen et al. (1999)3a Population 233 6 7.7 7.7
Cubo et al. (2000)41 Outpatient clinic 88 5 7.3 7.3
Giladi et al. (2000)42 Outpatient clinic 172 5 33
Larsen et al. (2000)43a Population 240 6 7.6 7.6
Krishnan et al. (2003)44 Outpatient clinic 126 5 12.7
Rating scale
Mindham (1970)45 Inpatient psychiatric hospital 89 3 89
Tison et al. (1995)46 Outpatient clinic and nursing 60 6 32.7
home
Meara et al. (1999)47 General Practice 132 5 64
Schrag et al. (2000)1a General Practice 92 5 19.6
Happe et al. (2001)48 Outpatient clinic 56 4 76.4
Schrag et al. (2001)49a General Practice 97 5 19.6
Shulman et al. (2001)50a Outpatient clinic 99 3 36
Happe et al. (2002)51 Outpatient clinic 116 4 37.1
Marinus et al. (2002)52 Outpatient clinic 177 4 38.4
Schrag et al. (2002)53 General Practice 128 5 20
Shulman et al. (2002)4 Outpatient clinic 101 3 44
Rojo et al. (2003)54 Outpatient clinic 353 4 56.9
Hely et al. (2005)55 Outpatient clinic 52 4 53.6
Holroyd et al. (2005)56 Outpatient clinic 100 4 15
Kang et al. (2005)57 Population 193 5 13
Prado and Barbosa (2005)58 Outpatient clinic 60 4 38.3
Kirsch-Darrow et al. (2006)59 Outpatient clinic 80 3 26.3
Weintraub et al. (2006)60 Outpatient clinic 130 4 36.2
Weighted mean 5.1 17 22 13 35
a
Studies not included in the calculation of the weighted mean because they are based on the same, cumulative or joint databases (see under Selection
of Studies).

Movement Disorders, Vol. 23, No. 2, 2008

 THE PREVALENCE OF DEPRESSION IN PD 187

TABLE 3. Prevalence (%) of major depressive disorder and DISCUSSION

clinically relevant depressive symptoms in different settings
This is the first extensive review of the prevalence of
Major depressive Clinically relevant depressive disorders in Parkinson’s disease that takes the
disorder depressive symptoms
different settings and diagnostic approaches of the vari-
Number of Number of ous studies into account. It shows that the average prev-
Population studies Prevalence studies Prevalence
alence of major depressive disorder in PD is 17%, which
General population 4 8.1 5 10.8 is substantial, but less than the prevalence rates that are
General practice 0 2 42.3
Outpatient setting 11 24.0 25 40.4 usually quoted. Minor depression was present in 22%
Inpatient setting 1 21.7 3 54.3 and dysthymia in 13% of PD patients. In PD patients in
Nursing home 0 1 32.7 the general population these numbers are lower, while
they are higher in hospital outpatient and inpatient set-
tings. We could not confirm that the prevalence of major
depression is lower when structured interviews are used
The prevalence of clinically significant depressive symp-
as opposed unstructured clinical interviews to confirm
toms was 35%. While dysthymia may be diagnosed in
diagnostic criteria, as is reported by others11; in this
the presence of major depressive disorder or minor de-
review, the use of structured interviews leads to higher
pression (the concept of “double depression”), it is sur-
prevalence rates.
prising that none of the studies have looked at both minor
Two earlier reviews on the prevalence of depression in
depression and dysthymia at the same time.
PD have been published. Both were part of a more
The influence of setting on the prevalence of depres-
extensive review that also included the etiology and/or
sive disorders is shown in Table 3. For major depressive
treatment of depression in PD as well. Both used a
disorder, population studies report significantly lower
prevalences than studies in outpatient samples (␹2 ⫽ similar search strategy, but neither performed a quality
78.4, df ⫽ 1, P ⬍ 0.001) and hospital inpatient settings assessment before including studies. In the study by
(␹2 ⫽ 16.3, df ⫽ 1, P ⬍ 0.001). Slaughter et al., which included 45 studies, the setting
For the prevalence of clinically significant depressive was not considered. Reported average prevalences of the
symptoms, population studies also report significantly 11 included studies that used diagnostic criteria were
lower prevalences than studies in respectively general significantly higher than those of our review: 25% for
practices, outpatient settings, inpatient settings, and nurs- major depressive disorder, 37% for minor depression,
ing homes (␹2 ⫽ 143.5, df ⫽ 1, P ⬍ 0.001; ␹2 ⫽ 288.6, and 23% for dysthymia.61 Clinically significant depres-
df ⫽ 1, P ⬍ 0.001; ␹2 ⫽ 335.6, df ⫽ 1, and P ⬍ 0.001; sion was present in 42% of PD patients. The discrepancy
␹2 ⫽ 27.2, df ⫽ 1, P ⬍ 0.001 respectively). Studies in with our findings is probably due to the fact that 7 of the
hospital inpatient settings report significantly higher 11 studies included in the review were not included in
prevalences than studies in the population, general prac- our analysis because of an insufficient quality rating.
tices, outpatient settings, and nursing homes (␹2 ⫽ 335.6, Veazey et al. reviewed 16 studies and gave a range for
df ⫽ 1, P ⬍ 0.001; ␹2 ⫽ 9.8, df ⫽ 1, P ⫽ 0.002; ␹2 ⫽ prevalence rate depression of 7% to 76%.62 In this re-
33.2, df ⫽ 1, and P ⬍ 0.001; ␹2 ⫽ 9.4, df ⫽ 1, P ⫽ view, the prevalence of major depressive disorder in
0.002, respectively). studies that utilized clinical interviews to establish DSM
The reported prevalence of major depressive disorder criteria ranged from 7.3% to 32%; when self-report ques-
in studies using a (semi) structured interview to establish tionnaires were used the prevalence ranged from 27.3%
DSM criteria ranges from 2.3% to 55.6% with a to 76%. In community-based prevalence studies, the
weighted mean of 19%. In studies using DSM criteria reported rate of MD was 7.7%. When populations of
without a structured interview the prevalence rates of outpatients were used, the rates of MD ranged from 7.3%
major depressive disorder ranges from 2.9% to 7.7% to 32%. It is not clear to the authors how a similar search
with a weighted mean of 7%. strategy would yield so few studies. No (weighted)
Clinically significant depressive symptoms were means were calculated.
present in 2.7% to 57.8% with a weighted mean of 33% This study has several limitations. First of all, the
in studies using a (semi) structured interview, 7.3% to combined prevalence of clinically relevant depressive
47% with a weighted mean of 27% in studies using DSM symptoms, which in this study is 35%, may have been
criteria, and in 13% to 89% with a weighted mean of influenced by the relatively large number of studies that
42% in studies using a cut-off on a depression rating have focused on major depression only. The fact that
scale. major depression may be superimposed on dysthymia

Movement Disorders, Vol. 23, No. 2, 2008

188 J.S.A.M. REIJNDERS ET AL.

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Movement Disorders, Vol. 23, No. 2, 2008