Movement Disorders

Vol. 22, No. 8, 2007, pp. 1061–1068

© 2007 Movement Disorder Society CME

Viewpoint

Diagnostic Criteria for Psychosis in Parkinson’s Disease:

Report of an NINDS, NIMH Work Group

Bernard Ravina, MD, MSCE,1* Karen Marder, MD, MPH,2 Hubert H. Fernandez, MD,3
Joseph H. Friedman, MD,4 William McDonald, MD,5 Diane Murphy, PhD,6 Dag Aarsland, MD,7
Debra Babcock, MD, PhD,6 Jefferey Cummings, MD,8 Jean Endicott, PhD,9 Stewart Factor, MD,10
Wendy Galpern, MD, PhD,6 Andrew Lees, MD,11 Laura Marsh, MD,12,13 Mark Stacy, MD,14
Katrina Gwinn-Hardy, MD,6 Valerie Voon, MD,6 and Christopher Goetz, MD15
1
Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
2
Department of Neurology, Columbia University New York Presbyterian, Medical Center College of Physicians and Surgeons,
New York, New York, USA
3
Department of Neurology, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA
4
Department of Clinical Neurosciences, Brown University, Warwick, Rhode Island, USA
5
Department of Psychiatry, Emory University, Atlanta, Georgia, USA
6
National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, Maryland, USA
7
Norwegian Centre for Movement Disorders, Stavanger University Hospital and Institute of Clinical Medicine, University of
Bergen, Norway, USA
8
Reed Neurological Research Center, University of California, Los Angeles, California, USA
9
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York, USA
10
Department of Neurology, Emory University, Atlanta, Georgia, USA
11
Reta Lila Weston Institute of Neurological Studies, University College, London, United Kingdom
12
Department of Psychiatry, Johns Hopkins University, Baltimore, Maryland, USA
13
Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA
14
Department of Neurology, Duke University, Durham, North Carolina, USA
15
Rush University Medical Center, Rush University Medical Center, Chicago, Illinois, USA

Abstract: There are no standardized diagnostic criteria for
psychosis associated with Parkinson’s disease (PDPsy). As part
of an NIH sponsored workshop, we reviewed the existing
literature on PDPsy to provide criteria that distinguish PDPsy
from other causes of psychosis. Based on these data, we pro-
pose provisional criteria for PDPsy in the style of the Diagnos-
tic and Statistical Manual of Mental Disorders IV-TR. PDPsy
This article is part of the journal’s CME program. The CME form
can be found on page 1214 and is available online at http://www.
movementdisorders.org/education/activities.html
*Correspondence to: Dr. Bernard Ravina, 1351 Mt. Hope Ave., Suite
223, Rochester, NY 14620. E-mail: Bernard.ravina@ctcc.rochester.edu
Received 24 October 2006; Accepted 4 December 2006
Published online 31 January 2007 in Wiley InterScience (www.
interscience.wiley.com). DOI: 10.1002/mds.21382
has a well-characterized temporal and clinical profile of hallu-
cinations and delusions, which is different than the pattern seen
in other psychotic disorders such as substance induced psycho-
sis or schizophrenia. PDPsy is associated with a poor prognosis
of chronic psychosis, nursing home placement, and death.
Medications used to treat Parkinson’s disease (PD) contribute
to PDPsy but may not be sufficient or necessary contributors to
PDPsy. PDPsy is associated with Lewy bodies pathology,
imbalances of monoaminergic neurotransmitters, and visuospa-
tial processing deficits. These findings suggest that PDPsy may
result from progression of the disease process underlying PD,
rather than a comorbid psychiatric disorder or drug intoxica-
tion. PDPsy is not adequately described by existing criteria for
psychotic disorders. We established provisional diagnostic cri-
teria that define a constellation of clinical features not shared by
other psychotic syndromes. The criteria are inclusive and con-

1061
1062 B. RAVINA ET AL.
tain descriptions of the full range of characteristic symptoms,
chronology of onset, duration of symptoms, exclusionary diag-
noses, and associated features such as dementia. These criteria
require validation and may be refined, but form a starting point
There are no standardized diagnostic criteria for psy-
chosis in patients with Parkinson’s disease (PD). The
absence of an accepted definition complicates studies of
the epidemiology and pathophysiology of PD psychosis
(PDPsy) and is an obstacle for the assessment of treat-
ments. For these reasons, the National Institutes of Neu-
rological Disorders and Stroke, and the National Institute
of Mental Health hosted a workshop to consider diag-
nostic criteria for PDPsy.
The first goal of the workshop was to review the
literature on the epidemiology, pathogenesis, and phe-
nomenology of PDPsy to determine if existing data sup-
port a diagnosis that is clinically distinct from other
causes of psychosis, such as schizophrenia or substance
induced psychosis. The second goal was to formulate
provisional diagnostic criteria that could be tested for
reliability and validity and refined as appropriate. Instru-
ments for rating the severity of psychosis in PD were also
reviewed, and their critique will be the subject of a report
sponsored by the Movement Disorders Society Task
Force on Ratings Scales in PD. Here we present the
evidence relevant to the formulation of PD-specific fea-
tures of psychosis and provide provisional diagnostic
criteria for PDPsy in the format of the Diagnostic and
Statistical Manual of Mental Disorders IV-TR (DSM
IV-TR).
Methods
Participants were divided into three groups to review
literature on (1) clinical features and outcomes, (2) the
epidemiology and pathophysiology of PDPsy and (3)
differential diagnosis. PubMed searches (from 1950 to
September, 2005) were conducted using PD and psycho-
sis hallucinations delusions in combination with each of
the following terms: clinical course, functional outcome,
clinical features, dopamine dopaminergic drugs, sleep
REM, dementia, delirium, depression (late life late onset
depression), diagnosis, diagnostic criteria, dopamine
dysregulation syndrome, epidemiology, etiology, inci-
dence, mania, pathophysiology, prevalence, and schizo-
phrenia. Additionally, we searched the terms dementia
with Lewy bodies (DLB) and Alzheimer’s disease (AD)
and psychosis in combination with clinical course, clin-
ical features, and dopamine dopaminergic drugs. The
resulting articles were then screened by 2 of the authors
Movement Disorders, Vol. 22, No. 8, 2007
for studies of the epidemiology and pathophysiology of PDPsy,
and are a potential indication for therapy development. © 2007
Movement Disorder Society
Key words: Parkinson’s; psychosis; diagnosis.
(BR, WG) before distribution to meeting participants to
determine that they dealt specifically with PD and that
they were original contributions. The work group then
considered 45 articles on clinical features and outcomes,
71 articles on the epidemiology and pathophysiology,
and 14 on the differential diagnosis of PDPsy. Each of
the groups met in advance of the workshop to review the
materials and consolidate the data for workshop
participants.
Terminology
Historically, the term psychosis has had a number of
different definitions, none of which are uniformly ac-
cepted. As noted in the DSM IV-TR, the narrowest
definition of psychosis requires hallucinations and delu-
sions with loss of insight. However, broader definitions
of psychosis are allowed for DSM IV-TR defined diag-
noses, such as brief psychotic disorder, which may re-
quire only disorganized speech or behavior. For the
purposes of establishing diagnostic criteria in PD, par-
ticipants agreed to specific definitions of potentially rel-
evant symptoms for PDPsy as a point of reference1
Delusions are false, fixed, idiosyncratic beliefs that are
maintained despite evidence to the contrary. Hallucina-
tions are abnormal perceptions without a physical stim-
ulus that can involve any sensory modality and may be
simple or complex in form. We have included presence
hallucinations and illusions, which are not a part of the
description of other psychotic disorders. These are phe-
nomenologically similar to hallucinations and are com-
monly described in studies of PDPsy. Presence halluci-
nations consist of the experience that someone is present
when nobody is actually there. These are not strictly
hallucinations in that the sensory modality is not clear,
but are often classified as hallucinations rather than de-
lusions. Illusions are misperceptions of real stimuli that
are often visual in nature.
Clinical Features and Outcomes
Visual hallucinations are the most common psychotic
symptoms in PDPsy.2-5 In some studies, more than 90% of
all psychotic patients experienced visual hallucinations.6
Visual hallucinations are generally well formed, consisting
of people or animals, and less commonly inanimate ob-
jects.7 The content tends to be reoccurring. The content of
 DIAGNOSTIC CRITERIA FOR PSYCHOSIS IN PD
auditory hallucinations ranges from indistinct whispers or
music to threatening voices.3,8,9 Auditory hallucinations
variably co-occur with visual hallucinations (8%–13%) and
are less likely to be seen in isolation.3,8 This pattern is in
contrast to the auditory hallucinations typical of schizophre-
nia. Similarly, in PD tactile, olfactory, and gustatory hallu-
cinations are relatively uncommon and generally occur with
visual hallucinations.8,10
The hallucinatory experience tends to be present in-
termittently, lasting seconds to minutes at a time.11 The
frequency can vary, but most studies register the pres-
ence of hallucinations when they occur at least one time
per week. Often, they occur several times per day. Hal-
lucinations tend to occur during times of low ambient
stimulation, most typically in the evening or when the
patient is alone in a quiet environment. Presence and
passage (fleeting, vague images in the peripheral vision)
hallucinations and visual illusions are often referred to as
“minor” hallucinations.4 These “minor” phenomena are
common in some studies, occurring in up to 40% of
patients,12 but are less likely to be disruptive and are,
therefore, less likely to be spontaneously reported than
other PDPsy features.4 Delusions are commonly para-
noid, consisting of beliefs about spousal infidelity or
abandonment.13 Grandiose, somatic, persecutory,9 and
religious delusions also occur, but are less frequently
reported in clinical series.14
PDPsy typically occurs in advanced PD patients, 10 or
more years after the initial diagnosis of PD.8,15 Goetz et
al. compared typical 58 PD patients who developed
psychosis at least one year or longer after starting levo-
dopa to 12 patients, who developed psychosis within 3
months of starting levodopa.16 After 5 years of follow-
up, the 12 early hallucinators all had alternate diagnoses,
most frequently DLB or AD, or had an underlying psy-
chiatric diagnosis prior to the onset of PD that reemerged
acutely during dopaminergic therapy. At the onset of
symptoms, the early hallucinators were more likely to
have persistent visual hallucinations during the day with
frightening content and accompanying nonvisual hallu-
cinations than PD patients with the more typical late-
onset hallucinations.
Most patients with hallucinations report retained in-
sight initially.17-19 A historical distinction has been
drawn between hallucinations with retained insight,
termed “Benign Hallucinations”, and those with loss of
insight, occasionally referred to as “Malignant Halluci-
nations”.19 This is reflected in the primary rating scale
for measuring the severity of PD, the Unified PD Rating
Scale (UPDRS). Although there is little longitudinal
data, it is thought that most patients with hallucinations
with retained insight ultimately lose this insight and/or
1063
develop delusions.19 As insight is lost, symptoms may
become more threatening and debilitating. In this sense,
“Benign Hallucinations” is an inaccurate term, since
their presence bodes a progressive condition. All forms
of hallucinations in PDPsy tend to persist, so that while
each hallucinatory episode is brief, the hallucinatory
state, once established, is a chronic one.12,20 “Minor”
phenomenon such as visual illusions are more likely than
visual hallucinations to remit for sustained periods, but
overall they are likely to recur and continue.12 Symptoms
continue or reoccur after antipsychotics are discontin-
ued21,22 and symptoms may persist or reoccur among
patients treated with antipsychotics.23
PDPsy is associated with increased caregiver bur-
den,24 nursing home placement,25 and increased mortal-
ity.23 A case-control study examined PD patients who
entered nursing homes and compared each of them with
2 community-dwelling PD subjects who were matched
for age, gender, and PD duration. The investigators com-
pared motor disability, dementia, and hallucinations as
putative risk factors for nursing home placement. The
only statistically differentiating features were the pres-
ence and severity of hallucinations, with 82% of the
nursing home subjects having this behavior compared to
5% of the subjects living in the community.26 A recent
study followed 59 subjects with an average age of 71
after completing a clinical trial of clozapine for PDPsy.
Two years later, 25% of participants were deceased, 42%
were in nursing homes, and 68% were diagnosed with
dementia.23 A retrospective study of 39 subjects treated
with clozapine with a mean age of 76 showed a 44%
mortality rate over 5 years.27 No control population was
used as a comparator in these studies, but results suggest
that psychosis is a poor prognostic sign.
Epidemiology and Pathogenesis
Estimates of the prevalence of PDPsy vary widely.15
For example, in a community based sample there was a
25% life time prevalence28 of psychotic phenomenon
compared to nearly 50% in some clinic based sam-
ples.4,29 Methodological issues contributing to this vari-
ability include different definitions of psychosis, assess-
ment periods (e.g. ever never vs. current), methods of
ascertainment, and sample populations. Some studies
have focused only on hallucinations, but did not assess
illusions or delusions.2,3 Most studies are clinic-based
and therefore the prevalence figures may not be applica-
ble beyond referral centers. For these reasons, it is dif-
ficult to estimate true prevalence of PDPsy. But in clinic
based samples of patients on dopaminergic therapy, sev-
eral studies suggest a cross-sectional prevalence in the
range of 25 to 30%.13,30,31
Movement Disorders, Vol. 22, No. 8, 2007
1064 B. RAVINA ET AL.
Several studies have examined comorbid clinical fea-
tures. Many of these studies were cross-sectional and it is
therefore not possible to determine if these associated
features are risk factors or accompaniments of psychosis.
Results are somewhat consistent, however, and show that
cognitive impairment,8,28,30 depression,4,28,30 PD motor
severity,4,30 axial impairment,4,12 sleep disturbances,4,12
and visual disturbances12 are associated with psychosis.
Several of these are also risk factors for dementia in PD
and dementia and PDPsy are strongly associated.32 For
example, in one cross sectional study, visual hallucina-
tions were reported by 70% of patients with dementia but
only 10% of patients without dementia.33 Similarly, in
another cross sectional study, dementia is closely asso-
ciated with hallucinations, delusions and other behav-
ioral symptoms, as recorded on the Neuropsychiatric
Inventory.34 Despite these findings, there is significant
variability in the results of epidemiological studies, most
of which were cross sectional, and uncertainty about the
role and impact of risk factors. This uncertainty high-
lights the need for a prospective, longitudinal study of
incident PDPsy.
The relationship of psychotic phenomenon to antipar-
kinsons medications remains unclear. Levodopa and
other PD medications have long been linked to PDPsy,35
which is sometimes referred to as drug-induced psycho-
sis. Some studies have suggested that certain classes of
medications such as dopamine agonists and anticholin-
ergics appear more likely to induce psychotic phenome-
non than levodopa, but all treatments, including surgical
interventions, have been associated with cases of new
onset or exacerbation of hallucinations.36-39 The majority
of PD patients who develop psychotic symptoms have
been on antiparkinsons medication for several years. But
the development of psychotic symptoms has been noted
in several studies shortly after the initiation or increase of
dopaminergic therapies.35-37 Reduction in dopaminergic
and other antiparkinsons medications, when possible, is
the recommended first line of therapy.40,41
Because almost all patients in PDPsy studies were on
antiparkinsons medications, it is difficult to assess the
extent to which hallucinations occur without these med-
ications. An analysis of historical documents on PD from
the nineteenth and early twentieth century prior to levo-
dopa usage failed to document clear cases of hallucina-
tions and psychotic behaviors of the type described
above, except in the context of late dementia, depression
or post-encephalitic parkinsonism.42 Nonetheless, the co-
occurrence of medications and psychosis does not nec-
essarily imply a causal relationship. Arguing against a
sufficient role for antiparkinsons drugs is the observation
that there are not systematic differences in PD medica-
Movement Disorders, Vol. 22, No. 8, 2007
tions between patients with and without psychosis.2,28
Furthermore, when PD patients with occasional halluci-
nations were given high dose infusions of levodopa in a
double blind trial, no hallucinations were induced.43 As-
sociated clinical features, such as dementia, distinguish
hallucinators from nonhallucinators rather than medica-
tions.4,28 These findings suggest that disease-related fac-
tors, in interaction with medications, account for psy-
chotic features, rather than medication alone. The fact
that PDPsy commonly occurs in advanced PD with de-
mentia suggests that patients may have underlying cor-
tical LB pathology that could contribute to spontaneous
hallucinations.44,45
The pathophysiology of PDPsy remains unclear and
several factors may interact to precipitate PDPsy. Hard-
ing et al. showed that visual hallucinations are associated
with LBs in the amygdala and parahippocampus, with
early hallucinations relating to higher LB densities in
parahippocampal and inferior temporal cortices.46,47 In
another study of 788 autopsy cases of Parkinsonism, the
presence of visual hallucinations was 92.9% specific for
LB Parkinsonism (PD and DLB combined) with a pos-
itive predictive value of 93.4%. Taken together, these
studies support a role of LB pathology, particularly in the
ventral temporal regions of the brain, in the development
of psychotic symptoms.48
Another previously proposed hypothesis is that dener-
vation hypersensitivity of mesolimbic and mesocortical
dopaminergic receptors predisposes patients to a hyper-
sensitivity response which manifests as psychosis.49,50
Other neurotransmitters, particularly serotonin and ace-
tylcholine, may play a role. Birkmayer and Riederer
suggested a possible serotonergic/dopaminergic imbal-
ance, and postmortem studies show variable degrees of
serotonergic loss among PD patients.51 Supporting this
hypothesis is the finding that atypical antipsychotics with
efficacy in PDPsy, such as clozapine, have a strong
affinity for the 5-HT2 receptor.52 There is consistent
evidence for widespread cholinergic denervation in
PD,53 and imbalances of serotonergic and cholinergic
input, particularly in the temporal or parietal cortices,
have been suggested as a possible explanation for psy-
chosis in DLB.54 Impaired visuospatial processing,
which occurs early in PD, has been linked to PDPsy.55,56
Specific deficits include difficulties with color and con-
trast vision. Electrophysiological studies have demon-
strated a prolonged visual evoked potential in individuals
with PD and visual hallucinations.57 PDPsy patients have
been found to respond to visual stimuli with greater
frontal and subcortical activation and less visual cortical
activation than nonhallucinating PD subjects.58 Died-
erich et al. have proposed a model that integrates many
 DIAGNOSTIC CRITERIA FOR PSYCHOSIS IN PD
of these findings. The model posits that the visual pro-
cessing deficits and the observed neurochemical abnor-
malities lead to an imbalance with a relative reduction in
visual information and an inability to suppress internally
generated imagery.59
Differential Diagnosis
There are several disorders that must be differentiated
from PDPsy. The diagnosis of PDPsy cannot be made in
the setting of delirium related to a variety of metabolic,
toxic, or infectious causes, as well as acute drug intoxi-
cation from antiparkinsonian drugs, narcotics, or other
agents. As such, PDPsy should only be considered if the
psychotic symptoms persist when delirium has resolved.
The differential for PDPsy includes other neurodegen-
erative disorders with Parkinsonism with or without de-
mentia, such as progressive supranuclear palsy, cortico-
basal ganglionic degeneration, DLB, and primary
psychiatric disorders that may co-occur with PD includ-
ing schizophrenia, schizoaffective disorder, brief psy-
chotic disorder, delusional disorder, both bipolar and
unipolar mood disorders with psychotic features, and
substance induced psychosis.
DLB can be difficult to discriminate from PDPsy with
accompanying dementia. DLB is defined by progressive
cognitive decline associated with at least two of the
following: fluctuating cognition, recurrent well formed
visual hallucinations, or spontaneous parkinsonism.60
The temporal course is the main distinction between
DLB and PDPsy with dementia. A diagnosis of DLB
should be considered when dementia occurs prior to the
onset of Parkinsonism. PD-associated dementia should
be considered if the dementia follows the onset of motor
symptoms. This distinction between DLB and PD-asso-
ciated dementia is subjective, but has implications for
clinical management, despite underlying similarities in
neuropathology.45 Similarly, the distinction between AD
with extrapyramidal features and PDPsy should be based
on the root diagnosis of PD or AD and the well known
differences in the patterns and temporal evolution of
dementia.61
The clinical symptoms including the history of the
psychosis should help differentiate other psychiatric dis-
orders that might co-occur with PD. For example, in the
Goetz et al. study previously described,16 psychosis as-
sociated with primary psychiatric conditions occurred
very early in the course of PD (first 3 months), had an
unrelenting course, did not fluctuate during the day and
night, and was characterized by fear, prominent paranoia,
and nonvisual hallucinations. This study and others sug-
gest that psychosis due to comorbid psychiatric condi-
tions can be distinguished from PDPsy.8 Psychotic mood
1065
disorders (bipolar and unipolar depression with psy-
chotic features) are usually distinguished by mood con-
gruent (e.g., delusions of guilt, worthlessness in the case
of psychotic depression) psychotic symptoms in the con-
text of prominent affective symptoms.1 PDPsy patients
typically have mood unrelated psychotic symptoms (e.g.,
seeing cats running across the floor), although mood
congruent symptoms are also possible. When mood con-
gruent symptoms are present this should prompt the
clinician to investigate an underlying mood disorder.
Schizophrenia and schizoaffective disorder are differ-
entiated from PDPsy by the onset of psychotic symptoms
in late adolescence and early adulthood (years before the
onset of sporadic PD), a deteriorating clinical course,
grossly disorganized speech, and negative symptoms
(e.g., affective flattening, alogia, and avolition).1 Nega-
tive symptoms such as apathy and reduced spontaneous
speech are seen in PD patients; however, they may
fluctuate with medication administration. Patients with
schizophrenia can have a later onset after age 50, but this
is relatively rare. Differentiation from PDPsy may be-
come more complex when elderly patients with schizo-
phrenia develop Parkinsonism after years of neuroleptic
treatment.
By definition, a brief psychotic disorder lasts for less
than one month,1 in contrast to the prolonged duration of
PDPsy. PD patients who had either hallucinations or
delusions for less than 1 month could meet criteria for
brief psychotic disorder. Illusions are not included in the
criteria for this diagnosis.
Delusional disorder typically begins in middle or late
life. The delusions, unlike schizophrenia, are not bi-
zarre.1 Typically the patient does not have hallucinations.
Hallucinations, when present, are more commonly olfac-
tory or tactile (e.g., delusion that one is infested with
lice).
Substance induced psychotic disorder is diagnosed
when the psychosis is judged to be due to the direct
physiological effects of a substance.1 Substance-induced
psychotic disorders arise in association with intoxication
or withdrawal and are generally not persistent. This is
quite different than the pattern seen in PDPsy in which
hallucinations arise after years of exposure to antiparkin-
sons medications and persist indefinitely.4
Consensus Summary
PDPsy has a well characterized clinical profile con-
sisting of primarily of paranoid delusions and visual
hallucinations that may be accompanied by other hallu-
cinations. This pattern is distinctly different than the
auditory hallucinations and thought disorder seen in
young adulthood in schizophrenia.1 The clear sensorium
Movement Disorders, Vol. 22, No. 8, 2007
1066 B. RAVINA ET AL.
TABLE 1. Proposed diagnostic criteria for PD associated
psychosis
Characteristic symptoms
Presence of at least one of the following symptoms
(specify which of the symptoms fulfill the criteria):
Illusions
False sense of presence
Hallucinations
Delusions
Primary diagnosis
UK brain bank criteria for PD
Chronology of the onset of symptoms of psychosis
The symptoms in Criterion A occur after the onset of PD
Duration
The symptom(s) in Criterion A are recurrent or continuous
for 1 mo
Exclusion of other causes
The symptoms in Criterion A are not better accounted for
by another cause of Parkinsonism such as dementia with
Lewy bodies, psychiatric disorders such as
schizophrenia, schizoaffective disorder, delusional
disorder, or mood disorder with psychotic features, or a
general medical condition including delirium
Associated features: (specify if associated)
With/without insight
With/without dementia
With/without treatment for PD (specify drug, surgical,
other)
and retained insight that is characteristic of PDPsy in its
early phases is distinctive from delirium. PDPsy tends to
worsen over time and is associated with a poor prognosis
of continued hallucinations, nursing home placement,
and death. Medications for PD contribute to PDPsy, but
medications alone do not appear to be sufficient and it is
unclear if they are necessary. The pathophysiology of
PDPsy is associated with worsening of deficits in mono-
aminergic transmitters and visuospatial processing defi-
cits that are well known findings in PD. Those findings,
along with the high frequency of psychosis and the
temporal evolution of symptoms, suggest that PDPsy
may be a manifestation of progression of the underlying
disease process rather than the overlap of a comorbid pri-
mary psychiatric disorder or transient drug-intoxication.
Formulation of Diagnostic Criteria
Based on the findings summarized in this paper, diag-
nostic criteria for PDPsy were considered, discussed, and
finally ratified (Table 1). These criteria describe a dis-
tinctive constellation of clinical features that are not
shared by other psychotic syndromes. The key compo-
nents of the definition are:
● Characteristic symptoms: We have incorporated the
full spectrum of features seen in PDPsy, including
hallucinations and delusions and the “minor” phenom-
ena of illusions and sense of presence. These latter
Movement Disorders, Vol. 22, No. 8, 2007
symptoms are not clearly included in the DSM IV-TR
definition of psychosis, but data indicate that the tra-
ditional distinctions of minor and benign hallucina-
tions are not prognostically accurate and these phe-
nomena are associated with continued and worsening
psychosis. We have incorporated the full spectrum of
PDPsy manifestations in order to be inclusive. We
recognize that the inclusion of “minor” symptoms
may be controversial, but documentation of these
symptoms will provide the data to refine the criteria in
the future. Misperceptions or illusions that are clini-
cally judged to be due to a primary visual disorder,
such as cataracts or macular degeneration, are not
intended to fulfill criteria for PDPsy by this definition.
● Primary diagnosis and chronology of symptom onset:
The criteria require that a diagnosis of PD be made
prior to the onset of psychotic symptoms and that the
diagnosis of PD is consistent with current clinical
standards. This excludes patients with DLB and is
consistent with the current diagnostic criteria for
DLB.60 We recognize that there is likely considerable
phenotypic and pathological overlap between patients
with PDPsy and DLB, but the criteria are intended to
operationally define psychosis in those patients who
present initially with a clinical diagnosis of PD.
● Duration: In general, PDPsy is a stable or progressive
disorder. For this reason the criteria require that the
psychotic symptoms be recurrent or continuous for at
least 1 month, distinguishing it from a brief psychotic
disorder and most cases of delirium.
● Exclusion of other causes: In addition to excluding
DLB by virtue of the primary diagnosis and timeline,
depression with mood congruent psychotic features,
delirium, and primary psychiatric conditions charac-
terized by psychosis may be considered as part of the
differential diagnosis. Thus, the approach to the dif-
ferential diagnosis of PDPsy must be tailored to each
case.
● Associated features: We have included antiparkinsons
medications as a modifier rather than as a necessary
feature for the diagnosis of PDPsy, which may be the
most controversial aspect of these criteria. We did this
for three main reasons. First, studies have not demon-
strated a direct causal relationship between pharmaco-
logical and surgical treatments for PD and PDPsy.
Second because of this indirect relationship, it would
be difficult to operationally define a dose or duration
of a treatment needed to qualify a patient for a diag-
nosis of PDPsy, and third the presence of psychosis in
the absence of medications raises concerns about other
causes of psychosis. The most direct way to deal with
this concern is to focus attention on alternative and
 DIAGNOSTIC CRITERIA FOR PSYCHOSIS IN PD
exclusionary diagnoses, which has been covered in
other aspects of these criteria.
Future Directions
These provisional criteria are intended to be inclusive,
and to provide a common definition that will facilitate
studies of the epidemiology and pathophysiology of
PDPsy. They define a categorical diagnosis and have
face and content validity. These criteria are not a mea-
sure of psychosis severity, which must be assessed with
a rating scale. Additionally, the need for treatment of
PDPsy remains a clinical decision. The impact of the
criteria will be to facilitate comparisons across observa-
tional and interventional studies. For example, the crite-
ria may allow for the comparison of the incidence and
prevalence of PDPsy in different settings and popula-
tions and could provide a clear regulatory indication that
will facilitate the development of treatments for PDPsy.
These criteria may be modified in the future as additional
data become available. The first step in establishing their
usefulness is to determine their inter-rater reliability. The
next step is to consider if the criteria are valid based on
diagnostic stability and ability to discriminate PDPsy
from other disorders. The immediate and long-term value
of these criteria depends upon their acceptance, use, and
appropriate modification by the PD clinical research
community.
Acknowledgments: Financial support was received from
the National Institutes of Health (NINDS NIMH), Acadia Phar-
maceuticals, and Ovation Pharmaceuticals. We thank Lynn
Morin of NINDS for her administrative support of this project
and Dr. Murat Emre for his review of the manuscript.
Disclosures: Dr. Ravina has received fees for consulting and
research from Acadia, Boehringer Ingelheim, EnVivo, Medi-
vation, and Novartis Pharmaccuticals and from the National
Institutes of Health (NIH). Dr. Endicott has received research
support from Abbott, Bristol-Myers, Cyberonics, Interneuron,
Merck, Parke-Davis, Pfizer, Upjohn, and Wyeth- Ayerst; has
served as a consultant or advisory board member for Abbott,
AstraZeneca, Berlex, Bristol-Myers Squibb, Cbyeronics, Eli
Lilly, GlaxoSmithKline, Novartis, Otsuka, Janssen, Ovation,
Pfizer, Sanofi-Synthelabo Research, and Wyeth-Ayerst. Dr.
Friedman has received fees for consulting, speaking, or re-
search from Ovation, Acadia, Novartis, Teva, Boehring-Ingle-
heim, Glaxo-SmithKline, Cephlon, and Solvay. Impax Pharma-
ceuticals, Boehringer-Ingelheim, Merck KGaA, Merck and
Company, Kiowa Pharmaceuticals, Ovation Pharmaceuticals,
EMD Pharmaceuticals, GlaxoSmithKline, Solstice Neuro-
science, Solvay Pharmaceuticals and has received compensa-
tion form In the Movement Disorders Society and Parkinson’s
Disease Foundation. Dr. Marsh has received fees for consult-
ing, speaking or research from Acadia, Ovation, Eli Lilly,
Forrest, Essai, Pfizer, and Astra-Zenceca. Dr. McDonald has
received fees for consulting, research, speaking or stock from
National Alliance for Research in Schizophrenia and Depres-
sion, American Foundation for Suicide Prevention, Fuqua
1067
Foundation, NIH, NeuroNetics, Jenssen, Forest, Bristol-Mey-
ers Squibb, Solvay, Amgen, Teva, Pfizer, and Abbott.
REFERENCES
1. Diagnostic and statistical manual of mental disorders, 4th ed.
Washington, DC: American Psychiatric Association; 1994.
2. Sanchez-Ramos JR, Ortoll R, Paulson GW. Visual hallucinations
associated with Parkinson disease. Arch Neurol 1996;53:1265-
1268.
3. Inzelberg R, Kipervasser S, Korczyn AD. Auditory hallucinations
in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1998;64:
533-535.
4. Fenelon G, Mahieux F, Huon R, Ziegler M. Hallucinations in
Parkinson’s disease: prevalence, phenomenology and risk factors.
Brain 2000;123 (Part 4):733-745.
5. Papapetropoulos S, Mash DC. Psychotic symptoms in Parkinson’s
disease. From description to etiology. J Neurol 2005;252:753-764.
6. Graham JM, Grunewald RA, Sagar HJ. Hallucinosis in idiopathic
Parkinson’s disease. J Neurol Neurosurg Psychiatry 1997;63:434-
440.
7. Greene P, Cote L, Fahn S. Treatment of drug-induced psychosis in
Parkinson’s disease with clozapine. Adv Neurol 1993;60:703-706.
8. Marsh L, Williams JR, Rocco M, et al. Psychiatric comorbidities in
patients with Parkinson disease and psychosis. Neurology 2004;
63:293-300.
9. Factor SA, Molho ES. Threatening auditory hallucinations and
Cotard syndrome in Parkinson disease. Clin Neuropharmacol
2004;27:205-207.
10. Aarsland D, Ballard C, Larsen JP, McKeith I. A comparative study
of psychiatric symptoms in dementia with Lewy bodies and Par-
kinson’s disease with and without dementia. Int J Geriatr Psychi-
atry 2001;16:528-536.
11. Barnes J, David AS. Visual hallucinations in Parkinson’s disease:
a review and phenomenological survey. J Neurol Neurosurg Psy-
chiatry 2001;70:727-733.
12. de Maindreville AD, Fenelon G, Mahieux F. Hallucinations in
Parkinson’s disease: a follow-up study. Mov Disord 2005;20:212-
217.
13. Marsh L. Psychosis in Parkinson’s disease. Curr Treat Options
Neurol 2004;6:181-189.
14. Diederich NJ, Pieri V, Goetz CG. Coping strategies for visual
hallucinations in Parkinson’s disease. Mov Disord 2003;18:831-
832.
15. Papapetropoulos S. Drug-induced psychosis in Parkinson disease:
phenomenology and correlations among psychosis rating instru-
ments. Clin Neuropharmacol 2006;29:59.
16. Goetz CG, Vogel C, Tanner CM, Stebbins GT. Early dopaminergic
drug-induced hallucinations in parkinsonian patients. Neurology
1998;51:811-814.
17. Wolters EC, Berendse HW. Management of psychosis in Parkin-
son’s disease. Curr Opin Neurol 2001;14:499-504.
18. Wolters EC. Intrinsic and extrinsic psychosis in Parkinson’s dis-
ease. J Neurol 2001;248 (Suppl 3):III22-III27.
19. Goetz CG, Fan W, Leurgans S, Bernard B, Stebbins GT. The
malignant course of “benign hallucinations” in Parkinson disease.
Arch Neurol 2006;63:713-716.
20. Goetz CG, Leurgans S, Pappert EJ, Raman R, Stemer AB. Pro-
spective longitudinal assessment of hallucinations in Parkinson’s
disease. Neurology 2001;57:2078-2082.
21. Pollak P, et al. Clozapine in drug induced psychosis in Parkinson’s
disease: a randomized, placebo controlled study with open follow
up. J Neurol Neurosurg Psychiatry 2004;75:689-695.
22. Fernandez HH, Trieschmann ME, Okun MS. Rebound psychosis:
effect of discontinuation of antipsychotics in Parkinson’s disease.
Mov Disord 2005;20:104-105.
23. Factor SA, et al. Longitudinal outcome of Parkinson’s disease
patients with psychosis. Neurology 2003;60:1756-1761.
Movement Disorders, Vol. 22, No. 8, 2007
1068 B. RAVINA ET AL.
24. Aarsland D, Larsen JP, Karlsen K, Lim NG, Tandberg E. Mental
symptoms in Parkinson’s disease are important contributors to
caregiver distress. Int J Geriatr Psychiatry 1999;14:866-874.
25. Aarsland D, Larsen JP, Tandberg E, Laake K. Predictors of nursing
home placement in Parkinson’s disease: a population-based, pro-
spective study. J Am Geriatr Soc 2000;48:938-942.
26. Goetz CG, Stebbins GT. Mortality and hallucinations in nursing
home patients with advanced Parkinson’s disease. Neurology
1995;45:669-671.
27. Fernandez HH, Donnelly EM, Friedman JH. Long-term outcome
of clozapine use for psychosis in parkinsonian patients. Mov
Disord 2004;19:831-833.
28. Aarsland D, Larsen JP, Cummins JL, Laake K. Prevalence and
clinical correlates of psychotic symptoms in Parkinson disease: a
community-based study. Arch Neurol 1999;56:595-601.
29. Hely MA, Morris JG, Reid WG, Trafficante R. Sydney multicenter
study of Parkinson’s disease: non-L-dopa-responsive problems
dominate at 15 years. Mov Disord 2005;20:190-199.
30. Holroyd S, Currie L, Wooten GF. Prospective study of hallucina-
tions and delusions in Parkinson’s disease. J Neurol Neurosurg
Psychiatry 2001;70:734-738.
31. Giladi N, et al. Risk factors for dementia, depression and psychosis
in long-standing Parkinson’s disease. J Neural Transm 2000;107:
59-71.
32. Rippon GA, Marder KS. Dementia in Parkinson’s disease. Adv
Neurol 2005;96:95-113.
33. Fenelon G, Mahieux F. Hallucinations and dementia. Prevalence,
clinical presentation and pathophysiology. Rev Neurol (Paris)
2004;160:S31–S43.
34. Aarsland D, et al. Range of neuropsychiatric disturbances in pa-
tients with Parkinson’s disease. J Neurol Neurosurg Psychiatry
1999;67:492-496.
35. Goodwin FK. Psychiatric side effects of levodopa in man. JAMA
1971;218:1915-1920.
36. Rascol O, et al. A five-year study of the incidence of dyskinesia in
patients with early Parkinson’s disease who were treated with
ropinirole or levodopa. 056 Study Group. N Engl J Med 2000;342:
1484-1491.
37. Parkinson Study Group. Pramipexole vs. levodopa as initial treat-
ment for Parkinson disease: a randomized controlled trial. JAMA
2000;284:1931-1938.
38. Herzog J, et al. Manic episode with psychotic symptoms induced
by subthalamic nucleus stimulation in a patient with Parkinson’s
disease. Mov Disord 2003;18:1382-1384.
39. Herzog J, et al. Two-year follow-up of subthalamic deep brain
stimulation in Parkinson’s disease. Mov Disord 2003;18:1332-
1337.
40. Friedman A, Sienkiewicz J. Psychotic complications of long-term
levodopa treatment of Parkinson’s disease. Acta Neurol Scand
1991;84:111-113.
41. Friedman JH, Factor SA. Atypical antipsychotics in the treatment
of drug-induced psychosis in Parkinson’s disease. Mov Disord
2000;15:201-211.
42. Fenelon G, Goetz CG, Karenberg A. Hallucinations in Parkinson
disease in the prelevodopa era. Neurology 2006;66:93-98.
Movement Disorders, Vol. 22, No. 8, 2007
43. Goetz CG, et al. Intravenous levodopa in hallucinating Parkinson’s
disease patients: high-dose challenge does not precipitate halluci-
nations. Neurology 1998;50:515-517.
44. Harding AJ, Halliday GM. Cortical Lewy body pathology in the
diagnosis of dementia. Acta Neuropathol (Berl) 2001;102:355-
363.
45. Aarsland D, Perry R, Brown A, Larsen JP, Ballard C. Neuropa-
thology of dementia in Parkinson’s disease: a prospective, com-
munity-based study. Ann Neurol 2005;58:773-776.
46. Harding AJ, Broe GA, Halliday GM. Visual hallucinations in
Lewy body disease relate to Lewy bodies in the temporal lobe.
Brain 2002;125:391-403.
47. Harding AJ, Stimson E, Henderson JM, Halliday GM. Clinical
correlates of selective pathology in the amygdala of patients with
Parkinson’s disease. Brain 2002;125:2431-2445.
48. Williams DR, Lees AJ. Visual hallucinations in the diagnosis of
idiopathic Parkinson’s disease: a retrospective autopsy study. Lan-
cet Neurol 2005;4:605-610.
49. Wolters EC. Dopaminomimetic psychosis in Parkinson’s disease
patients: diagnosis and treatment. Neurology 1999;52:S10 –S13.
50. Moskovitz C, Moses H, III, Klawans HL. Levodopa-induced psy-
chosis: a kindling phenomenon. Am J Psychiatry 1978;135:669-
675.
51. Birkmayer W, Riederer P. Responsibility of extrastriatal areas for
the appearance of psychotic symptoms (clinical and biochemical
human post-mortem findings). J Neural Transm 1975;37:175-182.
52. The Parkinson Study Group. Low-dose clozapine for the treatment
of drug-induced psychosis in Parkinson’s disease. N Engl J Med
1999;340:757-763.
53. Perry EK, et al. Cholinergic correlates of cognitive impairment in
Parkinson’s disease: comparisons with Alzheimer’s disease. J Neu-
rol Neurosurg Psychiatry 1985;48:413-421.
54. Perry EK, et al. Evidence of a monoaminergic-cholinergic imbal-
ance related to visual hallucinations in Lewy body dementia.
J Neurochem 1990;55:1454-1456.
55. Bodis-Wollner I. Neuropsychological and perceptual defects in
Parkinson’s disease. Parkinsonism Relat Disord 2003;9 (Suppl
2):S83–S89.
56. Mosimann UP, et al. Visual perception in Parkinson disease de-
mentia and dementia with Lewy bodies. Neurology 2004;63:2091-
2096.
57. Diederich NJ, et al. Poor visual discrimination and visual halluci-
nations in Parkinson’s disease. Clin Neuropharmacol 1998;21:289-
295.
58. Stebbins GT, et al. Altered cortical visual processing in PD with
hallucinations: an fMRI study. Neurology 2004;63:1409-1416.
59. Diederich NJ, Goetz CG, Stebbins GT. Repeated visual hallucina-
tions in Parkinson’s disease as disturbed external internal percep-
tions: focused review and a new integrative model. Mov Disord
2005;20:130-140.
60. McKeith IG, et al. Diagnosis and management of dementia with
Lewy bodies: third report of the DLB Consortium. Neurology
2005;65:1863-1872.
61. Paulsen JS, et al. Incidence of and risk factors for hallucinations
and delusions in patients with probable AD. Neurology 2000;54:
1965-1971.