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Abstract
Neuropsychiatric complications are an under recognized and undertreated aspect of Parkinson’s disease (PD). A gamut of psychiatric
disturbances can occur in PD and include depression, anxiety, psychosis, dementia, impulse control disorders, apathy, and sleep disturbances.
They substantially affect the lives of the patients and their caregivers and have negative impact on the quality of life. Optimal assessment and
treatment is the key to manage these patients.
Introduction Depression
Parkinson’s disease (PD) was first described as “shaking palsy” Depression is one of the most common psychiatric disturbances
by British Physician James Parkinson in 1817.[1] It is widely in PD. Prevalence of depression in patients with PD is
accepted that PD is a multisystem disorder characterized approximately 20–40%.[6] Other psychiatric disorders such
by degeneration of not only nigrostriatal dopaminergic as anxiety, psychosis, apathy, and insomnia are frequently
system, but also serotonergic and noradrenergic brainstem comorbid with PD. Presence of depression in PD is predictive
areas and cholinergic frontal regions. The clinical features of rapid progression of motor and cognitive impairment and
include both the motor as well as nonmotor symptoms. portends a poor prognosis. It can also be a premotor feature of
Motor symptoms include tremor, bradykinesia, rigidity, and PD presenting years before the onset of motor symptoms.[7‑9]
postural instability.[2] Various nonmotor features range from It has been found that female sex, patients with right‑sided
cognitive and behavioral symptoms, autonomic dysfunction, motor symptoms, or with more severe cognitive impairment
and sleep disturbances. [3] Because of the predominant and akinetic rigid subtype compared to tremor predominant
psychiatric comorbidities associated with PD, it is essentially variant have more chances of developing depression.[6,10]
a neuropsychiatric disorder. [4] Presence of psychiatric
disturbances in patients with PD have negative effects on Clinical features of depression may mimic those of PD.
the quality of life leading to excess disability, poor cognitive Hypomimia, motor slowness, sleep disturbances, and fatigue
and motor outcomes, increased risk of hospitalization, and can occur even in nondepressed Parkinson’s patients. The
increased distress to the caregivers.[5] Psychiatric complications clinical profile of depression in patients with PD varies slightly
are an under recognized and undertreated aspect of PD. from patients with idiopathic depression. Parkinsonian patients
have higher rates of anxiety, dysphoria, irritability, pessimism,
suicidal ideation without suicidal behavior, and less rates of self
Classification
Neuropsychiatric complications in PD can be divided into Address for correspondence: Dr. Sahil Mehta,
two types: Department of Neurology, Postgraduate Institute of Medical Education and
Research, Chandigarh, India.
• Disease‑related E‑Mail: mehtasahilpgi@gmail.com
• Treatment‑related.
These are elaborated in Table 1.
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DOI:
10.4103/2349-0977.168248 How to cite this article: Kharbanda PS, Sharma S, Mehta S. Neuropsychiatric
aspects of Parkinson’s disease. Astrocyte 2015;2:25-30.
guilt and reproach.[11] The severity ranges from mild dysthymia Electroconvulsive therapy can also be used in severe and
to major depression. Major depression accounts for about 50% refractory depression. It temporarily improves parkinsonism
of the patients. Features of depression may fluctuate with the for a few days to weeks.[19‑21] Efficacy is similar to depressed
motor fluctuations and be present only in the off phase.[10,12] nonPD patients and is based on case reports only.
As the disease advances, the risk of developing depression
Various antidepressants used for depression are summarized
also increases.
in Table 2 with their doses and side effects.
The occurrence of depression in patients with PD is not simply
an emotional reaction to illness but has a biological basis. Parkinson’s Disease Dementia
Dysfunction of the striatothalamic frontal and basotemporal
Prevalence of dementia in patients with PD is around 30%
limbic circuits has been implicated in the pathophysiology of
with this number increasing to 80% in patients with course
depression. In addition to the deficiency of dopamine, serotonin
of more than 10 years.[22] Presence of cognitive dysfunction
and nor epinephrine also play a role in various neuropsychiatric
and dementia is associated with increased mortality, increased
manifestations including depression. [13] Disruption of
chances of hospitalization, and worse quality of life. There
dopaminergic efferents from ventral tegmental area to the
is a “12 month rule” to differentiate PD dementia (PDD)
orbitofrontal or prefrontal cortex along with disruption of
from dementia with Lewy bodies. Presence of parkinsonism
efferents from orbitofrontal cortex to the serotonergic neurons
at least 1 year prior to the onset of dementia favors PDD.[23]
in the dorsal raphe nucleus are thought to be responsible for
Patients with certain characteristics are more prone to develop
depression in PD.
dementia. These include older age at PD onset, nontremor
Tr e a t m e n t i n v o l v e s b o t h p h a r m a c o l o g i c a l a n d predominant phenotype, longer disease duration, male sex,
nonpharmacological therapies. Psychotherapy should be presence of psychosis, greater severity of motor symptoms,
offered initially, especially in patients with less severe and presence of postural instability or gait impairment.[24‑26]
symptoms. There are no systematic clinical trials of the
Dementia in PD is classically described as sub cortical with
treatment of depression in patients with PD. However, open
dysexecutive syndrome and absence of aphasia, apraxia,
label studies have shown efficacy of both selective serotonin
and agnosia. Clinically, patients can have mild cognitive
reuptake inhibitors (SSRIs) and tricyclic antidepressants,
impairment or frank dementia. Neuropsychological testing
despite a theoretical risk of worsening of parkinsonian
reveals impaired attention, executive and visuospatial
symptoms with SSRIs.[14‑16] Adverse effects of SSRIs include
dysfunction, and problems in retrieval. Tests of semantic
nausea, headache, tremor, sweating, and sexual dysfunction.
and phonemic fluency are impaired with inability to copy
Use of tricyclic antidepressants can lead to worsening of
intersecting pentagons.[24‑26] Patients with PDD improve on
orthostatic hypotension, constipation, urinary retention, and
recall with external cues. Cognitive impairment in PD is
cognitive problems. Dopamine agonists and selegiline have
frequently accompanied with other behavioral symptoms
also been shown to confer antidepressant properties.[17] There
such as psychosis, depression, apathy, and sleep disturbances.
is also a risk of development of serotonin syndrome with the
simultaneous use of Selegiline and SSRIs, though it is rarely Table 3 shows the differences between Alzheimer’s
encountered in the clinical practice.[18] dementia (AD) and PDD.
Degeneration of dopaminergic neurons leading to dopaminergic
Table 1: Neuropsychiatric Disturbances in PD deficiency is mainly implicated in the pathogenesis of
dementia in PD. Disruption of striatofrontal connections is
Disease‑related Treatment‑related
responsible for the predominant executive dysfunction. Other
Depression Psychosis
neurotransmitter systems such as cholinergic deficiency due
Anxiety ICD
Apathy Dopamine dysregulation syndrome
to degeneration of nucleus basalis of Meynert and loss of nor
Dementia Excessive daytime somnolence
adrenergic and serotonergic neurons are also implicated in
Sleep disorders Effect of DBS the pathogenesis of PDD. Both alpha synuclein and AD‑like
PD: Parkinson’s disease, ICD: Impulse control disorders, DBS: Deep brain pathology play an important role in PDD. Neuropathological
stimulation specimens show the presence of cortical Lewy bodies along
loss of employment, and other health risks. Pathological improve sleep disturbances due to PD symptoms and can
gambling is defined as maladaptive gambling behavior despite relieve early morning dystonia.
deleterious consequences on familial, occupational, and
20–50% of PD patients have sleep apnea despite normal body
social functioning. Punding consists of an intense fascination
mass index. Upper airway muscle dysfunction may play a role
with repetitive handling, examining, sorting, and arranging
in the development of obstructive sleep apnea. Nocturnal stridor
of objects. Dopamine dysregulation syndrome is defined
more commonly occurs in patients with multiple system atrophy.
as compulsive use of high doses of dopaminergic drugs,
particularly levodopa, associated with severe behavioral Periodic leg movements of sleep are myoclonic jerks, which
symptoms with impaired social functioning. It was previously occur in nonrapid eye movement (REM) sleep. These are
referred as hedonic homeostatic dysregulation. Hoarding is associated with restless leg syndrome, which is characterized
defined as acquisition of and failure to discard a large number by unpleasant or painful sensations mainly affecting legs but
of items with little or no objective value, which in some cases can affect arms also. These unpleasant sensations are relieved
can lead to unsafe or unsanitary living conditions. by voluntary movement.[49] Symptoms follow a circadian
Risk factors involve dopamine receptor agonist treatment, pattern with onset in the evening hours when patients lie in bed
previous history of ICD behaviors, personal or family history of to sleep. Dopaminergic therapy shows excellent response.[50]
substance abuse, male sex, and younger age early onset PD.[40] REM sleep behavior disorder (RBD) involves vigorous
Eight percentage cases treated with dopamine agonists can physical activity while sleeping and patient can cause injury
develop ICD percent.[41] They are seen at both higher and low to self or others. It represents enactment of dreams and
doses (used for restless leg syndrome[42]) of dopamine agonists. predates the motor manifestation of PD.[51,52] Pathophysiology
On the contrary, only 1–4% of cases treated with levodopa involves degeneration of cholinergic pedunculopontine
develop ICD and that too at higher doses (>1000 mg/day). nucleus and reduced striatal dopaminergic activity. No
Amantadine use has also been associated with ICD in PD.[43] randomized controlled trials exist for the treatment of RBD.
Pathophysiology involves supersensitivity of D3 receptors.[44] No pharmacological intervention is necessary if symptoms
Initial reports in the literature were due to pramipexole only are mild and intermittent. Clonazepam is the drug of choice
but subsequent reports suggest class effect. and is effective in the doses of even 0.25 mg.[53] Serotonin
Treatment involves lowering or stopping the drug. It is antidepressants may increase risk of RBD and should be
usually reversible when dopamine agonists are the culprit avoided in susceptible individuals.
as levodopa is difficult to stop because of the requirement PD patients can suffer from drowsiness or fatigue during the
for motor control.[45] There are no prospective randomized day time. It may be intrinsic to disease or a peak effect of
trials of pharmacological treatment of ICD in PD. However, dopaminergic treatment. These features can be contributed
antidepressants such as citalopram, sertraline, and atypical by depression also. Excessive day time somnolence is more
antipsychotics such as clozapine and quetiapine have been
shown to be of benefit in various case reports. Deep brain
stimulation has also been considered in some cases of ICD with Table 4: Sleep Disturbances in PD
PD associated with higher dosages of dopamine replacement Category Specific disorders
therapy. Improvement is related to decrease in the dose of Disorders of sleep initiation Insomnia
dopaminergic medications postoperatively. and maintenance Sleep fragmentation (frequent
night‑time awakenings)
common with dopamine agonists and in patients who are 2. Lang AE, Lozano AM. Parkinson’s disease. First of two parts. N Engl J
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