Depression, Apathy, and Anxiety in Parkinson Disease

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CATEGORY 1 CME

Premiere Date: April 20, 2025

Expiration Date: October 20, 2026

This activity offers CE credits for:

1. Physicians (CME)

2. Other

All other clinicians either will receive a CME Attendance Certificate or may choose any of the types of CE credit being offered.

ACTIVITY GOAL

To understand the epidemiology of psychiatric and cognitive Parkinson disease symptoms and how best to assess and treat them.

LEARNING OBJECTIVES

1. Discuss the epidemiology of neuropsychiatric symptoms of Parkinson disease.

2. Describe the assessment of neuropsychiatric symptoms of Parkinson disease.

3. Enumerate the evidence-based treatments for neuropsychiatric symptoms of Parkinson disease.

TARGET AUDIENCE

This accredited continuing education (CE) activity is intended for psychiatrists, psychologists, primary care physicians, physician assistants, nurse practitioners, and other health care professionals who seek to improve their care for patients with mental health disorders.

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This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Physicians’ Education Resource,® LLC and Psychiatric Times®. Physicians’ Education Resource, LLC, is accredited by the ACCME to provide continuing medical education for physicians.

Physicians’ Education Resource, LLC, designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits.™ Physicians should claim only the credit commensurate with the extent of their participation in the activity.

This activity is funded entirely by Physicians’ Education Resource, LLC. No commercial support was received.

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This accredited CE activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this accredited CE activity is for continuing medical education purposes only and is not meant to substitute for the independent clinical judgment of a physician relative to diagnostic or treatment options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of Physicians’ Education Resource, LLC.

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Editor’s Note: A subsequent CME article will contain information on impulse control disorders, psychosis, and cognitive impairment in Parkinson disease.

Parkinson disease (PD) was first described in 1817 by James Parkinson.¹ PD is the most common movement disorder in the world and the 2nd most common neurodegenerative disorder after Alzheimer disease (AD). The Global Burden of Disease study states that the leading sources of disability around the world are neurological disorders, and among these, the fastest-growing disorder is PD.² Globally, the number of individuals with PD increased by 118% to 6.2 million from 1990 to 2015. It has been estimated that the number of individuals with PD in the world will more than double to approximately 14.2 million by 2040.³ Greater awareness of the disease, availability of more sensitive methods to identify and diagnose individuals with PD, an aging population, and possible increased exposure to environmental pollutants (eg, pesticides) are all postulated as possible reasons for this increase.⁴ Currently, there are nearly 1 million individuals with PD in the US, expected to rise to 1.2 million by 2030.⁵

Results of 1 meta-analysis found that worldwide there was a rise in prevalence of PD along with age.⁶ The prevalence of PD was 41/100,000 among individuals aged 40 to 49 years; 107/100,000 among individuals aged 50 to 59 years; 173/100,000 among individuals aged 55 to 64 years; 428/100,000 among individuals aged 60 to 69 years; 425/100,000 among individuals aged 65 to 74 years; 1087/100,000 among individuals aged 70 to 79 years; and 1903/100,000 among individuals older than 80 years. The investigators found that the prevalence of PD among individuals aged 70 to 79 years was significantly greater in Europe, North America, and Australia when compared with individuals of the same age range in Asia (1602/100,000 vs 646/100,000, P <.05).

Results of a recent study found that the age-standardized PD incidence estimates among individuals aged 65 years or older was 108-212/100,000 person-years (162-277/100,000 among men, and 66-161/100,000 among women).⁷ The PD incidence estimates in this study increased with age in the age ranges 65 to 74 years and 75 to 84 years, with the incidence estimates being higher among men when compared with women in all age groups. One meta-analysis found that the overall male/female prevalence ratio for PD was 1.18.⁸

When evaluating the risk for developing PD, one meta-analysis found that the strongest risk factor for the development of PD was having a family member with PD.⁹ Other risk factors were constipation, having a mood disorder, exposure to pesticides, head injury, rural living, using β-blockers, being involved in farming and agriculture, and using well water. Smoking, the use of coffee, hypertension, the use of nonsteroidal anti-inflammatory drugs, the use of calcium channel blockers, and the use of alcohol were all found to have a negative association with the development of PD. Table 1 enumerates the risk factors and negative factors associated with the development of PD.⁹

TABLE 1. Risk Factors and Negative Factors Associated With the Development of PD⁹

Genetics

Available evidence indicates that most cases of PD are sporadic and occur without a family history.¹⁰ It has been estimated that about 5% to 10% of all cases of PD are caused by penetrant monogenes.¹¹ The causes of autosomal dominant forms of PD include mutations in the SNCA, LRRK2, VPS35, and DNAJC13 genes. Although uncommon, autosomal recessive homozygous or compound heterozygous loss-of-function mutations have been noted in 3 genes, and they are responsible for a significant number of cases of early-onset (<50 years of age) PD. These 3 genes are the PRKN (Parkin/E3 ubiquitin protein ligase, 8.6% cases) gene, the PINK1 (PTEN-induced putative kinase 1, 3.7% cases) gene, and the DJ-1 (PD protein 7, 0.4% cases) gene.

Neuropathology of PD

PD is part of a group of disorders known as synucleinopathies.¹² These disorders are characterized by the presence of α-synuclein (α-Syn), which is a misfolded protein, and it creates inclusions in various parts of the nervous system. Lewy bodies (LBs) are the neuropathologic hallmark of PD. They are neuronal protein aggregates that are formed of α-Syn, ubiquitin, and parkin. These proteins form inclusions that eventually result in the destruction of neurons. Disease progression among individuals with PD is thought to be correlated with the gradual appearance of LBs.¹³ Among individuals with PD, gross macroscopic atrophy of the brain is not a common finding.¹⁴

Braak et al developed a neuropathologic staging scheme for PD.¹⁵ In this staging scheme, the authors proposed that the PD pathology primarily starts in the olfactory bulb and the autonomic enteric nervous system, with a retrograde caudo-rostral spread of pathology to finally reach the substantia nigra pars compacta (SNc).¹³ The Braak staging system is divided into 6 stages. This denotes the progression of LB pathology from the dorsal motor nucleus of the vagus nerve (stage 1), to the locus coeruleus (LC) (stage 2), SNc and amygdala (stage 3), and finally reaching the cortex (stages 4-6). One criticism of this staging system is that it just describes some specific subsets of individuals with PD: those with younger onset of symptoms, individuals with long duration of the illness, and individuals with predominantly motor symptoms and/or dementia symptoms just in later stages of the disease. A significant number of individuals with PD do not follow the clinical course based on the Braak staging system.¹⁶

Early stages of PD are characterized by nonmotor symptoms, whereas the motor symptoms of PD appear once the SNc is affected.¹³ Cognitive dysfunction occurs when there is involvement of LB pathology in the cortex. There is growing evidence that there are many pathologic changes identified in the brains of individuals that predate the development of LB pathology among individuals who subsequently develop PD: a reduced striatal dopamine transporter and VMAT2 binding, decreased nigrostriatal connectivity, and increased activation of astrocytes and microglia in the midbrain of these individuals.

Clinical Features

Clinical symptoms of PD include both motor and nonmotor symptoms.⁴ A diagnosis of PD is usually made in the late 50s with the onset of motor symptoms (early-stage PD).¹⁴ The motor symptoms include the classic triad of bradykinesia, rigidity, and resting tremors.¹⁷ The other motor symptoms that can occur include dysarthria, dystonia, and postural instability. These symptoms start unilaterally and this asymmetry remains throughout the individual’s life.¹⁴

The nonmotor symptoms include anosmia (loss of smell), micrographia, constipation, urinary dysfunction, orthostatic hypotension, fatigue, excessive daytime sleepiness (EDS), pain, rapid eye movement sleep behavior disorder (RBD), apathy, anxiety, depression, psychosis (hallucinations and delusions), mild cognitive impairment, and dementia.¹⁴ Some of these nonmotor symptoms, including anosmia, constipation, orthostatic hypotension, EDS, RBD, and depression, often start insidiously and precede the motor symptoms by many years, and should be considered prodromal symptoms of PD.⁴

Although the nonmotor symptoms are not specific to PD, when they occur, the risk for the individual to subsequently develop PD is significantly higher.⁴ For example, RBD is now considered to be a highly specific marker of future synucleinopathies, with more than 80% of individuals who develop RBD subsequently developing an α-Syn—related neurodegenerative disorder, including PD.¹⁸ RBD is seen in 25% to 58% of individuals with PD. The nonmotor symptoms often determine the quality of life of the individual with PD, as they become more prevalent with the progression of the disease process, the development of disability, and placement in skilled nursing facilities.¹⁴ Table 2 enumerates the symptoms of PD.

TABLE 2. Symptoms of Parkinson Disease

Neuropsychiatric symptoms (NPS) are common among individuals with PD, with cross-sectional studies indicating prevalence rates of 70% to 89%.¹⁹ Although common, these symptoms are often underrecognized and not adequately treated, adding to the disability caused by the illness.²⁰ NPS that are seen among individuals with PD include depression, apathy, anxiety, impulse control disorder (ICD), psychosis, and cognitive impairment including dementia.

Results of 1 updated literature review showed that the most frequent NPS among individuals with PD were depression (47.2%), apathy (45.5%), anxiety (42.9%), psychosis (19.4%), and ICDs (18.5%).²¹ Investigators noted that treatment with dopamine agonists was an important risk factor for the development of ICDs (P = .003). Additionally, they found that there was a cooccurrence of NPS with cognitive impairment (P = .007) among individuals with PD. The investigators noted that individuals with PD who had clinically significant NPS were older (P = .02), had longer duration of illness (P = .01), more severe motor symptoms (P ≤.001), and more cognitive deficits (P ≤ .001).

Another study that followed newly diagnosed individuals with PD for 36 months found that when compared with controls, depression, anxiety, apathy, and hallucinations were more frequent among individuals with PD at all time points (P < .05).¹⁹ Greater severity of motor symptoms at baseline was associated with worsening caregiver distress over time (P < .05), but was not associated with changes in cognition among individuals with PD. Additionally, greater burden of NPS was associated with a poorer quality of life at any time point (P < .001). A meta-analysis of 55 studies found an association between psychosis and cognitive impairment (standardized mean difference [SMD], 0.44), psychosis and disease progression (SMD, 0.46), depression and cognitive impairment (SMD, 0.37), depression and disease progression (SMD, 0.46), depression and disability (SMD, 0.42), and apathy and cognitive impairment (SMD, 0.60), indicating that depression, apathy, and psychosis are markers of a poorer prognosis among individuals with PD.²² Despite being common, NPS are poorly identified among individuals with PD. One study found that among individuals with NPS symptoms, depression, anxiety, and dementia were recognized in 38.7%, 9.5%, and 27.2% of the individuals, respectively.²³

In the next section, common NPS of PD and their treatments will be discussed.

Depression

Results of a recent systematic review and meta-analysis of 129 studies (38,304 individuals from 28 countries) found that the overall prevalence of depression in PD was 38%.²⁴ The investigators noted that female sex (risk ratio [RR], 1.16), lower education level (SMD), –0.199), and having a mutation of the GBA1 L444P gene were associated with the depression in PD. In addition, longer duration of illness (SMD, 0.094), medication complications (SMD, 0.487), more severe motor symptoms (SMD, 0.339), postural instability (RR, 1.35), lower cognitive scores (Mini Mental State Examination [MMSE], SMD, –0.218; Montreal Cognitive Assessment] (SMD, –0.356)], more behavioral symptoms (SMD, 1.116), more apathy (RR, 1.67), more fatigue (RR, 1.35), more anxiety (RR, 1.37), daytime somnolence (RR, 1.33), and orthostatic hypotension (RR, 1.60) were also associated with depression in PD. Available evidence indicates that depression among individuals with PD accelerates the worsening of motor symptoms, adds to the disability due to the illness, results in overall poorer quality of life, and is associated with greater mortality among these individuals.²⁵

Symptoms of depressive disorders that may overlap with those of PD include psychomotor retardation, restricted affect, fatigue, muscle tension, gastrointestinal symptoms, reduced appetite, decreased sleep, poor concentration, and impaired memory.²⁶ Hence, it is recommended that an inclusive approach should be used in making a diagnosis of depression in PD when these overlapping symptoms are present. It would be prudent to focus on emotional symptoms rather than neurovegetative symptoms when considering a diagnosis of depression in PD. A National Institute of Health—sponsored workshop recommended the following when assessing individuals with depression in PD: (1) the inclusion of subsyndromal depression in clinical research studies of depression in PD, (2) the specification of timing of assessments for individuals with PD with motor fluctuations, and (3) the use of informants when evaluating for cognitive impairment.²⁷

A diagnosis of depression in PD should be made using validated clinical criteria and structured diagnostic interviews whenever possible to avoid underdiagnosis.²⁸ Clinical rating scales can help quantify the symptoms of depression in these individuals. Results of a meta-analysis by Goodarzi et al showed that the 15-item Geriatric Depression Scale had a pooled sensitivity of 0.81 and specificity of 0.91 for detecting depression among individuals with PD.²⁹ The authors also found that sensitivity and specificity for detecting depression among individuals with PD were as follows for these screening tools: the Beck Depression Inventory (sensitivity of 0.79 and specificity of 0.85), the Montgomery-Åsberg Depression Rating Scale (sensitivity of 0.77 and specificity of 0.92), and the Unified Parkinson Disease Rating Scale (UPDRS; sensitivity of 0.72 and specificity of 0.80).

Results of a meta-analysis of randomized controlled trials (RCTs) that included data from 10 studies found that there was no benefit for selective serotonin reuptake inhibitors (SSRIs), when compared with placebo among individuals with PD who have depression (n = 6; RR, 1.06; P = .67).³⁰ The investigators found no difference in efficacy between SSRIs and tricyclic antidepressants (TCAs) (n = 3; RR, 0.75; P = .37) among these individuals. No difference between SSRIs and placebo in terms of tolerability (dropouts, RR, 1.28; P = .45) were noted. The results were similar when comparing the tolerability of SSRIs vs TCAs (dropouts; RR, 0.96; P = .88) among individuals with PD and depression.

A network meta-analysis of RCTs that compared the efficacy and acceptability treatments for depression in PD and included data from 11 studies found that there is insufficient evidence to support the efficacy of SSRIs, pramipexole, pergolide, and serotonin norepinephrine reuptake inhibitors (SNRIs) among individuals with PD who have depression.³¹ Additionally, the investigators found that TCAs were more efficacious than SSRIs, pramipexole, pergolide, and SNRIs. They also noted that TCAs, pramipexole, pergolide, and SNRIs were better tolerated than SSRIs among these individuals. However, subsequent studies indicate that SSRIs are evidence-based treatments for depression in PD.

Results of a meta-analysis of 9 RCTs found that the pooled effect of antidepressants for depression in PD was moderate (Cohen d = 0.71) but not significant.³² The investigators noted that the antidepressants showed a large (Cohen d = 1 .13) but nonsignificant effect for anxiety among individuals with PD. They also identified single trials of omega-3 supplementation (Cohen d = 0 .92), and cognitive behavioral therapy (CBT; Cohen d = 1.57) that showed large effects for depression in PD.

Results of a meta-analysis by Bomasang-Layno et al that included data from 20 RCTs among individuals with PD and depression found that the overall SMD for all pharmacologic interventions when compared with placebo was 0.30 (P = .054).³³ When comparing antidepressants with placebo, the SMD was 0.54 (P = .000). When comparing non-antidepressants (pergolide, pramipexole, memantine, and atomoxetine) with placebo, the SMD was –0.29 (P = .328). The pooled SMD for the SSRI/SNRIs was 0.45 (P = .003), and for the TCAs it was 0.74 (P = .108). For behavioral and other noninvasive treatments, the overall SMD was 0.87 (P = .000). CBT had the largest effect size in 2 studies (SMD, 1.24, and SMD, 1.22). Data from 2 repetitive transcranial magnetic stimulation (rTMS) studies showed that the overall SMD was 0.30. Overall, the medications were well tolerated among these individuals with no significant worsening of other PD symptoms. Sedation was noted with trazodone, memantine, pramipexole, and pergolide. Anticholinergic adverse effects were noted with TCAs.

Results of a meta-analysis showed that rTMS (n = 3; SMD, –0.86) improved depressive symptoms when compared with sham treatment.³⁴ The investigators did not find any difference between rTMS and antidepressants in the treatment of depressive symptoms (n = 3; SMD, –0.12). A second meta-analysis indicated that rTMS (n = 9; SMD, –0.62) improved depressive symptoms in the short term when compared with sham treatment.³⁵ The investigators did not identify any difference between rTMS and antidepressants in the short-term treatment of depressive symptoms (n = 5; SMD, –0.00). The investigators did not identify any long-term benefits with the use of rTMS when compared with sham treatment (n = 4; SMD, –0.56). They found that rTMS was well tolerated in the short term when compared with controls (adverse effects: n = 12; RR, 1.05). The investigators found that CBT was also beneficial for the short-term treatment of depression among individuals with PD (n = 3; SMD, –1.15).

Results of a meta-analysis of 14 studies found that electroconvulsive therapy (ECT) improved depressive symptoms among individuals with PD (n = 6; SMD, 1.33; P < .001).³⁶ ECT also improved psychotic symptoms (n = 5; SMD, 1.64; P < .001), motor symptoms (n = 13; SMD, 1.18; P < .001, and cognitive function (n = 6; SMD, 0.21; P = .002) among these individuals.

Evidence from these meta-analyses indicate that CBT, antidepressants (SSRIs, SNRIs, and TCAs), rTMS, and ECT may benefit individuals with PD who have depression, and these treatments are reasonably well tolerated among these individuals. Based on these data, we would recommend CBT and antidepressants as first-line treatments for depression in PD. rTMS would be considered as 2nd-line treatment, followed by ECT for more refractory symptoms.

Apathy

Apathy is a syndrome characterized by reduced initiative, decreased interests, and lack of emotional responsiveness.³⁷ Results of 1 meta-analysis showed that the prevalence of apathy among individuals with PD is 39.8%.³⁸ Investigators noted that apathy was associated with higher age (3.3 years), lower mean MMSE scores (–1.4 points), a greater risk of comorbid depression (RR, 2.3), higher UPDRS motor scores (6.5 points; 95% CI, 2.6-10.3), and greater disability (Hedges g = 0.5). A meta-analysis of 33 studies found that deep brain stimulation of the subthalamic nucleus among individuals with PD increases the risk of developing apathy postoperatively when compared with preoperatively (Hedges g = 0.34; P < .001), and with using medication only (Hedges g = 0.36; P = .004).³⁹

Among individuals with PD, apathy reduces the responsiveness to treatment for motor symptoms, worsens quality of life for the individual and their caregivers, increases cost of care, and increases risk of developing dementia.⁴⁰ Results of an 18-month longitudinal study showed that individuals with PD who have apathy are at greater risk for developing dementia when compared with individuals with PD who do not have apathy (P = .008).⁴¹ A meta-analysis of 8 studies indicated that individuals with PD and apathy have lower scores on global cognitive function (effect size [ES]) –0.40), long-term verbal memory (ES = –0.64), executive functioning including abstraction ability/concept formation (ES = –0.63), inhibition (ES = –0.76), generativity (ES = –0.55), processing speed/attention/working memory (ES = –0.42), and visuospatial and constructional ability (ES = –0.65).⁴²

Although the definitive mechanisms for development of apathy among individuals with PD have not yet been identified, the proposed mechanisms include dysfunction of the basal ganglia, especially the posterior and anterior cingulate cortices, nucleus accumbens, striatum, and the subthalamic nucleus.⁴⁰ It has been postulated that imbalances in dopamine may impair the individual’s sensitivity to reward, and thereby cause deficits in decision-making capacity. Some have postulated that in the prodromal stages of PD, apathy may be considered an amotivational behavioral syndrome due to dopaminergic and serotonergic denervation.⁴³ However, in advanced cases of PD, apathy should be considered a cognitive dysfunction syndrome due to diffuse neurotransmitter system impairments, the progression of LB pathology that results in cognitive decline, and the development of PD dementia.

Results of 1 systematic review found that the self-reported questionnaires—the 5-item version of the World Health Organization Well-Being Index (WHO-5) and the Neurasthenia Scale, along with the clinician-administered scales, the Starkstein Apathy Scale (SAS) and the Lille Apathy Rating Scale (LARS)—have clinical validity for the assessment of apathy among individuals with PD.⁴⁴ The authors indicated that the WHO-5 and the Neurasthenia Scale are useful for detecting the severity of apathy symptoms, whereas the SAS can be used to exclude the presence of apathy symptoms or to evaluate the psychological effects of drugs. The LARS is a clinically valid instrument that can be used to diagnose apathy. The authors opined that among individuals with poor insight into their illness, clinician-rated scales must be used. They concluded that self-reported questionnaires and clinician-administered rating scales should be considered as complimentary evaluation tools for the comprehensive assessment of apathy.

In a meta-analysis of 3 studies, investigators found that individuals with PD receiving rotigotine showed significant improvements in symptoms of apathy (mean difference [MD], –2.5; P = .002), compared with the control group.⁴⁵ In another meta-analysis of 2 studies, investigators found that dance therapy did not benefit individuals with PD and apathy (weighted mean difference [WMD], 0.07; P = .96).⁴⁶ A recent Bayesian network meta-analysis of 19 studies found that pharmacotherapy was better than brain stimulation (SMD, –0.43), exercise-based interventions (SMD, –0.66), nutritional supplements (SMD, –0.33), and placebo (SMD, –0.38) in improving apathy scores among individuals with PD.⁴⁷ A pooled analysis of 11 studies showed that pharmacotherapy was effective in improving apathy scores (SMD, –0.38; P < .001). There was no difference in efficacy noted between dopamine agonists (rotigotine [5 studies] and piribedil [1 study), rasagiline, exenatide, amantadine, and atomoxetine (SMD, –0.36; P = .003 vs SMD, –0.42; P < .001). A pooled analysis of 2 studies did not find brain stimulation to be effective for treating apathy (SMD, 0.04; P = .757) and found no significant effects for exercise-based interventions on apathy scores (SMD, 0.27; P = .388). Data from 4 studies showed that supplements did not improve apathy scores (SMD, –0.04; P = .650).

It can be inferred that dopamine agonists (rotigotine and piribedil), rasagiline, exenatide, amantadine, and atomoxetine may improve symptoms of apathy among individuals with PD.

Anxiety

Results of a meta-analysis of 49 studies found that average point prevalence of anxiety disorders among individuals with PD was 31%.⁴⁸ The investigators identified that generalized anxiety disorder (14.1%), was the most common anxiety disorder, followed by social phobia (13.8%), and clinically relevant anxiety that does not meet the criteria for any specific anxiety diagnoses (anxiety disorder, not otherwise specified, 13.3%). Specific phobia was seen in 13.0% of the individuals and panic disorder with or without agoraphobia was noted in 6.8% of individuals with PD. They found that 31.1% of individuals also met the criteria for 2 or more anxiety disorders at a given time point. They also found that the weighted average of clinically relevant anxiety symptoms assessed using a rating scale was lower (25.7%) than the weighted average of DSM-defined anxiety disorders (31%), indicating that the currently used anxiety rating scales are not appropriate for diagnosing anxiety disorders among individuals with PD.

In a case series, Dissanayaka et al found that age (< 62 years, OR, 4.20; P = .01), lower activities of daily living scores (OR, 1.19; P = .001), greater severity of PD symptoms (OR, 1.07-10.75; P = .02), experiencing dyskinesia and motor fluctuations (OR, 4.92; P = .01), PD age of onset (< 61 years, OR, 4.31; P = .05), and having a history of psychiatric illness (OR, 4.78; P = .007) were risk factors for the development of anxiety among individuals with PD.⁴⁹ In this study, 14% of the individuals with PD had a comorbid depressive disorder with anxiety. Female gender, neuroticism, harm-avoidance personality traits, and a history of anxiety have also been identified as risk factors for the development of anxiety among individuals with PD.⁵⁰ One study found that symptoms of anxiety more than depression, overall cognitive status, or motor stage of the disease affects the health-related quality of life among nondemented individuals with PD.⁵¹

Although prevalent, anxiety is identified in fewer than half of individuals with clinically significant anxiety among individuals with PD.⁵⁰ Hence, it is crucial to use validated scales to help identify this condition among individuals with PD. One systematic review found that Geriatric Anxiety Inventory has the best reported sensitivity (0.86) in identifying anxiety disorders among individuals with PD (specificity = 0.88).⁵² The observer-rated Parkinson Anxiety Scale was found to have a sensitivity of 0.71 and a specificity of 0.91.

Both nonpharmacologic and pharmacologic treatment modalities have been noted to be beneficial in the management of anxiety among individuals with PD.⁵³ Results of a meta-analysis of 6 trials showed that CBT was beneficial in treating anxiety among individuals with PD (SMD, –0.55; P = .0007).⁵⁴ Another meta-analysis of 4 studies found that yoga improves symptoms of anxiety among individuals with PD when compared with controls (SMD, –0.72; P < .00001).⁵⁵ A more recent meta-analysis found that when compared with non-CBT treatments (mindfulness training and body awareness training, SMD, –0.27; P = .66), treatment with CBT significantly improved symptoms of anxiety among individuals with PD (SMD, –0.85; P < .001).⁵⁶

A meta-analysis by Troeung et al did not identify any specific RCTs of any treatments for anxiety in PD.³² However, they noted that 3 of the depression trials also reported the effect of treatment on anxiety as a secondary outcome. This included 2 trials of antidepressants (citalopram vs desipramine, and paroxetine vs nortriptyline) and 1 trial of atomoxetine. The effect of citalopram (Cohen d = 0.95), desipramine (Cohen d = 0.93), and nortriptyline (Cohen d = 1.98) on anxiety among individuals with PD was significant. However, the effect of paroxetine on anxiety was nonsignificant (Cohen d = 0.76; 95% CI, –0.10-1.61). The pooled effect size for the antidepressants for the treatment of anxiety in PD was large but nonsignificant (Cohen d = 1.13; 95% CI, –0.67-2.94). In a subgroup analysis, the investigators found that the pooled effect size for TCAs on anxiety was large and significant (Cohen d = 1.40; 95% CI , 0.09-2.70), whereas the pooled effect size for SSRIs was nonsignificant (Cohen d = 0.85; 95% CI, –0.40-2.09). The effect of atomoxetine on anxiety in PD was significant (Cohen d = 1.29; 95% CI, 0.71-1.87).

Available evidence indicates that nonpharmacologic management strategies (CBT and yoga) and medications such as citalopram, desipramine, and atomoxetine are useful in treating anxiety among individuals with PD. CBT and yoga should be considered first-line treatments, with medications reserved for symptoms that do not respond adequately to these interventions.

Concluding Thoughts

Worldwide, there has been a rise in prevalence of PD along with age. Nonmotor symptoms may often precede the motor symptoms by many years and are often considered prodromal symptoms of PD. NPS are seen commonly among individuals with PD. ICDs, psychosis, and cognitive impairment among individuals with PD will be discussed in a forthcoming CME.

Dr Tampi is professor and chairman of the Department of Psychiatry at Creighton University School of Medicine and Catholic Health Initiatives Health Behavioral Health Services in Omaha, Nebraska. He is also an adjunct professor of psychiatry at Yale School of Medicine, New Haven, Connecticut. Ms Snyder is a medical student at Creighton University School of Medicine, Omaha.

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