CATEGORY 1 CME
Premiere Date: April 20, 2025
Expiration Date: October 20, 2026
This exercise gives CE credit for:
1. Physicians (CME)
2. Different
All different clinicians both will obtain a CME Attendance Certificates or might select any of the varieties of CE credit score being provided.
ACTIVITY GOAL
To know the epidemiology of psychiatric and cognitive Parkinson illness signs and the way finest to evaluate and deal with them.
LEARNING OBJECTIVES
1. Talk about the epidemiology of neuropsychiatric signs of Parkinson illness.
2. Describe the evaluation of neuropsychiatric signs of Parkinson illness.
3. Enumerate the evidence-based therapies for neuropsychiatric signs of Parkinson illness.
TARGET AUDIENCE
This accredited persevering with training (CE) exercise is meant for psychiatrists, psychologists, main care physicians, doctor assistants, nurse practitioners, and different well being care professionals who search to enhance their look after sufferers with psychological well being problems.
ACCREDITATION/CREDIT DESIGNATION/FINANCIAL SUPPORT
This exercise has been deliberate and carried out in accordance with the accreditation necessities and insurance policies of the Accreditation Council for Persevering with Medical Training (ACCME) by way of the joint providership of Physicians’ Training Useful resource,® LLC and Psychiatric Instances®. Physicians’ Training Useful resource, LLC, is accredited by the ACCME to supply persevering with medical training for physicians.
Physicians’ Training Useful resource, LLC, designates this enduring materials for a most of 1.5 AMA PRA Class 1 Credit.™ Physicians ought to declare solely the credit score commensurate with the extent of their participation within the exercise.
This exercise is funded fully by Physicians’ Training Useful resource, LLC. No business assist was acquired.
OFF-LABEL DISCLOSURE/DISCLAIMER
This accredited CE exercise might or might not talk about investigational, unapproved, or off-label use of medication. Individuals are suggested to seek the advice of prescribing data for any merchandise mentioned. The knowledge supplied on this accredited CE exercise is for persevering with medical training functions solely and isn’t meant to substitute for the unbiased scientific judgment of a doctor relative to diagnostic or therapy choices for a particular affected person’s medical situation. The opinions expressed within the content material are solely these of the person college members and don’t mirror these of Physicians’ Training Useful resource, LLC.
FACULTY, STAFF, AND PLANNERS’ DISCLOSURES AND CONFLICT OF INTEREST MITIGATION
Not one of the employees of Physicians’ Training Useful resource, LLC, or Psychiatric Instances or the planners or the authors of this instructional exercise have related monetary relationship(s) to reveal with ineligible firms whose main enterprise is producing, advertising and marketing, promoting, reselling, or distributing well being care merchandise utilized by or on sufferers.
For content-related questions, e-mail us at PTEditor@mmhgroup.com; for questions regarding the accreditation of this CME exercise or declare credit score, please contact information@gotoper.com and embody “Melancholy, Apathy, and Nervousness in Parkinson Illness” within the topic line.
HOW TO CLAIM CREDIT
Upon getting learn the article, please use the next URL to judge and request credit score: https://training.gotoper.com/exercise/ptcme25april. If you don’t have already got an account with Physicians’ Training Useful resource, LLC, you may be prompted to create one. You have to have an account to judge and request credit score for this exercise.
Editor’s Be aware: A subsequent CME article will include data on impulse management problems, psychosis, and cognitive impairment in Parkinson illness.
Parkinson illness (PD) was first described in 1817 by James Parkinson.1 PD is the commonest motion dysfunction on the planet and the 2nd most typical neurodegenerative dysfunction after Alzheimer illness (AD). The World Burden of Illness examine states that the main sources of incapacity around the globe are neurological problems, and amongst these, the fastest-growing dysfunction is PD.2 Globally, the variety of people with PD elevated by 118% to six.2 million from 1990 to 2015. It has been estimated that the variety of people with PD on the planet will greater than double to roughly 14.2 million by 2040.3 Better consciousness of the illness, availability of extra delicate strategies to establish and diagnose people with PD, an getting older inhabitants, and attainable elevated publicity to environmental pollution (eg, pesticides) are all postulated as attainable causes for this improve.4 At the moment, there are practically 1 million people with PD within the US, anticipated to rise to 1.2 million by 2030.5
Outcomes of 1 meta-analysis discovered that worldwide there was an increase in prevalence of PD together with age.6 The prevalence of PD was 41/100,000 amongst people aged 40 to 49 years; 107/100,000 amongst people aged 50 to 59 years; 173/100,000 amongst people aged 55 to 64 years; 428/100,000 amongst people aged 60 to 69 years; 425/100,000 amongst people aged 65 to 74 years; 1087/100,000 amongst people aged 70 to 79 years; and 1903/100,000 amongst people older than 80 years. The investigators discovered that the prevalence of PD amongst people aged 70 to 79 years was considerably better in Europe, North America, and Australia compared with people of the identical age vary in Asia (1602/100,000 vs 646/100,000, P <.05).
Outcomes of a current examine discovered that the age-standardized PD incidence estimates amongst people aged 65 years or older was 108-212/100,000 person-years (162-277/100,000 amongst males, and 66-161/100,000 amongst ladies).7 The PD incidence estimates on this examine elevated with age within the age ranges 65 to 74 years and 75 to 84 years, with the incidence estimates being increased amongst males compared with ladies in all age teams. One meta-analysis discovered that the general male/feminine prevalence ratio for PD was 1.18.8
When evaluating the chance for growing PD, one meta-analysis discovered that the strongest danger issue for the event of PD was having a member of the family with PD.9 Different danger elements have been constipation, having a temper dysfunction, publicity to pesticides, head harm, rural residing, utilizing β-blockers, being concerned in farming and agriculture, and utilizing nicely water. Smoking, using espresso, hypertension, using nonsteroidal anti-inflammatory medication, using calcium channel blockers, and using alcohol have been all discovered to have a detrimental affiliation with the event of PD. Desk 1 enumerates the chance elements and detrimental elements related to the event of PD.9
TABLE 1. Danger Elements and Unfavorable Elements Related With the Growth of PD9
Genetics
Out there proof signifies that the majority circumstances of PD are sporadic and happen with no household historical past.10 It has been estimated that about 5% to 10% of all circumstances of PD are attributable to penetrant monogenes.11 The causes of autosomal dominant types of PD embody mutations within the SNCA, LRRK2, VPS35, and DNAJC13 genes. Though unusual, autosomal recessive homozygous or compound heterozygous loss-of-function mutations have been famous in 3 genes, and they’re chargeable for a big variety of circumstances of early-onset (<50 years of age) PD. These 3 genes are the PRKN (Parkin/E3 ubiquitin protein ligase, 8.6% circumstances) gene, the PINK1 (PTEN-induced putative kinase 1, 3.7% circumstances) gene, and the DJ-1 (PD protein 7, 0.4% circumstances) gene.
Neuropathology of PD
PD is a part of a gaggle of problems referred to as synucleinopathies.12 These problems are characterised by the presence of α-synuclein (α-Syn), which is a misfolded protein, and it creates inclusions in numerous elements of the nervous system. Lewy our bodies (LBs) are the neuropathologic hallmark of PD. They’re neuronal protein aggregates which can be shaped of α-Syn, ubiquitin, and parkin. These proteins type inclusions that ultimately outcome within the destruction of neurons. Illness development amongst people with PD is regarded as correlated with the gradual look of LBs.13 Amongst people with PD, gross macroscopic atrophy of the mind just isn’t a standard discovering.14
Braak et al developed a neuropathologic staging scheme for PD.15 On this staging scheme, the authors proposed that the PD pathology primarily begins within the olfactory bulb and the autonomic enteric nervous system, with a retrograde caudo-rostral unfold of pathology to lastly attain the substantia nigra pars compacta (SNc).13 The Braak staging system is split into 6 levels. This denotes the development 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 at last reaching the cortex (levels 4-6). One criticism of this staging system is that it simply describes some particular subsets of people with PD: these with youthful onset of signs, people with lengthy period of the sickness, and people with predominantly motor signs and/or dementia signs simply in later levels of the illness. A big variety of people with PD don’t observe the scientific course based mostly on the Braak staging system.16
Early levels of PD are characterised by nonmotor signs, whereas the motor signs of PD seem as soon as the SNc is affected.13 Cognitive dysfunction happens when there may be involvement of LB pathology within the cortex. There’s rising proof that there are various pathologic adjustments recognized within the brains of people that predate the event of LB pathology amongst people who subsequently develop PD: a diminished striatal dopamine transporter and VMAT2 binding, decreased nigrostriatal connectivity, and elevated activation of astrocytes and microglia within the midbrain of those people.
Scientific Options
Scientific signs of PD embody each motor and nonmotor signs.4 A prognosis of PD is often made within the late 50s with the onset of motor signs (early-stage PD).14 The motor signs embody the basic triad of bradykinesia, rigidity, and resting tremors.17 The opposite motor signs that may happen embody dysarthria, dystonia, and postural instability. These signs begin unilaterally and this asymmetry stays all through the person’s life.14
The nonmotor signs embody anosmia (lack of scent), micrographia, constipation, urinary dysfunction, orthostatic hypotension, fatigue, extreme daytime sleepiness (EDS), ache, speedy eye motion sleep habits dysfunction (RBD), apathy, nervousness, despair, psychosis (hallucinations and delusions), gentle cognitive impairment, and dementia.14 A few of these nonmotor signs, together with anosmia, constipation, orthostatic hypotension, EDS, RBD, and despair, typically begin insidiously and precede the motor signs by a few years, and ought to be thought-about prodromal signs of PD.4
Though the nonmotor signs usually are not particular to PD, once they happen, the chance for the person to subsequently develop PD is considerably increased.4 For instance, RBD is now thought-about to be a extremely particular marker of future synucleinopathies, with greater than 80% of people who develop RBD subsequently growing an α-Syn—associated neurodegenerative dysfunction, together with PD.18 RBD is seen in 25% to 58% of people with PD. The nonmotor signs typically decide the standard of lifetime of the person with PD, as they turn out to be extra prevalent with the development of the illness course of, the event of incapacity, and placement in expert nursing services.14 Desk 2 enumerates the signs of PD.
TABLE 2. Signs of Parkinson Illness
Neuropsychiatric signs (NPS) are widespread amongst people with PD, with cross-sectional research indicating prevalence charges of 70% to 89%.19 Though widespread, these signs are sometimes underrecognized and never adequately handled, including to the incapacity attributable to the sickness.20 NPS which can be seen amongst people with PD embody despair, apathy, nervousness, impulse management dysfunction (ICD), psychosis, and cognitive impairment together with dementia.
Outcomes of 1 up to date literature overview confirmed that probably the most frequent NPS amongst people with PD have been despair (47.2%), apathy (45.5%), nervousness (42.9%), psychosis (19.4%), and ICDs (18.5%).21 Investigators famous that therapy with dopamine agonists was an essential danger issue for the event of ICDs (P = .003). Moreover, they discovered that there was a cooccurrence of NPS with cognitive impairment (P = .007) amongst people with PD. The investigators famous that people with PD who had clinically vital NPS have been older (P = .02), had longer period of sickness (P = .01), extra extreme motor signs (P ≤.001), and extra cognitive deficits (P ≤ .001).
One other examine that adopted newly identified people with PD for 36 months discovered that compared with controls, despair, nervousness, apathy, and hallucinations have been extra frequent amongst people with PD in any respect time factors (P < .05).19 Better severity of motor signs at baseline was related to worsening caregiver misery over time (P < .05), however was not related to adjustments in cognition amongst people with PD. Moreover, better burden of NPS was related to a poorer high quality of life at any time level (P < .001). A meta-analysis of 55 research discovered an affiliation between psychosis and cognitive impairment (standardized imply distinction [SMD], 0.44), psychosis and illness development (SMD, 0.46), despair and cognitive impairment (SMD, 0.37), despair and illness development (SMD, 0.46), despair and incapacity (SMD, 0.42), and apathy and cognitive impairment (SMD, 0.60), indicating that despair, apathy, and psychosis are markers of a poorer prognosis amongst people with PD.22 Regardless of being widespread, NPS are poorly recognized amongst people with PD. One examine discovered that amongst people with NPS signs, despair, nervousness, and dementia have been acknowledged in 38.7%, 9.5%, and 27.2% of the people, respectively.23
Within the subsequent part, widespread NPS of PD and their therapies will probably be mentioned.
Melancholy
Outcomes of a current systematic overview and meta-analysis of 129 research (38,304 people from 28 nations) discovered that the general prevalence of despair in PD was 38%.24 The investigators famous that feminine intercourse (danger ratio [RR], 1.16), decrease training stage (SMD), –0.199), and having a mutation of the GBA1 L444P gene have been related to the despair in PD. As well as, longer period of sickness (SMD, 0.094), remedy problems (SMD, 0.487), extra extreme motor signs (SMD, 0.339), postural instability (RR, 1.35), decrease cognitive scores (Mini Psychological State Examination [MMSE], SMD, –0.218; Montreal Cognitive Evaluation] (SMD, –0.356)], extra behavioral signs (SMD, 1.116), extra apathy (RR, 1.67), extra fatigue (RR, 1.35), extra nervousness (RR, 1.37), daytime somnolence (RR, 1.33), and orthostatic hypotension (RR, 1.60) have been additionally related to despair in PD. Out there proof signifies that despair amongst people with PD accelerates the worsening of motor signs, provides to the incapacity because of the sickness, leads to total poorer high quality of life, and is related to better mortality amongst these people.25
Signs of depressive problems that will overlap with these of PD embody psychomotor retardation, restricted have an effect on, fatigue, muscle pressure, gastrointestinal signs, diminished urge for food, decreased sleep, poor focus, and impaired reminiscence.26 Therefore, it’s endorsed that an inclusive method ought to be utilized in making a prognosis of despair in PD when these overlapping signs are current. It might be prudent to give attention to emotional signs slightly than neurovegetative signs when contemplating a prognosis of despair in PD. A Nationwide Institute of Well being—sponsored workshop advisable the next when assessing people with despair in PD: (1) the inclusion of subsyndromal despair in scientific analysis research of despair in PD, (2) the specification of timing of assessments for people with PD with motor fluctuations, and (3) using informants when evaluating for cognitive impairment.27
A prognosis of despair in PD ought to be made utilizing validated scientific standards and structured diagnostic interviews every time attainable to keep away from underdiagnosis.28 Scientific ranking scales will help quantify the signs of despair in these people. Outcomes of a meta-analysis by Goodarzi et al confirmed that the 15-item Geriatric Melancholy Scale had a pooled sensitivity of 0.81 and specificity of 0.91 for detecting despair amongst people with PD.29 The authors additionally discovered that sensitivity and specificity for detecting despair amongst people with PD have been as follows for these screening instruments: the Beck Melancholy Stock (sensitivity of 0.79 and specificity of 0.85), the Montgomery-Åsberg Melancholy Score Scale (sensitivity of 0.77 and specificity of 0.92), and the Unified Parkinson Illness Score Scale (UPDRS; sensitivity of 0.72 and specificity of 0.80).
Outcomes of a meta-analysis of randomized managed trials (RCTs) that included knowledge from 10 research discovered that there was no profit for selective serotonin reuptake inhibitors (SSRIs), compared with placebo amongst people with PD who’ve despair (n = 6; RR, 1.06; P = .67).30 The investigators discovered no distinction in efficacy between SSRIs and tricyclic antidepressants (TCAs) (n = 3; RR, 0.75; P = .37) amongst these people. No distinction between SSRIs and placebo when it comes to tolerability (dropouts, RR, 1.28; P = .45) have been famous. The outcomes have been comparable when evaluating the tolerability of SSRIs vs TCAs (dropouts; RR, 0.96; P = .88) amongst people with PD and despair.
A community meta-analysis of RCTs that in contrast the efficacy and acceptability therapies for despair in PD and included knowledge from 11 research discovered that there’s inadequate proof to assist the efficacy of SSRIs, pramipexole, pergolide, and serotonin norepinephrine reuptake inhibitors (SNRIs) amongst people with PD who’ve despair.31 Moreover, the investigators discovered that TCAs have been extra efficacious than SSRIs, pramipexole, pergolide, and SNRIs. Additionally they famous that TCAs, pramipexole, pergolide, and SNRIs have been higher tolerated than SSRIs amongst these people. Nevertheless, subsequent research point out that SSRIs are evidence-based therapies for despair in PD.
Outcomes of a meta-analysis of 9 RCTs discovered that the pooled impact of antidepressants for despair in PD was reasonable (Cohen d = 0.71) however not vital.32 The investigators famous that the antidepressants confirmed a big (Cohen d = 1 .13) however nonsignificant impact for nervousness amongst people with PD. Additionally they recognized single trials of omega-3 supplementation (Cohen d = 0 .92), and cognitive behavioral remedy (CBT; Cohen d = 1.57) that confirmed giant results for despair in PD.
Outcomes of a meta-analysis by Bomasang-Layno et al that included knowledge from 20 RCTs amongst people with PD and despair discovered that the general SMD for all pharmacologic interventions compared with placebo was 0.30 (P = .054).33 When evaluating antidepressants with placebo, the SMD was 0.54 (P = .000). When evaluating 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 different noninvasive therapies, the general SMD was 0.87 (P = .000). CBT had the biggest impact dimension in 2 research (SMD, 1.24, and SMD, 1.22). Knowledge from 2 repetitive transcranial magnetic stimulation (rTMS) research confirmed that the general SMD was 0.30. Total, the drugs have been nicely tolerated amongst these people with no vital worsening of different PD signs. Sedation was famous with trazodone, memantine, pramipexole, and pergolide. Anticholinergic antagonistic results have been famous with TCAs.
Outcomes of a meta-analysis confirmed that rTMS (n = 3; SMD, –0.86) improved depressive signs compared with sham therapy.34 The investigators didn’t discover any distinction between rTMS and antidepressants within the therapy of depressive signs (n = 3; SMD, –0.12). A second meta-analysis indicated that rTMS (n = 9; SMD, –0.62) improved depressive signs within the quick time period compared with sham therapy.35 The investigators didn’t establish any distinction between rTMS and antidepressants within the short-term therapy of depressive signs (n = 5; SMD, –0.00). The investigators didn’t establish any long-term advantages with using rTMS compared with sham therapy (n = 4; SMD, –0.56). They discovered that rTMS was nicely tolerated within the quick time period compared with controls (antagonistic results: n = 12; RR, 1.05). The investigators discovered that CBT was additionally useful for the short-term therapy of despair amongst people with PD (n = 3; SMD, –1.15).
Outcomes of a meta-analysis of 14 research discovered that electroconvulsive remedy (ECT) improved depressive signs amongst people with PD (n = 6; SMD, 1.33; P < .001).36 ECT additionally improved psychotic signs (n = 5; SMD, 1.64; P < .001), motor signs (n = 13; SMD, 1.18; P < .001, and cognitive operate (n = 6; SMD, 0.21; P = .002) amongst these people.
Proof from these meta-analyses point out that CBT, antidepressants (SSRIs, SNRIs, and TCAs), rTMS, and ECT might profit people with PD who’ve despair, and these therapies are moderately nicely tolerated amongst these people. Primarily based on these knowledge, we’d suggest CBT and antidepressants as first-line therapies for despair in PD. rTMS can be thought-about as 2nd-line therapy, adopted by ECT for extra refractory signs.
Apathy
Apathy is a syndrome characterised by diminished initiative, decreased pursuits, and lack of emotional responsiveness.37 Outcomes of 1 meta-analysis confirmed that the prevalence of apathy amongst people with PD is 39.8%.38 Investigators famous that apathy was related to increased age (3.3 years), decrease imply MMSE scores (–1.4 factors), a better danger of comorbid despair (RR, 2.3), increased UPDRS motor scores (6.5 factors; 95% CI, 2.6-10.3), and better incapacity (Hedges g = 0.5). A meta-analysis of 33 research discovered that deep mind stimulation of the subthalamic nucleus amongst people with PD will increase the chance of growing apathy postoperatively compared with preoperatively (Hedges g = 0.34; P < .001), and with utilizing remedy solely (Hedges g = 0.36; P = .004).39
Amongst people with PD, apathy reduces the responsiveness to therapy for motor signs, worsens high quality of life for the person and their caregivers, will increase price of care, and will increase danger of growing dementia.40 Outcomes of an 18-month longitudinal examine confirmed that people with PD who’ve apathy are at better danger for growing dementia compared with people with PD who would not have apathy (P = .008).41 A meta-analysis of 8 research indicated that people with PD and apathy have decrease scores on world cognitive operate (impact dimension [ES]) –0.40), long-term verbal reminiscence (ES = –0.64), govt functioning together with abstraction capacity/idea formation (ES = –0.63), inhibition (ES = –0.76), generativity (ES = –0.55), processing pace/consideration/working reminiscence (ES = –0.42), and visuospatial and constructional capacity (ES = –0.65).42
Though the definitive mechanisms for improvement of apathy amongst people with PD haven’t but been recognized, the proposed mechanisms embody dysfunction of the basal ganglia, particularly the posterior and anterior cingulate cortices, nucleus accumbens, striatum, and the subthalamic nucleus.40 It has been postulated that imbalances in dopamine might impair the person’s sensitivity to reward, and thereby trigger deficits in decision-making capability. Some have postulated that within the prodromal levels of PD, apathy could also be thought-about an amotivational behavioral syndrome attributable to dopaminergic and serotonergic denervation.43 Nevertheless, in superior circumstances of PD, apathy ought to be thought-about a cognitive dysfunction syndrome attributable to diffuse neurotransmitter system impairments, the development of LB pathology that leads to cognitive decline, and the event of PD dementia.
Outcomes of 1 systematic overview discovered that the self-reported questionnaires—the 5-item model of the World Well being Group Nicely-Being Index (WHO-5) and the Neurasthenia Scale, together with the clinician-administered scales, the Starkstein Apathy Scale (SAS) and the Lille Apathy Score Scale (LARS)—have scientific validity for the evaluation of apathy amongst people with PD.44 The authors indicated that the WHO-5 and the Neurasthenia Scale are helpful for detecting the severity of apathy signs, whereas the SAS can be utilized to exclude the presence of apathy signs or to judge the psychological results of medication. The LARS is a clinically legitimate instrument that can be utilized to diagnose apathy. The authors opined that amongst people with poor perception into their sickness, clinician-rated scales should be used. They concluded that self-reported questionnaires and clinician-administered ranking scales ought to be thought-about as complimentary analysis instruments for the great evaluation of apathy.
In a meta-analysis of three research, investigators discovered that people with PD receiving rotigotine confirmed vital enhancements in signs of apathy (imply distinction [MD], –2.5; P = .002), in contrast with the management group.45 In one other meta-analysis of two research, investigators discovered that dance remedy didn’t profit people with PD and apathy (weighted imply distinction [WMD], 0.07; P = .96).46 A current Bayesian community meta-analysis of 19 research discovered that pharmacotherapy was higher than mind stimulation (SMD, –0.43), exercise-based interventions (SMD, –0.66), dietary dietary supplements (SMD, –0.33), and placebo (SMD, –0.38) in enhancing apathy scores amongst people with PD.47 A pooled evaluation of 11 research confirmed that pharmacotherapy was efficient in enhancing apathy scores (SMD, –0.38; P < .001). There was no distinction in efficacy famous 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.
References
1. Tysnes OB, Storstein A. Epidemiology of Parkinson’s disease. J Neural Transm (Vienna). 2017;124(8):901-905.
2. GBD 2015 Neurological Disorders Collaborator Group. Global, regional, and national burden of neurological disorders during 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol. 2017;16(11):877-897.
3. Dorsey ER, Bloem BR. The Parkinson pandemic-a call to action. JAMA Neurol. 2018;75(1):9-10.
4. Armstrong MJ, Okun MS. Diagnosis and treatment of Parkinson disease: a review. JAMA. 2020;323(6):548-560.
5. Understanding Parkinson’s. Parkinson’s Foundation. Accessed September 27, 2024. https://www.parkinson.org/understanding-parkinsons/statistics
6. Pringsheim T, Jette N, Frolkis A, Steeves TD. The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2014;29(13):1583-1590.
7. Willis AW, Roberts E, Beck JC, et al; Parkinson’s Foundation P4 Group. Incidence of Parkinson disease in North America. NPJ Parkinsons Dis. 2022;8(1):170.
8. Zirra A, Rao SC, Bestwick J, et al. Gender differences in the prevalence of Parkinson’s disease. Mov Disord Clin Pract. 2022;10(1):86-93.
9. Noyce AJ, Bestwick JP, Silveira-Moriyama L, et al. Meta-analysis of early nonmotor features and risk factors for Parkinson disease. Ann Neurol. 2012;72(6):893-901.
10. Cherian A, Divya KP. Genetics of Parkinson’s disease. Acta Neurol Belg. 2020;120(6):1297-1305.
11. Cherian A, Divya KP, Vijayaraghavan A. Parkinson’s disease – genetic cause. Curr Opin Neurol. 2023;36(4):292-301.
12. Rajan S, Kaas B. Parkinson’s disease: risk factor modification and prevention. Semin Neurol. 2022;42(5):626-638.
13. Koeglsperger T, Rumpf SL, Schließer P, et al. Neuropathology of incidental Lewy body & prodromal Parkinson’s disease. Mol Neurodegener. 2023;18(1):32.
14. Poewe W, Seppi K, Tanner CM, et al. Parkinson disease. Nat Rev Dis Primers. 2017;3:17013.
15. Braak H, Del Tredici K, Rüb U, et al. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging. 2003;24(2):197-211.
16. Jellinger KA. Is Braak staging valid for all types of Parkinson’s disease? J Neural Transm (Vienna). 2019;126(4):423-431.
17. DeMaagd G, Philip A. Parkinson’s disease and its management: part 1: disease entity, risk factors, pathophysiology, clinical presentation, and diagnosis. P T. 2015;40(8):504-532.
18. Hu MT. REM sleep behavior disorder (RBD). Neurobiol Dis. 2020;143:104996.
19. Dlay JK, Duncan GW, Khoo TK, et al. Progression of neuropsychiatric symptoms over time in an incident Parkinson’s disease cohort (ICICLE-PD). Brain Sci. 2020;10(2):78.
20. Jones S, Torsney KM, Scourfield L, et al. Neuropsychiatric symptoms in Parkinson’s disease: aetiology, diagnosis and treatment. BJPsych Advances. 2020;26(6):333-342.
21. Macías-García P, Rashid-López R, Cruz-Gómez ÁJ, et al. Neuropsychiatric symptoms in clinically defined Parkinson’s disease: an updated review of literature. Behav Neurol. 2022;2022:1213393.
22. Burchill E, Watson CJ, Fanshawe JB, et al. The impact of psychiatric comorbidity on Parkinson’s disease outcomes: a systematic review and meta-analysis. Lancet Reg Health Eur. 2024;39:100870.
23. Hu M, Cooper J, Beamish R, et al. How well do we recognise non-motor symptoms in a British Parkinson’s disease population? J Neurol. 2011;258(8):1513-1517.
24. Cong S, Xiang C, Zhang S, et al. Prevalence and clinical aspects of depression in Parkinson’s disease: a systematic review and metaanalysis of 129 studies. Neurosci Biobehav Rev. 2022;141:104749.
25. Chikatimalla R, Dasaradhan T, Koneti J, et al. Depression in Parkinson’s disease: a narrative review. Cureus. 2022;14(8):e27750.
26. Marsh L. Depression and Parkinson’s disease: current knowledge. Curr Neurol Neurosci Rep. 2013;13(12):409.
27. Marsh L, McDonald WM, Cummings J, Ravina B; NINDS/NIMH Work Group on Depression and Parkinson’s Disease. Provisional diagnostic criteria for depression in Parkinson’s disease: report of an NINDS/NIMH Work Group. Mov Disord. 2006;21(2):148-158.
28. Gallagher DA, Schrag A. Psychosis, apathy, depression and anxiety in Parkinson’s disease. Neurobiol Dis. 2012;46(3):581-589.
29. Goodarzi Z, Mrklas KJ, Roberts DJ, et al. Detecting depression in Parkinson disease: a systematic review and meta-analysis. Neurology. 2016;87(4):426-437.
30. Skapinakis P, Bakola E, Salanti G, et al. Efficacy and acceptability of selective serotonin reuptake inhibitors for the treatment of depression in Parkinson’s disease: a systematic review and meta-analysis of randomized controlled trials. BMC Neurol. 2010;10:49.
31. Liu J, Dong J, Wang L, et al. Comparative efficacy and acceptability of antidepressants in Parkinson’s disease: a network meta-analysis. PLoS One. 2013;8(10):e76651.
32. Troeung L, Egan SJ, Gasson N. A meta-analysis of randomised placebo-controlled treatment trials for depression and anxiety in Parkinson’s disease. PLoS One. 2013;8(11):e79510.
33. Bomasang-Layno E, Fadlon I, Murray AN, Himelhoch S. Antidepressive treatments for Parkinson’s disease: a systematic review and meta-analysis. Parkinsonism Relat Disord. 2015;21(8):833-842.
34. Hai-Jiao W, Ge T, Li-Na Z, et al. The efficacy of repetitive transcranial magnetic stimulation for Parkinson disease patients with depression. Int J Neurosci. 2020;130(1):19-27.
35. Chen J, He P, Zhang Y, et al. Non-pharmacological treatment for Parkinson disease patients with depression: a meta-analysis of repetitive transcranial magnetic stimulation and cognitive-behavioral treatment. Int J Neurosci. 2021;131(4):411-424.
36. Takamiya A, Seki M, Kudo S, et al. Electroconvulsive therapy for Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2021;36(1):50-58.
37. Maher S, Donlon E, Mullane G, et al. Treatment of apathy in Parkinson’s disease and implications for underlying pathophysiology. J Clin Med. 2024;13(8):2216.
38. den Brok MG, van Dalen JW, van Gool WA, et al. Apathy in Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2015;30(6):759-769.
39. Zoon TJC, van Rooijen G, Balm GMFC, et al. Apathy induced by subthalamic nucleus deep brain stimulation in Parkinson’s disease: a meta-analysis. Mov Disord. 2021;36(2):317-326.
40. Mele B, Van S, Holroyd-Leduc J, et al. Diagnosis, treatment and management of apathy in Parkinson’s disease: a scoping review. BMJ Open. 2020;10(9):e037632.
41. Dujardin K, Sockeel P, Delliaux M, et al. Apathy may herald cognitive decline and dementia in Parkinson’s disease. Mov Disord. 2009;24(16):2391-2397.
42. D’Iorio A, Maggi G, Vitale C, et al. “Pure apathy” and cognitive dysfunctions in Parkinson’s disease: a meta-analytic study. Neurosci Biobehav Rev. 2018;94:1-10.
43. Béreau M, Van Waes V, Servant M, et al. Apathy in Parkinson’s disease: clinical patterns and neurobiological basis. Cells. 2023;12(12):1599.
44. Carrozzino D. Clinimetric approach to rating scales for the assessment of apathy in Parkinson’s disease: a systematic review. Prog Neuropsychopharmacol Biol Psychiatry. 2019;94:109641.
45. Wang HT, Wang L, He Y, Yu G. Rotigotine transdermal patch for the treatment of neuropsychiatric symptoms in Parkinson’s disease: a meta-analysis of randomized placebo-controlled trials. J Neurol Sci. 2018;393:31-38.
46. Zhang Q, Hu J, Wei L, et al. Effects of dance therapy on cognitive and mood symptoms in people with Parkinson’s disease: a systematic review and meta-analysis. Complement Ther Clin Pract. 2019;36:12-17.
47. Mai AS, Lee YS, Yong JH, et al. Treatment of apathy in Parkinson’s disease: a bayesian network meta-analysis of randomised controlled trials. Heliyon. 2024;10(4):e26107.
48. Broen MP, Narayen NE, Kuijf ML, et al. Prevalence of anxiety in Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2016;31(8):1125-1133.
49. Dissanayaka NN, Sellbach A, Matheson S, et al. Anxiety disorders in Parkinson’s disease: prevalence and risk factors. Mov Disord. 2010;25(7):838-845.
50. Dissanayaka NN, White E, O’Sullivan JD, et al. The clinical spectrum of anxiety in Parkinson’s disease. Mov Disord. 2014;29(8):967-975.
51. Hanna KK, Cronin-Golomb A. Impact of anxiety on quality of life in Parkinson’s disease. Parkinsons Dis. 2012;2012:640707.
52. Mele B, Holroyd-Leduc J, Smith EE, et al. Detecting anxiety in individuals with Parkinson disease: a systematic review. Neurology. 2018;90(1):e39-e47.
53. Chen JJ, Marsh L. Anxiety in Parkinson’s disease: identification and management. Ther Adv Neurol Disord. 2014;7(1):52-59.
54. Zhang Q, Yang X, Song H, Jin Y. Cognitive behavioral therapy for depression and anxiety of Parkinson’s disease: a systematic review and meta-analysis. Complement Ther Clin Pract. 2020;39:101111.
55. Ban M, Yue X, Dou P, Zhang P. The effects of yoga on patients with Parkinson’s disease: a meta-analysis of randomized controlled trials. Behav Neurol. 2021;2021:5582488.
56. Hong CT, Tan S, Huang TW. Psychotherapy for the treatment of anxiety and depression in patients with Parkinson disease: a meta-analysis of randomized controlled trials. J Am Med Dir Assoc. 2021;22(11):2289-2295.e2.
