Psychiatric aspects of Parkinson's disease

Sandeep Grover; Mansi Somaiya; Santhosh Kumar; Ajit Avasthi

doi:10.4103/0976-3147.143197

View/Download PDF

Buy Reprints

PDF

Translate this page into:

Review Article

6 (

); 65-76

doi:

10.4103/0976-3147.143197

Psychiatric aspects of Parkinson's disease

Sandeep Grover, Mansi Somaiya, Santhosh Kumar, Ajit Avasthi

Department of Psychiatry, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Address for correspondence: Dr. Sandeep Grover, Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012, India. E-mail: drsandeepg2002@yahoo.com

Licence

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Disclaimer:
This article was originally published by Medknow Publications & Media Pvt Ltd and was migrated to Scientific Scholar after the change of Publisher.

Abstract

Parkinson's disease (PD) is essentially characterized by the motor symptoms in the form of resting tremor, rigidity and bradykinesia. However, over the years it has been recognized that motor symptoms are just the “tip of the iceberg” of clinical manifestations of PD. Besides motor symptoms, PD characterized by many non-motor symptoms, which include cognitive decline, psychiatric disturbances (depression, psychosis and impulse control), sleep difficulties, autonomic failures (gastrointestinal, cardiovascular, urinary, thermoregulation) and pain syndrome. This review evaluates the various aspects of psychiatric disorders including cognitive decline and sleep disturbances in patients with PD. The prevalence rate of various psychiatric disorders is high in patients with PD. In terms of risk factors, various demographic, clinical and treatment-related variables have been shown to be associated with higher risk of development of psychiatric morbidity. Evidence also suggests that the presence of psychiatric morbidity is associated with poorer outcome. Randomized controlled trials, evaluating the various pharmacological and non-pharmacological treatments for management of psychiatric morbidity in patients with PD are meager. Available evidence suggests that tricyclic antidepressants like desipramine and nortriptyline are efficacious for management of depression. Among the antipsychotics, clozapine is considered to be the best choice for management of psychosis in patients with PD. Among the various cognitive enhancers, evidence suggest efficacy of rivastigmine in management of dementia in patients with PD. To conclude, this review suggests that psychiatric morbidity is highly prevalent in patients with PD. Hence, a multidisciplinary approach must be followed to improve the overall outcome of PD. Further studies are required to evaluate the efficacy of various other measures for management of psychiatric morbidity in patients with PD.

Keywords

Non-motor symptoms

Parkinson's disease

psychiatric manifestations

Show Related Articles from PubMed

Introduction

James Parkinson is attributed with rendering the first cogent description of Parkinson's disease (PD). He identified the hallmark features of the illness through descriptions of cases observed in the streets of London as well as his own patients.[1] Over time, PD or idiopathic PD has replaced the original term, paralysis agitans, for the clinical syndrome characterized by resting tremor, rigidity, bradykinesia in association with the specific pathological findings of depigmentation of the substantia nigra as a result of loss of melanin-laden dopaminergic neurons containing eosinophilic cytoplasmic inclusions (Lewy bodies).[1] PD is the second most common chronic neurodegenerative condition in older people especially beyond the age of 60. A number of studies have estimated the prevalence of PD in different countries and the findings of prevalence have varied widely. Studies suggest an incidence and prevalence rate of 1% in people aged above 65 years.[2] Data suggests that the occurrence of PD is significantly lower in Chinese, Japanese and African populations compared to those from Western countries.[3] There is no nationwide epidemiological data on the incidence and prevalence of PD from India. Data from door to door surveys in three different regions of India suggest a low prevalence rate of PD among Indians compared to Western studies.[4] Studies from India also suggest that prevalence of PD is high among Parsi population[5] and prevalence rate is higher in males, in those with family history of PD, in those with history of depression of more than 10 years prior to PD.[6]

Although the definition of PD is based on the presence of motor features, these are just the “tip of the iceberg.” It is now known that in addition to the typical motor symptoms of PD, the clinical picture includes many non-motor symptoms, with behavior problems often being the most common.[7] Many non-motor symptoms have been described that include cognitive declines, psychiatric disturbances (depression, psychosis and impulse control), autonomic failures (gastrointestinal, cardiovascular, urinary, sexual dysfunction, thermoregulation), sleep difficulties, and pain syndrome.[8] In fact it is suggested that in advanced PD, non-motor symptoms dominate the clinical picture and are associated with severe disability, impaired quality of life, and shortened life expectancy.[1 7] Non-motor symptoms like depressive disorders, anxiety disorders, cognitive decline, pain, fatigue, insomnia, and autonomic dysfunction are shown to be associated with poor health-related quality of life of individuals with PD.[4] Although non-motor symptoms greatly influence the health-related quality of life of PD patients, more than 50% of existing non-motor symptoms are not identified in clinical practice.[9] In the advanced stages of disease, non-motor symptoms are major determinants of loss of independence, caregiver strain, and nursing home placement.[10] Among the various non-motor symptoms, psychiatric comorbidity is quite common and disabling. In terms of etiopathogenesis, it is suggested that the non-motor symptoms have the common etiopathogenesis as that of PD or it may be due to medications used for management of PD or as a reaction to the physical illness and its consequences. In most cases it is more often than not multifactorial in origin.[11] In terms of common etiopathogenesis, hypothesis involving various neurotransmitters like dopamine, serotonin and acetylcholine/noradrenaline have been reported for various psychiatric disorders. However, some of the researchers suggest that attempting to understand the etiopathogenesis on the basis of single neurotransmitter may be too simplistic and development of various neuropsychiatric manifestations is related to alteration in many neurotransmitters.[11]

This review attempts to look at the existing information on various psychiatric conditions, like depression, psychosis, anxiety disorders, sleep disturbances and cognitive deficits in patients with PD. The data is organized in the form of epidemiology, risk factors and management of these conditions in patients with PD. For this review we searched the electronic databases of PUBMED, Google Scholar, PsychINFO, Scopus and Ovid. Cross-searches of electronic and hand search of key references yielded other relevant material. To carry out the electronic searches we used the terms of PD, prevalence, incidence, epidemiology, depression, mania, anxiety, psychosis, sleep disturbances, insomnia, hypersomnia, excessive daytime sleepiness, restless leg syndrome, sleep related movement disorders, parasomnias, dementia, mild/minimal cognitive impairment, non-motor symptoms, psychiatric morbidity, impulse dyscontrol, compulsive behavior, dopamine dyscontrol, apathy, anhedonia, suicide, suicidal behavior in various combinations. All the relevant articles were reviewed and the relevant data were extracted. Then the data was organized to mainly understand the epidemiology, risk factors and management of various psychiatric manifestations in patients with PD.

Risk of Parkinson's disease in patients with psychiatric disorders

The influence of mental illness early in life on the subsequent risk of PD and its clinical picture remain obscure. Several studies have identified certain psychiatric illnesses, particularly anxiety, depression and schizophrenia as risk factors for PD.[12] Anxiety has been suggested to be one of the earliest manifestations of PD in several case-control and cohort studies.[13 14]

Depression in Parkinson's disease

Depression has been reported to be very common in patients with PD. In fact the relationship of depression and PD follows a vicious cycle, with the presence of either increasing the risk of other disorder. The risk of PD is patients with depressive disorders have been reported to be more than that seen in general population.[15 16] A large sample retrospective study of a matched cohort of 23,180 participants (4,634 patients with depression and 18,544 control patients), reported that patients with depression were 3.24 times more likely to develop PD compared with the control patients.[17] Another register-based study that had data of 105,416 subjects evaluated the history of depression in patients diagnosed with PD and reported a life time prevalence of depression prior to onset of PD to be 9.2% compared to 4% in the control population and the difference between the two groups was statistically significant and the odds of having depression in patients with PD was 2.5.[18] Few studies have evaluated the incidence of depression in patients with PD and reported the incidence rate to be 1.86-5.1% per year.[19 20]

Overall many studies have evaluated the prevalence of depression in patients with PD.[21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76] Most of these studies are clinic based,[21 22 23 24 25 26 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71] limited to outpatient of single study site,[22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 61 62 63 64 65 66 67 68 73 74 75] cross-sectional in design[21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74] and have evaluated 28-353 patients.[21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73] Other studies have also evaluated the prevalence of depressive disorders in patients with PD in the inpatient setting[21 67] and in population-based study samples.[27 30 31 32 33 34 35 36 37 43 63 69] One multicentric study included 1072 patients from 55 hospitals and evaluated the prevalence of depressive disorders.[76] Many of these studies are based on evaluation of patients for depression by using various structured interview schedules like Composite International Diagnostic Interview (CIDI),[35] structured clinical interview for DSM-IIIR,[29 30 31 36 37 38 44 52 53 54] or have used DSM-IV criteria,[55 58 60 67 68 69] to evaluate the prevalence of depressive disorders. Some studies have relied only on rating scales like Beck Depression Inventory,[40 46 47 50 51 65] Center for Epidemiologic studies - depression scale,[28 45] Hospital Anxiety and depression scale,[49] Zung self-rated depression scale[62] and Geriatric depression rating scale.[39 56 63 66] Although studies have varied in the reporting of depression, these studies have reported prevalence rates of major depression, minor depression, dysthymia and clinically relevant depressive symptoms. The prevalence rates have varied from 2.7% to 55.6%[25 26 27 28 29 30 31 32 33 34 35 36 37 38 42 43 44 52 53 54 55 56 57 58 59 67 68 69 70 71 72 73] for major depression, 13% to 34.5%[25 26 54 67 70 71 72] for minor depression and 2.2% to 31.3%[22 29 34 35 36 52 57 58 72] for dysthymia. The prevalence rate of clinically significant depressive features has varied from 2.7% to 89%.[21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 72 73 74] The very high rate, i.e. 89% was reported in one of the old studies involving the inpatients.[26] In general prevalence rates in the community samples have been in the lower range, varying between 2.7% and 13%,[27 30 31 32 33 35 37 43 63] but these are still higher than the rates seen in reference population. One meta-analysis that included 10 studies reported the prevalence rate for major depression (24.8%), minor depression (36.6%) and dysthymia (22.5%).[72]

Various risk factors for development of depression in patients with PD include advanced/more severe disease,[34 49 56 69 70 71 72] anxiety,[72] cognitive impairment,[23 24 25 26 27 28 29 30 31 32 39 56 62 67 69 70 71 72 73] psychosis,[32 60 72] longer duration of illness,[69 70 71] early and late stage of disease,[25] motor disability,[32 34] bradykinesia,[36 39 73] akinetic-rigid type of PD,[36] dystonia,[57] presence of tremor,[23] presence of motor fluctuations,[32 69] more evidence of atypical parkinsonism,[32] gait and balance impairment,[31 39 73] more alexithymia,[67] younger age,[32] higher daily doses of levodopa,[23 32 48] presence of sleep disorders,[32 33 48] restless leg syndrome[55] and female gender.[56] When compared to drug naïve patients those on antiparkinsonian medications have higher rates of depression (75.5% versus 59.2%).[76] In term of impact of depression, studies have consistently shown deterioration of scores on activities of daily living.[25 26 32 34 69]

With regards to treatment of depression in patients with PD, few randomized controlled trials (RCTs) have evaluated the efficacy of various antidepressant medications. The various RCTs have evaluated the efficacy of selective serotonin reuptake inhibitors (sertraline, citalopram, fluoxetine, paroxetine, and fluvoxamine), tricyclic antidepressants (TCAs), pramiprexole and repetitive transcranial magnetic stimulation (rTMS). One meta-analysis, which included 10 RCTs (6 compared SSRIs with placebo; 5 compared SSRIs with TCAs, 1 compared with rTMS and 1 compared SSRIs with pramiprexole) reported that the response rate for SSRIs to be 36%, which was not different from that seen with placebo (34%). When the response rate of SSRIs was compared with TCAs, the response rate for TCAs was higher than SSRIs (57% versus 41%).[77] Another recent meta-analysis that included 11 RCTs calculated the odds ratio for the efficacy of various agents. In this meta-analysis when TCAs were used as the comparison arm, the odds ratio for efficacy of SSRIs was -0.69 (95% CI -1.28 to -0.10). The odds ratio for pramiprexole was -0.73 (95% CI -1.71 to -0.26), pergolide was -1.97 (95% CI -3.67 to 0.27) and for serotonin nor-epinephrine reuptake inhibitors (SNRIs) was SNRIs -0.86 (95% CI -1.86 to 0.15) and that of placebo was -1.24 (95% CI -1.99 to -0.50). When compared with placebo the odds ratio for TCAs was 1.24 (95% CI 0.50 -1.99), SSRIs was 0.55 (95% CI -0.03 to1.13), pramiprexole 0.51 (95% CI -0.12 to 1.15), pergolide -0.73 (95% CI -0.25 to 0.80) and that of SNRIs 0.38 (95% CI -0.42 to 1.19). On the basis of these findings, the authors concluded that the evidence does not support the use of SSRIs, pramiprexole, pergolide and SNRIs as antidepressants in patients with PD. In this meta-analysis when the acceptability of various antidepressants was evaluated, the authors found that TCAs, pramiprexole, pergolide and SNRIs are more tolerated than the SSRIs. Accordingly the authors suggested that TCAs should preferably be used for management of depression in patients with PD.[78] Data also supports the use of ECT for depression in patients with PD. A review of studies published during 1975 to 1990 reported that in 21 studies, 70% of PD patient's showed improvement in psychiatric disturbances (including depression) and 50% patients showed improvement in PD symptoms too.[79] Reports published after 1990 also have reported the beneficial effect of ECT in both symptoms of depression and PD per se.[80 81] However, these studies suggest high rates of transient inter-treatment delirium necessitating the postponement/termination.[80 81] An occasional open-label study has also evaluated the beneficial effect of cognitive behavior therapy for management of depression in patients with CBT and report significant improvement in the Hamilton Depression Rating Scale scores.[82 83 84 85] Other studies have shown that caregiver participation and executive functioning predict the response to CBT in patients with PD.[85] A recent meta-analysis evaluated the effect of deep brain stimulation (DBS) on depressive and anxiety symptoms in PD patients. The authors concluded that DBS, especially that is focused on the subthalamic nucleus (STN) is useful in management of depressive symptoms in short term; however, the effect wanes off with time.[86] There is some evidence to support the use of rTMS for management of depression in patients with PD.[87]

Based on available evidence for depression in patients with PD and that for management of depression per se some of the authors have suggested certain steps in the management of depression. At the first step, whenever a patient with PD presents with depression there is a need to assess the relationship of depression with medications used for the management of PD and if required dose of anti-parkinsonian medications should be adjusted. If this does not help then based on the severity of depressive symptoms, treatment strategies must be selected. If a patient has only mild depression, use of psychotherapeutic interventions like supportive psychotherapy or cognitive behavior therapy should be used as the first-line treatment. For moderate depression one of the antidepressants or CBT can be considered and in patients with severe depression additionally ECT should be considered as an option.[88] Although TCAs are found to be most efficacious, some authors recommend cautious use of TCAs because of the anticholinergic side effects. However, the recent Movement Disorder Society (MDS) Task Force on Evidence-Based Medicine (EBM) Review of Treatments for PD suggests that new studies have not suggested any safety concerns with regards to use of TCAs in patients with PD.[89] In general, it is suggested that TCAs antidepressants with least sedative properties and little anticholinergic effects, like desipramine and nortriptyline, should be used, as the evidence supports their efficacy in patients with PD.[89 90] ECT is recommended in patients with severe depression who are suicidal and those who cannot wait for the required time for the treatment response through medications.[90]

Anxiety disorders in Parkinson's disease

Anxiety disorders are also highly prevalent in patients with PD with a range of 19.8% to 67%.[91] In general studies that have relied upon rating scales/questionnaire[92 93 94] report higher prevalence of anxiety disorders, compared to those that are based on the structured clinical interviews.[58 95 96] Studies that have compared the prevalence of clinically significant anxiety symptoms with age-matched controls have reported significantly higher prevalence in those with PD.[97] Some authors have attempted to categorize anxiety symptoms/disorders in patients with PD into primary anxiety disorder, anxiety secondary to other psychiatric comorbidities (e.g. depression, psychosis), anxiety secondary to the use of antiparkinsonian medications (e.g. levodopa, pergolide etc), anxiety secondary to fluctuation of motor symptoms (on/off periods), anxiety as a prodromal symptom of PD and anxiety secondary to the impairment and limitations caused by PD.[98] The most common anxiety disorders in patients with PD are panic disorder,[58] generalized anxiety disorder, and social phobia.[58 95] However, some authors suggest that anxiety disorder not otherwise specified (NOS) to be the most common type of anxiety disorder in patients with PD.[98] Although few studies suggest a correlation of higher level of anxiety with left-sided lesions, but most studies report no relationship between severity of motor symptoms and levels of anxiety.[99 100] Other risk factors reported for anxiety disorder/symptoms in patients with PD include female gender,[93] younger age,[93] young onset PD,[95] more depressive symptoms,[93] worst sleep quality,[93] severity of PD,[96] postural instability,[96] gait dysfunction,[96] higher rates of motor fluctuations,[95] morning dystonia,[95] symptom clustering and experience of dyskinesia.[96]

There are no controls or definitive studies that have evaluated various antianxiety medications for management of anxiety disorders in patients with PD. However, studies that have evaluated the effect of antidepressants and other modalities in patients with depression have assessed the effect of these interventions on anxiety symptoms. Thus, the recommendations are usually based on the data available for elderly populations without PD. However, certain issues must be kept in mind while evaluating and managing anxiety in patients with PD. Since some antiparkinsonian medications may be associated with the presence or variations of anxiety symptoms, it is extremely important to adjust the dose and to be aware of the effects of the medications used for the treatment of PD, with replacement of the medication when the anxiety symptoms are not tolerated. In addition, the control of motor fluctuations is indispensable for a better evaluation of anxiety symptoms. Specific anxiety disorders should be investigated based on the clinical characteristics of the anxiety symptoms, since different anxiety disorders have peculiarities that should be considered both at diagnosis and during treatment. In patients who suffer panic attacks during off periods, treatment should be directed at reducing time off by adjusting the dose of the antiparkinsonian medication. Among the various antianxiety medications, SSRIs are considered to be the first line of treatment. Other options include TCAs and benzodiazepines. However, in general it is suggested to avoid these medications in elderly and when used should be used for the minimum possible period of time and at the lowest possible dose. Benzodiazepines are known to increase the risk of falls and fractures in the elderly population and are associated with a greater cognitive decline at high doses. Further, benzodiazepines may be related to the worsening of parkinsonian symptoms and they may also lead to abuse and dependence.[101] Non-pharmacological measures like psychoeducation, relaxation practices, sleep hygiene, and social measures for adaptation to PD can also be tried. There is some evidence to suggest the usefulness of cognitive behavior therapy, DBS and rTMS in management of anxiety symptoms associated with depression in patients with PD.[83 84 85 86 87 102]

Psychosis in Parkinson's disease

Psychosis is generally not considered as a primary symptom of idiopathic PD, although there are case reports of psychosis in patients with PD from the pre-levodopa era.[103] The inability to reliably discriminate post-encephalitic Parkinsonism from idiopathic PD and the lack of recognition of the numerous parkinsonian disorders that are not idiopathic PD make these reports suspect. In fact some authors suggest that the occurrence of psychotic symptoms in an untreated PD patient constitutes an “atypical” feature and cast doubt on the diagnosis.[104]

However, in recent times many studies have evaluated the prevalence of psychosis in patients with PD.[105 106 107 108 109 110 111 112 113 114 115 116 117] The time frames that have been considered by these studies have varied from last 1 week to last 6 months.[104 106 107 108 109 110 111 114 115 116 117] Some of these studies have concentrated just on evaluation of hallucination[50 105 108 112 114 117] whereas others evaluated other psychotic symptoms also along with hallucinations.[104 116 109 110 115 116] Some of the studies have relied on questionnaires like hallucination questionnaire,[105] Queen Square Visual Hallucination Inventory,[116] University of Miami Parkinson's disease hallucinations questionnaire[117] to evaluate the prevalence of psychosis, whereas some have used DSM-IV criteria to study the prevalence of psychosis.[104 110 112 115] The sample size of these studies has varied from 70 to 422 subjects[104 105 107 108 109 110 111 112 114 115 116 117] and most of these studies have a followed-up prospective study design[93 94 95 96 97 98 99 100 102 103 104 105] with an occasional retrospective study.[104 108] Most of these studies recruited participants from the patient population attending the movement disorder clinics[104 105 106 107 108 109 110 111 112 114 115 116 117] with occasional studies based on the community-based population.[50 108] The prevalence of psychosis (or visual hallucinations) in these studies has varied from 15.8% to 75%.[104 105 106 107 108 109 110 111 112 113 114 115 116 117] A 12-year longitudinal follow-up study that evaluated PD-associated psychosis (PDP) on the basis of rating of 2 or more on the Unified Parkinson Disease Rating Scale thought disorder (UPDRS-TD) item 2 or those taking antipsychotic drugs reported development of hallucinations and delusions in 60% of patients. The incidence rate of PDP was 79.7 per 1000 person-years.[118] Among the various psychiatric symptoms, visual hallucinations have been reported to be the most common symptoms with a prevalence rate of 16-38%.[104 105 106 107 108 109 110 115 116 117] Studies that have evaluated other symptoms have reported prevalence of auditory hallucinations to be 0-22%,[104 105 106 107 108 109 110 111 114 115 116 117] delusions to be 1-14%[104 106 110 115] and other minor psychotic symptoms to be 17.4-72%.[109 115 116] The risk factors associated with development of psychosis/hallucinations in patients with PD include cognitive decline (dementia, Mini-Mental State Examination scores of ≤24, global cognitive impairment),[104 105 106 107 108 109 110 111 112 114 115] age,[105 108 115] age of onset of motor symptoms,[112] longer duration of disease,[105 109 115 116] history of depression,[105] or history of sleep disorder,[105] modified Hoehn-Yahr stage of ≥4,[116] postural instability,[106] rapid progression of the motor component of the disease,[106] severity of motor symptoms,[115] treated with a direct-acting dopamine receptor agonist,[106] higher depressive score,[108 109 110] comorbid affective disorders,[104] daytime somnolence,[109] worse visual acuity,[110] higher severity of illness,[110] positive family history of dementia[114] and presence of REM (rapid eye movement) sleep behavior disorders.[115] In the longitudinal follow-up study risk factors for development of psychosis were higher age at onset, higher baseline levodopa-equivalent doses, probable REM sleep behavior disorder (RBD) at baseline, and follow-up time were independent risk factors of incident PDP.[118]

In terms of management of psychosis in patients with PD, first step involves evaluation for delirium and relationship of psychosis with antiparkinsonian medications. If the patient does not have delirium and the psychosis is possibly related to use of antiparkinsonian medications then efforts should be made to reduce these medications. In this regard, if the patient is on multiple antiparkinsonian agents, efforts should be made to reduce the drugs to the lowest effective dose, in the order of anticholinergics, selegiline, amantadine, dopamine receptor agonists, catechol-O-methyltransferase inhibitors and lastly levodopa. However, if reduction in anti-PD medications to the lowest dose tolerable without exacerbation of motor symptoms doesn't improve psychosis, use antipsychotic medications is warranted. Studies have evaluated the efficacy of various atypical antipsychotic, i.e. clozapine, olanzapine, risperidone and quetiapine in patients with PD (for review see).[89] Based on the evidence, clozapine is considered to be the best choice for management of psychosis in patients with PD.[89]

Cognitive deficits in Parkinson's disease

Dementia is quite common in PD, especially in the late stages.[119] Cognitive impairment of a lesser severity is also common in patients with PD without dementia, designated as mild cognitive impairment (MCI) of PD, or PD-MCI.[120 121] Patients with PD with MCI have an increased risk of developing dementia, compared with those without.[119 120] Many studies have evaluated the prevalence of MCI in patients with PD.[119 120 122 123 124 125 126] However, these studies have differed in the definition of MCI. Further some of these studies have evaluated the incident cohorts[119 122 123 125] and other has evaluated MCI in prevalence cohorts[120 124 125 126] in samples drawn from community population,[119 122 123 124] with occasional clinic-based studies.[120 124 125 126] Sample sizes of these studies has varied from 72 to 1346[119 120 122 123 124 125 126] and the prevalence rate of MCI has varied from 18.9% to 55%.[119 120 122 123 124 125 126] The risk factors identified in these studies to be related to MCI were male gender,[125] increasing age,[124 125] higher UPDRS motor scores,[120 122 125] higher disease severity,[124 125] lower premorbid intelligence quotient,[122] lower educational level,[123] longer duration of illness,[120 126] use of anti-anxiety medications,[124] increasing severity of daytime sleepiness,[124] depression,[125] higher postural instability and gait disorder.[126]

As with other abnormalities, the prevalence rate of dementia in PD is also variable.[119 121 127 128 129 130 131 132 133 134] In a systematic review of literature, authors reported the point prevalence of dementia in PD to be 31.3% and the incidence rate is increased four to six times as compared to controls. The cumulative prevalence is very high with at least 75% of PD patients who survive for more than 10 years developing dementia. The mean time from onset of PD to dementia is approximately 10 years.[119] The most established risk factors for early dementia are old age,[119 121 125 127 128 129 130 131 132 133] severity of motor symptoms,[127 128] in particular postural and gait disturbances,[119 127 128] MCI[119 121 125 127 128 129 130 131 132 133] and visual hallucinations.[119 127 128]

Data suggests that the cognitive profile of PD dementia may be different from that of Alzheimer's dementia. Patients with PD dementia have higher dysfunction in the domains of attention, executive and visuo-spatial functioning with lesser involvement of memory and language. Many of the cognitive deficits observed in PD patients resemble impairments demonstrated by patients with damage to the frontal lobes.[121 128]

Management of dementia associated with PD involves making the correct diagnosis after excluding the other causes of dementia. In terms of treatment, studies have evaluated the efficacy of donepezil, rivastigmine, galantamine and memantine.[89] Of these agents, only rivastigmine has been conclusively found to be efficacious in dementia associated with PD.[89]

Sleep disorders in Parkinson's disease

Sleep disorders are very common in patients with PD and have a significant negative impact on their quality of life.[135] The sleep-related problems in patients with PD can be broadly classified into daytime manifestations, nocturnal sleep disturbance, sleep-related movement disorders and parasomnias. The daytime sleep manifestations include excessive daytime sleepiness (EDS). The nocturnal sleep disturbances include insomnia and obstructive sleep apnea. The common sleep-related movement disorder include restless leg syndrome. The common parasomnias include RBD. As with depression and anxiety disorders, sleep disorders are also reported to increase the risk of development of PD in the later life.[136 137 138 139 140 141] A longitudinal population-based prospective study reported increased risk of PD in patients with EDS. This risk persists after controlling for various confounders like mid-life cigarette smoking and coffee drinking, bowel movement frequency, cognitive functions, depressed mood, and insomnia. Overall, EDS was associated with a three-fold increase in the risk of developing PD.[137] Clinic-based studies that have looked at the risk of developing PD in patients with sleep disorder have mainly focused on RBD and these studies suggest that when the patients with RBD are followed over the period, 16-65% of patients develop PD[138 139 140 141] and the incidence of PD increases with longer follow-up duration.[138 139 140 141]

Many population-based studies have evaluated the incidence of sleep disorders in patients with PD.[142 143 144 145] These studies suggest that about 50% of patients have insomnia,[142 144] 14.7% have RBD[142] and 8% have EDS.[145] When the cohorts were followed up, it was seen that the incidence of sleep disorders increased with progress and increasing duration of PD.[74 146 147 148 149] Among the various types of sleep disorders, usually the frequency of EDS and RBD increases[142 144 145 146 149] but that of insomnia is reported to be relatively stable.[74 143] However, clinic-based studies have not come up with such consistent findings.[150 151 152 153] The risk factors that have been reported to be associated with onset of sleep disorder in patients with PD include older age,[144 145 152] male gender,[142 145] use of higher doses of dopaminergic drugs,[142 144 152] presence of cognitive impairment[144 145] and presence of hallucinations.[142 144 148]

Studies that have evaluated the prevalence of various sleep disorders in patients with PD have come up with varying rates, mainly because of different methods of ascertainment. Some of these studies are population based,[142 143 144 145] whereas others have focused on clinic attending population.[45 146 147 148 149 150 151 152 153] These studies suggest that the prevalence of EDS vary from 15% to 87%,[45 146 147 148 150 151 153] insomnia vary from 40% to 50%,[143 153] restless leg syndrome vary from 0% to 50%[144 145 153] and that of RBD varies from 25% to 50% in patients with PD.[142 146 149]

The presence of sleep disorder, especially multiple sleep disorders is known to predict other symptoms of PD.[154] A cross-sectional study suggested that the presence of at least two sleep disorders predicted significantly higher more overall non-motor symptoms, higher scores on the individual measures of multiple symptoms, quality of life, fatigue, depression and cognitive decline.[146] Studies also suggest that the presence of subjective insomnia is independently associated with depressed mood (odds ratio [OR] =1.79), autonomic symptoms (OR = 1.77), fatigue (OR = 1.19), and age (OR = 0.61). Subjective daytime sleepiness is reported to be associated with dosage of dopaminergic medication (OR = 1.74) and fatigue (OR = 1.14).[155]

Management of sleep disorders involves proper diagnosis. Accordingly, for proper diagnosis it is important to obtain a proper history from the patient and the bed partner. Besides this patient may have to undergo investigations like polysomnography, actigraphy and multiple sleep latency test.[156 157 158] Once the diagnosis is made there is a need to look for the cause that involves review of patient's medications, comorbid conditions and sleep hygiene. It is important to know that in small doses, levodopa may improve the sleep, however, in higher doses it may be associated with impairment in sleep. Other antiparkinsonian agents have also been implicated in development of confusion that may exacerbate sleep problems. Excessive daytime sedation can be caused by dopaminergic drugs–with dopamine agonists than with levodopa that is dose dependent. EDS may occur when dopamine agonist dose is increased. Dopaminergic agents have also been shown to influence the REM sleep.[156]

Once the diagnosis is made, depending on the sleep disorder, sleep hygiene should be used as the first line of treatment. In terms of pharmacological management although the studies have evaluated the efficacy of dopaminergic agents, pergolide, eszopiclone, and melatonin, etc., the evidence is not sufficient to recommend these medications.[89] For EDS, studies have evaluated the usefulness of modafinil, but these studies do not suggest that modafinil is more efficacious than placebo.[89] Clonazepam is recommended as the first-line agent for management of RBD, although there are no RCTs for the use of the same.[156] For RLS too, there is lack of data from the RCTs. However, there is some evidence to support the use of long-acting dopamine agonist like cabergoline that may be effective.[159 160]

Anhedonia in Parkinson's disease

Although anhedonia is understood as a symptom of depression in patients with PD, studies suggest that it may be characteristic of PD itself which could be due to the dysfunction of the dopamine reward pathway in the mesolimbic area.[161] Studies that have evaluated the prevalence of anhedonia have reported a range of 7% to 45.7%. With regards to the prevalence of anhedonia and depression, studies suggest a strong correlation between the two; however, in many patients anhedonia is present in the absence of depression.[162 163 164 165 166 167] Studies also suggest an association between anhedonia and apathy.[164] Studies are inconclusive with regard to the relationship of anhedonia with severity of motor symptoms.[168] With regards to management of anhedonia, which is independent of depression, no studies have specifically evaluated the efficacy of any pharmacological agent.

Apathy in Parkinson's disease

Apathy is understood as a “reduced interest and participation in normal purposeful behavior, lack of initiative with problems in initiation or sustaining an activity to completion, lack of concern or indifference and a flattening of affect.”[169] Many studies have evaluated the prevalence of apathy in patients with PD using different scales and have reported a prevalence rate of 16.5-70%, depending on the assessment procedure and the study population.[164 169 170 171 172 173 174] Evidence suggests that apathy in PD is not related to depression, anxiety, severity of motor symptoms.[164 169] However, some of the recent studies suggest high level of comorbidity between apathy and depression in patients with PD.[175] However, some studies suggest that apathy may be a side effect of DBS[176 177] and other suggest that apathy in PD is determined by the level of cognitive impairment.[178] Recent evidence suggests that in non-depressed non-demented patients, apathy may in fact be a predictor of cognitive decline and dementia in PD.[178]

Impulsive-compulsive disorders in PD

Many studies have reported high rate of impulsive compulsive disorders (ICD) in patients with PD. These disorders are suggested to arise from aberrant or excessive dopamine receptor stimulation. Recent studies that have reported the cumulative life time prevalence of Impulsive compulsive disorders in patients with PD have reported a prevalence rate of 35.9 to 60%.[178 179] These rates are much higher than those reported for individual disorders in the older studies as reviewed by Evans, et al.[180] The prevalence of various ICD in patients with PD has been reviewed by Evans, et al.[180] and the rates for pathological gambling has been reported to be 2.3% to 9.3% and that of hypersexuality is reported to vary from 0.9% to 13%. Evidence also suggests that the rates of ICDs are higher in those receiving dopaminergic agents, especially direct D2/D3 dopamine agonists and reduction or resolution of ICDs with reduction or discontinuation of dopaminergic agents.[181]

The factors associated with pathological gambling include younger age of onset, higher scores on impulsive sensation seeking personality traits, personal or immediate family history of alcohol use disorders, use of dopamine agonist agents, dose of dopamine agonists and duration of dopamine agonist therapy.[178 180] The risk factors for hypersexuality in PD include male gender, early age of onset, use of dopamine agonist agents and depression.[180] The rate for compulsive buying has been reported to vary from 0.4% to 5.7% and that of Binge eating disorder to be 4.3%.[180] The rates of punding have varied from 1.4% to 8%.[180] The risk factors that have been identified to be associated with punding include younger age of onset for PD, high impulsivity, poor quality of life and use of dopamine receptor agonists.[180]

Dopamine dysregulation syndrome

Data suggest that few patients of PD develop addiction to dopamine agonist drugs. This is known as dopamine dysregulation syndrome (DDS). The prevalence for this syndrome is reported to be 3-4% among patients attending specialist PD centers.[180] Problems with decision making are thought to be responsible for addictive behaviors. The risk factors for DDS include younger age of onset, longer duration of illness, use of higher dose of dopaminergic agents, history of past experimental drug use, higher depressive symptoms, high level of impulsivity and history of alcohol intake.[181] Studies also suggest that DDS, ICDs and punding often coexist in PD receiving dopaminergic agents.[181 182]

Suicidal behavior in Parkinson's disease

Suicidal behavior includes suicidal ideations, suicidal gestures, attempted suicide and completed suicide. Compared to other aspects, little information is available about suicidal behavior in patients with PD. A longitudinal follow-up study of 8 years duration reported the risk of death in patients with PD due to suicide to be 5.3 times higher than expected.[183] Studies that have evaluated suicidal behaviors have reported rates of suicidal ideations/death in patients with PD to vary from 22.7% to 30%.[183 184 185] The risk factors for suicidal ideations/death include depression, anxiety, hopelessness, level of education level, age of onset of PD, duration of illness, and history of impulse-control disorder (ICD).[183] The odds ratio for suicidal ideation/death in patients with PD for different risk factors are 4.6 to 5.9 (depression), 2.45 to 19.2 (psychosis), 1.2 (hopelessness), 2.92 (severity of depression) and 4.97 to 6.08 (impulse control disorder) in various studies.[183 185] Other studies have reported increased risk for suicidal ideations with increasing severity of depression with odds ratio of 2.92.[185]

Conclusion

Existing data suggest that PD should not be considered only as a motor disorder. In addition to the motor symptoms, patients with PD have very high prevalence of non-motor symptoms. Among the various non-motor symptoms, psychiatric manifestations are very common and are associated with impairment in quality of life and higher treatment costs. Hence, there is a need to identify these symptoms and treat them adequately to optimize the outcome of patients with PD. Comprehensive management of PD calls for an inter-disciplinary approach that should include mental health professionals. From the psychiatrist point of view, it is important to understand that various psychiatric manifestations in patients with PD may be due to the same neuro-degenerative process that is responsible for the motor symptoms; additionally the psychiatric symptoms may be associated with the medications used for management of motoric symptoms of PD. In terms of future research, there is a need to improve understanding about some of the phenomena like ICDs, apathy and anhedonia. Existing data also suggest that there are only very few RCTs that have evaluated the efficacy of various psychotropics and various psychological treatments in the management of various psychiatric manifestations of PD and there is an urgent need to expand the literature.

Source of Support: Nil.

Conflict of Interest: None declared.

References

Samii A, Nutt JG, Ransom BR, . Parkinson's disease. Lancet. 2004;363:1783-93.
[Google Scholar]
Van Den Eeden SK, Tanner CM, Bernstein AL, Fross RD, Leimpeter A, Bloch DA, . Incidence of Parkinson's disease: Variation by age, gender, and race/ethnicity. Am J Epidemiol. 2003;157:1015-22.
[Google Scholar]
de Lau LM, Koudstaal PJ, Hofman A, Breteler MM, . Parkinson disease is more prevalent than people think. Research results. Ned Tijdschr Geneeskd. 2009;153:63-8.
[Google Scholar]
Das SK, Biswas A, Roy T, Banerjee TK, Mukherjee CS, Raut DK, . A random sample survey for prevalence of major neurological disorders in Kolkata. Indian J Med Res. 2006;124:163-72.
[Google Scholar]
Yadav R, Shukla G, Goyal V, Singh S, Behari M, . A case control study of women with Parkinson's disease and their fertility characteristics. J Neurol Sci. 2012;319:135-8.
[Google Scholar]
Sanyal J, Chakraborty DP, Sarkar B, Banerjee TK, Mukherjee SC, Ray BC, . Environmental and familial risk factors of Parkinsons disease: Case-control study. Can J Neurol Sci. 2010;37:637-42.
[Google Scholar]
Fernandez HH, . Nonmotor complications of Parkinson disease. Cleve Clin J Med. 2012;79(Suppl 2):S14-8.
[Google Scholar]
Modugno N, Lena F, Di Biasio F, Cerrone G, Ruggieri S, Fornai F, . A clinical overview of non-motor symptoms in Parkinson's disease. Arch Ital Biol. 2013;151:148-68.
[Google Scholar]
Weintraub D, Comella CL, Horn S, . Parkinson's disease-Part 1: Pathophysiology, symptoms, burden, diagnosis, and assessment. Am J Manag Care. 2008;14(Suppl):S40-8.
[Google Scholar]
Aarsland D, Larsen JP, Tandberg E, Laake K, . Predictors of nursing home placement in Parkinson's disease: A population-based, prospective study. J Am Geriatr Soc. 2000;48:938-42.
[Google Scholar]
Thanvi BR, Munshi SK, Vijaykumar N, Lo TC, . Neuropsychiatric non-motor aspects of Parkinson's disease. Postgrad Med J. 2003;79:561-5.
[Google Scholar]
Lin HL, Lin HC, Chen YH, . Psychiatric diseases predated the occurrence of Parkinson disease: A retrospective cohort study. Ann Epidemiol. 2014;24:206-13.
[Google Scholar]
Bower JH, Grossardt BR, Maraganore DM, Ahlskog JE, Colligan RC, Geda YE, . Anxious personality predicts an increased risk of Parkinson's disease. Mov Disord. 2010;25:2105-13.
[Google Scholar]
Weisskopf MG, Chen H, Schwarzschild MA, Kawachi I, Ascherio A, . Prospective study of phobic anxiety and risk of Parkinson's disease. Mov Disord. 2003;18:646-51.
[Google Scholar]
Leentjens AF, Van den Akker M, Metsemakers JF, Lousberg R, Verhey FR, . Higher incidence of depression preceding the onset of Parkinson's disease: A register study. Mov Disord. 2003;18:414-8.
[Google Scholar]
Schuurman AG, van den Akker M, Ensinck KT, Metsemakers JF, Knottnerus JA, Leentjens AF, . Increased risk of Parkinson's disease after depression: A retrospective cohort study. Neurology. 2002;58:1501-4.
[Google Scholar]
Shen CC, Tsai SJ, Perng CL, Kuo BI, Yang AC, . Risk of Parkinson disease after depression: A nationwide population-based study. Neurology. 2013;81:1538-44.
[Google Scholar]
Leentjens AF, Van den Akker M, Metsemakers JF, Troost J, . The incidence of Parkinson's disease in the Netherlands: Results from a longitudinal general practice-based registration. Neuroepidemiology. 2003;22:311-2.
[Google Scholar]
Dooneief G, Mirabello E, Bell K, Marder K, Stern Y, Mayeux R, . An estimate of the incidence of depression in idiopathic Parkinson's disease. Arch Neurol. 1992;49:305-7.
[Google Scholar]
Kulkantrakorn K, Jirapramukpitak T, . A prospective study in one year cumulative incidence of depression after ischemic stroke and Parkinson's disease: A preliminary study. J Neurol Sci. 2007;263:165-8.
[Google Scholar]
Mindham RH, . Psychiatric symptoms in Parkinsonism. J Neurol Neurosurg Psychiatry. 1970;33:188-91.
[Google Scholar]
Santamaria J, Tolosa E, Valles A, . Parkinson's disease with depression: A possible subgroup of idiopathic parkinsonism. Neurology. 1986;36:1130-3.
[Google Scholar]
Mayeux R, Marder K, Cote LJ, Denaro J, Hemenegildo N, Mejia H, . The frequency of idiopathic Parkinson's disease by age, ethnic group, and sex in northern Manhattan, 1988-1993. Am J Epidemiol. 1995;142:820-7.
[Google Scholar]
Brown RG, MacCarthy B, . Psychiatric morbidity in patients with Parkinson's disease. Psychol Med. 1990;20:77-87.
[Google Scholar]
Starkstein SE, Preziosi TJ, Forrester AW, Robinson RG, . Specificity of affective and autonomic symptoms of depression in Parkinson's disease. J Neurol Neurosurg Psychiatry. 1990;53:869-73.
[Google Scholar]
Starkstein SE, Mayberg HS, Leiguarda R, Preziosi TJ, Robinson RG, . A prospective longitudinal study of depression, cognitive decline, and physical impairments in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry. 1992;55:377-82.
[Google Scholar]
Hantz P, Caradoc-Davies G, Caradoc-Davies T, Weatherall M, Dixon G, . Depression in Parkinson's disease. Am J Psychiatry. 1994;151:1010-4.
[Google Scholar]
Tison F, Wenning GK, Daniel SE, Quinn NP, . The pathophysiology of parkinsonism in multiple system atrophy. Eur J Neurol. 1995;2:435-44.
[Google Scholar]
Starkstein SE, Sabe L, Petracca G, Chemerinski E, Kuzis G, Merello M, . Neuropsychological and psychiatric differences between Alzheimer's disease and Parkinson's disease with dementia. J Neurol Neurosurg Psychiatry. 1996;61:381-7.
[Google Scholar]
Aarsland D, Tandberg E, Larsen JP, Cummings JL, . Frequency of dementia in Parkinson disease. Arch Neurol. 1996;53:538-42.
[Google Scholar]
Tandberg E, Larsen JP, Aarsland D, Cummings JL, . The occurrence of depression in Parkinson's disease. A community-based study. Arch Neurol. 1996;53:175-9.
[Google Scholar]
Tandberg E, Larsen JP, Aarsland D, Laake K, Cummings JL, . Risk factors for depression in Parkinson disease. Arch Neurol. 1997;54:625-30.
[Google Scholar]
Tandberg E, Larsen JP, Karlsen K, . A community-based study of sleep disorders in patients with Parkinson's disease. Mov Disord. 1998;13:895-9.
[Google Scholar]
Liu CY, Wang SJ, Fuh JL, Lin CH, Yang YY, Liu HC, . The correlation of depression with functional activity in Parkinson's disease. J Neurol. 1997;244:493-8.
[Google Scholar]
de Rijk C, Bijl RV, . Prevalence of mental disorders in persons with Parkinson's disease. Ned Tijdschr Geneeskd. 1998;142:27-31.
[Google Scholar]
Starkstein SE, Petracca G, Chemerinski E, Tesón A, Sabe L, Merello M, . Depression in classic versus akinetic-rigid Parkinson's disease. Mov Disord. 1998;13:29-33.
[Google Scholar]
Aarsland D, Karlsen K, . Neuropsychiatric aspects of Parkinson's disease. Curr Psychiatry Rep. 1999;1:61-8.
[Google Scholar]
Karlsen KH, Larsen JP, Tandberg E, Maeland JG, . Influence of clinical and demographic variables on quality of life in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry. 1999;66:431-5.
[Google Scholar]
Meara J, Bhowmick BK, Hobson P, . Accuracy of diagnosis in patients with presumed Parkinson's disease. Age Ageing. 1999;28:99-102.
[Google Scholar]
Schrag A, Jahanshahi M, Quinn N, . What contributes to quality of life in patients with Parkinson's disease? J Neurol Neurosurg Psychiatry. 2000;69:308-12.
[Google Scholar]
Cubo E, Alvarez E, Morant C, de Pedro Cuesta J, Martínez Martín P, Génova R, . Burden of disease related to Parkinson's disease in Spain in the year 2000. Mov Disord. 2005;20:1481-7.
[Google Scholar]
Giladi N, Treves TA, Paleacu D, Shabtai H, Orlov Y, Kandinov B, . Risk factors for dementia, depression and psychosis in long-standing Parkinson's disease. J Neural Transm. 2000;107:59-71.
[Google Scholar]
Larsen JP, Karlsen K, Tandberg E, . Clinical problems in non-fluctuating patients with Parkinson's disease: A community-based study. Mov Disord. 2000;15:826-9.
[Google Scholar]
Leentjens AF, Verhey FR, Luijckx GJ, Troost J, . The validity of the Beck Depression Inventory as a screening and diagnostic instrument for depression in patients with Parkinson's disease. Mov Disord. 2000;15:1221-4.
[Google Scholar]
Happe S, Berger K, . FAQT Study Investigators. The association of dopamine agonists with daytime sleepiness, sleep problems and quality of life in patients with Parkinson's disease--a prospective study. J Neurol. 2001;248:1062-7.
[Google Scholar]
Schrag A, Trimble M, . Poetic talent unmasked by treatment of Parkinson's disease. Mov Disord. 2001;16:1175-6.
[Google Scholar]
Shulman LM, Taback RL, Rabinstein AA, Weiner WJ, . Non-recognition of depression and other non-motor symptoms in Parkinson's disease. Parkinsonism Relat Disord. 2002;8:193-7.
[Google Scholar]
Happe S, Berger K, . FAQT Study Investigators. The association between caregiver burden and sleep disturbances in partners of patients with Parkinson's disease. Age Ageing. 2002;31:349-54.
[Google Scholar]
Marinus J, Leentjens AF, Visser M, Stiggelbout AM, van Hilten JJ, . Evaluation of the hospital anxiety and depression scale in patients with Parkinson's disease. Clin Neuropharmacol. 2002;25:318-24.
[Google Scholar]
Schrag A, Ben-Shlomo Y, Quinn N, . How valid is the clinical diagnosis of Parkinson's disease in the community? J Neurol Neurosurg Psychiatry. 2002;73:529-34.
[Google Scholar]
Shulman LM, . Is there a connection between estrogen and Parkinson's disease? Parkinsonism Relat Disord. 2002;8:289-95.
[Google Scholar]
Anguenot A, Loll PY, Neau JP, Ingrand P, Gil R, . Depression and Parkinson's Disease: Study of a series of 135 Parkinson's patients. Can J Neurol Sci. 2002;29:139-46.
[Google Scholar]
Naarding P, Leentjens AF, van Kooten F, Verhey FR, . Disease-specific properties of the rating scale for depression in patients with stroke, Alzheimer's dementia, and Parkinson's disease. J Neuropsychiatry Clin Neurosci. 2002;14:329-34.
[Google Scholar]
Weintraub D, Moberg PJ, Duda JE, Katz IR, Stern MB, . Recognition and treatment of depression in Parkinson's disease. J Geriatr Psychiatry Neurol. 2003;16:178-83.
[Google Scholar]
Krishnan PR, Bhatia M, Behari M, . Restless legs syndrome in Parkinson's disease: A case-controlled study. Mov Disord. 2003;18:181-5.
[Google Scholar]
Rojo A, Aguilar M, Garolera MT, Cubo E, Navas I, Quintana S, . Depression in Parkinson's disease: Clinical correlates and outcome. Parkinsonism Relat Disord. 2003;10:23-8.
[Google Scholar]
Lauterbach EC, . The neuropsychiatry of Parkinson's disease and related disorders. Psychiatr Clin North Am. 2004;27:801-25.
[Google Scholar]
Nuti A, Ceravolo R, Piccinni A, Dell'Agnello G, Bellini G, Gambaccini G, . Psychiatric comorbidity in a population of Parkinson's disease patients. Eur J Neurol. 2004;11:315-20.
[Google Scholar]
Ertan FS, Ertan T, Kiziltan G, Uyguçgil H, . Reliability and validity of the Geriatric Depression Scale in depression in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2005;76:1445-7.
[Google Scholar]
Papapetropoulos S, Gonzalez J, Lieberman A, Villar JM, Mash DC, . Dementia in Parkinson's disease: A post-mortem study in a population of brain donors. Int J Geriatr Psychiatry. 2005;20:418-22.
[Google Scholar]
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;20:190-9.
[Google Scholar]
Holroyd S, Currie LJ, Wooten GF, . Depression is associated with impairment of ADL, not motor function in Parkinson disease. Neurology. 2005;64:2134-5.
[Google Scholar]
Kang GA, Bronstein JM, Masterman DL, Redelings M, Crum JA, Ritz B, . Clinical characteristics in early Parkinson's disease in a central California population-based study. Mov Disord. 2005;20:1133-42.
[Google Scholar]
Prado RC, Barbosa ER, . Depression in Parkinson's disease: Study of 60 cases. Arq Neuropsiquiatr. 2005;63:766-71.
[Google Scholar]
Kirsch-Darrow L, Fernandez HH, Marsiske M, Okun MS, Bowers D, . Dissociating apathy and depression in Parkinson disease. Neurology. 2006;67:33-8.
[Google Scholar]
Weintraub D, Morales KH, Duda JE, Moberg PJ, Stern MB, . Frequency and correlates of co-morbid psychosis and depression in Parkinson's disease. Parkinsonism Relat Disord. 2006;12:427-31.
[Google Scholar]
Costa A, Peppe A, Carlesimo GA, Pasqualetti P, Caltagirone C, . Alexithymia in Parkinson's disease is related to severity of depressive symptoms. Eur J Neurol. 2006;13:836-41.
[Google Scholar]
Visser M, Leentjens AF, Marinus J, Stiggelbout AM, van Hilten JJ, . Reliability and validity of the Beck depression inventory in patients with Parkinson's disease. Mov Disord. 2006;21:668-72.
[Google Scholar]
Wichowicz HM, Slawek J, Derejko M, Cuba³a WJ, . Factors associated with depression in Parkinson's disease: A cross-sectional study in a Polish population. Eur Psychiatry. 2006;21:516-20.
[Google Scholar]
Antonini A, Barone P, . Dopamine agonist-based strategies in the treatment of Parkinson's disease. Neurol Sci. 2008;29(Suppl 5):S371-4.
[Google Scholar]
Barone P, Antonini A, Colosimo C, Marconi R, Morgante L, Avarello TP, . PRIAMO Study Group. The PRIAMO study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease. Mov Disord. 2009;24:1641-9.
[Google Scholar]
Chen JJ, Marsh L, . Depression in Parkinson's disease: Identification and management. Pharmacotherapy. 2013;33:972-83.
[Google Scholar]
Cubo E, Bernard B, Leurgans S, Raman R, . Cognitive and motor function in patients with Parkinson's disease with and without depression. Clin Neuropharmacol. 2000;23:331-4.
[Google Scholar]
Happe S, Schrödl B, Faltl M, Müller C, Auff E, Zeitlhofer J, . Sleep disorders and depression in patients with Parkinson's disease. Acta Neurol Scand. 2001;104:275-80.
[Google Scholar]
Happe S, Lüdemann P, Berger K, . FAQT Study Investigators. The association between disease severity and sleep-related problems in patients with Parkinson's disease. Neuropsychobiology. 2002;46:90-6.
[Google Scholar]
Ossowska K, Lorenc-Koci E, . Depression in Parkinson's disease. Pharmacol Rep. 2013;65:1545-57.
[Google Scholar]
Skapinakis P, Bakola E, Salanti G, Lewis G, Kyritsis AP, Mavreas V, . 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.
[Google Scholar]
Liu J, Dong J, Wang L, Su Y, Yan P, Sun S, . Comparative efficacy and acceptability of antidepressants in Parkinson's disease: A network meta-analysis. PLoS One. 2013;8:e76651.
[Google Scholar]
Faber R, Trimble MR, . Electroconvulsive therapy in Parkinson's disease and other movement disorders. Mov Disord. 1991;6:293-303.
[Google Scholar]
Moellentine C, Rummans T, Ahlskog JE, Harmsen WS, Suman VJ, O’Connor MK, . Effectiveness of ECT in patients with Parkinsonism. J Neuropsychiatry Clin Neurosci. 1998;10:187-93.
[Google Scholar]
Oh JJ, Rummans TA, O’Connor MK, Ahlskog JE, . Cognitive impairment after ECT in patients with Parkinson's disease and psychiatric illness. Am J Psychiatry. 1992;149:271.
[Google Scholar]
Farabaugh A, Locascio JJ, Yap L, Growdon J, Fava M, Crawford C, . Cognitive-behavioral therapy for patients with Parkinson's disease and comorbid major depressive disorder. Psychosomatics. 2010;51:124-9.
[Google Scholar]
Dobkin RD, Menza M, Allen LA, Gara MA, Mark MH, Tiu J, . Cognitive behaviour therapy for depression in Parkinson's disease: A randomized, controlled trial. Am J Psychiatry. 2011;168:1066-74.
[Google Scholar]
Dobkin RD, Menza M, Allen LA, Tiu J, Friedman J, Bienfait KL, . Telephone-based cognitive-behavioral therapy for depression in Parkinson disease. J Geriatr Psychiatry Neurol. 2011;24:206-14.
[Google Scholar]
Dobkin RD, Rubino JT, Allen LA, Friedman J, Gara MA, Mark MH, . Predictors of treatment response to cognitive-behavioral therapy for depression in Parkinson's disease. J Consult Clin Psychol. 2012;80:694-9.
[Google Scholar]
Couto MI, Monteiro A, Oliveira A, Lunet N, Massano J, . Depression and anxiety following deep brain stimulation in Parkinson's disease: Systematic review and meta-analysis. Acta Med Port. 2014;27:372-82.
[Google Scholar]
Epstein CM, Evatt ML, Funk A, Girard-Siqueira L, Lupei N, Slaughter L, . An open study of repetitive transcranial magnetic stimulation in treatment-resistant depression with Parkinson's disease. Clin Neurophysiol. 2007;118:2189-94.
[Google Scholar]
Leentjens AF, . Depression in Parkinson's disease: Conceptual issues and clinical challenges. J Geriatr Psychiatry Neurol. 2004;17:120-6.
[Google Scholar]
Seppi K, Weintraub D, Coelho M, Perez-Lloret S, Fox SH, Katzenschlager R, . The movement disorder society evidence-based medicine review update: Treatments for the non-motor symptoms of Parkinson's disease. Mov Disord. 2011;26(Suppl 3):S42-80.
[Google Scholar]
Veazey C, Aki S, Cook KF, Lai EC, Kunik ME, . Prevalence and treatment of depression in Parkinson's disease. J Neuropsychiatry Clin Neurosci. 2005;17:310-23.
[Google Scholar]
Cully JA, Johnson M, Moffett ML, Khan M, Deswal A, . Depression and anxiety in ambulatory patients with heart failure. Psychosomatics. 2009;50:592-8.
[Google Scholar]
Siri C, Cilia R, De Gaspari D, Villa F, Goldwurm S, Marco C, . Psychiatric symptoms in Parkinson's disease assessed with the SCL-90R self-reported questionnaire. Neurol Sci. 2010;31:35-40.
[Google Scholar]
Nègre-Pagès L, Grandjean H, Lapeyre-Mestre M, Montastruc JL, Fourrier A, Lépine JP, . DoPaMiP Study Group. Anxious and depressive symptoms in Parkinson's disease: The French cross-sectionnal DoPaMiP study. Mov Disord. 2010;25:157-66.
[Google Scholar]
Leentjens AF, Dujardin K, Marsh L, Richard IH, Starkstein SE, Martinez-Martin P, . Anxiety rating scales in Parkinson's disease: A validation study of the Hamilton anxiety rating scale, the Beck anxiety inventory, and the hospital anxiety and depression scale. Mov Disord. 2011;26:407-15.
[Google Scholar]
Pontone GM, Williams JR, Anderson KE, Chase G, Goldstein SA, Grill S, . Prevalence of anxiety disorders and anxiety subtypes in patients with Parkinson's disease. Mov Disord. 2009;24:1333-8.
[Google Scholar]
Dissanayaka NN, Sellbach A, Matheson S, O’Sullivan JD, Silburn PA, Byrne GJ, . Anxiety disorders in Parkinson's disease: Prevalence and risk factors. Mov Disord. 2010;25:838-45.
[Google Scholar]
Pontone GM, Williams JR, Anderson KE, Chase G, Goldstein SR, Grill S, . Anxiety and self-perceived health status in Parkinson's disease. Parkinsonism Relat Disord. 2011;17:249-54.
[Google Scholar]
Chagas MH, Tumas V, Loureiro SR, Correa AC, Najabayashi TJK, Crippa JA, . Does the association between anxiety and Parkinson's disease really exist. A literature review? Curr Psychiatry Rev. 2009;5:29-36.
[Google Scholar]
Menza MA, Robertson-Hoffman DE, Bonapace AS, . Parkinson's disease and anxiety: Comorbidity with depression. Biol Psychiatry. 1993;34:465-70.
[Google Scholar]
Cummings JL, . Depression and Parkinson's disease: A review. Am J Psychiatry. 1992;149:443-54.
[Google Scholar]
Walsh K, Bennett G, . Parkinson's disease and anxiety. Postgrad Med J. 2001;77:89-93.
[Google Scholar]
Troeung L, Egan SJ, Gasson N, . A waitlist-controlled trial of group cognitive behavioural therapy for depression and anxiety in Parkinson's disease. BMC Psychiatry. 2014;14:19.
[Google Scholar]
Borek LL, Amick MM, Friedman JH, . Non-motor aspects of Parkinson's disease. CNS Spectr. 2006;11:541-54.
[Google Scholar]
Marsh L, . Psychosis in Parkinson's disease. Curr Treat Options Neurol. 2004;6:181-9.
[Google Scholar]
Sanchez-Ramos JR, Ortoll R, Paulson GW, . Visual hallucinations associated with Parkinson disease. Arch Neurol. 1996;53:1265-8.
[Google Scholar]
Graham C, Ballard C, Saad K, . Variables which distinguish patients fulfilling clinical criteria for dementia with Lewy bodies from those with Alzheimer's disease. Int J Geriatr Psychiatry. 1997;12:314-8.
[Google Scholar]
Inzelberg R, Kipervasser S, Korczyn AD, . Auditory hallucinations in Parkinson's disease. J Neurol Neurosurg Psychiatry. 1998;64:533-5.
[Google Scholar]
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.
[Google Scholar]
Fénelon G, Mahieux F, Huon R, Ziégler M, . Hallucinations in Parkinson's disease: Prevalence, phenomenology and risk factors. Brain. 2000;123:733-45.
[Google Scholar]
Holroyd S, Currie L, Wooten GF, . Prospective study of hallucinations and delusions in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2001;70:734-8.
[Google Scholar]
Schrag A, Ben-Shlomo Y, Quinn N, . How common are complications of Parkinson's disease? J Neurol. 2002;249:419-23.
[Google Scholar]
Merims D, Shabtai H, Korczyn AD, Peretz C, Weizman N, Giladi N, . Antiparkinsonian medication is not a risk factor for the development of hallucinations in Parkinson's disease. J Neural Transm. 2004;111:1447-53.
[Google Scholar]
Marsh L, Williams JR, Rocco M, Grill S, Munro C, Dawson TM, . Psychiatric comorbidities in patients with Parkinson disease and psychosis. Neurology. 2004;63:293-300.
[Google Scholar]
Paleacu D, Schechtman E, Inzelberg R, . Association between family history of dementia and hallucinations in Parkinson disease. Neurology. 2005;64:1712-5.
[Google Scholar]
Pacchetti C, Manni R, Zangaglia R, Mancini F, Marchioni E, Tassorelli C, . Relationship between hallucinations, delusions, and rapid eye movement sleep behavior disorder in Parkinson's disease. Mov Disord. 2005;20:1439-48.
[Google Scholar]
Williams DR, Warren JD, Lees AJ, . Using the presence of visual hallucinations to differentiate Parkinson's disease from atypical parkinsonism. J Neurol Neurosurg Psychiatry. 2008;79:652-5.
[Google Scholar]
Papapetropoulos S, Katzen H, Schrag A, Singer C, Scanlon BK, Nation D, . A questionnaire-based (UM-PDHQ) study of hallucinations in Parkinson's disease. BMC Neurol. 2008;8:21.
[Google Scholar]
Forsaa EB, Larsen JP, Wentzel-Larsen T, Goetz CG, Stebbins GT, Aarsland D, . A 12-year population-based study of psychosis in Parkinson disease. Arch Neurol. 2010;67:996-1001.
[Google Scholar]
Aarsland D, Kurz MW, . The epidemiology of dementia associated with Parkinson disease. J Neurol Sci. 2010;289:18-22.
[Google Scholar]
Caviness JN, Driver-Dunckley E, Connor DJ, Sabbagh MN, Hentz JG, Noble B, . Defining mild cognitive impairment in Parkinson's disease. Mov Disord. 2007;22:1272-7.
[Google Scholar]
Biundo R, Weis L, Facchini S, Formento-Dojot P, Vallelunga A, Pilleri M, . Cognitive profiling of Parkinson disease patients with mild cognitive impairment and dementia. Parkinsonism Relat Disord. 2014;20:394-9.
[Google Scholar]
Foltynie T, Brayne CE, Robbins TW, Barker RA, . The cognitive ability of an incident cohort of Parkinson's patients in the UK. The CamPaIGN study. Brain. 2004;127:550-60.
[Google Scholar]
Muslimovic D, Post B, Speelman JD, Schmand B, . Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology. 2005;65:1239-45.
[Google Scholar]
Mamikonyan E, Moberg PJ, Siderowf A, Duda JE, Have TT, Hurtig HI, . Mild cognitive impairment is common in Parkinson's disease patients with normal Mini-Mental State Examination (MMSE) scores. Parkinsonism Relat Disord. 2009;15:226-31.
[Google Scholar]
Aarsland D, Muniz G, Matthews F, . Nonlinear decline of mini-mental state examination in Parkinson's disease. Mov Disord. 2011;26:334-7.
[Google Scholar]
Sollinger AB, Goldstein FC, Lah JJ, Levey AI, Factor SA, . Mild cognitive impairment in Parkinson's disease: Subtypes and motor characteristics. Parkinsonism Relat Disord. 2010;16:177-80.
[Google Scholar]
Emre M, . Dementia in Parkinson's disease: Cause and treatment. Curr Opin Neurol. 2004;17:399-404.
[Google Scholar]
Poewe W, Gauthier S, Aarsland D, Leverenz JB, Barone P, Weintraub D, . Diagnosis and management of Parkinson's disease dementia. Int J Clin Pract. 2008;62:1581-7.
[Google Scholar]
Burn DJ, . The treatment of cognitive impairment associated with Parkinson's disease. Brain Pathol. 2010;20:672-8.
[Google Scholar]
Robottom BJ, Weiner WJ, . Dementia in Parkinson's disease. Int Rev Neurobiol. 2009;84:229-44.
[Google Scholar]
Sabbagh MN, Adler CH, Lahti TJ, Connor DJ, Vedders L, Peterson LK, . Parkinson disease with dementia: Comparing patients with and without Alzheimer pathology. Alzheimer Dis Assoc Disord. 2009;23:295-7.
[Google Scholar]
Pagonabarraga J, Kulisevsky J, . Cognitive impairment and dementia in Parkinson's disease. Neurobiol Dis. 2012;46:590-6.
[Google Scholar]
Perez F, Helmer C, Foubert-Samier A, Auriacombe S, Dartigues JF, Tison F, . Risk of dementia in an elderly population of Parkinson's disease patients: A 15-year population-based study. Alzheimers Dement. 2012;8:463-9.
[Google Scholar]
Pfeiffer C, Wagner ML, . Clozapine therapy for Parkinson's disease and other movement disorders. Am J Hosp Pharm. 1994;51:3047-53.
[Google Scholar]
Martinez-Martin P, . Nonmotor symptoms and health-related quality of life in early Parkinson's disease. Mov Disord. 2014;29:166-8.
[Google Scholar]
Sobreira Neto MA, Pereira MA, Sobreira ES, Chagas MH, Rodrigues GR, Fernandes RM, . Sleep-related eating disorder in two patients with early-onset Parkinson's disease. Eur Neurol. 2011;66:106-9.
[Google Scholar]
Abbott RD, Ross GW, White LR, Tanner CM, Masaki KH, Nelson JS, . Excessive daytime sleepiness and subsequent development of Parkinson disease. Neurology. 2005;65:1442-6.
[Google Scholar]
Schenck CH, Bundlie SR, Mahowald MW, . Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology. 1996;46:388-93.
[Google Scholar]
Iranzo A, Molinuevo JL, Santamaría J, Serradell M, Martí MJ, Valldeoriola F, . Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: A descriptive study. Lancet Neurol. 2006;5:572-7.
[Google Scholar]
Postuma RB, Gagnon JF, Vendette M, Montplaisir JY, . Markers of neurodegeneration in idiopathic rapid eye movement sleep behaviour disorder and Parkinson's disease. Brain. 2009;132:3298-307.
[Google Scholar]
Postuma RB, Gagnon JF, Vendette M, Montplaisir JY, . Idiopathic REM sleep behavior disorder in the transition to degenerative disease. Mov Disord. 2009;24:2225-32.
[Google Scholar]
Gjerstad MD, Boeve B, Wentzel-Larsen T, Aarsland D, Larsen JP, . Occurrence and clinical correlates of REM sleep behaviour disorder in patients with Parkinson's disease over time. J Neurol Neurosurg Psychiatry. 2008;79:387-91.
[Google Scholar]
Gjerstad MD, Wentzel-Larsen T, Aarsland D, Larsen JP, . Insomnia in Parkinson's disease: Frequency and progression over time. J Neurol Neurosurg Psychiatry. 2007;78:476-9.
[Google Scholar]
Gjerstad MD, Alves G, Wentzel-Larsen T, Aarsland D, Larsen JP, . Excessive daytime sleepiness in Parkinson disease: Is it the drugs or the disease? Neurology. 2006;67:853-8.
[Google Scholar]
Gjerstad MD, Aarsland D, Larsen JP, . Development of daytime somnolence over time in Parkinson's disease. Neurology. 2002;58:1544-6.
[Google Scholar]
Onofrj M, Thomas A, D’Andreamatteo G, Iacono D, Luciano AL, Di Rollo A, . Incidence of RBD and hallucination in patients affected by Parkinson's disease: 8-year follow-up. Neurol Sci. 2002;23(Suppl 2):S91-4.
[Google Scholar]
de Maindreville AD, Fénelon G, Mahieux F, . Hallucinations in Parkinson's disease: A follow-up study. Mov Disord. 2005;20:212-7.
[Google Scholar]
Goetz CG, Wuu J, Curgian LM, Leurgans S, . Hallucinations and sleep disorders in PD: Six-year prospective longitudinal study. Neurology. 2005;64:81-6.
[Google Scholar]
Sinforiani E, Pacchetti C, Zangaglia R, Pasotti C, Manni R, Nappi G, . REM behavior disorder, hallucinations and cognitive impairment in Parkinson's disease: A two-year follow up. Mov Disord. 2008;23:1441-5.
[Google Scholar]
Larsen JP, Tandberg E, . Sleep disorders in patients with Parkinson's disease: Epidemiology and management. CNS Drugs. 2001;15:267-75.
[Google Scholar]
Hobson DE, Lang AE, Martin WR, Razmy A, Rivest J, Fleming J, . Excessive daytime sleepiness and sudden-onset sleep in Parkinson disease: A survey by the Canadian Movement Disorders Group. JAMA. 2002;287:455-63.
[Google Scholar]
Chung S, Bohnen NI, Albin RL, Frey KA, Müller ML, Chervin RD, . Insomnia and sleepiness in Parkinson disease: Associations with symptoms and comorbidities. J Clin Sleep Med. 2013;9:1131-7.
[Google Scholar]
Prudon B, Duncan GW, Khoo TK, Yarnall AJ, Anderson KN, . Primary sleep disorder prevalence in patients with newly diagnosed Parkinson's disease. Mov Disord. 2014;29:259-62.
[Google Scholar]
Neikrug AB, Maglione JE, Liu L, Natarajan L, Avanzino JA, Corey-Bloom J, . Effects of sleep disorders on the non-motor symptoms of Parkinson disease. J Clin Sleep Med. 2013;9:1119-29.
[Google Scholar]
Chung WS, Lin CL, Chen YF, Chiang JY, Sung FC, Chang YJ, . Sleep disorders and increased risk of subsequent acute coronary syndrome in individuals without sleep apnea: A nationwide population-based cohort study. Sleep. 2013;36:1963-8.
[Google Scholar]
Dhawan V, Healy DG, Pal S, Chaudhuri KR, . Sleep-related problems of Parkinson's disease. Age Ageing. 2006;35:220-8.
[Google Scholar]
Friedman JH, Millman RP, . Sleep disturbances and Parkinson's disease. CNS Spectr. 2008;13(Suppl 4):12-7.
[Google Scholar]
Comella CL, . Sleep disturbances in Parkinson's disease. Curr Neurol Neurosci Rep. 2003;3:173-80.
[Google Scholar]
Chaudhuri KR, Bhattacharya K, Porter MC, . The use of cabergoline in nocturnal parkinsonian disabilities causing sleep disruption: A parallel study with controlled-release levodopa. Eur J Neurol. 1999;6(Suppl 5):S11-5.
[Google Scholar]
Ghatani T, Agapito C, Bhattacharya K, Clough C, Ray Chaudhuri K, . Comparative audit of pergolide and cabergoline therapy in the treatment of nocturnal “off” periods causing sleep disruption in Parkinson's disease. Eur J Neurol. 2001;8(Suppl 1):8-11.
[Google Scholar]
Loas G, Krystkowiak P, Godefroy O, . Anhedonia in Parkinson's disease: An overview. J Neuropsychiatry Clin Neurosci. 2012;24:444-51.
[Google Scholar]
Lemke MR, Brecht HM, Koester J Kraus PH, Reichmann H, . Anhedonia, depression, and motor functioning in Parkinson's disease during treatment with pramipexole. J Neuropsychiatry Clin Neurosci. 2005;17:214-20.
[Google Scholar]
Santangelo G, Morgante L, Savica R, Marconi R, Grasso L, Antonini A, . PRIAMO Study Group. Anhedonia and cognitive impairment in Parkinson's disease: Italian validation of the Snaith-Hamilton Pleasure Scale and its application in the clinical routine practice during the PRIAMO study. Parkinsonism Relat Disord. 2009;15:576-81.
[Google Scholar]
Pluck GC, Brown RG, . Apathy in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2002;73:636-42.
[Google Scholar]
Isella V, Iurlaro S, Piolti R, Ferrarese C, Frattola L, Appollonio I, . Physical anhedonia in Parkinson's disease. J NeurolNeurosurg Psychiatry. 2003;74:1308-11.
[Google Scholar]
Fujiwara S, Kimura F, Hosokawa T, Ishida S, Sugino M, Hanafusa T, . Anhedonia in Japanese patients with Parkinson's disease. Geriatr Gerontol Int. 2011;11:275-81.
[Google Scholar]
Miura S, Kida H, Nakajima J, Noda K, Nagasato K, Ayabe M, . Anhedonia in Japanese patients with Parkinson's disease: Analysis using the Snaith-Hamilton Pleasure Scale. Clin Neurol Neurosurg. 2012;114:352-5.
[Google Scholar]
Assogna F, Cravello L, Caltagirone C, Spalletta G, . Anhedonia in Parkinson's disease: A systematic review of the literature. Mov Disord. 2011;26:1825-34.
[Google Scholar]
Dujardin K, Sockeel P, Devos D, Delliaux M, Krystkowiak P, Destée A, . Characteristics of apathy in Parkinson's disease. Mov Disord. 2007;22:778-84.
[Google Scholar]
Aarsland D, Larsen JP, Lim NG, Janvin C, Karlsen K, Tandberg E, . Range of neuropsychiatric disturbances in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry. 1999;67:492-6.
[Google Scholar]
Starkstein SE, Mayberg HS, Preziosi TJ, Andrezejewski P, Leiguarda R, Robinson RG, . Reliability, validity, and clinical correlates of apathy in Parkinson's disease. J Neuropsychiatry Clin Neurosci. 1992;4:134-9.
[Google Scholar]
Levy ML, Cummings JL, Fairbanks LA, Masterman D, Miller BL, Craig AH, . Apathy is not depression. J Neuropsychiatry Clin Neurosci. 1998;10:314-9.
[Google Scholar]
Kirsch-Darrow L, Fernandez HH, Marsiske M, Okun MS, Bowers D, . Dissociating apathy and depression in Parkinson disease. Neurology. 2006;67:33-8.
[Google Scholar]
Isella V, Melzi P, Grimaldi M, Iurlaro S, Piolti R, Ferrarese C, . Clinical, neuropsychological, and morphometric correlates of apathy in Parkinson's disease. Mov Disord. 2002;17:366-71.
[Google Scholar]
Starkstein SE, Merello M, Jorge R, Brockman S, Bruce D, Power B, . The syndromal validity and nosological position of apathy in Parkinson's disease. Mov Disord. 2009;24:1211-6.
[Google Scholar]
Saint-Cyr JA, Trépanier LL, Kumar R, Lozano AM, Lang AE, . Neuropsychological consequences of chronic bilateral stimulation of the subthalamic nucleus in Parkinson's disease. Brain. 2000;123:2091-108.
[Google Scholar]
Trépanier LL, Kumar R, Lozano AM, Lang AE, Saint-Cyr JA, . Neuropsychological outcome of GPi pallidotomy and GPi or STN deep brain stimulation in Parkinson's disease. Brain Cogn. 2000;42:324-47.
[Google Scholar]
Callesen MB, Weintraub D, Damholdt MF, Møller A, . Impulsive and compulsive behaviors among Danish patients with Parkinson's disease: Prevalence, depression, and personality. Parkinsonism Relat Disord. 2014;20:22-6.
[Google Scholar]
Rohde K, Riedel O, Lueken U, Rietzel S, Fauser M, Ossig C, . Impulsive-compulsive behaviours in a German Parkinson's disease outpatient sample. Fortschr Neurol Psychiatr. 2013;81:503-10.
[Google Scholar]
O’Sullivan SS, Evans AH, Lees AJ, . Dopamine dysregulation syndrome: An overview of its epidemiology, mechanisms and management. CNS Drugs. 2009;23:157-70.
[Google Scholar]
Evans AH, Strafella AP, Weintraub D, Stacy M, . Impulsive and compulsive behaviors in Parkinson's disease. Mov Disord. 2009;24:1561-70.
[Google Scholar]
Callesen MB, Scheel-Krüger J, Kringelbach ML, Møller A, . A systematic review of impulse control disorders in Parkinson's disease. J Parkinsons Dis. 2013;3:105-38.
[Google Scholar]
Kostiæ VS, Pekmezoviæ T, Tomiæ A, Jecmenica-Lukiæ M, Stojkoviæ T, Spica V, . Suicide and suicidal ideation in Parkinson's disease. J Neurol Sci. 2010;289:40-3.
[Google Scholar]
Myslobodsky M, Lalonde FM, Hicks L, . Are patients with Parkinson's disease suicidal? J Geriatr Psychiatry Neurol. 2001;14:120-4.
[Google Scholar]
Nazem S, Siderowf AD, Duda JE, Brown GK, Ten Have T, Stern MB, . Suicidal and death ideation in Parkinson's disease. Mov Disord. 2008;23:1573-9.
[Google Scholar]

Introduction

Risk of Parkinson's disease in patients with psychiatric disorders
Depression in Parkinson's disease
Anxiety disorders in Parkinson's disease
Psychosis in Parkinson's disease
Cognitive deficits in Parkinson's disease
Sleep disorders in Parkinson's disease
Anhedonia in Parkinson's disease
Apathy in Parkinson's disease
Impulsive-compulsive disorders in PD
Dopamine dysregulation syndrome
Suicidal behavior in Parkinson's disease

Conclusion

Fulltext Views
1,304

PDF downloads
257

View/Download PDF
Download Citations

BibTeX
RIS

Show Sections

[1] Samii A, Nutt JG, Ransom BR, . Parkinson's disease. Lancet. 2004;363:1783-93.
[Google Scholar]

[2] Van Den Eeden SK, Tanner CM, Bernstein AL, Fross RD, Leimpeter A, Bloch DA, . Incidence of Parkinson's disease: Variation by age, gender, and race/ethnicity. Am J Epidemiol. 2003;157:1015-22.
[Google Scholar]

[3] de Lau LM, Koudstaal PJ, Hofman A, Breteler MM, . Parkinson disease is more prevalent than people think. Research results. Ned Tijdschr Geneeskd. 2009;153:63-8.
[Google Scholar]

[4] Das SK, Biswas A, Roy T, Banerjee TK, Mukherjee CS, Raut DK, . A random sample survey for prevalence of major neurological disorders in Kolkata. Indian J Med Res. 2006;124:163-72.
[Google Scholar]

[5] Yadav R, Shukla G, Goyal V, Singh S, Behari M, . A case control study of women with Parkinson's disease and their fertility characteristics. J Neurol Sci. 2012;319:135-8.
[Google Scholar]

[6] Sanyal J, Chakraborty DP, Sarkar B, Banerjee TK, Mukherjee SC, Ray BC, . Environmental and familial risk factors of Parkinsons disease: Case-control study. Can J Neurol Sci. 2010;37:637-42.
[Google Scholar]

[7] Fernandez HH, . Nonmotor complications of Parkinson disease. Cleve Clin J Med. 2012;79(Suppl 2):S14-8.
[Google Scholar]

[8] Modugno N, Lena F, Di Biasio F, Cerrone G, Ruggieri S, Fornai F, . A clinical overview of non-motor symptoms in Parkinson's disease. Arch Ital Biol. 2013;151:148-68.
[Google Scholar]

[9] Weintraub D, Comella CL, Horn S, . Parkinson's disease-Part 1: Pathophysiology, symptoms, burden, diagnosis, and assessment. Am J Manag Care. 2008;14(Suppl):S40-8.
[Google Scholar]

[10] Aarsland D, Larsen JP, Tandberg E, Laake K, . Predictors of nursing home placement in Parkinson's disease: A population-based, prospective study. J Am Geriatr Soc. 2000;48:938-42.
[Google Scholar]

[11] Thanvi BR, Munshi SK, Vijaykumar N, Lo TC, . Neuropsychiatric non-motor aspects of Parkinson's disease. Postgrad Med J. 2003;79:561-5.
[Google Scholar]

[12] Lin HL, Lin HC, Chen YH, . Psychiatric diseases predated the occurrence of Parkinson disease: A retrospective cohort study. Ann Epidemiol. 2014;24:206-13.
[Google Scholar]

[13] Bower JH, Grossardt BR, Maraganore DM, Ahlskog JE, Colligan RC, Geda YE, . Anxious personality predicts an increased risk of Parkinson's disease. Mov Disord. 2010;25:2105-13.
[Google Scholar]

[14] Weisskopf MG, Chen H, Schwarzschild MA, Kawachi I, Ascherio A, . Prospective study of phobic anxiety and risk of Parkinson's disease. Mov Disord. 2003;18:646-51.
[Google Scholar]

[15] Leentjens AF, Van den Akker M, Metsemakers JF, Lousberg R, Verhey FR, . Higher incidence of depression preceding the onset of Parkinson's disease: A register study. Mov Disord. 2003;18:414-8.
[Google Scholar]

[16] Schuurman AG, van den Akker M, Ensinck KT, Metsemakers JF, Knottnerus JA, Leentjens AF, . Increased risk of Parkinson's disease after depression: A retrospective cohort study. Neurology. 2002;58:1501-4.
[Google Scholar]

[17] Shen CC, Tsai SJ, Perng CL, Kuo BI, Yang AC, . Risk of Parkinson disease after depression: A nationwide population-based study. Neurology. 2013;81:1538-44.
[Google Scholar]

[18] Leentjens AF, Van den Akker M, Metsemakers JF, Troost J, . The incidence of Parkinson's disease in the Netherlands: Results from a longitudinal general practice-based registration. Neuroepidemiology. 2003;22:311-2.
[Google Scholar]

[19] Dooneief G, Mirabello E, Bell K, Marder K, Stern Y, Mayeux R, . An estimate of the incidence of depression in idiopathic Parkinson's disease. Arch Neurol. 1992;49:305-7.
[Google Scholar]

[20] Kulkantrakorn K, Jirapramukpitak T, . A prospective study in one year cumulative incidence of depression after ischemic stroke and Parkinson's disease: A preliminary study. J Neurol Sci. 2007;263:165-8.
[Google Scholar]

[21] Mindham RH, . Psychiatric symptoms in Parkinsonism. J Neurol Neurosurg Psychiatry. 1970;33:188-91.
[Google Scholar]

[22] Santamaria J, Tolosa E, Valles A, . Parkinson's disease with depression: A possible subgroup of idiopathic parkinsonism. Neurology. 1986;36:1130-3.
[Google Scholar]

[23] Mayeux R, Marder K, Cote LJ, Denaro J, Hemenegildo N, Mejia H, . The frequency of idiopathic Parkinson's disease by age, ethnic group, and sex in northern Manhattan, 1988-1993. Am J Epidemiol. 1995;142:820-7.
[Google Scholar]

[24] Brown RG, MacCarthy B, . Psychiatric morbidity in patients with Parkinson's disease. Psychol Med. 1990;20:77-87.
[Google Scholar]

[25] Starkstein SE, Preziosi TJ, Forrester AW, Robinson RG, . Specificity of affective and autonomic symptoms of depression in Parkinson's disease. J Neurol Neurosurg Psychiatry. 1990;53:869-73.
[Google Scholar]

[26] Starkstein SE, Mayberg HS, Leiguarda R, Preziosi TJ, Robinson RG, . A prospective longitudinal study of depression, cognitive decline, and physical impairments in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry. 1992;55:377-82.
[Google Scholar]

[27] Hantz P, Caradoc-Davies G, Caradoc-Davies T, Weatherall M, Dixon G, . Depression in Parkinson's disease. Am J Psychiatry. 1994;151:1010-4.
[Google Scholar]

[28] Tison F, Wenning GK, Daniel SE, Quinn NP, . The pathophysiology of parkinsonism in multiple system atrophy. Eur J Neurol. 1995;2:435-44.
[Google Scholar]

[29] Starkstein SE, Sabe L, Petracca G, Chemerinski E, Kuzis G, Merello M, . Neuropsychological and psychiatric differences between Alzheimer's disease and Parkinson's disease with dementia. J Neurol Neurosurg Psychiatry. 1996;61:381-7.
[Google Scholar]

[30] Aarsland D, Tandberg E, Larsen JP, Cummings JL, . Frequency of dementia in Parkinson disease. Arch Neurol. 1996;53:538-42.
[Google Scholar]

[31] Tandberg E, Larsen JP, Aarsland D, Cummings JL, . The occurrence of depression in Parkinson's disease. A community-based study. Arch Neurol. 1996;53:175-9.
[Google Scholar]

[32] Tandberg E, Larsen JP, Aarsland D, Laake K, Cummings JL, . Risk factors for depression in Parkinson disease. Arch Neurol. 1997;54:625-30.
[Google Scholar]

[33] Tandberg E, Larsen JP, Karlsen K, . A community-based study of sleep disorders in patients with Parkinson's disease. Mov Disord. 1998;13:895-9.
[Google Scholar]

[34] Liu CY, Wang SJ, Fuh JL, Lin CH, Yang YY, Liu HC, . The correlation of depression with functional activity in Parkinson's disease. J Neurol. 1997;244:493-8.
[Google Scholar]

[35] de Rijk C, Bijl RV, . Prevalence of mental disorders in persons with Parkinson's disease. Ned Tijdschr Geneeskd. 1998;142:27-31.
[Google Scholar]

[36] Starkstein SE, Petracca G, Chemerinski E, Tesón A, Sabe L, Merello M, . Depression in classic versus akinetic-rigid Parkinson's disease. Mov Disord. 1998;13:29-33.
[Google Scholar]

[37] Aarsland D, Karlsen K, . Neuropsychiatric aspects of Parkinson's disease. Curr Psychiatry Rep. 1999;1:61-8.
[Google Scholar]

[38] Karlsen KH, Larsen JP, Tandberg E, Maeland JG, . Influence of clinical and demographic variables on quality of life in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry. 1999;66:431-5.
[Google Scholar]

[39] Meara J, Bhowmick BK, Hobson P, . Accuracy of diagnosis in patients with presumed Parkinson's disease. Age Ageing. 1999;28:99-102.
[Google Scholar]

[40] Schrag A, Jahanshahi M, Quinn N, . What contributes to quality of life in patients with Parkinson's disease? J Neurol Neurosurg Psychiatry. 2000;69:308-12.
[Google Scholar]

[41] Cubo E, Alvarez E, Morant C, de Pedro Cuesta J, Martínez Martín P, Génova R, . Burden of disease related to Parkinson's disease in Spain in the year 2000. Mov Disord. 2005;20:1481-7.
[Google Scholar]

[42] Giladi N, Treves TA, Paleacu D, Shabtai H, Orlov Y, Kandinov B, . Risk factors for dementia, depression and psychosis in long-standing Parkinson's disease. J Neural Transm. 2000;107:59-71.
[Google Scholar]

[43] Larsen JP, Karlsen K, Tandberg E, . Clinical problems in non-fluctuating patients with Parkinson's disease: A community-based study. Mov Disord. 2000;15:826-9.
[Google Scholar]

[44] Leentjens AF, Verhey FR, Luijckx GJ, Troost J, . The validity of the Beck Depression Inventory as a screening and diagnostic instrument for depression in patients with Parkinson's disease. Mov Disord. 2000;15:1221-4.
[Google Scholar]

[45] Happe S, Berger K, . FAQT Study Investigators. The association of dopamine agonists with daytime sleepiness, sleep problems and quality of life in patients with Parkinson's disease--a prospective study. J Neurol. 2001;248:1062-7.
[Google Scholar]

[46] Schrag A, Trimble M, . Poetic talent unmasked by treatment of Parkinson's disease. Mov Disord. 2001;16:1175-6.
[Google Scholar]

[47] Shulman LM, Taback RL, Rabinstein AA, Weiner WJ, . Non-recognition of depression and other non-motor symptoms in Parkinson's disease. Parkinsonism Relat Disord. 2002;8:193-7.
[Google Scholar]

[48] Happe S, Berger K, . FAQT Study Investigators. The association between caregiver burden and sleep disturbances in partners of patients with Parkinson's disease. Age Ageing. 2002;31:349-54.
[Google Scholar]

[49] Marinus J, Leentjens AF, Visser M, Stiggelbout AM, van Hilten JJ, . Evaluation of the hospital anxiety and depression scale in patients with Parkinson's disease. Clin Neuropharmacol. 2002;25:318-24.
[Google Scholar]

[50] Schrag A, Ben-Shlomo Y, Quinn N, . How valid is the clinical diagnosis of Parkinson's disease in the community? J Neurol Neurosurg Psychiatry. 2002;73:529-34.
[Google Scholar]

[51] Shulman LM, . Is there a connection between estrogen and Parkinson's disease? Parkinsonism Relat Disord. 2002;8:289-95.
[Google Scholar]

[52] Anguenot A, Loll PY, Neau JP, Ingrand P, Gil R, . Depression and Parkinson's Disease: Study of a series of 135 Parkinson's patients. Can J Neurol Sci. 2002;29:139-46.
[Google Scholar]

[53] Naarding P, Leentjens AF, van Kooten F, Verhey FR, . Disease-specific properties of the rating scale for depression in patients with stroke, Alzheimer's dementia, and Parkinson's disease. J Neuropsychiatry Clin Neurosci. 2002;14:329-34.
[Google Scholar]

[54] Weintraub D, Moberg PJ, Duda JE, Katz IR, Stern MB, . Recognition and treatment of depression in Parkinson's disease. J Geriatr Psychiatry Neurol. 2003;16:178-83.
[Google Scholar]

[55] Krishnan PR, Bhatia M, Behari M, . Restless legs syndrome in Parkinson's disease: A case-controlled study. Mov Disord. 2003;18:181-5.
[Google Scholar]

[56] Rojo A, Aguilar M, Garolera MT, Cubo E, Navas I, Quintana S, . Depression in Parkinson's disease: Clinical correlates and outcome. Parkinsonism Relat Disord. 2003;10:23-8.
[Google Scholar]

[57] Lauterbach EC, . The neuropsychiatry of Parkinson's disease and related disorders. Psychiatr Clin North Am. 2004;27:801-25.
[Google Scholar]

[58] Nuti A, Ceravolo R, Piccinni A, Dell'Agnello G, Bellini G, Gambaccini G, . Psychiatric comorbidity in a population of Parkinson's disease patients. Eur J Neurol. 2004;11:315-20.
[Google Scholar]

[59] Ertan FS, Ertan T, Kiziltan G, Uyguçgil H, . Reliability and validity of the Geriatric Depression Scale in depression in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2005;76:1445-7.
[Google Scholar]

[60] Papapetropoulos S, Gonzalez J, Lieberman A, Villar JM, Mash DC, . Dementia in Parkinson's disease: A post-mortem study in a population of brain donors. Int J Geriatr Psychiatry. 2005;20:418-22.
[Google Scholar]

[61] 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;20:190-9.
[Google Scholar]

[62] Holroyd S, Currie LJ, Wooten GF, . Depression is associated with impairment of ADL, not motor function in Parkinson disease. Neurology. 2005;64:2134-5.
[Google Scholar]

[63] Kang GA, Bronstein JM, Masterman DL, Redelings M, Crum JA, Ritz B, . Clinical characteristics in early Parkinson's disease in a central California population-based study. Mov Disord. 2005;20:1133-42.
[Google Scholar]

[64] Prado RC, Barbosa ER, . Depression in Parkinson's disease: Study of 60 cases. Arq Neuropsiquiatr. 2005;63:766-71.
[Google Scholar]

[65] Kirsch-Darrow L, Fernandez HH, Marsiske M, Okun MS, Bowers D, . Dissociating apathy and depression in Parkinson disease. Neurology. 2006;67:33-8.
[Google Scholar]

[66] Weintraub D, Morales KH, Duda JE, Moberg PJ, Stern MB, . Frequency and correlates of co-morbid psychosis and depression in Parkinson's disease. Parkinsonism Relat Disord. 2006;12:427-31.
[Google Scholar]

[67] Costa A, Peppe A, Carlesimo GA, Pasqualetti P, Caltagirone C, . Alexithymia in Parkinson's disease is related to severity of depressive symptoms. Eur J Neurol. 2006;13:836-41.
[Google Scholar]

[68] Visser M, Leentjens AF, Marinus J, Stiggelbout AM, van Hilten JJ, . Reliability and validity of the Beck depression inventory in patients with Parkinson's disease. Mov Disord. 2006;21:668-72.
[Google Scholar]

[69] Wichowicz HM, Slawek J, Derejko M, Cuba³a WJ, . Factors associated with depression in Parkinson's disease: A cross-sectional study in a Polish population. Eur Psychiatry. 2006;21:516-20.
[Google Scholar]

[70] Antonini A, Barone P, . Dopamine agonist-based strategies in the treatment of Parkinson's disease. Neurol Sci. 2008;29(Suppl 5):S371-4.
[Google Scholar]

[71] Barone P, Antonini A, Colosimo C, Marconi R, Morgante L, Avarello TP, . PRIAMO Study Group. The PRIAMO study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease. Mov Disord. 2009;24:1641-9.
[Google Scholar]

[72] Chen JJ, Marsh L, . Depression in Parkinson's disease: Identification and management. Pharmacotherapy. 2013;33:972-83.
[Google Scholar]

[73] Cubo E, Bernard B, Leurgans S, Raman R, . Cognitive and motor function in patients with Parkinson's disease with and without depression. Clin Neuropharmacol. 2000;23:331-4.
[Google Scholar]

[74] Happe S, Schrödl B, Faltl M, Müller C, Auff E, Zeitlhofer J, . Sleep disorders and depression in patients with Parkinson's disease. Acta Neurol Scand. 2001;104:275-80.
[Google Scholar]

[75] Happe S, Lüdemann P, Berger K, . FAQT Study Investigators. The association between disease severity and sleep-related problems in patients with Parkinson's disease. Neuropsychobiology. 2002;46:90-6.
[Google Scholar]

[76] Ossowska K, Lorenc-Koci E, . Depression in Parkinson's disease. Pharmacol Rep. 2013;65:1545-57.
[Google Scholar]

[77] Skapinakis P, Bakola E, Salanti G, Lewis G, Kyritsis AP, Mavreas V, . 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.
[Google Scholar]

[78] Liu J, Dong J, Wang L, Su Y, Yan P, Sun S, . Comparative efficacy and acceptability of antidepressants in Parkinson's disease: A network meta-analysis. PLoS One. 2013;8:e76651.
[Google Scholar]

[79] Faber R, Trimble MR, . Electroconvulsive therapy in Parkinson's disease and other movement disorders. Mov Disord. 1991;6:293-303.
[Google Scholar]

[80] Moellentine C, Rummans T, Ahlskog JE, Harmsen WS, Suman VJ, O’Connor MK, . Effectiveness of ECT in patients with Parkinsonism. J Neuropsychiatry Clin Neurosci. 1998;10:187-93.
[Google Scholar]

[81] Oh JJ, Rummans TA, O’Connor MK, Ahlskog JE, . Cognitive impairment after ECT in patients with Parkinson's disease and psychiatric illness. Am J Psychiatry. 1992;149:271.
[Google Scholar]

[82] Farabaugh A, Locascio JJ, Yap L, Growdon J, Fava M, Crawford C, . Cognitive-behavioral therapy for patients with Parkinson's disease and comorbid major depressive disorder. Psychosomatics. 2010;51:124-9.
[Google Scholar]

[83] Dobkin RD, Menza M, Allen LA, Gara MA, Mark MH, Tiu J, . Cognitive behaviour therapy for depression in Parkinson's disease: A randomized, controlled trial. Am J Psychiatry. 2011;168:1066-74.
[Google Scholar]

[84] Dobkin RD, Menza M, Allen LA, Tiu J, Friedman J, Bienfait KL, . Telephone-based cognitive-behavioral therapy for depression in Parkinson disease. J Geriatr Psychiatry Neurol. 2011;24:206-14.
[Google Scholar]

[85] Dobkin RD, Rubino JT, Allen LA, Friedman J, Gara MA, Mark MH, . Predictors of treatment response to cognitive-behavioral therapy for depression in Parkinson's disease. J Consult Clin Psychol. 2012;80:694-9.
[Google Scholar]

[86] Couto MI, Monteiro A, Oliveira A, Lunet N, Massano J, . Depression and anxiety following deep brain stimulation in Parkinson's disease: Systematic review and meta-analysis. Acta Med Port. 2014;27:372-82.
[Google Scholar]

[87] Epstein CM, Evatt ML, Funk A, Girard-Siqueira L, Lupei N, Slaughter L, . An open study of repetitive transcranial magnetic stimulation in treatment-resistant depression with Parkinson's disease. Clin Neurophysiol. 2007;118:2189-94.
[Google Scholar]

[88] Leentjens AF, . Depression in Parkinson's disease: Conceptual issues and clinical challenges. J Geriatr Psychiatry Neurol. 2004;17:120-6.
[Google Scholar]

[89] Seppi K, Weintraub D, Coelho M, Perez-Lloret S, Fox SH, Katzenschlager R, . The movement disorder society evidence-based medicine review update: Treatments for the non-motor symptoms of Parkinson's disease. Mov Disord. 2011;26(Suppl 3):S42-80.
[Google Scholar]

[90] Veazey C, Aki S, Cook KF, Lai EC, Kunik ME, . Prevalence and treatment of depression in Parkinson's disease. J Neuropsychiatry Clin Neurosci. 2005;17:310-23.
[Google Scholar]

[91] Cully JA, Johnson M, Moffett ML, Khan M, Deswal A, . Depression and anxiety in ambulatory patients with heart failure. Psychosomatics. 2009;50:592-8.
[Google Scholar]

[92] Siri C, Cilia R, De Gaspari D, Villa F, Goldwurm S, Marco C, . Psychiatric symptoms in Parkinson's disease assessed with the SCL-90R self-reported questionnaire. Neurol Sci. 2010;31:35-40.
[Google Scholar]

[93] Nègre-Pagès L, Grandjean H, Lapeyre-Mestre M, Montastruc JL, Fourrier A, Lépine JP, . DoPaMiP Study Group. Anxious and depressive symptoms in Parkinson's disease: The French cross-sectionnal DoPaMiP study. Mov Disord. 2010;25:157-66.
[Google Scholar]

[94] Leentjens AF, Dujardin K, Marsh L, Richard IH, Starkstein SE, Martinez-Martin P, . Anxiety rating scales in Parkinson's disease: A validation study of the Hamilton anxiety rating scale, the Beck anxiety inventory, and the hospital anxiety and depression scale. Mov Disord. 2011;26:407-15.
[Google Scholar]

[95] Pontone GM, Williams JR, Anderson KE, Chase G, Goldstein SA, Grill S, . Prevalence of anxiety disorders and anxiety subtypes in patients with Parkinson's disease. Mov Disord. 2009;24:1333-8.
[Google Scholar]

[96] Dissanayaka NN, Sellbach A, Matheson S, O’Sullivan JD, Silburn PA, Byrne GJ, . Anxiety disorders in Parkinson's disease: Prevalence and risk factors. Mov Disord. 2010;25:838-45.
[Google Scholar]

[97] Pontone GM, Williams JR, Anderson KE, Chase G, Goldstein SR, Grill S, . Anxiety and self-perceived health status in Parkinson's disease. Parkinsonism Relat Disord. 2011;17:249-54.
[Google Scholar]

[98] Chagas MH, Tumas V, Loureiro SR, Correa AC, Najabayashi TJK, Crippa JA, . Does the association between anxiety and Parkinson's disease really exist. A literature review? Curr Psychiatry Rev. 2009;5:29-36.
[Google Scholar]

[99] Menza MA, Robertson-Hoffman DE, Bonapace AS, . Parkinson's disease and anxiety: Comorbidity with depression. Biol Psychiatry. 1993;34:465-70.
[Google Scholar]

[100] Cummings JL, . Depression and Parkinson's disease: A review. Am J Psychiatry. 1992;149:443-54.
[Google Scholar]

[101] Walsh K, Bennett G, . Parkinson's disease and anxiety. Postgrad Med J. 2001;77:89-93.
[Google Scholar]

[102] Troeung L, Egan SJ, Gasson N, . A waitlist-controlled trial of group cognitive behavioural therapy for depression and anxiety in Parkinson's disease. BMC Psychiatry. 2014;14:19.
[Google Scholar]

[103] Borek LL, Amick MM, Friedman JH, . Non-motor aspects of Parkinson's disease. CNS Spectr. 2006;11:541-54.
[Google Scholar]

[104] Marsh L, . Psychosis in Parkinson's disease. Curr Treat Options Neurol. 2004;6:181-9.
[Google Scholar]

[105] Sanchez-Ramos JR, Ortoll R, Paulson GW, . Visual hallucinations associated with Parkinson disease. Arch Neurol. 1996;53:1265-8.
[Google Scholar]

[106] Graham C, Ballard C, Saad K, . Variables which distinguish patients fulfilling clinical criteria for dementia with Lewy bodies from those with Alzheimer's disease. Int J Geriatr Psychiatry. 1997;12:314-8.
[Google Scholar]

[107] Inzelberg R, Kipervasser S, Korczyn AD, . Auditory hallucinations in Parkinson's disease. J Neurol Neurosurg Psychiatry. 1998;64:533-5.
[Google Scholar]

[108] 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.
[Google Scholar]

[109] Fénelon G, Mahieux F, Huon R, Ziégler M, . Hallucinations in Parkinson's disease: Prevalence, phenomenology and risk factors. Brain. 2000;123:733-45.
[Google Scholar]

[110] Holroyd S, Currie L, Wooten GF, . Prospective study of hallucinations and delusions in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2001;70:734-8.
[Google Scholar]

[111] Schrag A, Ben-Shlomo Y, Quinn N, . How common are complications of Parkinson's disease? J Neurol. 2002;249:419-23.
[Google Scholar]

[112] Merims D, Shabtai H, Korczyn AD, Peretz C, Weizman N, Giladi N, . Antiparkinsonian medication is not a risk factor for the development of hallucinations in Parkinson's disease. J Neural Transm. 2004;111:1447-53.
[Google Scholar]

[113] Marsh L, Williams JR, Rocco M, Grill S, Munro C, Dawson TM, . Psychiatric comorbidities in patients with Parkinson disease and psychosis. Neurology. 2004;63:293-300.
[Google Scholar]

[114] Paleacu D, Schechtman E, Inzelberg R, . Association between family history of dementia and hallucinations in Parkinson disease. Neurology. 2005;64:1712-5.
[Google Scholar]

[115] Pacchetti C, Manni R, Zangaglia R, Mancini F, Marchioni E, Tassorelli C, . Relationship between hallucinations, delusions, and rapid eye movement sleep behavior disorder in Parkinson's disease. Mov Disord. 2005;20:1439-48.
[Google Scholar]

[116] Williams DR, Warren JD, Lees AJ, . Using the presence of visual hallucinations to differentiate Parkinson's disease from atypical parkinsonism. J Neurol Neurosurg Psychiatry. 2008;79:652-5.
[Google Scholar]

[117] Papapetropoulos S, Katzen H, Schrag A, Singer C, Scanlon BK, Nation D, . A questionnaire-based (UM-PDHQ) study of hallucinations in Parkinson's disease. BMC Neurol. 2008;8:21.
[Google Scholar]

[118] Forsaa EB, Larsen JP, Wentzel-Larsen T, Goetz CG, Stebbins GT, Aarsland D, . A 12-year population-based study of psychosis in Parkinson disease. Arch Neurol. 2010;67:996-1001.
[Google Scholar]

[119] Aarsland D, Kurz MW, . The epidemiology of dementia associated with Parkinson disease. J Neurol Sci. 2010;289:18-22.
[Google Scholar]

[120] Caviness JN, Driver-Dunckley E, Connor DJ, Sabbagh MN, Hentz JG, Noble B, . Defining mild cognitive impairment in Parkinson's disease. Mov Disord. 2007;22:1272-7.
[Google Scholar]

[121] Biundo R, Weis L, Facchini S, Formento-Dojot P, Vallelunga A, Pilleri M, . Cognitive profiling of Parkinson disease patients with mild cognitive impairment and dementia. Parkinsonism Relat Disord. 2014;20:394-9.
[Google Scholar]

[122] Foltynie T, Brayne CE, Robbins TW, Barker RA, . The cognitive ability of an incident cohort of Parkinson's patients in the UK. The CamPaIGN study. Brain. 2004;127:550-60.
[Google Scholar]

[123] Muslimovic D, Post B, Speelman JD, Schmand B, . Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology. 2005;65:1239-45.
[Google Scholar]

[124] Mamikonyan E, Moberg PJ, Siderowf A, Duda JE, Have TT, Hurtig HI, . Mild cognitive impairment is common in Parkinson's disease patients with normal Mini-Mental State Examination (MMSE) scores. Parkinsonism Relat Disord. 2009;15:226-31.
[Google Scholar]

[125] Aarsland D, Muniz G, Matthews F, . Nonlinear decline of mini-mental state examination in Parkinson's disease. Mov Disord. 2011;26:334-7.
[Google Scholar]

[126] Sollinger AB, Goldstein FC, Lah JJ, Levey AI, Factor SA, . Mild cognitive impairment in Parkinson's disease: Subtypes and motor characteristics. Parkinsonism Relat Disord. 2010;16:177-80.
[Google Scholar]

[127] Emre M, . Dementia in Parkinson's disease: Cause and treatment. Curr Opin Neurol. 2004;17:399-404.
[Google Scholar]

[128] Poewe W, Gauthier S, Aarsland D, Leverenz JB, Barone P, Weintraub D, . Diagnosis and management of Parkinson's disease dementia. Int J Clin Pract. 2008;62:1581-7.
[Google Scholar]

[129] Burn DJ, . The treatment of cognitive impairment associated with Parkinson's disease. Brain Pathol. 2010;20:672-8.
[Google Scholar]

[130] Robottom BJ, Weiner WJ, . Dementia in Parkinson's disease. Int Rev Neurobiol. 2009;84:229-44.
[Google Scholar]

[131] Sabbagh MN, Adler CH, Lahti TJ, Connor DJ, Vedders L, Peterson LK, . Parkinson disease with dementia: Comparing patients with and without Alzheimer pathology. Alzheimer Dis Assoc Disord. 2009;23:295-7.
[Google Scholar]

[132] Pagonabarraga J, Kulisevsky J, . Cognitive impairment and dementia in Parkinson's disease. Neurobiol Dis. 2012;46:590-6.
[Google Scholar]

[133] Perez F, Helmer C, Foubert-Samier A, Auriacombe S, Dartigues JF, Tison F, . Risk of dementia in an elderly population of Parkinson's disease patients: A 15-year population-based study. Alzheimers Dement. 2012;8:463-9.
[Google Scholar]

[134] Pfeiffer C, Wagner ML, . Clozapine therapy for Parkinson's disease and other movement disorders. Am J Hosp Pharm. 1994;51:3047-53.
[Google Scholar]

[135] Martinez-Martin P, . Nonmotor symptoms and health-related quality of life in early Parkinson's disease. Mov Disord. 2014;29:166-8.
[Google Scholar]

[136] Sobreira Neto MA, Pereira MA, Sobreira ES, Chagas MH, Rodrigues GR, Fernandes RM, . Sleep-related eating disorder in two patients with early-onset Parkinson's disease. Eur Neurol. 2011;66:106-9.
[Google Scholar]

[137] Abbott RD, Ross GW, White LR, Tanner CM, Masaki KH, Nelson JS, . Excessive daytime sleepiness and subsequent development of Parkinson disease. Neurology. 2005;65:1442-6.
[Google Scholar]

[138] Schenck CH, Bundlie SR, Mahowald MW, . Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology. 1996;46:388-93.
[Google Scholar]

[139] Iranzo A, Molinuevo JL, Santamaría J, Serradell M, Martí MJ, Valldeoriola F, . Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: A descriptive study. Lancet Neurol. 2006;5:572-7.
[Google Scholar]

[140] Postuma RB, Gagnon JF, Vendette M, Montplaisir JY, . Markers of neurodegeneration in idiopathic rapid eye movement sleep behaviour disorder and Parkinson's disease. Brain. 2009;132:3298-307.
[Google Scholar]

[141] Postuma RB, Gagnon JF, Vendette M, Montplaisir JY, . Idiopathic REM sleep behavior disorder in the transition to degenerative disease. Mov Disord. 2009;24:2225-32.
[Google Scholar]

[142] Gjerstad MD, Boeve B, Wentzel-Larsen T, Aarsland D, Larsen JP, . Occurrence and clinical correlates of REM sleep behaviour disorder in patients with Parkinson's disease over time. J Neurol Neurosurg Psychiatry. 2008;79:387-91.
[Google Scholar]

[143] Gjerstad MD, Wentzel-Larsen T, Aarsland D, Larsen JP, . Insomnia in Parkinson's disease: Frequency and progression over time. J Neurol Neurosurg Psychiatry. 2007;78:476-9.
[Google Scholar]

[144] Gjerstad MD, Alves G, Wentzel-Larsen T, Aarsland D, Larsen JP, . Excessive daytime sleepiness in Parkinson disease: Is it the drugs or the disease? Neurology. 2006;67:853-8.
[Google Scholar]

[145] Gjerstad MD, Aarsland D, Larsen JP, . Development of daytime somnolence over time in Parkinson's disease. Neurology. 2002;58:1544-6.
[Google Scholar]

[146] Onofrj M, Thomas A, D’Andreamatteo G, Iacono D, Luciano AL, Di Rollo A, . Incidence of RBD and hallucination in patients affected by Parkinson's disease: 8-year follow-up. Neurol Sci. 2002;23(Suppl 2):S91-4.
[Google Scholar]

[147] de Maindreville AD, Fénelon G, Mahieux F, . Hallucinations in Parkinson's disease: A follow-up study. Mov Disord. 2005;20:212-7.
[Google Scholar]

[148] Goetz CG, Wuu J, Curgian LM, Leurgans S, . Hallucinations and sleep disorders in PD: Six-year prospective longitudinal study. Neurology. 2005;64:81-6.
[Google Scholar]

[149] Sinforiani E, Pacchetti C, Zangaglia R, Pasotti C, Manni R, Nappi G, . REM behavior disorder, hallucinations and cognitive impairment in Parkinson's disease: A two-year follow up. Mov Disord. 2008;23:1441-5.
[Google Scholar]

[150] Larsen JP, Tandberg E, . Sleep disorders in patients with Parkinson's disease: Epidemiology and management. CNS Drugs. 2001;15:267-75.
[Google Scholar]

[151] Hobson DE, Lang AE, Martin WR, Razmy A, Rivest J, Fleming J, . Excessive daytime sleepiness and sudden-onset sleep in Parkinson disease: A survey by the Canadian Movement Disorders Group. JAMA. 2002;287:455-63.
[Google Scholar]

[152] Chung S, Bohnen NI, Albin RL, Frey KA, Müller ML, Chervin RD, . Insomnia and sleepiness in Parkinson disease: Associations with symptoms and comorbidities. J Clin Sleep Med. 2013;9:1131-7.
[Google Scholar]

[153] Prudon B, Duncan GW, Khoo TK, Yarnall AJ, Anderson KN, . Primary sleep disorder prevalence in patients with newly diagnosed Parkinson's disease. Mov Disord. 2014;29:259-62.
[Google Scholar]

[154] Neikrug AB, Maglione JE, Liu L, Natarajan L, Avanzino JA, Corey-Bloom J, . Effects of sleep disorders on the non-motor symptoms of Parkinson disease. J Clin Sleep Med. 2013;9:1119-29.
[Google Scholar]

[155] Chung WS, Lin CL, Chen YF, Chiang JY, Sung FC, Chang YJ, . Sleep disorders and increased risk of subsequent acute coronary syndrome in individuals without sleep apnea: A nationwide population-based cohort study. Sleep. 2013;36:1963-8.
[Google Scholar]

[156] Dhawan V, Healy DG, Pal S, Chaudhuri KR, . Sleep-related problems of Parkinson's disease. Age Ageing. 2006;35:220-8.
[Google Scholar]

[157] Friedman JH, Millman RP, . Sleep disturbances and Parkinson's disease. CNS Spectr. 2008;13(Suppl 4):12-7.
[Google Scholar]

[158] Comella CL, . Sleep disturbances in Parkinson's disease. Curr Neurol Neurosci Rep. 2003;3:173-80.
[Google Scholar]

[159] Chaudhuri KR, Bhattacharya K, Porter MC, . The use of cabergoline in nocturnal parkinsonian disabilities causing sleep disruption: A parallel study with controlled-release levodopa. Eur J Neurol. 1999;6(Suppl 5):S11-5.
[Google Scholar]

[160] Ghatani T, Agapito C, Bhattacharya K, Clough C, Ray Chaudhuri K, . Comparative audit of pergolide and cabergoline therapy in the treatment of nocturnal “off” periods causing sleep disruption in Parkinson's disease. Eur J Neurol. 2001;8(Suppl 1):8-11.
[Google Scholar]

[161] Loas G, Krystkowiak P, Godefroy O, . Anhedonia in Parkinson's disease: An overview. J Neuropsychiatry Clin Neurosci. 2012;24:444-51.
[Google Scholar]

[162] Lemke MR, Brecht HM, Koester J Kraus PH, Reichmann H, . Anhedonia, depression, and motor functioning in Parkinson's disease during treatment with pramipexole. J Neuropsychiatry Clin Neurosci. 2005;17:214-20.
[Google Scholar]

[163] Santangelo G, Morgante L, Savica R, Marconi R, Grasso L, Antonini A, . PRIAMO Study Group. Anhedonia and cognitive impairment in Parkinson's disease: Italian validation of the Snaith-Hamilton Pleasure Scale and its application in the clinical routine practice during the PRIAMO study. Parkinsonism Relat Disord. 2009;15:576-81.
[Google Scholar]

[164] Pluck GC, Brown RG, . Apathy in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2002;73:636-42.
[Google Scholar]

[165] Isella V, Iurlaro S, Piolti R, Ferrarese C, Frattola L, Appollonio I, . Physical anhedonia in Parkinson's disease. J NeurolNeurosurg Psychiatry. 2003;74:1308-11.
[Google Scholar]

[166] Fujiwara S, Kimura F, Hosokawa T, Ishida S, Sugino M, Hanafusa T, . Anhedonia in Japanese patients with Parkinson's disease. Geriatr Gerontol Int. 2011;11:275-81.
[Google Scholar]

[167] Miura S, Kida H, Nakajima J, Noda K, Nagasato K, Ayabe M, . Anhedonia in Japanese patients with Parkinson's disease: Analysis using the Snaith-Hamilton Pleasure Scale. Clin Neurol Neurosurg. 2012;114:352-5.
[Google Scholar]

[168] Assogna F, Cravello L, Caltagirone C, Spalletta G, . Anhedonia in Parkinson's disease: A systematic review of the literature. Mov Disord. 2011;26:1825-34.
[Google Scholar]

[169] Dujardin K, Sockeel P, Devos D, Delliaux M, Krystkowiak P, Destée A, . Characteristics of apathy in Parkinson's disease. Mov Disord. 2007;22:778-84.
[Google Scholar]

[170] Aarsland D, Larsen JP, Lim NG, Janvin C, Karlsen K, Tandberg E, . Range of neuropsychiatric disturbances in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry. 1999;67:492-6.
[Google Scholar]

[171] Starkstein SE, Mayberg HS, Preziosi TJ, Andrezejewski P, Leiguarda R, Robinson RG, . Reliability, validity, and clinical correlates of apathy in Parkinson's disease. J Neuropsychiatry Clin Neurosci. 1992;4:134-9.
[Google Scholar]

[172] Levy ML, Cummings JL, Fairbanks LA, Masterman D, Miller BL, Craig AH, . Apathy is not depression. J Neuropsychiatry Clin Neurosci. 1998;10:314-9.
[Google Scholar]

[173] Kirsch-Darrow L, Fernandez HH, Marsiske M, Okun MS, Bowers D, . Dissociating apathy and depression in Parkinson disease. Neurology. 2006;67:33-8.
[Google Scholar]

[174] Isella V, Melzi P, Grimaldi M, Iurlaro S, Piolti R, Ferrarese C, . Clinical, neuropsychological, and morphometric correlates of apathy in Parkinson's disease. Mov Disord. 2002;17:366-71.
[Google Scholar]

[175] Starkstein SE, Merello M, Jorge R, Brockman S, Bruce D, Power B, . The syndromal validity and nosological position of apathy in Parkinson's disease. Mov Disord. 2009;24:1211-6.
[Google Scholar]

[176] Saint-Cyr JA, Trépanier LL, Kumar R, Lozano AM, Lang AE, . Neuropsychological consequences of chronic bilateral stimulation of the subthalamic nucleus in Parkinson's disease. Brain. 2000;123:2091-108.
[Google Scholar]

[177] Trépanier LL, Kumar R, Lozano AM, Lang AE, Saint-Cyr JA, . Neuropsychological outcome of GPi pallidotomy and GPi or STN deep brain stimulation in Parkinson's disease. Brain Cogn. 2000;42:324-47.
[Google Scholar]

[178] Callesen MB, Weintraub D, Damholdt MF, Møller A, . Impulsive and compulsive behaviors among Danish patients with Parkinson's disease: Prevalence, depression, and personality. Parkinsonism Relat Disord. 2014;20:22-6.
[Google Scholar]

[179] Rohde K, Riedel O, Lueken U, Rietzel S, Fauser M, Ossig C, . Impulsive-compulsive behaviours in a German Parkinson's disease outpatient sample. Fortschr Neurol Psychiatr. 2013;81:503-10.
[Google Scholar]

[180] O’Sullivan SS, Evans AH, Lees AJ, . Dopamine dysregulation syndrome: An overview of its epidemiology, mechanisms and management. CNS Drugs. 2009;23:157-70.
[Google Scholar]

[181] Evans AH, Strafella AP, Weintraub D, Stacy M, . Impulsive and compulsive behaviors in Parkinson's disease. Mov Disord. 2009;24:1561-70.
[Google Scholar]

[182] Callesen MB, Scheel-Krüger J, Kringelbach ML, Møller A, . A systematic review of impulse control disorders in Parkinson's disease. J Parkinsons Dis. 2013;3:105-38.
[Google Scholar]

[183] Kostiæ VS, Pekmezoviæ T, Tomiæ A, Jecmenica-Lukiæ M, Stojkoviæ T, Spica V, . Suicide and suicidal ideation in Parkinson's disease. J Neurol Sci. 2010;289:40-3.
[Google Scholar]

[184] Myslobodsky M, Lalonde FM, Hicks L, . Are patients with Parkinson's disease suicidal? J Geriatr Psychiatry Neurol. 2001;14:120-4.
[Google Scholar]

[185] Nazem S, Siderowf AD, Duda JE, Brown GK, Ten Have T, Stern MB, . Suicidal and death ideation in Parkinson's disease. Mov Disord. 2008;23:1573-9.
[Google Scholar]

Psychiatric aspects of Parkinson's disease

Abstract

Keywords

Non-motor symptoms

Parkinson's disease

psychiatric manifestations

Introduction

Risk of Parkinson's disease in patients with psychiatric disorders

Depression in Parkinson's disease

Anxiety disorders in Parkinson's disease

Psychosis in Parkinson's disease

Cognitive deficits in Parkinson's disease

Sleep disorders in Parkinson's disease

Anhedonia in Parkinson's disease

Apathy in Parkinson's disease

Impulsive-compulsive disorders in PD

Dopamine dysregulation syndrome

Suicidal behavior in Parkinson's disease

Conclusion

References

Suggested read for related articles: