Depression In Parkinson's Disease Research Articles

A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease

To evaluate the efficacy and safety of a selective serotonin reuptake inhibitor (SSRI) and a serotonin and norepinephrine reuptake inhibitor (SNRI) in the treatment of depression in Parkinson disease (PD). A total of 115 subjects with PD were enrolled at 20 sites. Subjects were randomized to receive an SSRI (paroxetine; n = 42), an SNRI (venlafaxine extended release [XR]; n = 34), or placebo (n = 39). Subjects met DSM-IV criteria for a depressive disorder, or operationally defined subsyndromal depression, and scored >12 on the first 17 items of the Hamilton Rating Scale for Depression (HAM-D). Subjects were followed for 12 weeks (6-week dosage adjustment, 6-week maintenance). Maximum daily dosages were 40 mg for paroxetine and 225 mg for venlafaxine XR. The primary outcome measure was change in the HAM-D score from baseline to week 12. Treatment effects (relative to placebo), expressed as mean 12-week reductions in HAM-D score, were 6.2 points (97.5% confidence interval [CI] 2.2 to 10.3, p = 0.0007) in the paroxetine group and 4.2 points (97.5% CI 0.1 to 8.4, p = 0.02) in the venlafaxine XR group. No treatment effects were seen on motor function. Both paroxetine and venlafaxine XR significantly improved depression in subjects with PD. Both medications were generally safe and well tolerated and did not worsen motor function. This study provides Class I evidence that paroxetine and venlafaxine XR are effective in treating depression in patients with PD.

A comparison of nine scales to detect depression in Parkinson disease

The Methods of Optimal Depression Detection in Parkinson's Disease (MOOD-PD) study compared the psychometric properties of 9 depression scales to provide guidance on scale selection in Parkinson disease (PD). Patients with PD (n = 229) from community-based neurology practices completed 6 self-report scales (Beck Depression Inventory [BDI]-II, Center for Epidemiologic Studies Depression Rating Scale-Revised [CESD-R], 30-item Geriatric Depression Scale [GDS-30], Inventory of Depressive Symptoms-Patient [IDS-SR], Patient Health Questionnaire-9 [PHQ-9], and Unified Parkinson's Disease Rating Scale [UPDRS]-Part I) and were administered 3 clinician-rated scales (17-item Hamilton Depression Rating Scale [HAM-D-17], Inventory of Depressive Symptoms-Clinician [IDS-C], and Montgomery-Åsberg Depression Rating Scale [MADRS] and a psychiatric interview. DSM-IV-TR diagnoses were established by an expert panel blinded to the self-reported rating scale data. Receiver operating characteristic curves were used to estimate the area under the curve (AUC) of each scale. All scales performed better than chance (AUC 0.75-0.85). Sensitivity ranged from 0.66 to 0.85 and specificity ranged from 0.60 to 0.88. The UPDRS Depression item had a smaller AUC than the BDI-II, HAM-D-17, IDS-C, and MADRS. The CESD-R also had a smaller AUC than the MADRS. The remaining AUCs were statistically similar. The GDS-30 may be the most efficient depression screening scale to use in PD because of its brevity, favorable psychometric properties, and lack of copyright protection. However, all scales studied, except for the UPDRS Depression, are valid screening tools when PD-specific cutoff scores are used.

Studies of Depression-Related States in Animal Models of Parkinsonism

The diagnosis of Parkinson's disease (PD) is solely based on movement disorders, but several non-motor deficits are common in PD. Depression often precedes the movement dysfunctions and continues to be a major concern during all stages of the disease. The pathophysiology of parkinsonian depression is largely unknown, but appears to partly differ from depression in patients without PD. Because of the increased awareness of the negative impact of depression on the quality of life of PD patients, there is a growing interest in developing animal models of parkinsonism that also recapitulate the depressive-like symptomatology. This review introduces paradigms for measurement of depression-like behaviors in rodents and summarizes data on behavioral, neurochemical and pharmacological changes in experimental PD models with relevance for depression-related states.

Effects of depression and social support on comprehension and recall of informed consent information among Parkinson disease patients and their caregivers.

Relatively little attention has focused on the impact of psychiatric conditions on human subjects' comprehension of consent information. The purpose of this randomized study was to determine whether depression affects comprehension and recall of informed consent information among persons with Parkinson's disease and their caregivers and to evaluate the effects of support on comprehension and recall during the consent process. Comprehension and recall of information were assessed using a modified version of the Modified Quality of Informed Consent Questionnaire, taken 1 week and 1 month later, and scored using a consensus-based algorithm. Participants also completed the Center for Epidemiologic Studies Depression Scale. Data analyses were conducted on 129 patients and caregivers (t-tests, Fisher's exact tests, and ANCOVAs). T-tests showed no significant differences in comprehension and recall between depressed and nondepressed participants at 1 week and 1 month. However, ANCOVA showed patients with a support person present had significantly higher comprehension and recall at 1 week but not at 1 month compared with controls. Caregivers present with a patient had lower comprehension/recall than those without a patient present (p = 0.02). Having a support person present during the informed consent process helps depressed PD patients better retain information in the short-term, but effects diminish over the long-term. Implications for interventions will be discussed.

Depression in Parkinson disease—epidemiology, mechanisms and management

Depression occurs in around 35% of patients with Parkinson disease (PD) and is often persistent. Symptoms of depression can be evident in individuals at the time of diagnosis and might develop in the premotor stage of the disease. The underlying mechanisms of depression in PD are not known in detail, but changes in brain structure, signaling by neurotransmitters, and levels of inflammatory and neurotrophic factors are all suggested to contribute to its development. Psychosocial factors and pain could also have roles in depression. Changes in dopaminergic, noradrenergic and serotonergic systems in patients with PD might help to explain the incidence of depression in these individuals. Antidepressants that have dual serotonergic and noradrenergic effects are the drugs of choice for treating depression in PD. However, antiparkinsonian drugs might have beneficial effects not only on the motor symptoms of disease, but also on a patient's mood. Deep brain stimulation can worsen depression in some patients, but a preliminary study has suggested that transcranial magnetic stimulation could improve symptoms of depression. This Review describes the frequency and course of depression in patients with PD. The mechanisms that underlie depression in this disease are also discussed, and the management strategies for these patients are highlighted.

Telephone-Based Cognitive–Behavioral Therapy for Depression in Parkinson Disease

Although face-to-face cognitive-behavioral therapy (CBT) was found to be beneficial for the treatment of depression in Parkinson disease (dPD) in a recent randomized-controlled trial, access to care was identified as a critical issue that needs to be addressed in order to improve the management of this nonmotor complication in PD. The purpose of this study was to examine the feasibility and effect of telephone-based CBT for dPD. Twenty-one depressed people with PD participated in a National Institutes of Health-sponsored uncontrolled pilot trial of telephone-based CBT in an academic medical center from October 2009 to February 2011. The Hamilton Depression Rating Scale was the primary outcome. Treatment was provided to people with PD for 10 weeks, modified for delivery over the phone, and supplemented with 4 separate phone-based caregiver educational sessions. Assessments were completed at baseline and 5 (midpoint), 10 (end-of-treatment), and 14 weeks (follow-up) post-enrollment. Twenty (95%) people with PD completed the study treatment. Phone-based CBT was associated with significant improvements in depression, anxiety, negative thoughts, and coping. Mean Hamilton Depression Rating Scale change from baseline to week 10 was 7.91 points (P < .001, Cohen d = 1.21). Telephone-based CBT may be a feasible and helpful approach for treating dPD and warrants further exploration in randomized-controlled trials. Results were comparable to those observed in the few in-person cognitive-behavioral treatment studies for dPD conducted to date.

Depressive Symptoms in Parkinson Disease: Degree of Association and Rate of Agreement of Clinician-Based and Self-Report Measures

Depression in Parkinson disease (PD) is associated with faster disease progression, lower activities of daily living, and more severe cognitive impairment. Even mild symptoms of depression may impact outcomes in patients with PD. Nevertheless, a low rate of agreement has been reported between patient and clinician ratings of depression, suggesting that clinicians may underestimate depression in patients with PD. However, to accurately compare the rates of agreement, comparable estimates are needed so that patient and clinician ratings have similar meaning (eg, mild, moderate, severe, etc). The purpose of this study was to examine this question by investigating the degree of association and rate of agreement of levels of symptom severity among self-report and clinician ratings using established cutoffs that correspond to more comparable estimates of these levels for both patient and clinician. Our findings suggest that patient's self-report of depressive symptoms was significantly correlated with clinician-based report irrespective of the stage of disease. Moreover, patients demonstrated a 72% rate of agreement with clinicians in classifying symptoms as asymptomatic, mildly symptomatic, or fully symptomatic, a rate significantly higher than the rate of 35% previously reported. This difference in rate of agreement may be accounted for using varying criteria for severity levels across the studies. Findings suggest that clinician and patient reports show a high rate of agreement across a range of depressive symptoms and that self-report measures may provide a relatively efficient means of detecting depressive symptoms especially if patients are disinclined to initiate their report.

S.22.02 Biochemical and imaging findings in Parkinsonian depression

for depression [1]. This study also showed that the degree of psychopathology is driven by severity of PD. Consistent with this, a systematic review by Reijnders et al. summarized a mean crosssectional prevalence of 17% for major depression across studies, and highlighted that 22% of patients might suffer from minor depression and 35% for clinically relevant depressive symptoms [2]. Beyond depression most other types of psychopathology in PD remain poorly studied. Lacking appropriate longitudinal studies, the role and the meaning of psychopathology − even for more frequently studied depression − remains unclear. Pathophysiological and psychosocial mechanisms still remain speculative. Despite the high prevalence of psychopathological and indications that the presence of mental disorders might at least adversely affect functioning and prognosis [3], their frequent denomination as mere “non-motor” symptoms might signify that mental disorders in PD are undertreated. The GEPAD study suggests that treatment rates for depression (42.3%) were slightly better than those for anxiety (16%).

Neuroanatomical correlates of depression and apathy in Parkinson's disease: Magnetic resonance imaging studies

Depression and apathy are among the most common neuropsychiatric disturbances in Parkinson's disease (PD), and among the most important factors associated with a poor quality of life. However, their neural bases remain unclear. The results of the magnetic resonance imaging (MRI) studies on depression in PD differ dramatically. Some of them proposed a role of morphologic changes in the mediodorsal thalamus. In contrast to previous voxel-based morphometry (VBM) data, our study did not confirm a decrease in gray matter (GM) density in any brain region of depressed PD patients. Instead, a more severe white matter (WM) loss in the right frontal lobe was found, including the anterior cingulate bundle and the inferior orbitofrontal (OF) region. We suggested that the negative correlation between the severity of depression and WM density in the right OF region reinforces the hypothesis of depression in PD as a “disconnection syndrome”. Only one MRI study using VBM found that high apathy scores correlated with low GM density values in the right (posterior) cingulate gyrus and the bilateral inferior frontal gyrus, in line with the findings in Alzheimer's disease and elderly adults with major depression.

Apathy, but not depression, reflects inefficient cognitive strategies in Parkinson's disease.

BackgroundThe relationship between apathy, depression and cognitive impairment in Parkinson's disease (PD) is still controversial. The objective of this study is to investigate whether apathy and depression are associated with inefficient cognitive strategies in PD.MethodsIn this prospective clinical cohort study conducted in a university-based clinical and research movement disorders center we studied 48 PD patients. Based on clinical evaluation, they were classified in two groups: PD with apathy (PD-A group, n = 23) and PD without apathy (PD-NA group, n = 25). Patients received clinical and neuropsychological evaluations. The clinical evaluation included: Apathy Evaluation Scale-patient version, Hamilton Depression Rating Scale-17 items, the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr staging system; the neuropsychological evaluation explored speed information processing, attention, working memory, executive function, learning abilities and memory, which included several measures of recall (immediate free, short delay free, long delay free and cued, and total recall).FindingsPD-A and PD-NA groups did not differ in age, disease duration, treatment, and motor condition, but differed in recall (p<0.001) and executive tasks (p<0.001). Immediate free recall had the highest predictive value for apathy (F = 10.94; p = 0.002). Depression and apathy had a weak correlation (Pearson index = 0.3; p<0.07), with three items of the depression scale correlating with apathy (Pearson index between .3 and.4; p<0.04). The depressed and non-depressed PD patients within the non-apathetic group did not differ.ConclusionApathy, but not depression, is associated with deficit in implementing efficient cognitive strategies. As the implementation of efficient strategies relies on the fronto-striatal circuit, we conclude that apathy, unlike depression, is an early expression of executive impairment in PD.

Factors associated with depression in Parkinson's disease

Depression is common in Parkinson's disease (PD) and contributes significantly to a reduced quality of life in PD patients. The determinants of depression in PD are complex and poorly understood. We investigated the factors associated with depression in PD. PD patients were recruited from Neurology clinics. A validated method was used to screen for a lifetime history of depression. 'Depressed' patients were identified by a score of >6 in the Geriatric Depression Scale (GDS-15) or by having had prescribed treatment for depression. 'Never depressed' patients were recognised by a score of <5 in the GDS-15 with no signs of a history of depression. A newly developed and validated questionnaire was used to collect other information. Depression was identified in 66% of the 639 PD patients who met the inclusion criteria. Depression was associated with an increased severity of illness as evidenced by higher Unified PD Rating Scale scores and a higher Hoehn and Yahr stage. Other clinical factors associated with disease severity were also more frequently observed in depressed patients. Similar to findings in non-PD samples, depressed PD patients were more likely to have a lower education level, a history of smoking and to regularly use non-aspirin based NSAIDs or analgesics. Comorbidities such as anxiety, memory problems, hallucinations, sleep disturbances and postural hypotension were more common in depressed PD patients. To avoid patient exhaustion of over-surveying, some factors within the psychological domain were not examined. Our results provide a focus for future intervention strategies.

Bupropion as the treatment of choice in depression associated with Parkinson’s disease and it’s various treatments

Parkinson disease (PD) is a chronic progressive degenerative disorder that affects over 6 million people worldwide. It is manifested by motor and psychiatric signs. The latter inflicts up to 88% of PD patients. With the prolongation of life expectancy, it is presumed that the prevalence of PD will further rise, together with comorbid depression. As a result, the need for an adequate therapeutic answer for compounded PD with depression is called for urgently. Several theories try to explain the trigger of depression in PD patients by impaired activity in dopamine, norepinephrine and serotonin systems. Various treatment to combat depressive symptoms in PD patients were proposed and are in use, with ambiguous results and disturbing side effects. These anti-depressive modalities include SSRI's, SNRI, TCA, NRI and ECT. Dopamine agonists showed some anti-depressant activity in several studies in depressive PD, but may cause side effects such as dizziness, somnolence, confusion and even hallucinations. The role of dopamine agonists in the treatment of depression is still being explored because of no sufficient number of controlled studies in this area. Our hypothesis is to suggest NDRI - Bupropion - as the first line of treatment in PD patients with depression, in PD induced depression and/or in depression triggered by one of the treatments given for PD. Dual norepinephrine and dopamine reuptake inhibition is associated with unique clinical profile that compounds together anti-depressant efficacy without serotonin associated side effects such as weight gain, sedation, sexual dysfunction. Bupropion, as mainly dopaminergic and noradrenergic anti-depressant can alleviate therapeutically depressive symptoms associated with PD. Clinical controlled studies on Bupropion use in PD depressed patients are required to support this hypothesis.

Regional patterns of brain tissue loss associated with depression in Parkinson disease

To investigate, using MRI and voxel-based morphometry (VBM), whether specific patterns of gray matter (GM) and white matter (WM) loss are associated with depression in patients with Parkinson disease (PD). Forty patients with PD and 26 healthy subjects were studied. Patients were diagnosed with depression using DSM-IV criteria. The Hamilton Depression Rating Scale (HDRS) was administered to patients. The topographic distribution of brain tissue loss in patients with PD and controls was assessed using VBM as implemented in Statistical Parametric Mapping (SPM5). Twenty-four patients with PD were diagnosed as nondepressed (PD-NDep) and 16 as having depression (PD-Dep). Patient groups were similar in terms of clinical findings, except for the HDRS score (p < 0.001). Compared to controls, patients with PD showed common GM loss in the right anterior cingulate (AC) cortex and insula, and in the left middle frontal and angular gyri (p < 0.001). No regions of WM loss common to PD-NDep and PD-Dep patients relative to healthy controls were found. PD-Dep vs PD-NDep patients showed WM loss in the right AC bundle and inferior orbitofrontal (OF) region (p < 0.001). In patients with PD, HDRS score correlated with WM loss in the right inferior OF region (r = -0.51, p < 0.05). Tissue loss in several WM regions within the cortical-limbic network occurs in PD-Dep vs PD-NDep patients. Such pattern of brain atrophy overlaps with key regions involved in major depressive disorders, suggesting an increased vulnerability of this neural circuit in PD. This may partially account for the high prevalence of depression in PD.

Higher dopamine transporter density in Parkinson’s disease patients with depression

Depression is a frequent non-motor symptom in Parkinson's disease (PD) with increasing rates with the progression of the disease. Molecular imaging studies have shown a reduction of dopamine transporter (DAT) density in depressed PD patients (dPD); however, DAT role in the pathophysiology of PD depression is not clear since clinical matching was inappropriate and DAT reduction could be attributed to PD severity. To further examine the role of DAT in PD depression, this study compared thoroughly matched depressed vs. non-depressed PD patients (ndPD). Twenty PD patients (n = 10 ndPD; n = 10 dPD) matched for age and disease severity were submitted to brain SPECT imaging with [(99m)Tc]-TRODAT-1, a DAT radioligand. DAT-binding potential was calculated using regions of interest bilaterally drawn in the striatum, caudate, and putamen. Depression was defined according to Beck Depression Inventory (BDI; cut-off >18). Mean BDI scores were higher in dPD (25.0 +/- 5.6) than in ndPD patients (8.0 +/- 1.9, p < 0.0001). DAT density was greater on dPD especially in the left caudate (dPD 0.87 +/- 0.19 vs. ndDP 0.69 +/- 0.18, p = 0.02) and right putamen (dPD 0.37 +/- 0.07 vs. ndPD 0.28 +/- 0.13, p = 0.03) than in ndPD patients. Our results suggest that in vivo DAT density is increased in dPD patients as compared to ndPD, suggesting that DAT is implicated in the pathophysiology of PD depression.

The impact of antidepressant treatment on cognitive functioning in depressed patients with Parkinson's disease.

Depression is associated with more rapid cognitive decline in Parkinson's disease. The goal of this study was to examine the impact of the acute (8-week) and longer-term (24-week) antidepressant treatment on cognition in Parkinson's disease and to detail cognitive predictors of treatment response. Fifty-two depressed Parkinson's disease patients were enrolled in an NIH-funded randomized, controlled trial of nortriptyline, paroxetine, and placebo. Neuropsychological testing was performed at baseline and weeks 8 and 24. Higher baseline scores on measures of executive functioning, speed of processing, and verbal memory were associated with antidepressant response. Treatment responders did not exhibit larger gains in cognition than nonresponders. Findings warrant replication.

Cognitive–Behavioral Therapy for Patients With Parkinson’s Disease and Comorbid Major Depressive Disorder

Depression has been recognized as a common feature of Parkinson's disease (PD), and is the most prevalent psychiatric disorder in PD patients.The authors sought to determine whether cognitive-behavioral therapy (CBT) is effective in the treatment of depression within the context of PD (dPD).The authors enrolled 8 depressed PD patients into an open treatment study of 12 weeks of individual CBT treatment.There was a significant linear decrease in mean Hamilton Rating Scale for Depression (17-item) scores over Weeks 0 to 12, and 57% of patients (4/7) met criteria for remission at endpoint.This uncontrolled study suggests that CBT may be effective in treating dPD and may be an alternative or adjunct to pharmacological treatment.

Cognitive-Behavioral Therapy for Patients With Parkinson's Disease and Comorbid Major Depressive Disorder

Depression has been recognized as a common feature of Parkinson's disease (PD), and is the most prevalent psychiatric disorder in PD patients. The authors sought to determine whether cognitive-behavioral therapy (CBT) is effective in the treatment of depression within the context of PD (dPD). The authors enrolled 8 depressed PD patients into an open treatment study of 12 weeks of individual CBT treatment. There was a significant linear decrease in mean Hamilton Rating Scale for Depression (17-item) scores over Weeks 0 to 12, and 57% of patients (4/7) met criteria for remission at endpoint. This uncontrolled study suggests that CBT may be effective in treating dPD and may be an alternative or adjunct to pharmacological treatment.

Pramipexole for Depression in Parkinson Disease

Is pramipexole better than placebo for the treatment of mildly to moderately depressed, nondemented people with Parkinson disease (PD)? To find out, researchers conducted a 12-week, double blind, placebo-controlled, multicenter, manufacturer-sponsored trial involving 296 patients with mild-to-moderate depressive symptoms and PD without motor fluctuations. Pramipexole was statistically superior to placebo in reducing scores on the Beck Depression Inventory (the primary outcome) and on two other depression scales, while also improving motor …

P01-72 - Depression and neuropsychological functions in different stages of Parkinson's disease

IntroductionThe issue of the association between depression and neurocognitive functions is of special interest due to the strong relation between primary depressive symptoms and cognitive impairments, but this relationship in PD is far from clear at present.ObjectivesTo examine the influence of depression on cognitive and speech performance in various stages of PD.MethodsForty four patients with PD were recruited from the neurology department, University Hospital of Patras in Greece. All patients satisfied PDSBB criteria and dementia was ruled out (MMSE &lt; 24) in all cases. Patients were then divided into six groups, based on severity of PD symptoms and presence of depression. Stage of disease severity was determined using the Hoehn - Yahr Rating Scale. Presence and severity of depression was established using the Beck Depression Inventory and DSM -IV-TR diagnostic criteria for major depressive disorder and dysthymia. Patients were further assessed with a detailed neuropsychological battery and the dysarthria examination battery. All patients were receiving standard medications for their PD symptoms.ResultsDeficits in executive functions, prosody and speech intelligibility were most profound in the late stage depressed PD group. Phonetic impairments were most profound across all stages compared to articulatory and prosodic impairments.ConclusionsDepressed mood may exacerbate cognitive and speech impairments and affective variables should be an integral part in the treatment of PD in all stages of the disease process, but especially in the later stages.

Occurrence Risk and Structure of Depression in Parkinson Disease With and Without Dementia: Results From the GEPAD Study

This study examined the age- and gender-specific risk of depression in demented and non-demented participants, its symptom structure, and associated clinical factors in a nationwide random sample of n = 1449 outpatients with Parkinson disease (PD). Depression ratings were based on a cross-sectional clinical assessment including the clinical Montgomery-Asberg Depression Rating Scale (MADRS > or = 14). Parkinson disease severity was rated according to Hoehn and Yahr (HY) and the Unified Parkinson's Disease Rating Scale. Diagnosis of dementia was based on Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition; DSM-IV) criteria. 25.2% (CI: 22.8-27.5) of all patients met study criteria for depression. Additionally, 8.4% of patients did not exceed the MADRS cut-off but were currently being treated with antidepressants, possibly suggesting a corrected (upper limit) total prevalence of 33.6%. Females were more likely depressive than males (29.3% vs 22.4%). In both genders, depression risk was elevated 2- to 4-fold depending on HY stage. Overall, highest rates in non-demented patients were found in females at stages IV to V (53.7%, CI: 37.7-69.6). Demented patients were more likely to meet depression criteria than non-demented (up to 76.2%, 95% CI: 60.5-87.9). Depression symptom profiles for demented PD patients (as compared to non-demented) revealed no structural differences but consistently higher symptom scores. Neither age at onset of PD nor duration of disease were significantly linked with depression. Depression rates are already substantially elevated at early PD stages, emphasizing the need for a thorough examination of mood disorders in all patients with PD. Depression is associated with PD severity and dementia but not with age, age at onset of PD, or disease duration. The differential associations with dementia and the statistical independence of dementia and depression also suggest that depression could not be regarded as a mere demoralisation syndrome.