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Issei Shinmei,1,2 Kei Kobayashi,3 Yuki Oe,1 Yuriko Takagishi,1,4 Ayako Kanie,1 Masaya Ito,1 Yoshitake Takebayashi,1,5 Miho Murata,3 Masaru Horikoshi,1 Roseanne D Dobkin6 1National Center for Cognitive Behavioral Therapy and Research, National Center of Neurology and Psychiatry, Tokyo, Japan; 2Department of Neuropsychiatry, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan; 3Department of Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan; 4Department of Psychology, Surugadai University, Saitama, Japan; 5Risk Analysis Research Center, The Institute of Statistical Mathematics, Tokyo, Japan; 6Department of Psychiatry, Rutgers-Robert Wood Johnson Medical school, NJ, USA Objectives: This study evaluated the feasibility of cognitive behavioral therapy (CBT) for Japanese Parkinson’s disease (PD) patients with depression. To increase cultural acceptability, we developed the CBT program using manga, a type of Japanese comic novel.Methods: Participants included 19 non-demented PD patients who had depressive symptoms (GRID-Hamilton Rating Scale for Depression score ≥8). A CBT program comprising six sessions was individually administered. We evaluated the feasibility and safety of the CBT program in terms of the dropout rate and occurrence of adverse events. The primary outcome was depressive symptom reduction in the GRID-Hamilton Rating Scale for Depression upon completion of CBT. Secondary outcomes included changes in the self-report measures of depression (Beck Depression Inventory-II, Hospital Anxiety and Depression Scale-Depression), anxiety (Hospital Anxiety and Depression Scale-Anxiety, State and Trait Anxiety Inventory, Overall Anxiety Severity and Impairment Scale), functional impairment, and quality of life (Medical Outcomes Study 36-Item Short-Form Health Survey).Results: Of the 19 participants (mean age =63.8 years, standard deviation [SD] =9.9 years; mean Hohen–Yahr score =1.7, SD =0.8), one patient (5%) withdrew. No severe adverse event was observed. The patients reported significant improvements in depression (Hedges’ g =-1.02, 95% confidence interval =-1.62 to -0.39). The effects were maintained over a 3-month follow-up period. Most of the secondary outcome measurements showed a small-to-moderate but nonsignificant effect size from baseline to post-intervention.Conclusion: This study provides preliminary evidence that CBT is feasible among Japanese PD patients with depression. Similar approaches may be effective for people with PD from other cultural backgrounds. The results warrant replication in a randomized controlled trial. Keywords: CBT, anxiety, Japan, dPD, comorbidity

Background: 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.Methods: 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.Results: 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).Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background and Objectives: It is widely cited that dementia occurs in up to 80% of patients with Parkinson disease (PD), but studies reporting such high rates were published over two decades ago, had relatively small samples, and had other limitations. We aimed to determine long-term dementia risk in PD using data from two large, ongoing, prospective, observational studies., Methods: Participants from the Parkinson's Progression Markers Initiative (PPMI), a multisite international study, and a long-standing PD research cohort at the University of Pennsylvania (Penn), a single site study at a tertiary movement disorders center, were recruited. PPMI enrolled de novo, untreated PD participants and Penn a convenience cohort from a large clinical center. For PPMI, a cognitive battery is administered annually, and a site investigator makes a cognitive diagnosis. At Penn, a comprehensive cognitive battery is administered either annually or biennially, and a cognitive diagnosis is made by expert consensus. Interval-censored survival curves were fit for time from PD diagnosis to stable dementia diagnosis for each cohort, using cognitive diagnosis of dementia as the primary end point and Montreal Cognitive Assessment (MoCA) score <21 and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I cognition score ≥3 as secondary end points for PPMI. In addition, estimated dementia probability by PD disease duration was tabulated for each study and end point., Results: For the PPMI cohort, 417 participants with PD (mean age 61.6 years, 65% male) were followed, with an estimated probability of dementia at year 10 disease duration of 9% (site investigator diagnosis), 15% (MoCA), or 12% (MDS-UPDRS Part I cognition). For the Penn cohort, 389 participants with PD (mean age 69.3 years, 67% male) were followed, with 184 participants (47% of cohort) eventually diagnosed with dementia. The interval-censored curve for the Penn cohort had a median time to dementia of 15 years (95% CI 13-15); the estimated probability of dementia was 27% at 10 years of disease duration, 50% at 15 years, and 74% at 20 years., Discussion: Results from two large, prospective studies suggest that dementia in PD occurs less frequently, or later in the disease course, than previous research studies have reported.

Depression is highly comorbid among individuals with Parkinson's Disease (PD), who often experience unique challenges to accessing and benefitting from empirically supported interventions like Cognitive Behavioral Therapy (CBT). Given the role of reward processing in both depression and PD, this study analyzed a subset (N = 25) of participants who participated in a pilot telemedicine intervention of PD-informed CBT, and also completed a Reward- and Punishment-Learning Task (RPLT) at baseline. At the conclusion of CBT, participants were categorized into treatment responders (n = 14) and non-responders (n = 11). Responders learned more optimally from negative rather than positive feedback on the RPLT, while this pattern was reversed in non-responders. Computational modeling suggested group differences in learning rate to negative feedback may drive the observed differences. Overall, the results suggest that a within-subject bias for punishment-based learning might help to predict response to CBT intervention for depression in those with PD. Plain Language Summary Performance on a Computerized Task may predict which Parkinson's Disease Patients benefit from Cognitive Behavioral Treatment of Clinical Depression Why was the study done? Clinical depression regularly arises in individuals with Parkinson's Disease (PD) due to the neurobiological changes with the onset and progression of the disease as well as the unique psychosocial difficulties associated with living with a chronic condition. Nonetheless, psychiatric disorders among individuals with PD are often underdiagnosed and likewise undertreated for a variety of reasons. The results of our study have implications about how to improve the accuracy and specificity of mental health treatment recommendations in the future to maximize benefits for individuals with PD, who often face additional barriers to accessing quality mental health treatment. What did the researchers do? We explored whether performance on a computerized task called the Reward- and Punishment-Learning Task (RPLT) helped to predict response to Cognitive Behavioral Therapy (CBT) for depression better than other predictors identified in previous studies. Twenty-five individuals with PD and clinical depression that completed a 10-week telehealth CBT program were assessed for: Demographics (Age, gender, etc.); Clinical information (PD duration, mental health diagnoses, levels of anxiety/depression, etc.); Neurocognitive performance (Memory, processing speed, impulse control, etc.); and RPLT performance. What did the researchers find? A total of 14 participants significantly benefitted from CBT treatment while 11 did not significantly benefit from treatment.There were no differences before treatment in the demographics, clinical information, and neurocognitive performance of those participants who ended up benefitting from the treatment versus those who did not.There were, however, differences before treatment in RPLT performance so that those individuals that benefitted from CBT seemed to learn better from negative feedback. What do the findings mean? Our results suggest that the CBT program benefitted those PD patients with clinical depression that seemed to overall learn best from avoiding punishment rather than obtaining reward which was targeted in CBT by focusing on increasing engagement in rewarding activities. The Reward- and Punishment-Learning Task hence may be a useful tool to help predict treatment response and provide more individualized recommendations on how to best maximize the benefits of psychotherapy for individuals with PD that may struggle to connect to mental health care. Caution is recommended about interpretating these results beyond this study as the overall number of participants was small and the data for this study were collected as part of a previous study so there was no opportunity to include additional measurements of interest., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gregory Pontone reports a relationship with ACADIA Pharmaceuticals Inc that includes: consulting or advisory. Gregory Pontone reports a relationship with GE Healthcare that includes: consulting or advisory. Kelly Mills reports a relationship with Tilosia that includes: consulting or advisory. Ruth Schneider reports a relationship with ACADIA Pharmaceuticals Inc that includes: funding grants. Ruth Schneider reports a relationship with Pfizer Inc that includes: funding grants. Ruth Schneider reports a relationship with Biohaven Ltd that includes: funding grants. Ruth Schneider reports a relationship with ESCAPE Bio that includes: consulting or advisory. none.

Background: Minor phenomena, including passage phenomena, feeling of presence, and illusions, are common and may represent a prodromal form of psychosis in Parkinson's disease (PD). We examined the prevalence and clinical correlates of minor phenomena, and their potential role as a risk factor for PD psychosis., Methods: A novel questionnaire, the Psychosis and Mild Perceptual Disturbances Questionnaire for PD (PMPDQ), was completed by Fox Insight cohort participants with and without PD. Additional assessments included the Non-Motor Symptoms Questionnaire (NMSQuest), REM Sleep Behavior Disorder Single Question Screen (RBD1Q), Movement Disorder Society-Unified Parkinson Disease Rating Scale Part II, demographic features, and medication usage. For participants with PD, we used regression models to identify clinical associations and predictors of incident psychosis over one year of follow-up., Results: Among participants with PD (n = 5950) and without PD (n = 1879), the prevalence of minor phenomena was 43.1% and 31.7% ( P < .001). Of the 3760 participants with PD and no baseline psychosis, independent correlates of minor phenomena included positive responses on the NMSQuest apathy/attention/memory (OR 1.7, 95% CI 1.3-2.1, P < .001) or sexual function domain (OR 1.3, 95% CI 1.1-1.6, P = .01) and positive RBD1Q (OR 1.3, 95% CI 1.05-1.5, P = .01). Independent risk factors for incident PD psychosis included the presence of minor phenomena (HR 3.0, 95% CI 2.4-3.9, P < .001), positive response on the NMSQuest apathy/attention/memory domain (HR 1.8, 95% CI 1.3-2.6, P < .001), and positive RBD1Q (HR 1.5, 95% CI 1.1-1.9, P = .004)., Conclusions: Minor phenomena are common, associated with specific non-motor symptoms, and an independent predictor of incident psychosis in PD., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RS: Has received research support from Acadia Pharmaceuticals, Biohaven Pharmaceuticals, and Pfizer and consulted for Escape Bio. PA: Nothing to disclose. RD: Nothing to disclose. KM: Has consulted for Tilosia. CK: Nothing to disclose. TM: Nothing to disclose. MK: Nothing to disclose. GP: Has consulted for Acadia Pharmaceuticals and receives funding from the NIH. MJN: Nothing to disclose.

Objectives: Anxiety is common in Parkinson's disease (PD), negatively impacting daily functioning and quality of life in PD patients and their families. This systematic review evaluates the effectiveness of different psychotherapeutic approaches for reducing anxiety in PD and provides recommendations for clinical practise., Methods: Following PRISMA guidelines, 36 studies were included and risk of bias was evaluated., Results: We identified cognitive behavioral therapy (CBT), mindfulness-based therapies, acceptance and commitment therapy, and psychodrama psychotherapies. There is good evidence-base for anxiety reduction using CBT approaches, but with mixed results for mindfulness-based therapies. Other therapeutic approaches were under researched. Most randomized control trials examined anxiety as a secondary measure. There was a paucity of interventions for anxiety subtypes. Secondarily, studies revealed the consistent exclusion of PD patients with cognitive concerns, an importance of care partner involvement, and a growing interest in remote delivery of psychotherapy interventions., Conclusions: Person-centered anxiety interventions tailored for PD patients, including those with cognitive concerns, and trials exploring modalities other than CBT, warrant future investigations., Clinical Implications: Practitioners should consider PD-specific anxiety symptoms and cognitive concerns when treating anxiety. Key distinctions between therapeutic modalities, therapy settings and delivery methods should guide treatment planning.

Background: Little is known about the impact of the dopamine system on development of cognitive impairment (CI) in Parkinson disease (PD)., Objectives: We used data from a multi-site, international, prospective cohort study to explore the impact of dopamine system-related biomarkers on CI in PD., Methods: PD participants were assessed annually from disease onset out to 7 years, and CI determined by applying cut-offs to four measures: (1) Montreal Cognitive Assessment; (2) detailed neuropsychological test battery; (3) Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) cognition score; and (4) site investigator diagnosis of CI (mild cognitive impairment or dementia). The dopamine system was assessed by serial Iodine-123 Ioflupane dopamine transporter (DAT) imaging, genotyping, and levodopa equivalent daily dose (LEDD) recorded at each assessment. Multivariate longitudinal analyses, with adjustment for multiple comparisons, determined the association between dopamine system-related biomarkers and CI, including persistent impairment., Results: Demographic and clinical variables associated with CI were higher age, male sex, lower education, non-White race, higher depression and anxiety scores and higher MDS-UPDRS motor score. For the dopamine system, lower baseline mean striatum dopamine transporter values ( P range 0.003-0.005) and higher LEDD over time ( P range <0.001-0.01) were significantly associated with increased risk for CI., Conclusions: Our results provide preliminary evidence that alterations in the dopamine system predict development of clinically-relevant, cognitive impairment in Parkinson's disease. If replicated and determined to be causative, they demonstrate that the dopamine system is instrumental to cognitive health status throughout the disease course., Trial Registration: Parkinson's Progression Markers Initiative is registered with ClinicalTrials.gov (NCT01141023)., (© 2023 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Introduction: Parkinson's disease (PD) is characterized by high-rates of depression with limited evidence-based treatment options to improve mood. Objective: To expand therapeutic options, we evaluated the feasibility and effect of a telehealth mindfulness-based cognitive therapy intervention adapted for PD (MBCT-PD) in a sample of participants with DSM-5 depressive disorders. Methods: Fifteen participants with PD and clinically-significant depression completed 9 sessions of MBCT-PD. Depression, anxiety, and quality of life were evaluated at baseline, endpoint, and 1-month follow-up. Results: Telehealth MBCT-PD was feasible and beneficial. Completion rates exceeded 85% and treatment satisfaction rates were high. Notable improvements were observed for depression, anxiety, and quality of life over the course of the trial. Conclusion: Telehealth MBCT-PD shows promise and warrants further evaluation via randomized clinical trial with more diverse participants. Such research holds the potential to expand the range of therapeutic options for depression in PD, thereby setting the stage for personalized care.

Introduction: Caregiver distress is prevalent in Parkinson's disease (PD) and predictive of negative health outcomes for both people with PD and caregivers. To identify future intervention targets, it is important to better elucidate the specific processes, such as criticism, that perpetuate burden., Objective: Evaluate the frequency and impact of criticism and reactivity to criticism in PD caregiving dyads., Methods: Eighty-three people with PD and their caregivers independently completed measures of criticism and physical and emotional health., Results: Criticism in the caregiving relationship was reported by 71.1% (n = 59) of people with PD and 80.7% (n = 67) of caregivers. Both perceived criticism and emotional reactivity to criticism were significant predictors of caregiver distress, adjusting for PD motor and non-motor symptom severity. In contrast, criticism was not related to PD depression., Conclusion: Criticism in the PD caregiving relationship is a clear target for psychotherapeutic intervention and may improve caregiver health and quality of life.

Objective: Anxiety is a prominent concern in Parkinson's disease (PD) that negatively impacts quality of life, increases functional disability, and complicates clinical management. Atypical presentations of anxiety are under-recognized and inadequately treated in patients with PD, compromising global PD care., Methods: This systematic review focuses on the prevalence, symptomology and clinical correlates of atypical presentations of PD-related anxiety following PRISMA guidelines., Results: Of the 60 studies meeting inclusion criteria, 14 focused on 'Anxiety Not Otherwise Specified (NOS)' or equivalent, 31 reported on fluctuating anxiety symptoms, and 22 reported on 'Fear of Falling (FOF)'. Anxiety NOS accounted for a weighted mean prevalence of 14.9%, fluctuating anxiety for 34.19%, and FOF for 51.5%. These latter two exceeded the average reported overall prevalence rate of 31% for anxiety disorders in PD. We identified a diverse array of anxiety symptoms related to motor and non-motor symptoms of PD, to complications of PD medication (such as "on" and "off" fluctuations, or both), and, to a lesser extent, to cognitive symptoms., Conclusion: Atypical anxiety is common, clinically relevant, and heterogeneous in nature. A better understanding of the phenomenology, clinical course, and pathophysiology of varied forms of atypical anxiety in PD is needed to improve recognition, advance therapeutic development and ultimately optimize quality of life in PD., (Copyright © 2022. Published by Elsevier Inc.)

In people with Parkinson's disease, neuropsychiatric signs and symptoms are common throughout the disease course. These symptoms can be disabling and as clinically relevant as motor symptoms, and their presentation can be similar to, or distinct from, their counterparts in the general population. Correlates and risk factors for developing neuropsychiatric signs and symptoms include demographic, clinical, and psychosocial characteristics. The underlying neurobiology of these presentations is complex and not well understood, with the strongest evidence for neuropathological changes associated with Parkinson's disease, mechanisms linked to dopaminergic therapy, and effects not specific to Parkinson's disease. Assessment instruments and formal diagnostic criteria exist, but there is little routine screening of these signs and symptoms in clinical practice. Mounting evidence supports a range of pharmacological and non-pharmacological interventions, but relatively few efficacious treatment options exist. Optimising the management of neuropsychiatric presentations in people with Parkinson's disease will require additional research, raised awareness, specialised training, and development of innovative models of care., Competing Interests: Declaration of interests DW received research funding or support from Michael J Fox Foundation for Parkinson's Research, Alzheimer's Therapeutic Research Initiative, Alzheimer's Disease Cooperative Study, the International Parkinson and Movement Disorder Society, and the National Institute on Aging; honoraria for consultancy from Acadia, Aptinyx, CHDI Foundation, Clintrex LLC (Alkahest, Aptinyx, Avanir, and Otsuka), Eisai, Enterin, Great Lake Neurotechnologies, Janssen, Sage, Scion, Signant Health, Sunovion, and Vanda; and license fee payments from the University of Pennsylvania for the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease and Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale. DA received grants from Roche Diagnostics and Sanofi; consulting fees from Enterin, Acadia, and Wiley; and participated as an advisory board member for Biogen and served as committee chair for Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment Lewy Body Dementias Professional Interest Area. KRC received honoraria for advisory boards from AbbVie, Britannia Pharmaceuticals, UCB, Pfizer, Jazz Pharma, GKC, Bial, Cynapsus, Novartis, Lobsor, Stada, Medtronic, Zambon, Profile Pharma, Sunovion, Roche, Theravance Biopharma, and Scion; honoraria for lectures from AbbVie, Britannia Pharmaceuticals, UCB, Mundipharma, Zambon, Novartis, Boeringer Ingelheim Neuroderm, and Sunovion; grants from Britannia Pharmaceuticals, AbbVie, UCB, GKC, Bial; and academic grants from the EU (Horizon 2020), Innovative Medicines Initiative EU, Parkinson's UK, UK National Institute for Health Research, Parkinson's Disease Non Motor Group, Kirby Laing Foundation, US Parkinson's Foundation, and UK Medical Research Council. RDD received grant support from the Michael J Fox Foundation for Parkinson's disease Research and the US Veteran Affairs Administration; honoraria for lectures from the World Parkinson Congress, Movement Disorders Society, and Englewood Healthcare System; and served as co-chair of the Cognitive and Psychiatric Working Group for the Parkinson Study Group, an executive steering committee member for the Parkinson's Progression Markers Initiative sponsored by the Michael J Fox Foundation for Parkinson's disease research, and a scientific advisory board member for the David Phinney Foundation for Parkinson's disease Research. AFGL received royalties from De Tijdstroom Publishers and Springer Media; payment and honoraria from the European Brain Council for presenting at the European Psychiatric Association conference in 2019; and served as a member of the editorial board for the Journal of Psychosomatic Research (Elsevier) and a member of the Parkinson's disease guideline committee for the Knowledge Institute of the Federation of Medical Specialists. AS received a grant from GE Healthcare to study late-onset depression and an honorarium from Movement Disorder Society for a lecture on depression in Parkinson's disease., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: For several decades, a myriad of factors have contributed to the inadequate diagnosis and management of depression in Parkinson's disease (PD), leaving up to 60% of significantly symptomatic patients untreated. Poor access to evidence-based neuropsychiatric care is one major barrier to achieving optimal Parkinson's outcomes., Objective: The goal of this study was to compare the efficacy of individual Parkinson's-informed, video-to-home cognitive-behavioral therapy (experimental group), to clinic-based treatment as usual (control group), for depression in PD., Method: Ninety United States military veterans with clinical diagnoses of both depression and PD were computer-randomized (1:1) to either the experimental or control group; randomization was stratified by baseline antidepressant use and blind to all other baseline data. The acute treatment period spanned 10 weeks and was followed by a 6-month extension phase. The Hamilton Depression Rating Scale was the a priori primary outcome. Depression treatment response was defined as a score ≤2 on the Clinical Global Impression Improvement Scale. All statistical analyses were intent to treat., Results: Video-to-home cognitive-behavioral therapy outperformed clinic-based treatment as usual across three separate depression measures (P < 0.001). Effects were observed at the end of acute treatment and maintained through 6-month follow-up. Number needed to treat (based on treatment response classification) was 2.5 with an absolute risk reduction of 40%., Conclusion: Video-to-home cognitive-behavioral therapy may be an effective intervention to bypass access barriers to specialized, evidence-based depression care in PD and to address the unmet neuropsychiatric treatment needs of the Parkinson's community. © 2021 International Parkinson and Movement Disorder Society., (© 2021 International Parkinson and Movement Disorder Society.)

Objective: To determine whether, for patients with depression and Parkinson disease (PD), telephone-based cognitive-behavioral treatment (T-CBT) alleviates depressive symptoms significantly more than treatment as usual (TAU), we conducted a randomized controlled trial to evaluate the efficacy of a 10-session T-CBT intervention for depression in PD, compared to TAU., Methods: Seventy-two people with PD (PWP) were randomized to T-CBT + TAU or TAU only. T-CBT tailored to PWPs' unique needs was provided weekly for 3 months, then monthly during 6-month follow-up. CBT targeted negative thoughts (e.g., "I have no control"; "I am helpless") and behaviors (e.g., social withdrawal, excessive worry). It also trained care partners to help PWP practice healthy habits. Blind raters assessed outcomes at baseline, midtreatment, treatment end, and 1 and 6 months post-treatment. Analyses were intent to treat., Results: T-CBT outperformed TAU on all depression, anxiety, and quality of life measures. The primary outcome (Hamilton Depression Rating Scale score) improved significantly in T-CBT compared to TAU by treatment end. Mean improvement from baseline was 6.53 points for T-CBT and -0.27 points for TAU ( p < 0.0001); gains persisted over 6-month follow-up ( p < 0.0001). Improvements were moderated by a reduction in negative thoughts in the T-CBT group only, reflecting treatment target engagement., Conclusions: T-CBT may be an effective depression intervention that addresses a significant unmet PD treatment need and bypasses access barriers to multidisciplinary, evidence-based care., Clinicaltrialsgov Identifier: NCT02505737., Classification of Evidence: This study provides Class I evidence that for patients with depression and PD, T-CBT significantly alleviated depressive symptoms compared to usual care., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Clinical research in Parkinson's disease (PD) faces practical and ethical challenges due to two interrelated problems: participant under-recruitment and lack of diversity. Fox Insight (FI) is a web-based longitudinal study collecting patient-reported outcomes and genetic data worldwide to inform therapeutic studies. FI's online platform provides an opportunity to evaluate online strategies for recruiting large, diverse research cohorts., Objective: This project aimed to determine 1) whether FI's digital marketing was associated with increased enrollment overall and from under-represented patient groups, compared to traditional recruitment methods; 2) the clinical and demographic characteristics of samples recruited online, and 3) the cost of this online recruitment., Method: FI recruitment during a 6-week baseline period without digital promotion was compared to recruitment during several periods of digital outreach. Separate online recruiting intervals included general online study promotion and unique Facebook and Google ad campaigns targeting under-represented subgroups: early PD, late/advanced PD, and residents of underrepresented/rural geographic areas., Results: Early PD, late PD, and geotargeting campaigns enrolled more individuals in their respective cohorts compared to baseline. All online campaigns also yielded greater total FI enrollment, attracting more participants who were non-White, Hispanic, older, female, and had lower educational attainment and income, and more medical comorbidities. Cost per new participant ranged from $21 (Facebook) to $108 (Google)., Conclusion: Digital marketing may allow researchers to increase, accelerate, and diversify recruitment for PD clinical studies, by tailoring digital ads to target PD cohort characteristics.

As Parkinson's disease (PD) is a heterogeneous disorder, personalized medicine is truly required to optimize care. In their current form, standard scores from paper and pencil symptom- measures traditionally used to track disease progression are too coarse (discrete) to capture the granularity of the clinical phenomena under consideration, in the face of tremendous symptom diversity. For this reason, sensors, wearables, and mobile devices are increasingly incorporated into PD research and routine care. These digital measures, while more precise, yield data that are less standardized and interpretable than traditional measures, and consequently, the two types of data remain largely siloed. Both of these issues present barriers to the broad clinical application of the field's most precise assessment tools. This protocol addresses both problems. Using traditional tasks to measure cognition and motor control, we test the participant, while co-registering biophysical signals unobtrusively using wearables. We then integrate the scores from traditional paper-and-pencil methods with the digital data that we continuously register. We offer a new standardized data type and unifying statistical platform that enables the dynamic tracking of change in the person's stochastic signatures under different conditions that probe different functional levels of neuromotor control, ranging from voluntary to autonomic. The protocol and standardized statistical framework offer dynamic digital biomarkers of physical and cognitive function in PD that correspond to validated clinical scales, while significantly improving their precision.

Parkinson disease (PD) is a progressive neurodegenerative disease with a higher prevalence of neuropsychiatric symptoms compared with the general population. Symptoms such as anxiety, depression, psychosis, impulse control disorders, and cognitive impairment cause a greater worsening of quality of life than even the motor symptoms that define PD. Despite the ubiquity and impact of neuropsychiatric symptoms, specialty mental healthcare is not routinely available, accessible, or integrated in most neurology practices. Currently, training in PD-specific mental healthcare is not standard in most programs, and the need for subspecialty-trained, mental healthcare providers will only increase over time, as the prevalence of PD will more than double by 2060. Many barriers limit extension of mental healthcare into existing models of integrated or multidisciplinary care and the community at large. Foundations and professional societies have played an important role in raising awareness of mental healthcare needs in PD; however, their initiatives to promote integrated or multidisciplinary care have traditionally focused on disciplines outside of mental health such as physical, occupational, and speech therapy. This article examines these issues and suggests strategies to better address mental healthcare needs for PD patients in the future., (Copyright © 2019 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Depression is among the most common and debilitating nonmotor complaints in Parkinson's disease (PD), yet there is a paucity of controlled research to guide treatment. Little research has focused on the extent to which specific depressive symptom profiles may dictate unique clinical recommendations to ultimately improve treatment outcomes. The current study examined the impact of cognitive behavioral therapy (CBT) on different types of depressive symptoms in PD. It was hypothesized that the cognitive (eg, guilt, rumination, and negative attitudes towards self) and behavioral (eg, avoidance and procrastination) symptoms targeted most intensively by the treatment protocol would show the most robust response. The extent to which stabilized antidepressant use moderated specific symptom change was examined on an exploratory basis., Method: Eighty depressed people with PD participated in a randomized controlled trial of CBT plus clinical management, versus clinical management only. Hamilton Depression Rating Scale (HAMD) and Beck Depression Inventory (BDI) subscale scores, reflecting depressive symptom heterogeneity in PD, were the focus of this investigation., Results: CBT response was associated with significant improvements in mood, sleep, anxiety, and somatic symptoms (HAMD), and negative attitudes toward self, performance impairment, and somatic symptoms (BDI). As hypothesized, the largest effect sizes were observed for cognitive and behavioral (vs somatic) symptoms of depression. Stabilized antidepressant use moderated the effect of CBT on somatic complaints (HAMD and BDI)., Conclusions: CBT may improve a diverse array of depressive symptoms in PD. Cognitive and behavioral (vs somatic) symptoms showed the greatest change. Combining CBT with antidepressants may help optimize the management of somatic complaints in depression in PD (dPD)., (© 2019 John Wiley & Sons, Ltd.)

High rates of depression are observed in Parkinson's disease, and limited access to care complicates management. The purpose of this pilot project was to evaluate the feasibility and impact of a personalized cognitive-behavioral telemedicine program for depression in Parkinson's disease (dPD). Thirty-four individuals with dPD and their carepartners participated in this pilot study. A 10-module self-help workbook, tailored to the unique needs of the dPD population, was created to be used as either a stand-alone intervention, with minimal therapist support, or a supplement to formal telephone-administered cognitive-behavioral therapy sessions. Improvements in depression, anxiety, quality of life, sleep, negative thoughts, and caregiver burden were observed over the course of the 4-month study, independent of treatment modality (guided self-help vs formal telephone-based psychotherapy). Future research will utilize randomized controlled designs and continue to focus on delivery models that can improve access to this and other evidence-based mental health interventions for dPD.

People with Parkinson's disease (PD) and their care partners frequently report cognitive decline as one of their greatest concerns. Mild cognitive impairment affects approximately 20-50% of people with PD, and longitudinal studies reveal dementia in up to 80% of PD. Through the Parkinson's Disease Foundation Community Choice Research Award Program, the PD community identified maintaining cognitive function as one of their major unmet needs. In response, a working group of experts across multiple disciplines was organized to evaluate the unmet needs, current challenges, and future opportunities related to cognitive impairment in PD. Specific conference goals included defining the current state in the field and gaps regarding cognitive issues in PD from patient, care partner, and healthcare professional viewpoints; discussing non-pharmacological interventions to help maintain cognitive function; forming recommendations for what people with PD can do at all disease stages to maintain cognitive health; and proposing ideas for how healthcare professionals can approach cognitive changes in PD. This paper summarizes the discussions of the conference, first by addressing what is currently known about cognitive dysfunction in PD and discussing several non-pharmacological interventions that are often suggested to people with PD. Second, based on the conference discussions, we provide considerations for people with PD for maintaining cognitive health and for healthcare professionals and care partners when working with people with PD experiencing cognitive impairment. Furthermore, we highlight key issues and knowledge gaps that need to be addressed in order to advance research in cognition in PD and improve clinical care., Competing Interests: J.G.G. has received consulting/advisory board honoraria from Acadia, Aptinyx, Biogen; grants/research support from Acadia, Biotie (site PI), Consolidated Anti-Aging, National Institutes of Health, National Parkinson Foundation, Michael J. Fox Foundation, Rush University; honoraria from American Academy of Neurology, International Parkinson and Movement Disorder Society, MedEdicus; and salary from Rush University Medical Center. B.A.V. has received salary from the Parkinson’s Foundation. R.C. has received research funding from the Canadian Institutes for Health Research (CIHR), Alberta Innovates Solutions, the Alzheimer Society of Canada, University of Alberta Hospital Foundation, and National Institutes of Health and is a site investigator for a pharmaceutical trial sponsored by Axovant (back up site); served on the Scientific advisory board for Michael J. Fox Foundation, the Parkinson’s Disease Foundation, Parkinson Canada, Editorial board for Frontiers in Aging Neurosciences, Dementia and Geriatric Cognitive Disorders, Parkinsonism and Related Disorders, and as safety monitor/scientific advisor for a Harvard University/Tel Aviv University trial of DCTMS and a Western University investigator initiated pharmaceutical trial. N.D. has received grant/research support from the National Institutes of Health, Parkinson’s Foundation, Michael J. Fox Foundation, Parkinson Council, Biotie, Abbvie and salary from the University of Pennsylvania. R.D. has received grant/research support from the Michael J. Fox Foundation, the Parkinson’s Unity Walk, the Veteran Affairs Administration, and the Parkinson’s Foundation; consulting fees from the Michael J. Fox Foundation and the University of Delaware; and salary from Rutgers University. T.E. has received grant/research support from the National Institutes of Health, American Parkinson Disease Association and salary support from Boston University. J.E.G. has received grant/research support from the National Institutes of Health, Florida Department of Health, the Harry T. Mangurian Foundation, and the Association for Frontotemporal Degeneration, serves as a scientific advisor for Axovant, Biogen, Eisai, and Eli Lilly; receives licensing fees from Pfizer, Lilly, Axovant, and Quintiles; conducts on-going clinical trials funded by Biogen, Axovant, and Janssen, and serves on the editorial boards of Neurodegenerative Disease Management, Alzheimer’s Disease and Associated Disorders, and Acta Neuropathologica. C.M. has received grant/research support from The Michael J. Fox Foundation, Canadian Institutes of Health Research, Movement Disorders Society; National Institutes of Health; served as a consultant to Accorda Therapeutics; received honoraria from EMD Serono, steering committee for National Parkinson Foundation; and salary from the University Health Network. J. Edwards serves on Data Safety Monitoring Boards on National Institutes of Health grants awarded to Posit Science Inc. She previously served as a limited consultant to Posit Science Inc. in 2007, and has worked as a consultant to Wilson Sonsini Goodrich & Rosati. J.F. has received grant support from the Patient Centered Outcomes Research Institute, National Institutes of Health, and salary from Mayo Clinic, Rochester, MN. J.K. serves as a site PI for clinical trials sponsored by Novartis and Lilly and as a consultant to John Hancock. L.S. has received grant/research support from the National Institutes of Health, the Michael J. Fox Foundation, and Biotie/Acorda. G.S. has received grant support from the Patient Centered Outcomes Research Institute and National Institutes of Health and the Florida Department of Health; consulting fees from Novartis, the NFL Concussion Settlement Program and book royalties; and salary from the University of Florida, Gainesville. C.T. has received grant/research support from National Institutes of Health; consulting/advisory board honoraria from UpToDate Inc., Viocare Food Intake Advisory Board; and salary from Rush University Medical Center. C.A.T. has received grant/research support from the National Institutes of Health and salary support from Boston University. E.U. has received grant/research support from Michael J. Fox Foundation, National Institutes of Health, Department of Veterans Affairs; honoraria from the American Academy of Neurology; and salary from University of Iowa and Department of Veterans Affairs. The remaing authors declare no competing interests.

The authors describe neuropsychological outcomes in people with Parkinson's disease (PD) after their participation in an NIH-sponsored, randomized, controlled trial of cognitive-behavioral treatment for depression. Improvements in mood were associated with modest gains in verbal memory and executive functioning over the 10-week treatment period and accounted for greater variance in neuropsychological outcomes at the end of treatment than other known correlates of cognitive functioning in PD, such as disease severity, age, and education. Baseline working memory and executive skills were also associated with depression improvement over time.

Objective: Dysfunctional voiding (DV) is an extremely common pediatric complaint. The goal of this study was to examine the relationship between DV and childhood temperament., Methods: Information about the voiding behaviors and temperaments of 50 children was examined using a case-control model. Caregivers were asked to fill out the Children's Behavior Questionnaire in order to rate their child on the dimensions of surgency, negative affect, and effortful control. The relationship between DV and these dimensions was then evaluated., Results: Males with DV were found to have lower effortful control than males with normal voiding habits. Females with DV did not demonstrate a difference in effortful control, but did demonstrate a higher rate of surgency., Conclusions: The results suggest that temperament does have an association with DV. These findings are in line with temperamental associations with other externalizing trouble behaviors and may inform potential treatment strategies for DV.

Background: Parkinson's disease (PD) is frequently complicated by co-occurring psychiatric problems such as depression and anxiety that negatively affect the course and management of the illness. Yet, in most cases, these psychiatric comorbidities are neither recognized nor treated to remission. The primary purpose of this study was to identify and describe barriers to mental health care utilization for people with PD. Secondary objectives included the assessment of attitudes and preferences regarding the need for mental health services in the PD community and the acceptability of telehealth interventions as a method for improving access and quality of care., Methods: A total of 769 people with PD completed an anonymous cross-sectional questionnaire assessing barriers to mental health care utilization in this medical population. Respondents were drawn from a national sample., Results: Commonly endorsed barriers to mental health care utilization in PD reflect the patients' incomplete understanding of mental health problems, access issues, and illness-specific concerns, as well as the inadequate screening and detection of psychiatric complications by medical providers and the need for more effective treatments in this medical population. Several demographic, medical, and psychiatric variables also influenced the likelihood of accessing mental health care. Interest in telehealth approaches to mental health treatment was high and, in several instances, correlated with perceived barriers to mental health care utilization., Conclusions: People with PD may encounter a multitude of barriers that impede their pursuit of mental health care. Clinical implications are discussed and further research is needed to replicate and extend these findings.

Objective: The purpose of this study was to examine predictors of treatment response to cognitive-behavioral therapy (CBT) for depression in Parkinson's disease (PD)., Method: The sample comprised 80 depressed (DSM-IV criteria) adults with PD (60% male) and their caregivers who participated in an National Institutes of Health-sponsored randomized-controlled trial of CBT vs. clinical monitoring from April 2007 until July 2010. Individually administered CBT was provided to people with PD for 10 weeks, modified to address the unique needs of the medical population, and supplemented with up to 4 separate caregiver educational sessions. Treatment response was defined a priori as a rating of depression much improved or very much improved on the Clinical Global Impression-Improvement Scale or ≥ 50% reduction in the baseline Hamilton Depression Rating Scale score. It was hypothesized (a priori) that caregiver participation in treatment, motor disability, psychiatric comorbidity, and executive functioning would be significant predictors of response to CBT at end-of-treatment (Week 10) and short-term follow-up (Week 14)., Results: At Week 10, caregiver participation was the only significant predictor of treatment response in the CBT group. At Week 14, both caregiver participation and executive functioning predicted response to CBT. Treatment group, baseline depression severity, executive functioning, motor disability, psychiatric comorbidity, marital status, and caregiver burden were also related to change in depression scores, for all participants, in secondary and exploratory models., Conclusions: Caregiver participation may enhance acute treatment response to psychosocial interventions for depression in PD. Further research is needed to extend and replicate these findings., (© 2012 American Psychological Association)

Objective: Despite the negative effects of depression in Parkinson's disease, there is currently no evidence-based standard of care. The purpose of this study was to examine the efficacy of individually administered cognitive-behavioral therapy (CBT), relative to clinical monitoring (with no new treatment), for depression in this medical population., Method: Eighty depressed (based on DSM-IV criteria) patients with Parkinson's disease participated in a randomized, controlled trial of CBT relative to clinical monitoring (1:1 ratio) in an academic medical center from April 2007 to July 2010. All patients continued to maintain stable medication regimens under the care of their personal physicians. The 17-item Hamilton Depression Rating Scale (HAM-D) total score was the primary outcome. CBT was modified to meet the unique needs of the Parkinson's disease population and provided for 10 weeks. Assessments were completed by blind raters at baseline and 5 (midpoint), 10 (end of treatment), and 14 weeks (follow-up evaluation) postrandomization., Results: The CBT group reported greater reductions in depression (change in HAM-D score) than the clinical monitoring group. At week 10, the mean HAM-D score change was 7.35 for CBT relative to 0.05 for clinical monitoring. CBT was also superior to clinical monitoring on several secondary outcomes (i.e., Beck Depression Inventory scores, anxiety, quality of life, coping, Parkinson's disease symptom ratings). There were more treatment responders in the CBT group than the clinical monitoring group (56% versus 8%, respectively)., Conclusions: CBT may be a viable approach for the treatment of depression in Parkinson's disease. Further research is needed to replicate and extend these findings.

Objective: Parkinson's disease (PD) is frequently complicated by depression and there is a paucity of controlled research that can inform the management of this disabling nonmotor complaint. A randomized controlled trial of nortriptyline, paroxetine, and placebo for the treatment of depression in PD (dPD) was recently completed. The purpose of this article is to describe the baseline pattern of depressive symptom presentation in PD, the specific symptoms of dPD that improve with pharmacotherapy, and the residual symptoms that remain in patients who meet a priori criteria for response or remission after acute treatment (8 weeks)., Setting: The Departments of Psychiatry and Neurology at Robert Wood Johnson Medical School, New Jersey., Participants: : Fifty-two depressed patients (major depression or dysthymia based on Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria) with Parkinson's disease (by research criteria)., Design/intervention: A randomized controlled trial of nortriptyline, paroxetine, and placebo., Measurement: The four subscales (core mood, anxiety, insomnia, and somatic) and individual items from the Hamilton Rating Scale for Depression-17 were the focus of this study. These measures were assessed at baseline and Week 8., Results: Baseline depressive symptoms were unrelated to motor functioning. Treatment response was associated with significant improvements in the core mood, anxiety, insomnia, and somatic symptoms seen in dPD. Residual symptoms, such as sadness and loss of interest, persisted in treatment responders in a milder form than was initially present., Conclusions: Antidepressants may influence all symptoms of dPD, including those that share great overlap with the physical disease process. Additional research regarding adjunctive interventions is needed to help optimize the management of dPD.

Background: Parkinson's disease (PD) affects patients' lives with more than just physical impairment. Many of the non-motor aspects of PD, such as cognitive impairment, depression, and sleep disturbances, are common and are associated with a variety of poor outcomes. However, at present, the pathophysiology and clinical management of these symptoms are poorly understood., Objective: The authors sought to determine the associations between various illness-associated cytokines, cortisol, and the non-motor symptoms of PD., Method: The authors examined a panel of cytokines (IL-1β, IL-6, IL-10, TNF-α) and cortisol in a cohort of 52 PD patients with depression., Results: There were a number of significant correlations between the non-motor symptoms and TNF-α. Specifically, the authors found that TNF-α (but not IL-1β, IL-6, IL-10, or cortisol) was significantly correlated with measures of cognition, depression, and disability. In regression analyses accounting for all variables, TNF-α was consistently significant in explaining variance in cognition, depression, sleep, and disability., Conclusion: These data are consistent with a growing body of literature that implicates inflammatory cytokines in neural and behavioral processes and further suggests that TNF-α may be involved in the production and/or maintenance of non-motor symptoms in PD.

Parkinson's disease (PD) is a common neurodegenerative disease affecting up to 1 million individuals in the United States. Sleep disturbances, typically in sleep maintenance, are found in up to 88% of these individuals and are associated with a variety of poor outcomes. Despite being common and important, there are few data to guide clinical care. We conducted a 6-week, randomized, controlled trial of eszopiclone and placebo in 30 patients with PD and insomnia. Patients with other primary sleep disorders (PSG defined) were excluded. The primary outcome was total sleep time (TST), and secondary measures included wake after sleep onset (WASO), number of awakenings, and quality of sleep, among others. The groups did not significantly differ on TST, but significant differences, favoring eszopiclone, did emerge in number of awakenings (P = 0.035), quality of sleep (P = 0.018), and in physician-rated CGI improvement (P = 0.035). There was also a trend toward significance in WASO (P = 0.071). There were no significant differences between groups in measures of daytime functioning. The drug was well tolerated, with 33% of patients on eszopiclone and 27% of patients on placebo reporting adverse events. Although modest in size, this is the first controlled study of the treatment of insomnia in patients with PD. Eszopiclone did not increase TST significantly but was superior to placebo in improving quality of sleep and some measures of sleep maintenance, which is the most common sleep difficulty experienced by patients with PD. Definitive trials of the treatment of sleep disorders in this population are warranted.

Impulse control disorders, including pathological gambling, binge eating, compulsive shopping and hypersexual behaviors, have frequently been reported as a side effect of dopaminergic medications for Parkinson's disease (PD). Here we describe a patient with PD who developed an unusual manifestation of impulsive behaviors, including cigarette smoking, associated with an increase in dopamine agonist medication. We postulate this to be related to an overstimulation of mesolimbic dopamine receptors responsible for reward-seeking behaviors. Further research is needed to examine impulsive cigarette smoking in PD., ((c) 2009 Elsevier Ltd. All rights reserved.)

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.

Scientific interest in the nonmotoric symptoms of Parkinson's disease (PD) has increased dramatically, and psychiatric symptoms (e.g., cognitive impairment, anxiety and mood disorders) are now considered prime targets for treatment optimization. Psychiatric complications in PD are quite common, affecting as many as 60 to 80% of patients. This study describes the case of a 74 year-old male with PD who presented with complaints of anxiety and trouble with memory and attention. A combined cognitive behavior therapy and cognitive enhancement intervention was delivered in ten 90-to-120 minute sessions. The patient showed a reduction in anxiety symptoms that was of sufficient magnitude to meet criteria for 'responder' status. His cognitive skills were mostly unchanged, despite the rigorous rehabilitation practice. Implications for treatment and strategies for enhancing therapeutic benefits are discussed.

Sleep disturbances are very common in patients with PD and are associated with a variety of negative outcomes. The evaluation of sleep disturbances in these patients is complex, as sleep may be affected by a host of primary sleep disorders, other primary medical or psychiatric conditions, reactions to medications, aging or the neuropathophysiology of PD itself. In this article, we review the evaluation of the common disturbances of sleep seen in PD. This includes the primary sleep disorders, the interaction of depression and insomnia, the impact that medications for PD have on sleep, as well as the role of factors such as nocturia, pain, dystonia, akinesia, difficulty turning in bed, and vivid dreaming. The treatment of sleep disturbances in PD is largely unstudied but recommendations based on clinical experience in PD and research studies in other geriatric populations can be made. Important principles include, diagnosis, treating the specific sleep disorder or co-occurring disorder, and control of the motor aspects of PD.

Parkinson's disease (PD) is a common neurodegenerative disease affecting up to one million individuals in the United States. Depression is found in 40 to 50% of these patients and is associated with a variety of poor outcomes for both patients and their families. Despite this, there are few evidence-based data to guide clinical care. This was an NIH-funded, randomized, controlled trial of paroxetine, nortriptyline, and placebo. It included an 8 week acute phase and a 16 week blind extension phase. This report details the impact of depression treatment on quality of life (QoL) and disability in the acute and extension phase of this study. Secondary outcomes included relapse, tolerability, safety, and the impact of depression treatment on PD physical functioning. Patients who had improvement in depression, compared with those who did not, had significant gains in measures of QoL and disability (PDQ-8, P = 0.0001; SF-36, P = 0.0001) at 8 weeks and maintained their gains in the extension phase. Patients who were on active drug were significantly less likely to relapse in the extension phase than those on placebo (P = 0.041). Though relatively modest in size, this trial provides the first controlled data on the impact of treatment of depression on QoL and disability in PD. It suggests that successfully treating depression in PD leads to important, sustained improvements in these outcomes and that patients who improve on antidepressants are less likely to relapse than are patients who initially improve on placebo., (2009 Movement Disorder Society.)

Background: Parkinson disease (PD) is a common neurodegenerative disease affecting up to 1 million individuals in the United States. Depression affects up to 50% of these patients and is associated with a variety of poor outcomes for patients and their families. Despite this, there are few evidence-based data to guide clinical care., Methods: An NIH-funded, randomized, controlled trial of paroxetine CR, nortriptyline, and placebo in 52 patients with PD and depression. The primary outcomes were the change in the Hamilton Depression Rating Scale (HAM-D) and the percentage of depression responders at 8 weeks., Results: Nortriptyline was superior to placebo for the change in HAM-D (p < 0.002); paroxetine CR was not. There was a trend for superiority of nortriptyline over paroxetine CR at 8 weeks (p < 0.079). Response rates favored nortriptyline (p = 0.024): nortriptyline 53%, paroxetine CR 11%, placebo 24%. In planned contrasts of response rates, nortriptyline was superior to paroxetine CR (p = 0.034). Nortriptyline was also superior to placebo in many of the secondary outcomes, including sleep, anxiety, and social functioning, while paroxetine CR was not. Both active drug treatments were well tolerated., Conclusions: Though relatively modest in size, this is the largest placebo-controlled trial done to date in patients with Parkinson disease (PD) and depression. Nortriptyline was efficacious in the treatment of depression and paroxetine CR was not. When compared directly, nortriptyline produced significantly more responders than did paroxetine CR. The trial suggests that depression in patients with PD is responsive to treatment and raises questions about the relative efficacy of dual reuptake inhibitors and selective serotonin reuptake inhibitors.

Objective: Sleep disturbances have been reported to be one of the most troubling manifestations of menopause. While hormone replacement therapy (HRT) has historically been considered a first-line treatment for menopausal insomnia, many women are now seeking alternative treatments due to concerns about the risks and side-effects of HRT. The goal of this study was to evaluate the effect of ramelteon, a selective melatonin receptor agonist, for the treatment of menopausal insomnia., Study Design: A total of 20 healthy peri- and postmenopausal women with insomnia participated in this six-week, prospective, open-label trial of ramelteon (8 mg) at an academic medical centre. Participants completed sleep-wake diaries on a daily basis for six weeks. Self-report measures of sleep impairment, daytime functioning, quality of life and mood were also completed on a bi-weekly basis., Results: Significant improvements in latency to sleep onset, total sleep time and sleep efficiency were observed in diary data while gains in sleep quality, sleep impairment, daytime functioning, quality of life and mood were found in self-report measures. There was no evidence of tolerance or rebound over the course of the trial., Conclusions: Overall, results suggest that ramelteon is an effective non-hormonal approach for the treatment of insomnia in menopause. Randomized-controlled trials are needed to further evaluate the efficacy of this intervention.

Depression is very common in Parkinson's disease (PD) and linked with a faster progression of physical symptoms, greater cognitive decline and poorer quality of life. Nonpharmacological approaches, such as cognitive-behavioral therapy (CBT), for the treatment of depression in PD (dPD) have received little experimental attention despite strong demonstrated efficacy in other geriatric and medical populations. Depressed PD patients often differ from the depressed non-PD elderly in that they present with increased rates of both executive dysfunction and comorbid psychiatric diagnoses, may differ in their depressive symptom presentation and typically have caregivers who are highly involved in their treatment. Therefore, it is not possible to conclude that empirically validated treatments in the depressed aged will generalize to those with PD. In order to be most effective for PD patients, CBT should be tailored to their unique needs. Additional controlled research is needed to further explore the efficacy of CBT for dPD.

The present study was conducted to examine the feasibility and effect of an individual cognitive-behavioral treatment (CBT) for depression that was modified to meet the unique needs of the PD patient and incorporated a separate social support intervention for caregivers. Fifteen PD patients with Major Depressive Disorder participated in the study with a caregiver. Patients received 10-14 sessions of modified individual CBT. Caregivers attended 3-4 psychoeducational sessions, occurring separately from the patients treatment sessions, which focused on strategies for offering appropriate support, and ways to respond to the patients' negative thoughts in a targeted manner. Patients experienced a significant reduction in depressive symptoms and negative cognitions, and an increased perception of social support over the course of treatment. Gains were maintained at 1-month follow-up. In conclusion, individual CBT, when modified appropriately, may be a feasible and effective option for PD depression. Larger, randomized controlled trials are needed to further evaluate the efficacy of this intervention and to identify specific mechanisms of change., ((c) 2007 Movement Disorder Society.)

Depression is one of the most common nonmotor features observed in Parkinson's disease (PD), affecting approximately 40% of patients. Depression in Parkinson's disease (dPD) significantly affects quality of life of both patients and their families and has been shown to be more predictive of distress than motor disability. Depression frequently goes unrecognized in this population, however, in part because the diagnosis is often complicated by the overlap of psychiatric and PD symptoms. The etiology of dPD is unclear; dopaminergic, serotonergic, and noradrenergic systems may be implicated. Options for managing dPD include antidepressant medication; cognitive-behavioral therapy; behavioral lifestyle interventions such as exercise; and, in refractory cases, noninvasive brain stimulation (electroconvulsive therapy, transcranial magnetic stimulation). Randomized controlled trials are needed to evaluate the efficacy of interventional approaches for dPD; several trials are currently underway.

Two case reports of women treated with an individual cognitive behavioral treatment (CBT) for menopausal hot flashes are presented. Both women reported substantial improvements in the number of hot flashes experienced as well as in their quality of life as measured by the Menopause Quality of Life Scale (MENQOL), the Hamilton Rating Scale for Depression (HAM-D), and the Hamilton Rating Scale for Anxiety (HAM-A). Improvements in hot flashes and quality of life were maintained 6 months after treatment ended. It is hypothesized that CBT reduces hot flashes by reducing central sympathetic activation, perceptions of stress, and self-critical thoughts. The long-term efficacy of CBT for hot flashes should be examined in large controlled clinical trials.

Minority women often have a unique set of beliefs and expectations about medical treatment. At this time, there is a dearth of research looking at how depressed minority women respond to pharmacological interventions for the sexual concomitants of depression. This was the first study to examine the impact of a medication switch, from a selective serotonin reuptake inhibitor to bupropion SR, on the sexual functioning of depressed minority women. Eighteen minority women (5 Hispanic, 10 African American, 2 Asian American, and 1 Native American), who were experiencing poor tolerability and/or lack of efficacy on an adequate trial of a selective serotonin reuptake inhibitor for depression, along with low sexual desire, were enrolled in this prospective open-label study. The selective serotonin reuptake inhibitor and bupropion SR were cross-tapered with a target dose of 150 to 300 mg of bupropion SR. The patients were followed for 10 weeks, and measures of sexual functioning and depression (Hamilton Rating Scale for Depression) were administered in an academic medical setting. Data were collected from July 2003 to December 2004. In the group as a whole, there were significant improvements in desire (F1,17 = 34.86, P < 0.001), arousal (F1,17 = 25.99, P < 0.001), and orgasm (F1,17 = 20.16, P < 0.001), on the Changes in Sexual Functioning Questionnaire. African-American women demonstrated the greatest improvement in depression (F1,16 = 9.55, P = 0.006), desire (F1,16 = 8.62, P = 0.01), and arousal (F1,16 = 8.83, P = 0.009) after the medication switch. Overall, this intervention appeared to be an effective treatment of low sexual desire in a diverse group of depressed minority women. The majority of women successfully completed the trial and planned to continue using bupropion SR after their participation in the study.

Despite the increasing number of non-Caucasians in the United States, the overwhelming majority of research into both depression and sexuality has been conducted with European-American (Caucasian) samples. Sexual dysfunction and depression often co-occur, impacting relationship satisfaction, quality of life, and treatment adherence. These issues may be particularly salient for African-American, Hispanic, and Asian-American women, yet this area of research has been relatively unexplored. Cultural factors may shape women's response to sexual dysfunction, resulting from the depression itself as well as antidepressant medication. Further research emphasizing gender and culture is needed to elucidate the prevalence, impact, and treatment of sexual dysfunction in specific groups of depressed minority women.