Cognitive behavioral therapy improves diverse profiles of depressive symptoms in Parkinson's disease.

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).

Personalized Telemedicine for Depression in Parkinson's Disease: A Pilot Trial.

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.

Guidance for switching from off-label antipsychotics to pimavanserin for Parkinson's disease psychosis: an expert consensus.

Patients with Parkinson's disease psychosis (PDP) are often treated with an atypical antipsychotic, especially quetiapine or clozapine, but side effects, lack of sufficient efficacy, or both may motivate a switch to pimavanserin, the first medication approved for management of PDP. How best to implement a switch to pimavanserin has not been clear, as there are no controlled trials or case series in the literature to provide guidance. An abrupt switch may interrupt partially effective treatment or potentially trigger rebound effects from antipsychotic withdrawal, whereas cross-taper involves potential drug interactions. A panel of experts drew from published data, their experience treating PDP, lessons from switching antipsychotic drugs in other populations, and the pharmacology of the relevant drugs, to establish consensus recommendations. The panel concluded that patients with PDP can be safely and effectively switched from atypical antipsychotics used off label in PDP to the recently approved pimavanserin by considering each agent's pharmacokinetics and pharmacodynamics, receptor interactions, and the clinical reason for switching (efficacy or adverse events). Final recommendations are that such a switch should aim to maintain adequate 5-HT2A antagonism during the switch, thus providing a stable transition so that efficacy is maintained. Specifically, the consensus recommendation is to add pimavanserin at the full recommended daily dose (34 mg) for 2-6 weeks in most patients before beginning to taper and discontinue quetiapine or clozapine over several days to weeks. Further details are provided for this recommendation, as well as for special clinical circumstances where switching may need to proceed more rapidly.

Neuropsychological outcomes after psychosocial intervention for depression in Parkinson's disease.

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.

Barriers to mental health care utilization in Parkinson's disease.

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.

Depression in Parkinson's disease: symptom improvement and residual symptoms after acute pharmacologic management.

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.

Telephone-based cognitive-behavioral therapy for depression in Parkinson disease.

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.

Sleep disturbances in Parkinson's disease.

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.

Treatment of insomnia in Parkinson's disease: a controlled trial of eszopiclone and placebo.

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.

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.

The role of inflammatory cytokines in cognition and other non-motor symptoms of Parkinson's disease.

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-1ß, 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-1ß, 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.

Telephone-based cognitive behavioral therapy for depression in Parkinson disease: A randomized controlled trial.

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.

The impact of treatment of depression on quality of life, disability and relapse in patients with Parkinson's disease.

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.

Escitalopram reduces hot flashes in nondepressed menopausal women: A pilot study.

BACKGROUND: Hot flashes are one of the most troubling manifestations of menopause, affecting about 80% of women. Due to recent controversies about hormone replacement therapy, many women seek alternative treatments. The use of antidepressants to treat hot flashes and other menopausal symptoms has been an active area of investigation. However, the majority of past research in this area has included women with significant medical or psychiatric histories that may influence treatment response. This was the first study to examine the impact of escitalopram on hot flashes, mood, sleep, and quality of life in a sample of healthy nondepressed menopausal women. METHODS: This study enrolled 25 menopausal women who had no significant psychiatric or medical history. All women were treated with escitalopram (10 to 20 mg flexibly dosed) for 8 weeks. The active treatment phase was preceded by a single-blind placebo lead-in period. RESULTS: Over the course of the study, women reported significant decreases in both hot flash frequency and severity as well as improvements in dysphoria, anxiety, quality of life, and sleep. CONCLUSION: These preliminary findings suggest that escitalopram may be a feasible and effective option for treating hot flashes and other menopausal symptoms in healthy women who might not ordinarily consider antidepressant treatment.

Efficacy of the team solutions program for educating patients about illness management and treatment.

OBJECTIVE: Despite the demonstrated efficacy of psychosocial approaches to schizophrenia treatment that include a psychoeducational component, such as illness management, the implementation of these approaches into routine mental health treatment has been slow. The authors sought to examine the efficacy of a comprehensive, modularized, psychoeducational program called Team Solutions, which was designed to educate patients with major mental illnesses about their illness and how to manage it. Team Solutions was chosen for study because it is available over the Internet and other venues at no cost and is used by mental health agencies across the United States and Canada. METHODS: Seventy-one persons with schizophrenia or schizoaffective disorder from three day treatment settings participated in this randomized, single-blind study. Participants were randomly assigned to attend one of two interventions: the Team Solutions intervention, which consisted of participating in a 24-week psychoeducational group focused on illness management, or treatment as usual. RESULTS: For participants who attended the experimental group, significant improvement was observed in knowledge about schizophrenia. In addition, client satisfaction was high. However, no changes were observed in symptoms or functioning. CONCLUSIONS: Results indicated that participation in the Team Solutions psychoeducational group improved participants' knowledge. However, participation in the program did not demonstrate superiority over treatment as usual with respect to secondary and tertiary outcomes, such as symptom severity, treatment adherence, and global functioning.

The management of fatigue in depressed patients.

Three quarters of patients who respond to treatment with the newer antidepressants still complain of fatigue. Fatigue is one of the most common and disturbing residual symptoms of depression. Increased serotonin activity in certain areas of the brain contributes to fatigue. It can be counteracted by dopaminergic agents which, interestingly, are enhanced by exercise. Specific steps that can be used to address residual fatigue include cognitive interventions based on those used to address somatoform disorders; graded aerobic exercise; dose reduction or discontinuation of fatigue-inducing antidepressants; and the prescription of such medications as dopaminergic antidepressants (bupropion), stimulants, thyroid preparations, and modafinil.

Residual symptoms in depression: can treatment be symptom-specific?

BACKGROUND: Most patients with depression continue to have symptoms after treatment. It is well documented that these "residual" symptoms are common and are associated with increases in suboptimal long-term outcomes such as relapse and disability. While it is clear that residual symptoms, as a group, contribute to poor outcomes, individual residual symptoms have received relatively little attention. To some extent, this lack of attention reflects an uncertainty in the field about the relationship of the syndrome of depression to the symptoms by which the syndrome is defined. METHOD: Recognizing that for clinicians and patients symptom relief is the goal of treatment, this article reviews the evidence that a symptomatic approach to individual residual symptoms is both feasible and useful. Evidence was gathered through a MEDLINE review of articles published in English from 1966 to 2002. Multiple keywords relating to symptoms, depression, and treatment were used. RESULTS: Many of the agents that psychiatrists use for augmentation of depression treatment, such as psychostimulants and alerting agents, atypical antipsychotics and mood stabilizers, and buspirone and benzodiazepines, have specific symptomatic effects, which raises the question of whether we are augmenting the core antidepressant effect or providing symptomatic relief. Fatigue, anxiety, sexual dysfunction, and sleep disturbances are all symptoms that are commonly leftover after treatment of depression. Some data indicate that treatment of these residual symptoms is efficacious and may affect the long-term outcome of depression. DISCUSSION: This discussion of the treatment of residual depressive symptoms raises a variety of research questions that should be addressed. Also implicit in this discussion are theoretical questions on the relationship between symptoms and syndrome.

Adjunct modafinil for the short-term treatment of fatigue and sleepiness in patients with major depressive disorder: a preliminary double-blind, placebo-controlled study.

BACKGROUND: Fatigue and sleepiness are primary symptoms of depression that may not resolve with antidepressant therapy. Modafinil is a novel agent that has been shown to improve wakefulness and lessen fatigue in a variety of conditions. In this study, we examined the utility of modafinil as an adjunct therapy to treat fatigue and sleepiness in patients with major depression who are partial responders to antidepressants. METHOD: Patients with partial response to anti-depressant therapy given for at least a 6-week period for a current major depressive episode (DSM-IV criteria) were enrolled in this 6-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Patients received once-daily doses (100-400 mg) of modafinil or matching placebo as adjunct treatment to ongoing antidepressant therapy. The effects of modafinil were evaluated using the Hamilton Rating Scale for Depression (HAM-D), the Fatigue Severity Scale (FSS), the Epworth Sleepiness Scale (ESS), the Clinical Global Impression of Change (CGI-C), and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Adverse events were monitored throughout the study. RESULTS: One hundred thirty-six patients were randomized to treatment, with 118 patients (87%) completing the study. Most patients (82%) were fatigued, and one half of patients (51%) were sleepy. Modafinil rapidly improved fatigue and daytime wakefulness, with significantly greater mean improvements from baseline than placebo in fatigue (FSS) scores at week 2 (p < .05) and sleepiness (ESS) scores at week 1 (p < .01); the differences between modafinil and placebo at week 6 were not statistically significant. Assessment of the augmentation effects of modafinil (HAM-D, CGI-C, and SF-36) did not significantly distinguish modafinil from placebo. Modafinil was well tolerated in combination with a variety of antidepressants. CONCLUSION: Modafinil may be a useful adjunct therapy for the short-term management of residual fatigue and sleepiness in patients who are partial responders to antidepressant therapy.