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.

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.

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.

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.

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.

Ramelteon for the treatment of insomnia in menopausal women.

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.

CBT for the treatment of depression in Parkinson's disease: a promising nonpharmacological approach.

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.

Cognitive-behavioral therapy for depression in Parkinson's disease: a pilot study.

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.

Bupropion improves sexual functioning in depressed minority women: an open-label switch study.

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.

Depression and sexual functioning in minority women: current status and future directions.

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.

Treatment of depression in Parkinson's disease.

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.