Depression: Weintraub D

Schrag A, Barone P, Brown RG, Leentjens AF, McDonald WM, Starkstein S, Weintraub D, Poewe W, Rascol O, Sampaio C, Stebbins GT, Goetz CG. · University Department of Clinical Neurosciences, Royal Free and University College Medical School, London, UK. · Mov Disord. · Pubmed #17394234 links to  free full text

Abstract: Depression is a common comorbid condition in Parkinson's disease (PD) and a major contributor to poor quality of life and disability. However, depression can be difficult to assess in patients with PD due to overlapping symptoms and difficulties in the assessment of depression in cognitively impaired patients. As several rating scales have been used to assess depression in PD (dPD), the Movement Disorder Society commissioned a task force to assess their clinimetric properties and make clinical recommendations regarding their use. A systematic literature review was conducted to explore the use of depression scales in PD and determine which scales should be selected for this review. The scales reviewed were the Beck Depression Inventory (BDI), Hamilton Depression Scale (Ham-D), Hospital Anxiety and Depression Scale (HADS), Zung Self-Rating Depression Scale (SDS), Geriatric Depression Scale (GDS), Montgomery-Asberg Depression Rating Scale (MADRS), Unified Parkinson's Disease Rating Scale (UPDRS) Part I, Cornell Scale for the Assessment of Depression in Dementia (CSDD), and the Center for Epidemiologic Studies Depression Scale (CES-D). Seven clinical researchers with clinical and research experience in the assessment of dPD were assigned to review the scales using a structured format. The most appropriate scale is dependent on the clinical or research goal. However, observer-rated scales are preferred if the study or clinical situation permits. For screening purposes, the HAM-D, BDI, HADS, MADRS, and GDS are valid in dPD. The CES-D and CSDD are alternative instruments that need validation in dPD. For measurement of severity of depressive symptoms, the Ham-D, MADRS, BDI, and SDS scales are recommended. Further studies are needed to validate the CSDD, which could be particularly useful for the assessment of severity of dPD in patients with comorbid dementia. To account for overlapping motor and nonmotor symptoms of depression, adjusted instrument cutoff scores may be needed for dPD, and scales to assess severity of motor symptoms (e.g., UPDRS) should also be included to help adjust for confounding factors. The HADS and the GDS include limited motor symptom assessment and may, therefore, be most useful in rating depression severity across a range of PD severity; however, these scales appear insensitive in severe depression. The complex and time-consuming task of developing a new scale to measure depression specifically for patients with PD is currently not warranted.

Simuni T, Lyons KE, Pahwa R, Hauser RA, Comella C, Elmer L, Weintraub D. · Department of Neurology, Northwestern University, Parkinson's Disease and Movement Disorders Center, Chicago, Ill, USA. · Eur Neurol. · Pubmed #19176961 links to  free full text

Abstract: The management of early Parkinson's disease (PD) involves the treatment of motor symptoms, and, increasingly, non-motor symptoms. Given the fast pace of clinical research in PD, clinicians are faced with the challenge of integrating the latest findings into the ongoing care of individual PD patients. Part 1 of this 2-part article reviews efficacy and safety data for the newest PD treatment options, as well as for established therapies. Part 2 of the article, presented here, reviews key data relevant to the assessment of potential neuroprotective therapies and the treatment of non-motor symptoms.

Weintraub D, Comella CL, Horn S. · Department of Psychiatry and Neurology, University of Pennsylvania, 3615 Chestnut St, Philadelphia, PA 19104, USA. · Am J Manag Care. · Pubmed #18402509 links to  free full text

Abstract: The nonmotor neuropsychiatric symptoms of Parkinson's disease, particularly depression, psychosis, and cognitive impairment/dementia, are major contributors to disability and a decline in quality of life. Their effect on patients may be more disabling than motor symptoms. Increasing awareness of the importance of recognizing and treating neuropsychiatric symptoms of this disease in the medical community is a focus of specialists and organizations. This article looks at useful screening measures to help clinicians recognize neuropsychiatric symptoms and offers suggestions for their effective treatment.

Weintraub D, Stern MB. · Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. · Am J Geriatr Psychiatry. · Pubmed #16223962 No free full text.

Abstract: Although Parkinson disease (PD) is primarily considered a movement disorder, the high prevalence of psychiatric complications suggests that it is more accurately conceptualized as a neuropsychiatric disease. Affective disorders, cognitive impairment, and psychosis are particularly common in PD and are associated with excess disability, worse quality of life, poorer outcomes, and caregiver distress. Yet, in spite of this and their frequent occurrence, there is incomplete understanding of the epidemiology, phenomenology, risk factors, neuropathophysiology, and optimal treatment strategies for these disorders. Psychiatric complications are typically comorbid, and there is great intra- and inter-individual variability in presentation. The hallmark neuropathophysiological changes that occur in PD plus the association between exposure to dopaminergic medications and certain psychiatric disorders suggest a neurobiological basis for most psychiatric symptoms, although psychological factors are probably involved in the development of affective disorders. Although antidepressants, antipsychotics, and cognition-enhancing agents are commonly prescribed in PD, controlled studies demonstrating efficacy and tolerability of these drugs are virtually nonexistent. Because of the high prevalence and complexity of psychiatric complications in PD, geriatric psychiatrists are in a position to offer valuable consultation and clinical care to this population. This article provides an overview of the epidemiology, pathophysiology, clinical presentation, and management of the most common psychiatric complications in PD.

Weintraub D, Morales KH, Moberg PJ, Bilker WB, Balderston C, Duda JE, Katz IR, Stern MB. · Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Mov Disord. · Pubmed #15954137 links to  free full text

Abstract: The objective of this study was to determine effect sizes for both antidepressant treatment and placebo for depression in Parkinson's disease (PD), and to compare the findings with those reported in elderly depressed patients without PD. Recent reviews have concluded that there is little empiric evidence to support the use of antidepressants in PD; however, available data has not been analyzed to determine the effect size for antidepressant treatment in PD depression. A literature review identified antidepressant studies in PD. Suitable studies were analyzed using meta-analytic techniques, and effect sizes were compared with those from antidepressant studies in elderly patients without PD. Large effect sizes were found for both active treatment and placebo in PD, but there was no difference between the two groups. In contrast, active treatment was superior to placebo in depressed elderly patients without PD. In PD, increasing age and a diagnosis of major depression were associated with better treatment response. Results also suggest that newer antidepressants are well tolerated in PD. Despite the high prevalence of depression and antidepressant use in PD, controlled treatment research has been almost nonexistent. Meta-analysis results suggest a large but nonspecific effect for depression treatment in PD. In addition, PD patients may benefit less from antidepressant treatment, particularly selective serotonin reuptake inhibitors, than do elderly patients without PD.

Hoeh N, Gyulai L, Weintraub D, Streim J. · University of Pennsylvania, Philadelphia 19104, USA. · J Geriatr Psychiatry Neurol. · Pubmed #14653429 No free full text.

Abstract: OBJECTIVE: Psychotic symptoms are seen in numerous psychiatric illnesses afflicting the elderly. This article reviews the efficacy of the pharmacologic management of psychotic symptoms in primary psychotic disorders, affective disorders, and neurodegenerative disorders. METHOD: A comprehensive literature review. RESULTS: Evidence to support the use of pharmacologic interventions to manage psychotic symptoms in elderly patients afflicted with primary psychotic disorders and affective disorders is limited by the absence of randomized, placebo-controlled trials (RCTs). The use of low-dose clozapine is supported by RCTs in Parkinson's disease. The efficacy of risperidone and olanzapine for the treatment of psychotic symptoms has been demonstrated by large RCTs in Alzheimer's disease. CONCLUSION: There is evidence of the efficacy of antipsychotic medications to manage psychotic symptoms in elderly patients. However, the absence of published evidence from RCTs in primary psychotic and affective disorders, and the limited evidence in the neurodegenerative illnesses, is notable.

Weintraub D, Taraborelli D, Morales KH, Duda JE, Katz IR, Stern MB. · University of Pennsylvania School of Medicine, Pennsylvania, USA. · J Neuropsychiatry Clin Neurosci. · Pubmed #16963587 links to  free full text

Abstract: Depression and antidepressant use are common in Parkinson's disease, but the benefit of selective serotonin reuptake inhibitor (SSRI) treatment in this population has not been established. The authors treated 14 Parkinson's disease patients with major depression with escitalopram in an open-label study. Although treatment was well tolerated and correlated with a significant decrease in Inventory of Depressive Symptomatology score, response and remission rates were only 21% and 14%, respectively. However, half of the subjects met Clinical Global Impression-Improvement criteria for response. In Parkinson's disease, either SSRIs may have limited antidepressant effects, or the use of existing depression diagnostic and rating instruments may be problematic.

Weintraub D, Newberg AB, Cary MS, Siderowf AD, Moberg PJ, Kleiner-Fisman G, Duda JE, Stern MB, Mozley D, Katz IR. · Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. · J Nucl Med. · Pubmed #15695780 links to  free full text

Abstract: We studied the correlation of striatal dopamine transporter (DAT) imaging with anxiety and depression symptoms in Parkinson's disease (PD). METHODS: Patients with idiopathic PD (n = 76) and age-matched healthy volunteers (n = 46) underwent SPECT brain scans with (99m)Tc-TRODAT-1, a radiolabeled tropane that selectively binds to the DAT. TRODAT-1 distribution volume ratios, a reflection of DAT availability, were calculated from the SPECT scan data for 6 regions of interest (ROIs) in the caudate and putamen. The association between neuropsychiatric symptoms (anxiety, depression, and fatigue) and DAT availability was explored for both subject groups, and the impact of disease severity on this association was examined in the PD group. RESULTS: PD patients showed lower DAT availability than did healthy volunteers in all examined regions (for all ROIs, P < 0.001). In PD patients, higher individual affective measures (for anxiety, r = -0.30 and P = 0.01; and for depression, r = -0.24 and P = 0.05) and total affect scores (r = -0.31; P = 0.01) were associated with diminished left anterior putamen DAT availability. The association between total affect scores and DAT availability was present only in the subset of patients with less severe PD (r = -0.35; P = 0.04), but subjects with the highest DAT availability did not show high total affect scores. No association between neuropsychiatric measures and DAT availability was found in the controls. CONCLUSION: These preliminary findings suggest that decreased DAT availability may be necessary for but not invariably associated with the development of affective symptoms in PD. This suggestion is consistent with previous research showing a link between depression and basal ganglia impairment, particularly involving the left hemisphere, and extends this finding to include anxiety.

Oslin DW, Ten Have TR, Streim JE, Datto CJ, Weintraub D, DiFilippo S, Katz IR. · Section of Geriatric Psychiatry, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pa., USA. · J Clin Psychiatry. · Pubmed #12927001 No free full text.

Abstract: BACKGROUND: In nursing home residents and other frail elderly patients, old age and potential drug-drug and drug-disease interactions may affect the relative safety and efficacy of medications. The purpose of this study was to examine the efficacy and tolerability of venlafaxine and sertraline for the treatment of depression among nursing home residents. METHOD: The study was a 10-week randomized, double-blind, controlled trial of venlafaxine (doses up to 150 mg/day) versus sertraline (doses up to 100 mg/day) among 52 elderly nursing home residents with a DSM-IV depressive disorder and, at most, moderate dementia. The primary measure of outcome was the Hamilton Rating Scale for Depression (HAM-D). Adverse events were monitored and recorded systematically during the trial. RESULTS: Twelve subjects were discontinued due to serious adverse events (SAE), 5 were discontinued due to other significant side effects, and 2 withdrew consent. Tolerability estimated by the time to termination was lower for venlafaxine than sertraline for serious adverse events (log rank statistic = 5.28, p =.022), for serious adverse events or side effects (log rank statistic = 8.08, p =.005), or for serious adverse events, side effects, or withdrawal of consent (log rank statistic = 10.04, p =.002). Mean (SD) HAM-D scores at baseline were 20.2 (3.4) for sertraline and 20.3 (3.7) for venlafaxine; intent-to-treat endpoint HAM-D scores were 12.2 (5.1) and 15.7 (6.2) (F = 3.45; p =.069). There were no differences in categorical responses for the intent-to-treat sample or completers. CONCLUSION: In this frail elderly population, venlafaxine was less well tolerated and, possibly, less safe than sertraline without evidence for an increase in efficacy. This unexpected finding demonstrates the need for systematic research on the safety of drugs in the frail elderly.

Weintraub D, Streim JE, Datto CJ, Katz IR, DiFilippo SD, Oslin DW. · Section of Geriatric Psychiatry, University of Pennsylvania, and Philadelphia VA Medical Center, USA. · J Geriatr Psychiatry Neurol. · Pubmed #12801161 No free full text.

Abstract: There has been limited research into defining what constitutes an adequate first-line antidepressant trial in elderly patients. The authors report the outcome of extended, high-dosage sertraline treatment in a sample of nursing home residents experiencing residual significant depressive symptoms after 10 weeks of treatment with sertraline at a final dosage of 100 mg/day. Subjects who had a Hamilton Depression Rating Scale score > or = 12 after 10 weeks of treatment with sertraline were eligible for the 8-week open-label extension phase, which involved titrating the sertraline dosage to 200 mg/day. The cumulative response rate was 52% for the extension phase, compared with 37% for the acute phase. Examining acute phase nonresponders, 39% responded during the extension phase. Rates of discontinuation due to adverse events were comparable in the 2 phases. Our findings suggest that an extended trial or high dosages of sertraline may benefit some depressed elderly patients with persistent depression after acute treatment.

Weintraub D. · Norton Psychiatric Center, Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, KY 40202, USA. · J Geriatr Psychiatry Neurol. · Pubmed #11281313 No free full text.

Abstract: Research on treatment-resistant depression in the elderly has been limited, and recommendations for clinical management have often been extrapolated from studies using nongeriatric patients. This report describes a series of 10 elderly patients with refractory depression who were treated with nortriptyline after failing to respond to an adequate trial of a serotonin reuptake inhibitor. Seven (70%) of the patients responded to the addition or substitution of nortriptyline. All seven of the responders have remained on nortriptyline for maintenance therapy, none of whom have experienced recurrence of their depression after an average treatment duration of 1 year. Response to nortriptyline occurred in about 4 weeks in most patients. The mean daily dose of nortriptyline was 54 mg, and the mean plasma level was 97 ng/mL. Minor side effects occurred in three patients. No patients developed significant electrocardiogram changes. Nortriptyline, possibly due to its different mechanism of action, may be effective as either an adjunctive or replacement antidepressant in some cases of geriatric depression that are resistant to serotonin reuptake inhibitors.

Phuong L, Garg S, Duda JE, Stern MB, Weintraub D. · Parkinson's Disease Research, Education and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA. · Parkinsonism Relat Disord. · Pubmed #19181560 No free full text.

Abstract: OBJECTIVE: To estimate the frequency and correlates of involuntary emotional expression disorder (IEED) in Parkinson's disease (PD) using the Center for Neurologic Study-Lability Scale (CNS-LS) and recently-proposed diagnostic criteria for IEED. BACKGROUND: IEED is characterized by uncontrollable emotional episodes, typically unrelated to or in excess of the underlying mood, and occurring with minimal or no stimulus. IEED has been reported to occur in many neurological disorders and neurodegenerative diseases, but its prevalence and correlates in PD have not been well studied. Additionally, there is no published research using recently-proposed IEED diagnostic criteria in any population. METHODS: 193 patients with idiopathic PD were assessed with a neuropsychiatric battery, including the CNS-LS and the 15-item Geriatric Depression Scale (GDS-15). A subset (N=100) was also administered a diagnostic interview by a blinded rater that applied criteria for both IEED and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) depressive disorders. RESULTS: Applying formal diagnostic criteria, 7.0% of patients were diagnosed with IEED, and an additional 7.0% had subsyndromal IEED symptoms. Applying recommended CNS-LS cutoff scores from other populations, either 42.5% (cutoff > or =13) or 16.6% (cutoff > or =17) screened positive for IEED. Depressive symptoms were associated with higher CNS-LS scores (B[SE]=0.27[.08], P=.001) but not with a diagnosis of IEED (odds ratio=1.1, [95% CI=1.0-1.3], P=.16). The CNS-LS had poor discriminant validity for an IEED diagnosis (AUC=.79, no cutoff value with sensitivity and specificity both >60%). CONCLUSIONS: IEED and depression are overlapping but distinct disorders in PD. IEED symptoms may occur in up to 15% of PD patients, but a disorder occurs in only half of those, suggesting that often IEED symptoms are not clinically significant in this population. The CNS-LS does not appear to be a good screening instrument for IEED in PD, in part due to its high correlation with depressive symptoms.

Leentjens AF, Dujardin K, Marsh L, Martinez-Martin P, Richard IH, Starkstein SE, Weintraub D, Sampaio C, Poewe W, Rascol O, Stebbins GT, Goetz CG. · Department of Psychiatry, Maastricht University Hospital, Maastricht, the Netherlands. · Mov Disord. · Pubmed #18792121 links to  free full text

Abstract: Anxiety syndromes are common in patients with Parkinson's disease (PD) with up to 30% suffering from panic disorder, and up to 11% from generalized anxiety disorder (GAD). Anxiety is associated with increased subjective motor symptoms, more severe gait problems, dyskinesias, freezing, and on/off fluctuations. Anxiety has a negative impact on health related quality of life and is strongly associated with depressive syndromes. Since a variety of anxiety scales have been used in PD patients, the Movement Disorder Society commissioned a task force to assess the clinimetric properties of these scales in PD. A systematic review was conducted to identify anxiety scales that have either been validated or used in patients with PD. Six anxiety rating scales were identified. These were the Beck anxiety inventory, the hospital anxiety and depression scale, the Zung self-rating anxiety scale and anxiety status inventory, the Spielberger state trait anxiety inventory, and the Hamilton anxiety rating scale. In addition, Item 5 (anxiety) of the neuropsychiatric inventory was included in the review. No scales met the criteria to be "recommended," and all scales were classified as "suggested." Essential clinimetric information is missing for all scales. Because several scales exist and have been used in PD, the task force recommends further studies of these instruments. If these studies show that the clinimetric properties of existing scales are inadequate, development of a new scale to assess anxiety in PD should be considered.

Leentjens AF, Dujardin K, Marsh L, Martinez-Martin P, Richard IH, Starkstein SE, Weintraub D, Sampaio C, Poewe W, Rascol O, Stebbins GT, Goetz CG. · Department of Psychiatry, Maastricht University Hospital, Maastricht, The Netherlands. · Mov Disord. · Pubmed #18709683 links to  free full text

Abstract: Apathy is a common condition in Parkinson's disease (PD) and is generally defined as a lack of motivation. It is associated with more severe cognitive dysfunction and a decrease in activities of daily living (ADL) performance. Anhedonia, the inability to experience pleasure, can be a symptom of both depressive and apathetic syndromes. The Movement Disorder Society (MDS) commissioned a task force to assess the clinimetric properties of apathy and anhedonia scales in PD patients. A systematic literature review was conducted to identify scales that have either been validated or used in PD patients. Apathy scales identified for review include the Apathy Evaluation Scale (AES), the Apathy Scale (AS), the Apathy Inventory (AI), and the Lille Apathy Rating Scale (LARS). In addition, item 4 (motivation/initiative) of the Unified Parkinson's Disease Rating Scale (UPDRS) and item 7 (apathy) of the Neuropsychiatric Inventory (NPI) were included. Anhedonia scales identified for review were the Snaith-Hamilton Pleasure Scale (SHAPS) and the Chapman scales for physical and social anhedonia. Only the AS is classified as "recommended" to assess apathy in PD. Although item 4 of the UPDRS also meets the criteria to be classified as recommended, it should be considered for screening only because of the obvious limitations of a single item construct. For the assessment of anhedonia, only the SHAPS meets the criteria of "Suggested." Information on the validity of apathy and anhedonia scales is limited because of the lack of consensus on diagnostic criteria for these conditions.

Nazem S, Siderowf AD, Duda JE, Brown GK, Ten Have T, Stern MB, Weintraub D. · Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Mov Disord. · Pubmed #18618660 links to  free full text

Abstract: Parkinson's disease (PD) is a chronic, disabling illness affecting primarily the elderly and is associated with a high prevalence of depression. Although these are known risk factors for suicidal and death ideation, little is known about the prevalence and correlates of such ideation in PD. A convenience sample of 116 outpatients with idiopathic PD at two movement disorders centers were administered a modified Paykel Scale for suicidal and death ideation, as well as an extensive psychiatric, neuropsychological, and neurological battery. Univariate and multivariate logistic regression models were used to determine the correlates of suicidal or death ideation. Current death ideation (28%) or suicide ideation (11%) were present in 30% of the sample, and 4% had a lifetime suicide attempt. On univariate logistic regression analysis, increasing severity of depression (odds ratio = 2.92, 95% CI 2.01-4.24, P < 0.001), impulse control disorder (ICD) behaviors sometime during PD (odds ratio = 6.08, 95% CI 1.90-19.49, P = 0.002), and psychosis (odds ratio = 2.45, 95% CI 1.05-5.69, P = 0.04) were associated with either ideation. On multivariate logistic regression analysis, only increasing severity of depressive symptoms (odds ratio = 2.76, 95% CI 1.88-4.07, P < 0.001) predicted suicidal or death ideation. In conclusion, active suicidal or death ideation occurs in up to one-third of PD patients. Comorbid psychiatric disorders, more than PD-related disease variables, are associated with this ideation, highlighting the need for a comprehensive approach to the clinical care of PD patients.

Oehlberg K, Barg FK, Brown GK, Taraborelli D, Stern MB, Weintraub D. · Department of Psychiatry, University of Pennsylvania. · J Geriatr Psychiatry Neurol. · Pubmed #18474721 links to  free full text

Abstract: Depression in Parkinson's disease (dPD) remains under recognized and under treated. As patients' beliefs may impact the reporting and treatment of depression, this study assessed the opinions of 38 dPD patients, approximately half with a self-reported poor response to antidepressant treatment, regarding the etiology and treatment of their depression using a semi-structured, audio-taped, qualitative interview. About half of the participants listed PD itself as a primary cause for their depressive symptoms, with most in this group citing psychosocial factors rather than PD-related neurobiological factors. Antidepressant therapy, psychotherapy, and self-initiated approaches were noted as preferred treatments for dPD. Many had concerns about antidepressant therapy, listing side-effects and medication dependency most frequently. About half raised concerns about psychotherapy with trust/discomfort, stigma, and transportation issues most frequently mentioned. This preliminary study suggests that many PD patients with clinically significant depressive symptoms attribute their depression to psychosocial factors and endorse nonpharmacologic treatment approaches.

Chen P, Kales HC, Weintraub D, Blow FC, Jiang L, Mellow AM. · Division of Geriatric Psychiatry, Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, USA. · J Geriatr Psychiatry Neurol. · Pubmed #17712099 links to  free full text

Abstract: We examined the impact of comorbid Parkinson's disease (PD) on depression treatment. Using national Veterans Affairs (VA) databases, fiscal year 2002 data were examined for 283 273 elderly males seen for depression. We compared 2 matched depression groups, one with (N = 7868) and one without (N = 7868) PD. In the 12-month period following a depression-related clinic visit, PD and non-PD patients were equally likely to fill an antidepressant prescription (77.8% vs. 77.4%), most commonly for a selective serotonin re-uptake inhibitor (SSRI) (62.9% vs 62.6%). Depressed PD patients had slightly higher rates of newer non-SSRI use (20.6% vs 19.2%, P < .05) and lower rates of tricyclic antidepressant use (7.4% vs 8.9%, P < .001). The presence of a PD diagnosis appears to have little impact on the frequency and type of antidepressant treatment. Efforts to improve the care of depressed PD patients should focus instead on improving recognition, ensuring adequacy of treatment, and evaluating the efficacy of existing antidepressants.

Ravina B, Camicioli R, Como PG, Marsh L, Jankovic J, Weintraub D, Elm J. · Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. · Neurology. · Pubmed #17581943 links to  free full text

Abstract: BACKGROUND: Depressive disorders may affect up to 50% of patients with Parkinson disease (PD) and are associated with increased disability and reduced quality of life. No previous study has systematically examined the impact of depressive symptoms in early, untreated PD. METHODS: We administered the 15-item Geriatric Depression Scale (GDS-15) as part of two NIH-sponsored phase II clinical trials in PD, enrolling 413 early, untreated PD subjects. We used linear mixed models to examine the relationship of depressive symptoms, measured by the GDS-15, with motor function and activities of daily living (ADLs), as measured by the Unified PD Rating Scale (UPDRS). A time-dependent Cox model was used to examine the effect of demographic and clinical outcome measures as predictors of investigator-determined time to need for symptomatic therapy for PD. RESULTS: A total of 114 (27.6%) subjects screened positive for depression during the average 14.6 months of follow-up. Forty percent of these subjects were neither treated with antidepressants nor referred for further psychiatric evaluation. Depression, as assessed by the GDS-15, was a significant predictor of more impairment in ADLs (p < 0.0001) and increased need for symptomatic therapy of PD (hazard ratio = 1.86; 95% CI 1.29, 2.68). CONCLUSIONS: Clinically important depressive symptoms are common in early Parkinson disease (PD), but are often not treated. Depressive symptoms are an important contributor to disability and the decision to start symptomatic therapy for motor-related impairment in early PD, highlighting the broad importance of identifying and treating depression in this population.

Weintraub D, Xie S, Karlawish J, Siderowf A. · Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA. · Int J Geriatr Psychiatry. · Pubmed #17562521 links to  free full text

Abstract: OBJECTIVE: Depression occurs frequently in patients with both Alzheimer's disease (AD) and Parkinson's disease (PD), but there has been little comparison of depression symptoms in the two populations. METHOD: The 15-item Geriatric Depression Scale (GDS-15) was administered as a depression screening instrument to 232 AD patients and 266 PD specialty care patients with at most mild dementia. Logistic regression models were used to determine disease-specific associations with individual GDS-15 items, and factor analysis was used to assess GDS-15 factor structure in the two populations. RESULTS: Controlling for total GDS-15 score and other covariates, AD patients reported more dissatisfaction with life (p = 0.03) and memory problems (p < 0.001), while PD patients reported more fearfulness (p = 0.01), helplessness (p < 0.01), a preference to stay at home (p = 0.02), and diminished energy (p < 0.01). Three factors were generated in PD (explaining 55% of the total variance) and five in AD (explaining 59% of the total variance), and the two main factors generated in both populations related primarily to unhappiness and negative thoughts. CONCLUSIONS: The factor structure of the GDS-15 is similar in AD and PD patients with at most mild stage dementia, but between-group differences on 6 of the GDS-15 items suggests the non-specificity of certain items in the two populations.

Weintraub D, Saboe K, Stern MB. · Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Mov Disord. · Pubmed #17546674 links to  free full text

Abstract: The purpose of this study was to compare the validity of the 15-item Geriatric Depression Scale (GDS-15) in nonelderly (<65 years), young-elderly (age, 65-75), and old-elderly (>75 years) patients with Parkinson's disease (PD). 57 nonelderly, 88 young-elderly, and 81 old-elderly PD patients were administered the GDS-15 and the Structured Clinical Interview for DSM-IV depression module. Receiver-operating characteristic (ROC) curves were plotted for GDS-15 scores against a DSM-IV diagnosis of major or minor depression. The discriminant validity of the GDS-15 was high for nonelderly, young-elderly, and old-elderly subjects (ROC area under curve = 0.92, 0.91, and 0.95, respectively), with optimal dichotomization at a cut-off of 4/5 (85% sensitivity and 84% specificity in nonelderly; 89% sensitivity and 82% specificity in young-elderly) and 5/6 (90% sensitivity and 90% specificity in old-elderly). In conclusion, the GDS-15 has comparable validity in younger and older PD patients, suggesting its appropriateness as a depression screening instrument in PD patients of all ages.

Chen P, Kales HC, Weintraub D, Blow FC, Jiang L, Ignacio RV, Mellow AM. · Division of Geriatric Psychiatry, Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA. · Int J Geriatr Psychiatry. · Pubmed #17133656 links to  free full text

Abstract: OBJECTIVE: To determine the frequency of depression in Parkinson's disease (PD) in routine clinical care, and to examine its association with co-morbid psychiatric and medical conditions and healthcare utilization. METHODS: Depression diagnoses and healthcare utilization data for all male veterans with PD age 55 or older seen in fiscal year 2002 (n = 41,162) were analyzed using Department of Veterans Affairs (VA) national databases. Frequencies of co-morbid disorders and healthcare utilization were determined for depressed and non-depressed patients; associations with depression were examined using multivariate logistic regression models. RESULTS: A depression diagnosis was recorded for 18.5% of PD patients, including major depression in 3.9%. Depression decreased in frequency and severity with increasing age. In multivariate logistic regression models, depressed patients had significantly greater psychiatric and medical co-morbidity, including dementia, psychosis, stroke, congestive heart failure, diabetes, and chronic obstructive pulmonary disease than non-depressed patients (all p < 0.01). Depressed PD patients were also significantly more likely to have medical (OR = 1.34, 95% CI = 1.25-1.44) and psychiatric hospitalizations (OR = 2.14, 95% CI = 1.83-2.51), and had more outpatient visits (p < 0.01), than non-depressed PD patients in adjusted models. CONCLUSION: Depression in PD in non-tertiary care settings may not be as common or as severe as that seen in specialty care, though these findings also may reflect under-recognition or diagnostic imprecision. The occurrence of depression in PD is associated with greater psychiatric and medical co-morbidity, and greater healthcare utilization. These findings suggest that screening for depression in PD is important and should be embedded in a comprehensive psychiatric, neuropsychological, and medical evaluation.

Cummings JL, Arciniegas DB, Brooks BR, Herndon RM, Lauterbach EC, Pioro EP, Robinson RG, Scharre DW, Schiffer RB, Weintraub D. · Alzheimer's Disease Center, Department of Neurology at David Geffen School of Medicine, University of California, Los Angeles, California, USA. · CNS Spectr. · Pubmed #16816786 links to  free full text

Abstract: Uncontrollable episodes of emotional expression occur in a variety of neurological conditions. This emotional disinhibition syndrome is characterized by episodes of crying or laughing that are unrelated to or out of proportion to the eliciting stimulus. This syndrome is common among patients with amyotrophic lateral sclerosis, multiple sclerosis, stroke, and traumatic brain injury and a variety of terms and definitions have been used to describe it. The confusing nomenclature has been a barrier to understanding, diagnosis, and treatment of this disorder. The authors propose a unifying term, involuntary emotional expression disorder (IEED), and provide diagnostic criteria for this disorder.

Weintraub D, Morales KH, Duda JE, Moberg PJ, Stern MB. · Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA. · Parkinsonism Relat Disord. · Pubmed #16797214 links to  free full text

Abstract: Though both psychosis and depression are common in Parkinson's disease (PD), it is not clear if an association between the two disorders exists. One hundred and thirty PD patients were divided into four groups based on a comprehensive psychiatric assessment: (1) no depression or psychosis (47.7%); (2) psychosis only (16.2%); (3) depression only (26.2%); and (4) psychosis and depression (10.0%). Co-morbid psychosis and depression did not occur more frequently than expected by chance (P=.77). Psychosis was associated with dopamine agonist use (P=.02), depression with mild-cognitive impairment (P=.03), and their co-occurrence with higher daily levodopa dosages (P<.01). These results suggest that psychosis and depression in PD are distinct neurobehavioral disorders.

Weintraub D, Oehlberg KA, Katz IR, Stern MB. · Department of Psychiatry, University of Pennsylvania, and the Parkinson's Disease Research, Education and Clinical Center, Philadelphia Veterans Affairs Medical Center 19104, USA. · Am J Geriatr Psychiatry. · Pubmed #16473982 links to  free full text

Abstract: OBJECTIVE: The objective of this study was to compare the sensitivity, specificity, and diagnostic accuracy of the 15-item Geriatric Depression Scale (GDS-15) and the Hamilton Depression Rating Scale (HDRS) in patients with Parkinson disease (PD). METHOD: A convenience sample of 148 outpatients with idiopathic PD receiving specialty care completed the GDS-15 and were administered the HDRS and Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID) depression module by a research psychiatrist or trained research assistant. Receiver-operating characteristic (ROC) curves were plotted for the GDS-15 and HDRS scores with a SCID diagnosis of a depressive disorder as the state variable. RESULTS: Thirty-two subjects (22%) were diagnosed with a depressive disorder. The discriminant validity of the GDS-15 and HDRS were both high (ROC area under the curve: 0.92 and 0.91, respectively), with greatest dichotomization for the GDS-15 at a cutoff of 4/5 (87% accuracy, 88% sensitivity, 85% specificity) and the HDRS at a cutoff of 9/10 (83% accuracy, 88% sensitivity, 78% specificity). CONCLUSIONS: The GDS-15 performs well as a screening instrument and in distinguishing depressed from nondepressed patients in PD. Its test characteristics are comparable to the HDRS. Because it is a brief instrument and can be self-administered, it is an excellent depression screening tool in this population.

Weintraub D, Cary MS, Stern MB, Taraborelli D, Katz IR. · Department of Psychiatry, University of Pennsylvania, and the Parkinson's Disease Research, Education and Clinical Center, Philadelphia Veterans Affairs Medical Center 19104, USA. · Am J Geriatr Psychiatry. · Pubmed #16473981 No free full text.

Abstract: OBJECTIVE: The aims of this study were to examine the daily affective experiences of patients with Parkinson disease (PD) and to determine their association with daily events and motor symptoms. Specifically, it was intended to test the hypothesis that PD, even in the absence of depression, is associated with anhedonia. METHOD: Nondepressed male subjects with PD (N=24) and a comparison group of healthy elderly males (N=23) completed daily affect rating scales and, for the patients with PD, a supplemental self-assessment questionnaire of PD-related symptoms for 4 consecutive weeks. The effect of daily events and PD-related symptoms on daily affect was examined using linear and logistic mixed regression models. RESULTS: Overall, patients with PD reported significantly less positive and more negative affect than healthy peers over time. There were similar, and expected, associations between negative events and affect in both groups. Although patients with PD reported far fewer positive events than control subjects, they reported as great an improvement in affect in response to them. Regarding self-reported PD-related symptoms, only increasing severity of core motor symptoms was independently associated with worse affect. CONCLUSIONS: Although the conclusions of this study are tempered by a comparison group that is not optimal, our results suggest that patients with PD do not demonstrate anhedonia in response to positive life events. The gross intergroup difference in daily events suggests the potential value of interventions that emphasize daily engagement in positive experiences to improve positive affective tone.