Depression: Starkstein S

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.

Jorge RE, Robinson RG, Arndt S, Starkstein S. · Department of Psychiatry, University of Iowa College of Medicine, Iowa City 52242, USA. · Am J Psychiatry. · Pubmed #14514497 links to  free full text

Abstract: OBJECTIVE: Poststroke depression has been shown to increase mortality for more than 5 years after the stroke. The authors assessed whether antidepressant treatment would reduce poststroke mortality over 9 years of follow-up. METHOD: A total of 104 patients were randomly assigned to receive a 12-week double-blind course of nortriptyline, fluoxetine, or placebo early in the recovery period after a stroke. Mortality data were obtained for all 104 patients 9 years after initiation of the study. Demographic and clinical measurements were collected at 3, 6, 9, 12, 18, and 24 months after the stroke. Survival data were analyzed by using the Kaplan-Meier method. RESULTS: Of the 104 patients, 50 (48.1%) had died by the time of the 9-year follow-up. Of 53 patients who were given full-dose antidepressants, 36 (67.9%) were alive at follow-up, compared with only 10 (35.7%) of 28 placebo-treated patients, a significant difference. Logistic regression analysis showed that the beneficial effect of antidepressants remained significant both in patients who were depressed and in those who were nondepressed at enrollment, after the effects of other factors associated with mortality (i.e., age, coexisting diabetes mellitus, and chronic relapsing depression) were controlled. There were no intergroup differences in severity of stroke, impairment in cognitive functioning and activities of daily living impairment, and other medications received. CONCLUSIONS: Treatment with fluoxetine or nortriptyline for 12 weeks during the first 6 months poststroke significantly increased the survival of both depressed and nondepressed patients. This finding suggests that the pathophysiological processes determining the increased mortality risk associated with poststroke depression last longer than the depression itself and can be modified by antidepressants.

Merello M, Starkstein S, Nouzeilles MI, Kuzis G, Leiguarda R. · Movement Disorders Section, Raul Carrea Institute for Neurological Research (FLENI), Montañeses 2325, 1428 Buenos Aires, Argentina. · J Neurol Neurosurg Psychiatry. · Pubmed #11606671 links to  free full text

Abstract: OBJECTIVE: Posteroventral pallidotomy (PVP) has proved to be an effective method for the treatment of Parkinson's disease. However, data on bilateral procedures are still limited. To assess the effects of bilateral globus pallidus (GPi) lesion and to compare it with a combination of unilateral GPi lesion plus contralateral GPi stimulation (PVP+PVS), an open blind randomised trial was designed. METHODS: A prospective series of patients with severe Parkinson's disease refractory to medical treatment, and severe drug induced dyskinesias, were randomised either to simultaneous bilateral PVP or simultaneous PVP+PVS. All patients were assessed with the core assessment programme for intracerebral transplantation (CAPIT), and a comprehensive neuropsychological and neuropsychiatric battery both before surgery and 3 months later. RESULTS: The severe adverse effects found in the first three patients subjected to bilateral PVP led to discontinuation of the protocol. All three patients developed depression and apathy. Speech, salivation, and swallowing, as well as freezing, walking, and falling, dramatically worsened. By contrast, all three patients undergoing PVP+PVS had a significant motor improvement. CONCLUSION: Bilateral simultaneous lesions within the GPi may produce severe motor and psychiatric complications. On the other hand, a combination of PVP+ PVS significantly improves parkinsonian symptoms not associated with the side effects elicited by bilateral lesions.

Robinson RG, Jorge RE, Clarence-Smith K, Starkstein S. · Department of Psychiatry, The University of Iowa, 200 Hawkins Dr, Iowa City, IA 52242, USA. · J Neuropsychiatry Clin Neurosci. · Pubmed #19622685 No free full text.

Abstract: Nefiracetam is a novel pyrrolidone-type nootropic compound shown in preliminary trials to increase blood flow and improve patient outlook and energy following stroke. Of 137 stroke patients with major depression, 70 also met published diagnostic criteria for apathy (51.1%) and were randomly assigned either to placebo or 600 mg or 900 mg of nefiracetam per day, and received at least 4 weeks of treatment. Using the group with at least 4 weeks of treatment as the intention-to-treat sample with last observation carried forward, repeated measures analysis of variance of Apathy Scale scores demonstrated a significant time-by-treatment interaction. Patients taking 900 mg nefiracetam had a significantly greater change in Apathy Scale scores compared to 600 mg of nefiracetam or placebo. Future studies should assess whether apathy without depression may respond to this novel treatment.

Bottini Bonfanti A, Etcheverry JL, Persi GG, Zezza H, Starkstein S, Gatto EM. · Instituto de Neurología de Buenos Aires (INBA). · Medicina (B Aires). · Pubmed #19435698 No free full text.

Abstract: Apathy is one of the most prominent non-motor symptoms in Parkinson Disease (PD). Its range of prevalence in PD has been estimated in 20 to 45%. The objective of this work is to assess the prevalence of apathy in PD patients, and its relation with depression and executive function impairment. Fifty seven PD patients (54% women), mean age of 68.7 years, and a disease duration of 7.5 years from diagnosis were included. We used the following scales: UPDRS, Hoehn & Yahr, Mini Mental State Examination, the 14-item Apathy Scale (AS), the Beck Depression Inventory, and Trail Making Test versions A and B (TMT), and Parkinson's Disease Quality of Life Questionnaire (PDQL). Apathy was identified in 31.6%; apathy without depression was present in 33.3% of patients. The TMT A and B were abnormal in 66.7% and 83.3% respectively of the apathetic patients vs. 46.2% and 61.5% in non-apathetic patients. Quality of life was impaired in apathetic patients. In our PD sample apathy is highly prevalent, has a great impact on quality of life and it may occur in the absence of depression. The alterations of TMT in apathetic patients contributes to suggest a positive relationship between apathy and the impairment of executive function secondary to the involvement of frontal-subcortical circuits.