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Biomedical subjects

William M McDonald

Publications and source records attributed to William M McDonald.

15 recordsLinked to original sources
PubMed2006

Provisional diagnostic criteria for depression in Parkinson's disease: report of an NINDS/NIMH Work Group.

Mood disorders are the most common psychiatric problem associated with Parkinson's disease (PD), and have a negative impact on disability and quality of life. Accurate diagnosis of depressive disturbances in PD is critical and will facilitate the testing and use of new interventions; however, there are no clear diagnostic criteria for depressive disorders in PD. In their current form, strict Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria are difficult to use in PD and require attribution of specific symptoms to PD itself or the depressive syndrome. Additionally, DSM criteria for major depression and dysthymia exclude perhaps half of PD patients with comorbid clinically significant depression. This review summarizes an NIH-sponsored workshop and describes recommended changes to DSM diagnostic criteria for depression for use in PD. Participants also recommended: (1) an inclusive approach to symptom assessment to enhance reliability of ratings in PD and avoid the need to attribute symptoms to a particular cause; (2) the inclusion of subsyndromal depression in clinical research studies of depression of PD; (3) the specification of timing of assessments for PD patients with motor fluctuations; and (4) the use of informants for cognitively impaired patients. The proposed diagnostic criteria are provisional and intended to be defined further and validated but provide a common starting point for clinical research in PD-associated depression.

Comorbidity↗
PubMed2006

Validity of the 30-item geriatric depression scale in patients with Parkinson's disease.

Depression in Parkinson's disease (dPD) is difficult to diagnose because depressive symptoms can overlap with symptoms of Parkinson's disease (PD). Subject-rated scales such as the 30-item Geriatric Depression Scale (GDS) may be useful in screening for dPD. There were 57 patients (33 men, 24 women; mean age, 58.6 years [SD +/- 8.4]) enrolled in a study of pallidotomy for intractable PD who were evaluated for depression before and after surgery. Subjects were evaluated using the 17-item Hamilton Depression Rating Scale (HDRS), Structured Clinical Interview for Diagnostic and Statistical Manual-III (SCID), and the GDS. SCID was used to diagnose major depression with confirmation by an expert geropsychiatrist. Receiver-operating curves (ROC) were used to identify cutoff points with maximal discriminant validity for diagnosing dPD. A total of 213 evaluation time points were included for the 52 patients with time points that included a valid SCID diagnosis, GDS, and HDRS. A ROC established points of maximum specificity/sensitivity for the GDS at a cutoff of 9/10 (sensitivity = 0.809, specificity = 0.837, positive predictive value [PPV] = 0.584, negative predictive value [NPV] = 0.939) and for the HDRS at a cutoff of 12/13 (sensitivity = 0.810, specificity = 0.821, PPV = 0.580, NPV = 0.934). The GDS was moderately correlated with the HDRS (Pearson's r = 0.54; P < 0.001). The GDS is useful in screening for dPD. A cutoff score of 9/10 has acceptable discriminant validity for dPD, and the GDS has a moderate correlation with the HDRS in PD patients.

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PubMed2006

The diagnosis and treatment of depression in Parkinson's disease.

Depression is common in Parkinson's disease (PD) and associated with considerable morbidity, including a worsening of motor symptoms and measures of quality of life. Therefore, patients with PD should be routinely screened for depressive symptoms with rating scales such as the Geriatric Depression Scale. Patients meeting criteria should be treated using established algorithms for the management of depression and associated symptoms such as insomnia, anxiety, psychosis, and mania. The algorithm outlined in this paper describes the importance of maintaining an adequate dose of medication over a medication trial that can last up to 12 weeks. To optimally monitor patients' progress, clinicians should also consider using rating scales that measure depression severity, such as the Montgomery-Asberg Depression Rating Scale and Beck Depression Inventory.

Journal Article↗
PubMed2006

Is ECT cost-effective? A critique of the National Institute of Health and Clinical Excellence's report on the economic analysis of ECT.

The report of the National Institute of Health and Clinical Excellence (NICE) on the economic analysis of electroconvulsive therapy (ECT) concludes that ECT and pharmacotherapy are "likely to be equally cost-effective" in the treatment of major depression. However, this economic analysis is acknowledged by the NICE report to be "crude and based on a number of uncertain assumptions." An evaluation by the Health Technology Assessment Committee of the National Coordinating Centre for Health Technology Assessment, commissioned and funded on behalf of NICE, provides a detailed cost comparison of ECT and pharmacotherapy in the treatment of major depression [Greenhalgh, Health Technol Assess, 9 (9) (2005) 1-156]. The Health Technology Assessment Committee analyzed data from separate studies of the efficacy of antidepressants and ECT. However, these data included few randomized controlled trials directly comparing the cost-effectiveness of ECT and medication in treatment-resistant depression. In the limited number of trials included in the report, there was a bias in favor of medication. For example, compared with the antidepressant trials, the ECT trials included more patients who had comorbid psychosis and treatment-resistant depression and would therefore have a more difficult treatment of depression. The Committee also evaluated data to determine that the relapse rate after pharmacological treatment is approximately 3 times the relapse rate after ECT. Although the report provides a format for analyzing the cost-effectiveness of ECT and recommends future directions for research, the conclusions reached by the Committee are relatively limited and should not be used as a template for future public policy.

Antidepressive Agents↗
PubMed2005

Mood disorders in the medically ill: scientific review and recommendations.

OBJECTIVE: The purpose of this review is to assess the relationship between mood disorders and development, course, and associated morbidity and mortality of selected medical illnesses, review evidence for treatment, and determine needs in clinical practice and research. DATA SOURCES: Data were culled from the 2002 Depression and Bipolar Support Alliance Conference proceedings and a literature review addressing prevalence, risk factors, diagnosis, and treatment. This review also considered the experience of primary and specialty care providers, policy analysts, and patient advocates. The review and recommendations reflect the expert opinion of the authors. STUDY SELECTION/DATA EXTRACTION: Reviews of epidemiology and mechanistic studies were included, as were open-label and randomized, controlled trials on treatment of depression in patients with medical comorbidities. Data on study design, population, and results were extracted for review of evidence that includes tables of prevalence and pharmacological treatment. The effect of depression and bipolar disorder on selected medical comorbidities was assessed, and recommendations for practice, research, and policy were developed. CONCLUSIONS: A growing body of evidence suggests that biological mechanisms underlie a bidirectional link between mood disorders and many medical illnesses. In addition, there is evidence to suggest that mood disorders affect the course of medical illnesses. Further prospective studies are warranted.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Prevalence, etiology, and treatment of depression in Parkinson's disease.

Parkinson's disease (PD) is primarily a disease of elderly individuals with a peak age at onset of 55 to 66 years. It is characterized by bradykinesia, rigidity, tremor, and postural instability; and affects approximately 1 million individuals in the US and is the second most common neurodegenerative disease next to Alzheimer's disease. The motor symptoms of PD are the focus of pharmacotherapy, yet the nonmotor symptoms (e.g., dementia, psychosis, anxiety, insomnia, autonomic dysfunction, and mood disturbances) can be the most disturbing, disabling, and misunderstood aspects of the disease. Depressive symptoms occur in approximately half of PD patients and are a significant cause of functional impairment for PD patients. There is accumulating evidence suggesting that depression in PD is secondary to the underlying neuroanatomical degeneration, rather than simply a reaction to the psychosocial stress and disability. The incidence of depression is correlated with changes in central serotonergic function and neurodegeneration of specific cortical and subcortical pathways. Understanding comorbid depression in PD may therefore add to the understanding of the neuroanatomical basis of melancholia.

Antiparkinson Agents↗
PubMed2003

Administration of ECT in a patient with an inoperable abdominal aortic aneurysm: serial imaging of the aorta during maintenance.

This case report reviews the treatment of a 74-year-old man with an abdominal aortic aneurysm, bipolar affective disorder, and Lewy body dementia who demonstrated a remarkable positive response to an acute and maintenance course of electroconvulsive therapy (ECT) treatment. This is the first report with serial imaging of an abdominal aortic aneurysm during maintenance ECT. There are limited alternative therapies for those patients who do not meet surgical criteria for an abdominal aortic repair because of dementing disorders. In patients who suffer comorbid mood disorders, ECT has been shown to be an effective option in preserving quality of life and successfully stabilizing the level of agitation.

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PubMed2002

Developing novel treatments for mood disorders: accelerating discovery.

This review was generated from discussions by the Pharmacologic and Somatic Treatments Section of the National Institute of Mental Health Strategic Plan for Mood Disorders Committee on advancing novel pharmacologic and somatic treatments for mood disorders. The opening section of the article summarizes in broad strokes, current pharmacologic treatments, and new directions in the field. Thereafter the topics focus on specific research initiatives that could advance the current therapeutics for mood disorders including new basic and clinical research in vivo human imaging procedures, somatic therapeutics, and the vast new area of pharmacogenetics. New scientific and technical opportunities exist today based on advances in basic neuroscience, opportunities in clinical testing, industry interest in advancing central nervous system therapeutics, and on active consumer advocacy groups. The question of how to bring all of these positive forces together to accelerate discovery in mood disorder thera-peutics is the topic of this article.

Animals↗
PubMed2002

Beneficial effects of testosterone replacement for the nonmotor symptoms of Parkinson disease.

OBJECTIVE: To investigate whether a single daily dose of testosterone replacement gel has beneficial effects on testosterone deficiency symptoms, cognitive function, nonmotor symptoms of Parkinson disease (PD), and motor symptoms of PD. BACKGROUND: Recently it has been observed that testosterone replacement therapy improves refractory nonmotor symptoms in testosterone-deficient men with PD. Many of the symptoms of testosterone deficiency are nonspecific and overlap with the nonmotor symptoms of PD, such as decreased enjoyment of life, lack of energy, sexual dysfunction, and depression. Replacement therapy for men with PD and comorbid testosterone deficiency may be an important addition to antiparkinsonian management strategies. METHODS: A prospective open-labeled pilot study of testosterone topical gel (5 g of AndroGel; Unimed Pharmaceutical Inc, Deerfield, Ill) administered daily to testosterone-deficient (free testosterone <80 pg/mL) men with PD. All 10 patients were followed up for 1 month and 6 patients were followed up for a total of 3 months. Patients were administered a battery of testosterone deficiency questionnaires, cognitive studies, and scales of PD nonmotor and motor function at baseline, 1, and 3 months. RESULTS: With the daily transdermal testosterone gel, patients had an average increase in levels of free testosterone from baseline (53 pg/mL) to a 1-month follow-up visit (131 pg/mL; P =.06) and to a 3-month follow-up visit (98 pg/mL; P =.04). Testosterone deficiency symptoms improved in these patients (St Louis Testosterone Deficiency Questionnaire) from baseline (7.9 deficiency symptoms) to 1 month (5.6 deficiency symptoms, P =.04) and 3 months (5.8 deficiency symptoms, P =.08). The Unified Parkinson's Disease Rating Scale IV showed improvement at 1 month (P =.008). Additionally, there were trends toward improvement in the following scales: Unified Parkinson's Disease Rating Scale I at the 3-month follow-up (P =.09), Letter Fluency at the 3-month follow-up (P =.08), and the Hamilton Anxiety Scale at the 1-month follow-up (P =.09). CONCLUSIONS: A daily dose of transdermal testosterone gel improved testosterone deficiency symptoms in men with PD. Although there were trends in improvement in other nonmotor and motor symptoms of PD, future placebo control studies will need to be powered to answer these important questions. Whether testosterone deficiency is simply a comorbidity in PD or whether it plays a role in the pathogenesis of disease also remains for future study.

Administration, Topical↗
PubMed2002

Refractory nonmotor symptoms in male patients with Parkinson disease due to testosterone deficiency: a common unrecognized comorbidity.

BACKGROUND: Many patients with Parkinson disease (PD) suffer from nonmotor symptoms including depression, anxiety, sexual dysfunction, decreased energy level, and an overall decline in quality of life. Comorbid depression, hypothyroidism, and sleep disorders may account for some, but not all, of these problems. Testosterone deficiency affects 20% to 25% of males over the age of 60 years in the general population and may cause signs and symptoms of the nonmotor symptoms seen in PD. We observed numerous patients with PD whose nonmotor symptoms were refractory to treatment. OBJECTIVE: To determine whether treatment of comorbid testosterone deficiency in male patients with PD can lead to improvements in refractory nonmotor symptoms. METHODS: Case studies were reviewed of the first 5 male patients who had PD with symptoms of testosterone deficiency who were treated in our clinic. All patients had low serum testosterone levels. Screening for testosterone deficiency symptoms using the St Louis Testosterone Deficiency Questionnaire was performed for 4 of the 5 patients. Additionally, to assess the prevalence of PD, total testosterone levels in 68 patients in our PD registry were sent for evaluation. RESULTS: Following testosterone replacement therapy, all 5 patients experienced significant improvements in their refractory nonmotor symptoms. Of 68 male patients with PD enrolled in our PD registry, 24 (35%) had plasma evidence of testosterone deficiency. We also noted that the risk of testosterone deficiency per decade was found to increase 2.8-fold per decade (P<.001), paralleling that which is found in the general elderly male population. CONCLUSIONS: The findings from this study reveal the heretofore unrecognized high prevalence of testosterone deficiency in elderly male patients with PD similar to that found in the general population. These symptoms, which may be refractory to antidepressants, anxiolytics, and antiparkinsonian medications, may respond to treatment with testosterone. More rigorous controlled studies will need to be undertaken to examine the treatment of this common comorbidity in male patients with PD.

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PubMed2002

Depression and Parkinson's disease: a new look at an old problem.

A National Institutes of Health (National Institute of Neurological Disorders and Stroke; National Institute of Mental Health; National Institute on Aging) working group meeting focused on the non-motor aspects of Parkinson's disease (PD). Below is the summary of the meeting presentations and recommendations for a research agenda on the epidemiology, assessment, circuitry, therapeutic approaches, and clinical trials of Parkinson's disease co-morbid with depression. A second summary will focus on PD and dementia.

Animals↗
PubMed2002

Pharmacologic treatment of geriatric mania.

The prevalence of geriatric mania is uncertain. Although there are high rates of mania in clinical and residential facilities, community based epidemiologic studies are limited. Given the difficulty in making an accurate diagnosis, geriatric mania appears to be underreported. Although the commonly held opinion is that onset and prevalence of mania decreases with age, there is contradictory evidence that, particularly in men, the incidence of new onset mania increases with age. Clinically, the diagnosis and treatment of geriatric mania is challenging, because these patients present with comorbid medical, neurologic, and dementing illnesses. This paper reviews presentations of mania in the elderly and updates the pharmacologic treatment of mania in the elderly. Although few of the studies target the elderly, the published data in younger patients on the use of the atypical antipsychotics, as well as the advent of newer anticonvulsants, have demonstrated promise in the treatment of older patients.

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PubMed2002

Anatomic location and laterality of MRI signal hyperintensities in late-life depression.

OBJECTIVES: Evidence is mounting linking cerebrovascular disease with the development of major depression in the elderly. Lesions in both white and gray matter have been associated with geriatric depression. In addition, the literature on poststroke depression suggests that left-sided lesions are associated with depression. We sought to examine the severity and location of white- and gray-matter lesions in a group of elderly depressives and nondepressed control subjects. METHOD: 115 depressed patients (69 with late onset, 46 with early onset) and 37 controls, all over age 45, received magnetic resonance imaging (MRI). Semiquantitative severity ratings and quantitative measurements of number and size of MRI hyperintensities were obtained, and groups were compared using Cochran-Mantel-Haenszel (CMH) analyses and repeated-measures analyses of covariance adjusting for age. RESULTS: Late-onset depressed patients had more severe hyperintensity ratings in deep white matter than early-onset patients and controls. Late- and early-onset patients had more severe subcortical gray-matter hyperintensities (particularly in the putamen) compared with controls. Left-sided white-matter lesions were significantly associated with older age of depression onset, whereas right-anterior white matter and left-subcortical lesions (particularly in the putamen) were associated with melancholia in the depressed group. CONCLUSION: These findings extend previous reports of an association between cerebrovascular disease and depression, as well as recent studies showing lateralized lesion involvement in geriatric depression. Such vascular pathology may disrupt neural pathways involved in affective processing and the maintenance of a normal mood and psychomotor state.

Age of Onset↗
PubMed2002

Depression in the elderly.

Depression is prevalent in the elderly and associated with increased morbidity and mortality. Diagnosis can be complicated by the presence of concomitant medical and/or psychiatric disorders, and it is important to exclude a number of factors, such as neurological disease, hormonal causes, chronic illness, or substance abuse, particularly alcohol. Although comorbid medical illness may contribute to depressive illness, depressive disorders are not a consequence of aging. Most classes of antidepressants that are effective in adult patients are effective in the elderly and, in general, they have shown comparable efficacy in terms of response rates. However, antidepressants vary in terms of their tolerability profiles, and treatment of the elderly is complicated by their sensitivity to medication side effects and the potential for serious adverse events, such as falling or delirium. A correct dosing strategy is particularly important for the elderly, whose treatment should usually start at low doses of antidepressants and increase slowly. It is possible to successfully treat elderly patients with depressive disorder, and antidepressant therapy should be selected on the basis of prior response to treatment, the adverse-event profile, and the potential for drug-drug interactions. Treatment should also take into account the likelihood of achieving and maintaining remission of symptoms in order to restore the patient to a baseline level of functioning appropriate for their age.

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