Simone Brockman

The syndromal validity and nosological position of apathy in Parkinson's disease†

Although apathy is among the most frequent behavioral changes in Parkinsons disease (PD), its diagnosis is still problematic, and the overlap with depression and dementia poorly studied. Aim of the study was validate specific criteria to diagnose apathy in PD, and to examine its association with subsyndromes of depression and dementia. A series of 164 patients with PD, 44 patients with “primary” depression and no PD, 23 patients with Alzheimers disease, and 26 age‐comparable healthy controls underwent a comprehensive psychiatric assessment that included a structured psychiatric interview and the Apathy Scale. A set of seven diagnostic criteria showed high sensitivity and specificity for clinically diagnosed apathy. Fifty‐two of the 164 patients with PD (32%) met diagnostic criteria for apathy. Eighty‐three percent of patients with apathy had comorbid depression and 56% had dementia. Only 5 of the 40 PD patients (13%) with neither depression nor dementia had apathy. We validated a set of standardized criteria for the diagnosis of apathy in PD. About one third of a series of patients attending a Movement Disorders Clinic showed apathy. Both depression and dementia were the most frequent comorbid conditions of apathy in PD.

A validation study of depressive syndromes in Parkinson's disease

The validity, sensitivity, and specificity of depressive symptoms for the diagnosis of major depression, minor depression, dysthymic disorder, and subsyndromal depression in Parkinsons disease (PD) were examined. A consecutive series of 173 patients with PD attending a Movement Disorders Clinic underwent a comprehensive psychiatric and neurological assessment. The symptoms of loss of interest/pleasure, changes in appetite or weight, changes in sleep, low energy, worthlessness or inappropriate guilt, psychomotor retardation/agitation, concentration deficits, and suicide ideation were all significantly associated with the presence of the DSM‐IV depressed mood criterion for major depression. The symptoms of changes in appetite, changes in sleep, low energy, low self‐esteem, poor concentration, and hopelessness were all significantly associated with the presence of the DSM‐IV criterion of sad mood for dysthymic disorder. Thirty percent of our sample met DSM‐IV diagnostic criteria for major depression, 20% met diagnostic criteria for dysthymic disorder, 10% met diagnostic criteria for minor depression, and 8% met clinical criteria for subsyndromal depression. Patients with either major or minor depression had significantly more severe deficits in activities of daily living, more severe cognitive impairments, and more severe Parkinsonism than patients with either dysthymic disorder or no depression. This study provides validation to the DSM‐IV diagnostic criteria for major depression and dysthymic disorder for use in PD. The categories of minor and subsyndromal depression may need further validation.

Psychiatric syndromes in Parkinson's disease

Purpose of review To examine progress about relevant behavioural and psychiatric disorders in Parkinsons disease, such as depression, apathy, psychosis, and impulse control disorder. Recent findings Several recent studies have characterized the phenomenology of depression in Parkinsons disease, and randomized controlled trials have demonstrated the efficacy of tricyclics, selective serotonin reuptake inhibitors and psychotherapy for depression in Parkinsons disease. Apathy is a valid behavioural syndrome in Parkinsons disease and is associated with depression and cognitive deficits. Psychosis is highly prevalent in the late stages of the disease, but there are few effective therapeutic modalities for this psychiatric condition. Impulse control disorders are also relatively frequent in Parkinsons disease, and are associated with comorbid psychiatric disorders. Summary Standardized criteria should be used to diagnose depression and apathy in Parkinsons disease. Psychotherapy and pharmacotherapy are useful treatment modalities for affective disorders in Parkinsons disease. Clozapine is still the most effective, albeit rarely used, treatment for psychosis in Parkinsons disease. Impulse control disorders are relatively frequent in Parkinsons disease and all patients should be screened for this complex disorder.

Clinical issues in the treatment of anxiety and depression in older adults with Parkinson’s disease

A significant proportion of persons affected by Parkinsons disease (PD) are over age 65 years. Mental health issues are often less a focus of treatment in this population than physical manifestations of the illness. Anxiety or depression alone, as well as comorbid depression and anxiety, are underrecognized in patients with PD and are associated with deleterious effects on physical and interpersonal functioning, negatively impacting quality of life and well‐being. We offer a brief overview of salient clinical points with respect to assessment and treatment approaches to enhance efficacy of the treatment of mental health symptoms in older adults with PD. Cognitive behavior therapy involves the patient learning to overcome behavioral avoidance associated with anxiety and challenge unhelpful negative cognitions. It is suggested that cognitive behavior therapy is an effective approach to treatment of anxiety and depression in PD and should be offered as a treatment to patients.

Diagnostic criteria for depression in Parkinson's disease: A study of symptom patterns using latent class analysis

Although major depression is one of the most frequent psychiatric disorders among patients with Parkinsons disease, diagnostic criteria have yet to be validated. The main aim of our study was to validate depressive symptoms using latent class analysis for use as diagnostic criteria for major depression in Parkinsons disease. We examined a consecutive series of 259 patients with Parkinsons disease admitted to 2 movement disorders clinics for regular follow‐ups. All patients were assessed with a comprehensive psychiatric interview that included structured assessments for depression, anxiety, and apathy. The main finding was that all 9 Diagnostic and Statistical Manual (4th edition) diagnostic criteria for major depression (ie, depressed mood, diminished interest or pleasure, weight or appetite changes, sleep changes, psychomotor changes, loss of energy, feelings of worthlessness or inappropriate guilt, poor concentration, and suicidal ideation) identified a patient class (severe depression group) with high statistical significance. Latent class analysis also demonstrated a patient class with minimal depressive symptoms (no‐depression group), and a third patient class with intermediate depressive symptoms (moderate depression). Anxiety and apathy were both significant comorbid conditions of moderate and severe depression. Taken together, our findings support the use of the full Diagnostic and Statistical Manual (4th edition) criteria for major depression for use in clinical practice and research in Parkinsons disease and suggest that anxiety may be included as an additional diagnostic criterion.

Apathy and Parkinson’s Disease

Opinion statementApathy, a frequent finding in Parkinson’s disease (PD), is significantly associated with depression and dementia. Few studies have examined the efficacy of psychotropic or psychological treatments of apathy in PD, and adequate randomized controlled trials are still lacking. There is anecdotal evidence that dopaminergic agonists may be a useful treatment modality. Levodopa may improve the loss of motivation in the “off” motor state, and dopaminergic agonists could be useful to treat apathy after the withdrawal of dopaminergic treatment in patients undergoing deep brain stimulation of the subthalamic nucleus. On the other hand, the selective norepinephrine reuptake inhibitor atomoxetine did not demonstrate efficacy in improving apathy in a randomized controlled trial with apathy as a secondary efficacy measure. Given the significant association between apathy and both depression and cognitive decline, future studies should examine whether improving mood and cognition may also have a positive impact upon apathy in PD. For those PD patients with “pure” apathy, specific psychotherapeutic techniques should be developed.

Diagnostic Criteria for Depression in Alzheimer Disease: A Study of Symptom Patterns Using Latent Class Analysis

CONTEXT Although depression in Alzheimer disease (AD) has a negative emotional and functional impact on patients and caregivers, specific criteria to diagnose depression in AD are still to be validated. OBJECTIVE To validate a set of diagnostic criteria for major depression in AD. DESIGN Cross-sectional design using latent cluster analysis (LCA). SETTING Participants were recruited from consecutive referrals to a Memory Clinic of a tertiary hospital. PARTICIPANTS A consecutive series of 971 outpatients with probable AD. MAIN OUTCOME MEASURE Clusters of patients with or without major depression as determined with LCA. RESULTS A LCA demonstrated three clusters that were considered to represent major depression, minor depression, and no depression. All nine Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for major depression were significantly associated with the major depression cluster. Although a diagnosis of generalized anxiety disorder (GAD) and apathy were also associated with the major depression cluster, irritability was not. CONCLUSIONS The DSM-IV criteria for major depression should be used unmodified to diagnose depression in AD. Future studies should determine whether GAD should be included as an additional diagnostic criterion.

Amygdala volumetric change following psychotherapy for posttraumatic stress disorder

The authors investigated the impact of eye movement desensitization and reprocessing (EMDR) and prolonged exposure (PE) on the volumes of the amygdala and hippocampus, structures known to be important in fear conditioning, in 20 patients with posttraumatic stress disorder (PTSD). Patients were randomly allocated to either EMDR or PE. Volumes were assessed before and after treatment via magnetic resonance imaging (MRI). Both groups showed significant improvements in PTSD symptoms. Left amygdala mean volume increased significantly following EMDR treatment only. No significant volumetric changes were found for the hippocampus.

The impact of emotional distress on motor blocks and festination in Parkinson's disease.

Recent studies suggest that depression and anxiety in patients with Parkinsons disease may predispose them to freezing. Although festination is also frequent, the association with emotional disorders has not been examined. The aim of the authors was to clarify the association between freezing and festination with anxiety, depressive disorders, and emotional distress. The authors examined a consecutive series of 95 patients with Parkinsons disease using comprehensive psychiatric assessments and a new instrument specifically designed to assess the severity of freezing, festination, and emotional distress (Motor Blocks and Festination Scale). All patients were assessed with the Motor Blocks and Festination Scale, the Mini International Neuropsychiatric Interview, and scales to measure the severity of mood and anxiety disorders. A linear regression analysis showed that both motor blocks and festination were significantly associated with emotional distress and deficits on activities of daily living. Conversely, there was no significant association between motor blocks or festination and generalized anxiety disorder, panic disorder, agoraphobia, social phobia, or depression. Motor blocks and festination are significantly associated with emotional distress, but no significant associations were found with anxiety or affective disorders.

A Randomized, Placebo-Controlled, Double-Blind Efficacy Study of Nefiracetam to Treat Poststroke Apathy

BACKGROUND To evaluate the efficacy of treatment with nefiracetam compared to placebo in poststroke apathy. METHODS A parallel group, randomized, placebo-controlled, double-blind two-center trial in patients with recent stroke and apathy was conducted in 2 tertiary teaching hospitals in Perth, Western Australia, between March 2010 and October 2014. Consenting patients hospitalized with stroke were screened for participation at the time of hospitalization and, if diagnosed with apathy 8-36 weeks later, they were randomized to 12 weeks of 900 mg/day nefiracetam or placebo. The primary efficacy parameter was change in apathy at 12 weeks defined by the 14-item Apathy Scale (AS). RESULTS Of 2514 patients screened, only 377 (15%) were eligible for the study after the first screening, 233 declined further participation, and 144 were assessed for apathy at 8-36 weeks post stroke to confirm eligibility. Twenty patients out of 106 with a complete psychiatric assessment had apathy (19%). Of this sample, 13 patients were randomized. Overall, the AS score decreased by a mean of 7.0 points (95% CI = -14.6 to .6), but there was no significant between-group difference at week 12 (mean paired t-tests, P > .14). CONCLUSIONS Treatment with nefiracetam did not prove to be more efficacious than placebo in ameliorating apathy in stroke. The main limitation was the very small sample randomized, highlighting the limitations of conducting drug trials for behavioral problems among stroke patients. Pharmacological studies of apathy in stroke will require a large multicenter study and a massive sample of patients.