Depression occurs in around 35% of patients with Parkinson disease (PD) and is often persistent. Symptoms of depression can be evident in individuals at the time of diagnosis and might develop in the premotor stage of the disease. The underlying mechanisms of depression in PD are not known in detail, but changes in brain structure, signaling by neurotransmitters, and levels of inflammatory and neurotrophic factors are all suggested to contribute to its development. Psychosocial factors and pain could also have roles in depression. Changes in dopaminergic, noradrenergic and serotonergic systems in patients with PD might help to explain the incidence of depression in these individuals. Antidepressants that have dual serotonergic and noradrenergic effects are the drugs of choice for treating depression in PD. However, antiparkinsonian drugs might have beneficial effects not only on the motor symptoms of disease, but also on a patient's mood. Deep brain stimulation can worsen depression in some patients, but a preliminary study has suggested that transcranial magnetic stimulation could improve symptoms of depression. This Review describes the frequency and course of depression in patients with PD. The mechanisms that underlie depression in this disease are also discussed, and the management strategies for these patients are highlighted.

Depression in Parkinson disease—epidemiology, mechanisms and management

The concurrent validity of the Hamilton Rating Scale for Depression (HAMD-17) and the Montgomery-Asberg Depression Rating Scale (MADRS) against the DSM-IV diagnosis ‘depressive disorder’ was assessed in patients with Parkinson's disease (PD). Sixty-three non-demented Parkinson's Disease (PD) patients who attended the outpatient department of an academic hospital were diagnosed according to a standardised research protocol. This protocol consisted of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) to establish the presence or absence of ‘depressive disorder’ according to the DSM-IV criteria, as well as the HAMD-17 and the MADRS. Receiver Operating Characteristics curves (ROC curves) were obtained and the positive and negative predictive values (PPV, NPV) were calculated for different cut-off scores. Maximum discrimination between depressed and non-depressed patients was reached at a cut-off score of 13/14 for the HAMD-17, and at 14/15 for the MADRS. At lower cut-offs, like 11/12 for the HAMD-17 and 14/15 for the MADRS, the high sensitivity and NPV make these scales good screening instruments. At higher cut-offs, such as 16/17 for the HAMD-17 and 17/18 for the MADRS, the high specificity and PPV make these instruments good diagnostic instruments. The diagnostics performance of the HAMD-17 is slightly better than that of the MADRS. This study shows that it is justified to use the HAMD-17 and the MADRS to measure depressive symptoms in both non-depressed and depressed PD patients, to diagnose depressive disorder in PD, and to dichotomize patient samples into depressed and non-depressed groups. Copyright © 2000 John Wiley & Sons, Ltd.

The validity of the Hamilton and Montgomery-Asberg depression rating scales as screening and diagnostic tools for depression in Parkinson's disease.

Wild Syrian rue (Peganum harmala L. family Zygophyllaceae) is well-known in Iran and various parts of this plant including, its seeds, bark, and root have been used as folk medicine. Recent years of research has demonstrated different pharmacological and therapeutic effects of P. harmala and its active alkaloids, especially harmine and harmaline. Analytical studies on the chemical composition of the plant show that the most important constituents of this plant are beta-carboline alkaloids such as harmalol, harmaline, and harmine. Harmine is the most studied among these naturally occurring alkaloids. In addition to P. harmala (Syrian rue), these beta-carbolines are present in many other plants such as Banisteria caapi and are used for the treatment of different diseases. This article reviews the traditional uses and pharmacological effects of total extract and individual active alkaloids of P. harmala (Syrian rue).

Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids.

This review examines the frequency of depression complicating Parkinson's disease (PD), its aetiology and clinical features, and also how it may be recognised and treated. Studies investigating the frequency of depression in PD have yielded figures ranging between 2.7% and 70%. Methodological differences account for much of the disparity. The aetiology of depression in PD is complex, and probably relates to both biological and exogenous factors. Dysfunction of multiple neurotransmitter systems, including the serotonergic system, may be involved. Mood disturbances resulting from deep brain stimulation of the subthalamic nucleus may provide a fruitful area for future research, and assist our understanding of the neural networks involved in mediating depression. Several recent studies have confirmed that depression in the PD patient is a major determinant of quality of life and that this is closely related to dysfunction in other clinically important health areas. The validity for many existing scales in the screening, diagnosis, and monitoring of depression in the PD patient has not been established. The Montgomery-Asberg Depression Rating Scale and the Hamilton Rating Scale for Depression appear to have good diagnostic sensitivity and specificity when compared with DSM-IV criteria. Recommendations for the optimal drug treatment of depression in PD are difficult to give, due to an inexplicable dearth of sizeable, placebo-controlled studies. A majority of physicians would probably now opt for a selective serotonin reuptake inhibitor in the depressed PD patient. There is no good evidence that these drugs are associated with a worsening of motor features, but they should probably not be coprescribed with selegiline, because of the risk of causing a potentially serious serotonin syndrome. Several studies have suggested that depression in the PD patient is associated with a more rapid deterioration in cognitive and motor functions, perhaps as a surrogate marker for more extensive brainstem cell loss.

Beyond the iron mask: towards better recognition and treatment of depression associated with Parkinson's disease.

Depression in neurodegenerative diseases: Common mechanisms and current treatment options

Introduction. Etiology of depression in Parkinsons disease (PD) is associated with serotonergic dysfunction. Previous studies, supporting this hypothesis, were performed on patients treated with antiparkinsonian drugs. To eliminate the influence of parkinsonian drug therapy and to elucidate significance of different biochemical pathways in PD associated with depression we determined levels of biogenic amines in cerebrospinal fluid (CSF) of 26 untreated “de novo” Parkinsonian patients.Material and methods. Patients were scored with the Hamilton depression scale (HD) and subdivided into groups with HD score ≥ 18 and HD score <18. Diagnosis of depression was made according to DSM III R. Both groups were matched for age and motor disability.Results. In both groups no significant differences appeared between CSF levels of dopamine, noradrenaline, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 3-methoxy-4-hydroxyphenylglycol and 5-hydroxyindole acetic acid, determined by high-performance liquid chromatography.Discussion. In contrast to previous studies on treated Parkinsonian patients no sign of altered serotonin metabolism especially in context with severity of depression in early stages of PD was found. Due to our results, we suggest, that biochemical markers of depression in CSF of PD may be influenced by antiparkinsonian therapy and that depression in PD may respond to serotonin reuptake inhibitors mainly in later stages of PD.

Depression in Parkinson's disease: biogenic amines in CSF of “de novo” patients

Der Nachweis erniedrigter Spiegel von 5-Hydroxyindolessigsaure (5-HIAA) im Liquor von depressiven Parkinson-Patienten fuhrte zu der Vermutung, das Anderungen im Serotonin-Metabolismus eine wesentliche Rolle bei der Genese von Depressionen bei M. Parkinson spielen konnten [1, 2], Die Bestimmung von 5-HIAA und anderer Monoamin-Metaboliten in diesen Studien erfolgte jedoch nach Durchfuhrung eines „drug-holiday” bei schon langere Zeit mit Antiparkinson-Medikamenten behandelten Patienten. In unserer Untersuchung bestimmten wir den Liquorgehalt von Homovanillinsaure (HVA), 4-Methoxy-3-hydroxyphenylglykol (MHPG) und 5-HIAA bei 32 bisher unbehandelten (de novo) Parkinson-Patienten mit und ohne Depression.

R. Prautsch

Papers

Depression in Parkinson's disease: biogenic amines in CSF of “de novo” patients

Morbus Parkinson und Depression: Bestimmung von Monoaminmetaboliten im Liquor von De-novo-Patienten