0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

1
Special Article   |    
Prevalence, Clinical Manifestations, Etiology, and Treatment of Depression in Parkinson's Disease
James R. Slaughter, M.D.; Kathleen A. Slaughter, B.S.N.R.N.C.; Dave Nichols, B.S.; Stacey E. Holmes, M.A.; Matthew P. Martens, M.A.
The Journal of Neuropsychiatry and Clinical Neurosciences 2001;13:187-196. doi:10.1176/appi.neuropsych.13.2.187
View Author and Article Information

Parkinson's DiseaseDepressionAntidepressants

Received March 9, 1999; revised May 31, 2000; accepted June 6, 2000. From the Department of Psychiatry and Neurology, University of Missouri School of Medicine, Columbia, Missouri. Address correspondence to Dr. Slaughter, University of Missouri, Department of Psychiatry and Neurology, One Hospital Drive, Columbia, MO 65212.

Abstract

To determine the extent to which depression complicates Parkinson's disease (PD), the authors analyzed the literature on depression in PD in order to report on its prevalence, clinical manifestations, and treatment. By means of MEDLINE literature searches, the analysis focused on 45 PD depression studies conducted from 1922 through 1998. The results indicate that the prevalence of depression is 31% for all PD patients. The clinical manifestations of PD depression include apathy, psychomotor retardation, memory impairment, pessimism, irrationality, and suicidal ideation without suicidal behavior. PD depression is effectively treated with a variety of antidepressants, most commonly at present the selective serotonin reuptake inhibitors. Anecdotal evidence supports the use of sertraline to treat PD depression.

Abstract Teaser
Figures in this Article

James Parkinson was the first person to describe Parkinson's disease (PD). In 1817 he discussed the indications of this disease in "An Essay on the Shaking Palsy," which he based on the observation of 6 patients.1 This illness, which is characterized by tremor, bradykinesia, rigidity, and postural abnormalities, has a prevalence rate in the United States of 187 per 100,000 and an annual incidence of 20 per 100,000. Worldwide, studies indicate a wide range of occurrence of PD, with prevalence rates ranging from 31 to 347 per 100,000.2

Parkinson's disease is frequently complicated by depression. Different criteria have been used when diagnosing depression in patients with PD, resulting in variable estimates of the occurrence of this condition. Consensus of opinion at present is that depression is one of the most common neuropsychiatric disturbances associated with PD.35 Some evidence suggests that depression is the prodromal symptom in a subgroup of persons with PD, characterized by a younger age at onset, decreased severity, and stronger family history of the disease.6

We undertook an analysis of the literature on depression complicating PD to determine the occurrence of depression, clinical manifestations, possible etiology, and treatment. Further review of the prevalence of depression in PD is necessary because of the wide range of criteria used for diagnosis. A review of its treatment is needed because of the availability of newer pharmaceutical agents for the treatment of depression.

To better elucidate the association of depression and PD, we conducted an analysis of all available English-language studies that reported the number of PD patients studied and the number of PD patients depressed. This enabled us to determine the prevalence of PD depression. Further review of these studies explicated clinical manifestations, the potential etiology of PD depression, and its treatment.

By means of a MEDLINE search of all available English-language studies of PD depression, and review of relevant journal articles' bibliographies, we identified original articles reporting prevalence rates of depression complicating PD. Keywords in the searches included Parkinson's disease, depression, and prevalence. The purpose of this literature search was to obtain every available English-language article that assessed depression in PD patients, regardless of the method used by the researchers. All articles that reported the prevalence of depression in a group of PD patients were analyzed for the rate of occurrence of depression. The majority of these analyzed articles were case series and not double-blind, placebo-controlled investigations. We reviewed the variance of depression occurrence in all of the articles obtained. We then determined an average rate of occurrence of depression in PD for all studies from 1922 to the conclusion of 1998 regardless of the diagnostic method used.

Next, we sorted the articles according to the means of diagnosis, separating the studies that used clinical diagnoses from those using either a depression instrument (e.g., Beck Depression Inventory) or DSM-III and DSM-III-R criteria. For each of the three criteria, we calculated an average rate of occurrence of depression. We then evaluated all studies obtained that used DSM-III or DSM-III-R criteria and reported rates of minor and major depression (where possible). In all, 45 studies regarding the prevalence of PD depression were assessed and reported.3,750 A MEDLINE literature search was also conducted to examine proposed etiologies and treatments for PD depression. The bibliographies of relevant articles revealed additional articles relevant to etiology and PD depression treatment.

+

Prevalence of PD Depression

Forty-five Parkinson's disease and depression prevalence reports were identified and reviewed. Our analysis begins with Patrick and Levy's 1922 study7 of 146 patients, in which 10 (7%) were determined to have depression. Mjones's 1949 study8 reported 40% of his PD patients to have depression. Three studies in the 1960s911 found occurrence of depression in patients ranging from 7% to 67%. In the 1970s, six studies1217 noted depression occurring in between 29% and 70% of patients assessed. In the 1980s, 21 studies1838 continued to report variability regarding the presence or absence of depression (12%—70%). The variability in reported depression persisted in the 1990s, with a range of reported depression between 7% and 68% in 13 studies.3,3950 When all studies were combined, the number of PD patients equaled 5,911, the number depressed 1,835, and the percentage depressed 31.0%. Please see t1 for the prevalence of PD depression in all the reports we obtained, broken down by method of diagnosis.

Of the 45 articles reviewed, 11 specifically used DSM-III and DSM-III-R criteria.3,20,21,26,31,37,38,44,46,48,50 DSM-III criteria were first used for depression diagnosis in Parkinson's patients in the study by Mayeux et al. in 1984,20 but this did not become commonplace until the late 1980s. The combined rate of occurrence of both major depression and minor depression found in these studies using DSM criteria was higher than the overall average prevalence of all studies examined. Please see t2 for a specific breakdown of all reports that used any type of DSM diagnosis. The diagnosis of minor depression typically involved dysthymic symptoms not present for 2 full years or more, although one study applied the term to "mild depressive symptoms."3 In the four studies reporting dysthymia, it was noted present in 48 of 213 PD patients evaluated, or 22.5%.20,21,48,50 Minor depression was diagnosed in three studies involving 155 of 423 PD patients evaluated, or 36.6%.3,38,46 Major depression was found in 278 of 1,119 patients evaluated, or 24.8%.3,20,21,26,37,38,46,48,50 When all diagnostic categories were combined—minor depression, major depression, and dysthymic disorder—500 of 1,179 PD patients were reported depressed, or 42.4%.

+

Clinical Manifestations of PD Depression

A review of the aforementioned studies revealed some proposed unique characteristics of depression complicating Parkinson's disease. Taylor et al.27 described episodes of "emotional upset" usually accompanying exacerbation of PD symptoms. Brown et al.51 noted "lowered arousal" involving apathy and diminished self-initiated planning, psychomotor retardation, and a mood that was "environmentally dependent" (involving an externalized locus of control for mood and mentation as well as movement) accompanied by marked decrease in concentration. Brown et al.51,52 noted a tendency for dysphoric states to complicate more the "off" than the "on" periods in PD. Cummings5 noted the following as the most reliable indicators of depression in Parkinson's disease: dysphoria, pessimism, irritability, sadness, and suicidal ideation.

Starkstein et al.,53 in a series of 105 patients (21 with major depression, 20 with minor depression, and 64 with no depression), observed that major depression significantly correlated with longer duration of Parkinson's disease and greater frequency of a personal history of depression prior to the onset of PD. Starkstein et al. considered that unilateral left hemispheric presentation of PD conveyed a greater risk of depression than right hemispheric presentation.

Although PD patients may experience more suicidal ideation, suicide is not common in the Parkinson's disease patient population.5,54 Stenager et al.54 reviewed the cause of death in 458 previously well-characterized PD patients (226 men, 232 women). Death certificates were examined for primary and secondary causes of death. When the PD patients' causes of death were compared with those in the general population, there was no increased risk for suicide in that patient population. It remains unclear why an increased rate of depression is not accompanied in PD patients by an increased risk of suicide.

Psychosis in PD is not uncommon and is often associated with an excess of dopaminergic agents. Whether psychotic depression is common in PD has not been established.55

+

PD Depression and Cognitive Impairment

Impaired cognition is an important comorbid condition in PD patients that may also affect the occurrence of depression. Cognitive impairment is associated with both the duration of PD and the severity of the movement disorder.56 This cognitive impairment is related to the bilateral hemispheric involvement of PD, and when PD manifests itself in a more unilateral fashion, cognitive deficits related to the involved hemisphere (verbal with left hemisphere, visuospatial with right hemisphere) are observed.57

Starkstein et al.53 found significantly greater cognitive impairment in PD with major depression than without major depression, as demonstrated by lower Mini-Mental State Examination (MMSE)58 scores for severely depressed patients. Starkstein et al. noted that PD patients with major depression experienced global impairments on neuropsychological measures but that their most severe impairment was on tests of frontal lobe function. Starkstein et al. described the following cognitive characteristics of depressed PD patients: more perseveration, more difficulties with shifting sets and with tracking and ordering of stimuli, decreased performance on verbal fluency and design tasks, poorer performance on digit span (reverse sequencing of digits), and decreased performance on visual scanning.

+

PD Personality Profile

It is unclear if there is a unique personality type that in some way predisposes one to PD (and hence to the development of depression). Todes and Lees59 observed that Charcot had described the Parkinson's personality as "industrious, introverted, inflexible, and morally rigid." However, the question arises of whether the disease might secondarily influence the personality (as well as the affective state). Might that personality manifest itself prior to the clear-cut movement disorder of Parkinson's disease?

The following terms describe the features most often attributed to the PD personality: cautious, subordinate, reflective, rigid, loyal, stoic, slow-tempered, frugal, orderly, persistent, inflexible, introspective, less emotional, and less talkative.6065 We consider the existence of a premorbid PD personality to be speculative. However, it is not unreasonable to allow for personality features related to neurochemical abnormalities of PD. Perhaps these features develop insidiously and reflect progressive neurochemical deficits. Further cognitive and behavioral changes might in turn then predispose further to the development of depression both from a neurochemical and a cognitive-behavioral perspective.

+

Proposed Etiology of PD Depression

Physical morbidity suggests that the etiology of depression complicating Parkinson's disease is likely related to the neuropathology of PD. Gotham et al.,66 Ehmann et al.,67 Cantello et al.,68 Brown and Jahanshahi,69 and others16,70,71 comparing depression in PD to depression in other medically ill patient populations found that PD did appear to result in a greater degree of depression than other comparable medical illnesses.

Tandberg et al.3 argue that PD depression is more likely due to neuropathological changes in the brain than to environmental and psychological factors. They base their conclusions on a study of 245 PD patients in which those with depression and those without depression were compared. Tandberg et al.3 noted that those meeting diagnostic criteria for major depression scores on the Montgomery-Åsberg Depression Rating Scale experienced greater cognitive impairment on the MMSE,58 as well as an increased risk of thought disorder measured by the Unified Parkinson's Disease Rating Scale (UPDRS) and greater impairment in activities of daily living. Starkstein et al.53 also observed greater cognitive impairment as measured by the MMSE, and they saw the pattern of deficits on neuropsychological measures that indicates greater involvement of frontal lobe functions than other brain regions. Cognitive impairment is associated with both duration of PD and severity of the movement disorder.57 Improvement in physical symptoms alone, however, does not predict recovery from depression.44

Mayeux et al.21 report the association of decreased levels of serotonin in the central nervous system, as measured by decreased levels of 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF). Levels of 5-HIAA were significantly lower for depressed PD patients (major depression or dysthymia) than nondepressed PD patients or control subjects. Further, patients diagnosed with major depression have lower 5-HIAA levels than those diagnosed with dysthymia.21 Paulus and Jellinger43 reported more severe reduction of dorsal raphe nucleus serotonergic neurons in the brains of PD depressed patients than nondepressed PD patients.

The role of other neuromodulator, neurotransmitter, and neuropeptide abnormalities associated with PD in the production of PD depression awaits elucidation. The decrease of dopamine in PD may confer an increased risk of depression. Dopamine neurons in the ventral tegmental area (VTA) deteriorate in the course of PD and may contribute to depressed mood.72 However, it is clear from our own anecdotal experience and that of others72,73 that dopaminergic agents alone do not alleviate depression. Norepinephrine may also play a part in PD depression. Chan-Palay and Asan74 noted a correlation of cell loss in locus ceruleus with "atypical depression" in PD. Chia et al.75 noted that PD depression correlates with decreased CSF levels of homovanillic acid and 3-methoxy-4-hydroxyphenyl glycol (MHPG), reflecting a presumed decrease in dopamine and norepinephrine. However, Paulus and Jellinger43 did not find a positive correlation of PD depression with a decrease in neurons in the locus ceruleus.

Rogers et al.29 suggested that PD patients with major depression might have progressive frontal lobe dysfunction, either secondary to pathologic changes in the frontal cortex itself or due to decreased dopaminergic input to the frontal cortex. Mayberg and Solomon73 proposed that selective disruption of the dopaminergic efferents from the VTA to the orbital frontal and prefrontal cortex, and/or disruption of the orbitofrontal cortex efferents to the dorsal raphe serotonergic neurons, may give rise to PD depression. They hypothesize that disruption of these connections at any point along these two major brainstem-to-frontal-lobe pathways may result in PD depression. If their hypothesis is correct, it remains to be explained why if disruption of the VTA-to-frontal-lobe pathways leads to some PD patients' depression then dopamine replacement alone does not result in amelioration of depression. Perhaps patients with these particular disruptions represent a subset of PD depressed patients who may in fact be responsive to dopaminergic agents but do not routinely have their depression subsequently identified because of this early response of their depression to dopamine. The remaining depressed PD patients may then be those with primary disruption of the serotoninergic pathway. This interplay of dopaminergic and serotonergic pathways in PD depression awaits further elucidation. The potential contribution of norepinephrine, glutamate, or other neurotransmitters and neuropeptides is much less clear at the present time.

In addition to the abnormalities of neurochemistry in PD, psychological factors play a role in PD depression. For example, there is an increased likelihood of early onset depression when Parkinson's disease begins before age 55, even though symptoms may not be severe at this younger age.38,76 Also, there is the possibility that the degree of disability resulting from the PD itself may convey a greater risk of depression in PD patients. However, Starkstein et al.44 note that physical improvement in PD symptoms per se does not predict a concomitant reduction in depression. It may be argued that although PD depression and PD disability from physical symptoms of PD are strongly correlated, this association may be more an indication of the severity of underlying neurochemical abnormalities than a psychological depressive reaction to the physical limitations of PD.

+

Pharmacological Treatment of PD Depression

Given the large number of PD patients who suffer from depression, it is surprising that few controlled clinical trials have been undertaken to evaluate the efficacy and tolerance of pharmaceutical treatment in this population. Of the four classes of antidepressants, tricyclics (TCAs), selective serotonin reuptake inhibitors (SSRIs), norepinephrine reuptake inhibitors, and combined reuptake inhibitors, only the TCAs have undergone the rigorous testing of placebo-controlled, double-blind clinical trials.5,77

TCAs such as amitriptyline and nortriptyline block the reuptake of serotonin and norepinephrine and produce long-term increases in sensitivity in these receptors.78 Formally, these medications have been the cornerstone in general antidepressant therapy and may be preferred by some neurologists who believe that their anticholinergic properties will contribute to the amelioration of underlying parkinsonian symptoms. However, anticholinergic side effects may induce unwanted conditions in PD patients, including delirium and memory impairment.79 TCAs are additionally associated with orthostatic hypotension due to alpha-adrenergic blockade. In the course of PD, many patients will experience lowering of blood pressure, and a blockade would be unwelcome. TCA adverse effects depend on plasma concentrations,80 and with advancing age, levels may insidiously become elevated.

Many clinicians prefer to use SSRIs in treating depression associated with PD. A recent survey of 49 investigators from the Parkinson's Study Group or PSG (this group has experience with over 23,000 PD patients) found that 51% of these physicians use SSRIs first when implementing drug therapy. This is contrasted with the 41% who use TCAs and the 8% who use "other" drugs.81

As previously noted, serotonin levels, as reflected by decreased 5-HIAA CSF levels, are lowest in those PD patients who meet the criteria for major depression,24 suggesting that SSRIs may be effective in treating PD depression. These medications have some benign side effects, but SSRIs are not associated with alterations in cardiac conduction80 or alpha-adrenergic blockade,82 and they neither decrease the seizure threshold78 nor possess significant quinidine-like properties.78,82 Possessing no significant anticholinergic properties, SSRIs avoid worsening memory function in PD patients, who are at increased risk of dementia.

Of some concern in using SSRIs is that they are metabolized in the liver by the cytochrome P450 enzyme (CYP) system and may therefore, via competitive inhibition, increase the risk of toxicity from other medications broken down by this system. Specifically, SSRIs competitively inhibit xenobiotic enzymes, which are responsible for the oxidative metabolism of exogenous substances.82 The main isoenzyme of interest when using these drugs is CYP 2D6, which is involved in metabolizing drugs such as haloperidol, perphenazine, thioridazine, TCAs, codeine, certain beta-blockers, type I-C anti-arrhythmics, methamphetamine, and phenytoin.82 Among the SSRIs, sertraline and citalopram show less competitive inhibition of CYP 2D6 than does fluoxetine or paroxetine and may carry less risk of toxicity.

Apart from the inhibition of the CYP system, there have been anecdotal reports of a "serotonin syndrome" resulting from the co-administration of antidepressants (including both SSRIs and TCAs) and selegiline.83 A survey of all investigators in the PSG (75% response) and a study of published cases revealed that in 0.24% (11 cases) of patients taking both an SSRI or TCA and selegiline, patients reported symptoms possibly consistent with the "serotonin syndrome."84 Only 2 of the 11 cases (0.04% of total population studied) were considered serious.84 However, because of these reports, the FDA has requested that the makers of selegiline notify physicians of the possible risk of co-administration of their product with antidepressants.

Concerns have been expressed by some members of the PSG that SSRIs may worsen motor function in PD patients. A recent survey of 49 investigators involved in the PSG found that 37% of physicians administering SSRIs reported at least one patient in whom they felt the drug had been associated with worsening motor function.81 However, 61% of these physicians continued using SSRIs preferentially to other medications, indicating that this potential risk may be overshadowed by the perceived benefits of these drugs. The survey admittedly did not determine the exact number of patients in whom such motor function impairment may have occurred, and therefore the number of cases may be relatively few. Additionally, PSG-published case reports indicate that discontinuation of the drug treatment will reverse any SSRI-induced motor effects.81 The most common reasons given by physicians for choosing SSRIs were the side effects profile and perceived greater efficacy of these drugs. Users of TCAs, on the other hand, noted the soporific benefit of TCAs and the physicians' experience with this class of medication81 as reasons to utilize them.

An open-label trial involving 15 patients taking sertraline for approximately 7 weeks found that 10 improved, 1 was unchanged, and 4 worsened (according to the Beck Depression Inventory).85 Their UPDRS scores and evaluations of individual energy levels were unchanged.85 Note that 2 of the 15 patients included in the final data discontinued treatment during the trial and 1 was taking a reduced dose of 25mg/day as opposed to the predetermined 50 mg/day.85 Our own unpublished experience with 10 consecutive patients on open-label sertraline (1 receiving 25 mg and 9 receiving 50 mg) revealed that 9 of 10 patients had moderate to complete resolution of depression symptoms on the Clinical Global Rating of Depression. The 10th patient reported an increase in anxiety and motor restlessness requiring discontinuation of sertraline and introduction of lorazepam 0.5 mg morning and afternoon and 1.0 mg at bedtime. After treatment of anxiety, this patient resumed sertraline 50 mg in the morning with resolution of depressive symptoms. No worsening of PD symptoms resulted from the sertraline treatment. No patient was considered to have a change in PD symptoms as measured by a clinical rating of Parkinson's symptoms by the treating neurologist.

Recent review articles concerning the treatment of depression in the elderly and/or PD patients indicate that medications such as venlafaxine, nefazodone, and mirtazapine may prove to be efficacious.80,83,86,87 These medications appear to have comparable efficacy to drugs more commonly used (TCAs, SSRIs) but may have fewer adverse side effects than TCAs.80,83,8690 However, an extensive literature search did not yield a case series or clinical trial of any of these newer drugs in PD patients. The few case reports on non-TCA and non-SSRI medications in PD are initially negative or lacking altogether. In one case the patient became "much worse" the day after starting on nefazodone and greatly improved after discontinuing the drug.91 A case report noted psychosis in a PD patient after mirtazapine was added to the patient's chronic levodopa regimen.92

Bupropion, thought to act by means of a norepinephrine effect, was reported by Goetz et al. to alleviate depression in 5 of 12 PD patients.93 Concerns have been noted regarding bupropion's potential to cause seizures and its dopaminergic effects.79,81,86,93 It may be most prudent to use bupropion after attempts with TCAs and SSRIs have failed.81

Although citalopram has been available in Europe for 10 years, our MEDLINE search of studies with depressed PD patients revealed no reports regarding citalopram usage in PD depression. Our MEDLINE search did not identify articles reporting venlafaxine usage with PD patients. Venlafaxine's dual effects on serotonin and norepinephrine may prove beneficial in PD patients deficient in these neurotransmitters. Its potential side effect of elevating blood pressure, which occurs in 3% of treated patients, may benefit hypotensive PD patients.

Double-blind control studies indicate the efficacy of TCAs in the pharmacotherapy of PD depression, although at the risk of potential lowering of blood pressure secondary to alpha-blockade, and of delirium and worsening of comorbid dementia from anticholinergic side effects. Current anecdotal experience with large numbers of patients by members of the PSG,82 ourselves, and others,85 suggests the efficacy of SSRIs in the resolution of PD depression.

+

Nonpharmacologic Treatment Interventions

Psychotherapy is often a very useful adjunctive therapy, especially in younger PD patients. In our experience cognitive-behavioral psychotherapy has been quite effective in helping patients adapt to a new, chronic disease. The usefulness of this treatment in the PD population remains uncertain; we are unaware of case series or controlled trial application of cognitive-behavioral or other psychotherapies.

Electroconvulsive therapy (ECT) has shown success in alleviating depression in Parkinson's disease patients.5,78,94 The antidepressant effect of this treatment is rapid. However, the positive response may be short-lived, and patients also may experience temporary delirium.78,91,95,96

Based on their review of the literature, Tom and Cummings78 suggest reserving ECT for PD depression to emergencies in patients whose suicidal plans necessitate its use as an emergency procedure. They also suggest that with appropriate precautions regarding the potential for delirium, PD depressed patients unresponsive to adequate trials of two antidepressants of different postulated modes of action (e.g., serotonin and norepinephrine) should be considered for ECT. The advisability of routine use of ECT in the treatment of PD patients awaits further elucidation.

Because of "mask-like-faces" and bradyphrenia, depressed PD patients may not be readily identified as depressed. Clinicians managing PD patients need to regularly inquire about their patients' mood status. The 45 studies we reviewed conclusively demonstrate that approximately one in three PD patients experience depression in the course of their disease. Early identification and treatment of depression alleviates significant comorbidity. Because depression is so common in PD patients, clinicians treating PD patients might consider routine use of a rating scale of depression such as the Geriatric Depression Scale.97

Fonda98 reported that patients who went on to develop PD had experienced, in the year prior to onset of movement symptoms, the new onset of depression, hyperirritability, and instability of emotion. Whether this association of prior depression with PD is real or is the result of a natural bias based on disease burden in retrospective analysis remains to be further elucidated.

Psychotherapy may be a useful adjunct to treatment of depressed PD patients. Literature reviewed here and our experiences suggest that depression occurs early in the course of the disease and also late in the course, even when dementia is a comorbid condition. Depression probably reflects a complex interplay of psychological reaction to the onset of PD symptoms and neurochemical changes such as diminished serotonin and nonepinephrine with additional potential contribution from dopamine and neuropeptide changes. Early in the course of PD, depression may be a psychological response to PD symptoms and may respond quite well to psychotherapy, although later PD depression may ensue primarily from altered neurochemistry.

As to why PD depression does not result in a markedly increase risk of suicide, as occurs for example in depressed Huntington's disease (HD) patients,99 we can only speculate at this time. We would propose that the striatal dysfunction in PD preferentially predisposes to mesial and ventrolateral frontal dysfunction, resulting in an apathetic depression, but leaves orbitofrontal function relatively intact. Conversely, orbitofrontal function may be significantly affected in HD patients, disinhibiting them and allowing for the increased risk of suicide noted in that population. The risk of suicide may also be influenced by the relative proportion of serotonin deficit to norepinephrine and dopamine levels.

PD depression is treatable. TCAs are of proven benefit as established by double-blind trials, although TCAs likely represent increased side effect risks for PD compared with SSRIs. Double-blind SSRI trials in PD have yet to be completed, although current anecdotal reports favor their application in PD depression. The largest case series available suggest the efficacy of sertraline for PD depression, as do our own anecdotal experiences. ECT is efficacious in PD depression but carries a heightened risk of delirium in PD patients. Psychotherapy is to be considered in the treatment of depressed PD patients, particularly early in the course of the disorder.

A heightened clinician awareness of PD depression and application of available treatment interventions will eliminate significant suffering in PD and enhance quality of life. The etiology and treatment of PD depression will benefit from further neurochemical, physiological, psychological, and pharmaceutical investigations.

Parkinson J: An Essay on the Shaking Palsy. London, Neely and Jones, 1817
 
Coffey CE, Cummings JL: Parkinson's disease and parkinsonism, in Textbook of Geriatric Neuropsychiatry, edited by Coffey CE, Cummings JL. Washington DC, American Psychiatric Press, 1994, pp 434-456
 
Tandberg E, Larsen JP, Aarsland D, et al: The occurrence of depression in Parkinson's disease: a community-based study. Arch Neurol  1996; 53:175-179
[PubMed]
 
Dooneief G, Mirabello E, Bell K, et al: An estimation of the incidence of depression in idiopathic Parkinson's disease. Arch Neurol  1992; 49:305-307
[PubMed]
 
Cummings JL: Depression and Parkinson's disease: a review. Am J Psychiatry  1992; 149:443-454
[PubMed]
 
Santamaria J, Tolosa E, Valles A: Parkinson's disease with depression: a possible subgroup of idiopathic parkinsonism. Neurology 1986; 36:1130-  1133
 
Patrick HT, Levy DM: Parkinson's disease: a clinical study of one hundred and forty-six cases. Arch Neurol Psychiatry 1922; 711-720
 
Mjones H: Paralysis agitans: a clinical and genetic study. Acta Psychiatr Scand Suppl  1949; 54:1-95
 
Strang RR: Imipramine in treatment of parkinsonism: a double-blind placebo study. British Medical Journal  1965; 2:33-34
[CrossRef] | [PubMed]
 
Hoehn MM, Yahr MD: Parkinsonism: onset, progression, and mortality. Neurology  1967; 17:427-442
[PubMed]
 
Warburton JW: Depressive symptoms in Parkinson patients referred for thalamotomy. J Neurol Neurosurg Psychiatry  1967; 30:368-370
[CrossRef] | [PubMed]
 
Brown GL, Wilson WP: Parkinsonism and depression. South Med J  1972; 65:540-545
[CrossRef] | [PubMed]
 
Celesia GG, Wanamaker WM: Psychiatric disturbances in Parkinson's disease. Diseases of the Nervous System  1972; 33:577-583
[PubMed]
 
Bernheimer H, Birkmayer W, Hornykiewicz O, et al: Brain dopamine and the syndromes of Parkinson and Huntington: clinical, morphological and neurochemical correlations. J Neurol Sci  1973; 20:415-455
[CrossRef] | [PubMed]
 
Mindham RHS, Marsden CD, Parkes JD: Psychiatric symptoms during l-dopa therapy for Parkinson's disease and their relationship to physical disability. Psychol Med  1976; 6:23-33
[CrossRef] | [PubMed]
 
Lesser RP, Fahn S, Snider SR, et al: Analysis of the clinical problems in parkinsonism and the complications of long-term levodopa therapy. Neurology 1979; 29:1253-  1260
 
Lieberman A, Dziatolowski M, Kupersmith M, et al: Dementia in Parkinson disease. Ann Neurol  1979; 6:355-359
[CrossRef] | [PubMed]
 
Presthus J: Psychiatric side-effects occurring in parkinsonism during long-term treatment with levodopa alone and in combination with other drugs, in Parkinson's Disease: Current Progress, Problems and Management, edited by Rinne UK, Kingler M, Stamm G. Amsterdam, Elsevier, 1980, pp 255-270
 
Mayeux R, Stern Y, Rosen J, et al: Depression intellectual impairment, and Parkinson disease. Neurology  1981; 31:645-650
[PubMed]
 
Mayeux R, Williams JBW, Stern Y, et al: Depression and Parkinson's disease. Adv Neurol  1984; 40:241-250
[PubMed]
 
Mayeux R, Stern Y, Cote L, et al: Altered serotonin metabolism in depressed patients with Parkinson's disease. Neurology  1984; 34:642-646
[PubMed]
 
Rondot P, de Recondo J, Coignet A, et al: Mental disorders in Parkinson's disease after treatment with l-dopa. Adv Neurol  1984; 40:259-269
[PubMed]
 
Gotham AM, Brown RG, Marsden CD: Depression in Parkinson's disease: a quantitative and qualitative analysis. J Neurol Neurosurg Psychiatry  1986; 49:381-389
[CrossRef] | [PubMed]
 
Mayeux R, Stern Y, Williams JBW, et al: Clinical and biochemical features of depression in Parkinson's disease. Am J Psychiatry  1986; 142:756-759
 
Oyebode JR, Barker WA, Blessed G, et al: Cognitive functioning in Parkinson's disease: in relation to prevalence of dementia and psychiatric diagnosis. Br J Psychiatry  1986; 149:720-725
[CrossRef] | [PubMed]
 
Santamaria J, Tolosa ES, Valles A, et al: Mental depression in untreated Parkinson's disease of recent onset. Adv Neurol  1986; 45:443-446
 
Taylor A, Saint-Cyr JA, Lang AE, et al: Parkinson's disease and depression: a critical re-evaluation. Brain  1986; 109:279-292
[CrossRef] | [PubMed]
 
Kostic VS, Djuricic BM, Covickovic-Sternic N, et al: Depression and Parkinson's disease: possible role of serotonergic mechanisms. J Neurol  1987; 234:94-96
[CrossRef] | [PubMed]
 
Rogers D, Lees AJ, Smith E, et al: Bradyphrenia in Parkinson's disease and psychomotor retardation in depressive illness: an experimental study. Brain  1987; 110:761-776
[CrossRef] | [PubMed]
 
Brown RG, MacCarthy B, Gotham AM, et al: Depression and disability in Parkinson's disease: a follow-up of 132 cases. Psychol Med  1988; 18:49-55
[CrossRef] | [PubMed]
 
Huber SJ, Paulson GW, Shuttleworth EC: Depression in Parkinson's disease. Neuropsychiatry Neuropsychol Behav Neurol  1988; 1:47-51
 
Mayeux R, Stern Y, Rosenstein R, et al: An estimate of the prevalence of dementia in idiopathic Parkinson's disease. Arch Neurol  1988; 45:260-262
[PubMed]
 
Bieliauskas LA, Glantz RH: Depression type in Parkinson disease. J Clin Exp Neuropsychol  1989; 11:597-604
[CrossRef] | [PubMed]
 
Brown RG, MacCarthy B, Jahanshahi M, et al: Accuracy of self-reported disability in patients with parkinsonism. Arch Neurol  1989; 46:955-959
[PubMed]
 
Dakof G, Mendelsohn G: Patterns of adaptation to Parkinson's disease. Health Psychology  1989; 8:355-372
[CrossRef] | [PubMed]
 
MacCarthy B, Brown R: Psychosocial factors in Parkinson's disease. Br J Clin Psychology  1989; 28:41-52
[CrossRef]
 
Sano M, Stern Y, Williams J, et al: Coexisting dementia and depression in Parkinson's disease. Arch Neurol 1989; 46:1284-  1286
 
Starkstein SE, Berthier ML, Bolduc PL, et al: Depression in patients with early versus late onset of Parkinson's disease. Neurology 1989; 37:1441-  1445
 
Brown RG, MacCarthy B: Psychiatric morbidity in patients with Parkinson's disease. Psychol Med  1990; 20:77-87
[CrossRef] | [PubMed]
 
Ehman TS, Beninger RJ, Gawel MJ, et al: Depressive symptoms in Parkinson's disease: a comparison with disabled control subjects. J Geriatr Psychiatry Neurol  1990; 3:3-9
[CrossRef] | [PubMed]
 
Huber SJ, Freidenberg DL, Paulson GW, et al: The pattern of depressive symptoms varies with progression of Parkinson's disease. J Neurol Neurosurg Psychiatry  1990; 53:275-278
[CrossRef] | [PubMed]
 
Poewe W, Luef G, Kleedorfer B, Emre M: The premorbid personality of patients with Parkinson's disease: a comparative study with healthy controls and patients with essential tremor. Adv Neurol  1990; 53:339-342
[PubMed]
 
Paulus W, Jellinger K: The neuropathologic basis of different clinical subgroups of Parkinson's disease. J Neuropathol Exp Neurol  1991; 50:743-455
[CrossRef] | [PubMed]
 
Starkstein SE, Mayberg HS, Leiguarda R, et al: A prospective longitudinal study of depression, cognitive decline, and physical impairments in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry  1992; 55:377-382
[CrossRef] | [PubMed]
 
Stern Y, Marder K, Xi Tang M, et al: Antecedent clinical features associated with dementia in Parkinson's disease. Neurology 1993; 43:1692-  1692
 
Hantz P, Caradoc-Davies G, Caradoc-Davies T, et al: Depression in Parkinson's disease. Am J Psychiatry 1994; 151:1010-  1014
 
Kostic VS, Filipovic SR, Lecid D, et al: Effect of age at onset on frequency of depression in Parkinson's disease. J Neurol Neurosurg Psychiatry 1994; 57:1265-  1267
 
Cole SA, Woodard JL, Juncos JL, et al: Depression and disability in Parkinson's disease. J Neuropsychiatry Clin Neurosci  1996; 8:20-25
[PubMed]
 
Pilo L, Ring H, Quinn R, et al: Depression in multiple system atrophy and in idiopathic Parkinson's disease: a pilot comparative study. Biol Psychiatry  1996; 39:803-807
[CrossRef] | [PubMed]
 
Starkstein SE, Petracca G, Chemerinski E, et al: Depression in classic versus akinetic-rigid Parkinson's disease. Mov Disord  1998; 13:29-33
[CrossRef]
 
Brown RG, Marsden CD, Quinn N, et al: Alterations in cognitive performance and effect-arousal during fluctuations in motor function in Parkinson's disease. J Neurol Neurosurg Psychiatry  1984; 47:454-465
[CrossRef] | [PubMed]
 
Brown RG, Jahanshahi M, Marsden CD: Response choice in Parkinson's disease: the effects of uncertainty and stimulus-response compatibility. Brain  1993; 4:869-885
 
Starkstein SE, Preziosi TJ, Bolduc PL, et al: Depression in Parkinson's disease. J Nerv Ment Dis  1990; 178:27-31
[CrossRef] | [PubMed]
 
Stenager EN, Wermuth L, Stenager E, et al: Suicide in patients with Parkinson's disease: an epidemiological study. Acta Psychiatr Scand  1994; 90:70-72
[CrossRef] | [PubMed]
 
Rafal R: Mental disorders in Parkinson's disease. Rhode Island Medical Journal  1986; 69:323-326
[PubMed]
 
Hietanen M, Teravainen H: The effect of age and disease onset on neuropsychological performance in Parkinson's disease. J Neurol Neurosurg Psychiatry  1988; 51:244-249
[CrossRef] | [PubMed]
 
Lees AJ, Smith E: Cognitive deficits in the early stages of Parkinson's disease. Brain  1983; 106:257-270
[CrossRef] | [PubMed]
 
Folstein MF, Folstein SE, McHugh PF: "Mini-Mental State": a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res  1975; 12:189-198
[CrossRef] | [PubMed]
 
Todes CJ, Lees AJ: The pre-morbid personality of patients with Parkinson's disease. J Neurol Neurosurg Psychiatry  1985; 48:97-100
[CrossRef] | [PubMed]
 
Hubble JP, Koller WC: The parkinsonian personality. Adv Neurol  1995; 65:43-48
[PubMed]
 
Ward CD, Duvoisin RC, Ince SE, et al: Parkinson's disease in 65 pairs of twins and in a set of quadruplets. Neurology  1983; 33:815-825
[PubMed]
 
Menza MA, Forman NE, Goldstein HS, et al: Parkinson's disease, personality, and dopamine. J Neuropsychiatry Clin Neurosci  1990; 2:282-287
[PubMed]
 
Hubble JP, Venkatesch R, Hassanein RES, et al: Personality and depression in Parkinson's disease. J Nerv Ment Dis  1993; 181:657-662
[CrossRef] | [PubMed]
 
Eatough VM, Kempster PA, Stern GM, et al: Premorbid personality and idiopathic Parkinson's disease, in Parkinson's Disease: Anatomy, Pathology, and Therapy (Advances in Neurology, vol 53), edited by Streifler MB, Korczyn AD, Melamed E, et al. New York, Raven, 1990, pp 335-337
 
Menza MA, Golve LI, Cody RA, et al: Dopamine-related personality traits in Parkinson's disease. Neurology  1993; 43:505-508
[PubMed]
 
Gotham AM, Brown RG, Marsden CD: Depression in Parkinson's disease: a qualitative and quantitative analysis. J Neurol Neurosurg Psychiatry. 1986; 49:381-389
 
Ehmann TS, Beninger RJ, Gawel MJ, et al: Depressive symptoms in Parkinson's disease: a comparison with disabled control subjects. J Geriatr Psychiatry Neurol  1990; 2:3-9
 
Cantello R, Gilli M, Riccio A, et al: Mood changes associated with "end-of-dose deterioration" in Parkinson's disease: a controlled study. J Neurol Neurosurg Psychiatry 1986; 49:1182-  1190
 
Brown R, Jahanshahi M: Depression in Parkinson's disease: a psychosocial viewpoint. Adv Neurol  1995; 65:61-84
[PubMed]
 
Warburton JW: Depressive symptoms in Parkinson patients referred for thalamotomy. J Neurol Neurosurg Psychiatry  1967; 30:368-370
[CrossRef] | [PubMed]
 
Horn S: Some psychological factors in parkinsonism. J Neurol Neurosurg Psychiatry  1974; 37:27-31
[CrossRef] | [PubMed]
 
Brown A, Gershon S: Dopamine and depression. J Neural Transm  1993; 91:75-109
[CrossRef]
 
Mayberg H, Solomon D: Depression in Parkinson's disease: a biochemical and organic viewpoint, in Behavioral Neurology of Movement Disorders (Advances in Neurology, vol 65), edited by Weiner WJ, Lang AE. New York, Raven, 1995, pp 49-60
 
Chan-Palay V, Asan E: Quantitation of catecholamine neurons of the locus coeruleus in senile dementia of the Alzheimer type and in Parkinson's disease with and without dementia and depression. J Comp Neurol 1989; 287: 373-392
 
Chia L, Cheng L, Chuo L et al: Studies of dementia, depression, electrophysiology and cerebrospinal fluid monoamine metabolites in patients with Parkinson's disease. J. Neurol Sci 1995; 133: 73-78
 
Santamaria J, Tolosa E, Valles A: Parkinson's disease with depression: a possible subgroup of idiopathic parkinsonism. Neurology 1988; 36:1130-  1133
 
Klaassen T, Verhey FRJ, Sneijders G, et al: Treatment of depression in Parkinson's disease: a meta-analysis. J Neuropsychiatry Clin Neurosci  1995; 7:281-286
[PubMed]
 
Silver JM, Yudofsky SC: Drug treatment of depression in Parkinson's disease, in Parkinson's Disease: Neurobehavioral Aspects, edited by Huber SJ, Cummings JL. New York, Oxford University Press, 1992, pp 240-254
 
Drevets WC: Geriatric depression: brain imaging correlates and pharmacologic considerations. J Clin Psychiatry 1994; 55(suppl A):71-81
 
Preskorn SH: Recent pharmacologic advances in antidepressant therapy for the elderly. Am J Med 1993; 94(suppl 5A):2S-12S
 
Richard IH, Kurlan R: A survey of antidepressant drug use in Parkinson's disease. Neurology 1997; 49:1168-  1170
 
Stoudemire A: New antidepressant drugs and the treatment of depression in the medically ill patient. Psychiatr Clin North Am  1996; 19:495-514
[CrossRef] | [PubMed]
 
Olanow C, Warren MD: A 61 year-old man with Parkinson's disease. JAMA  1996; 275:716-722
[CrossRef] | [PubMed]
 
Richard IH, Kurlan R, Tanner C, et al: Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson's disease. Neurology 1997; 48:1070-  1077
 
Hauser RA, Zesieweicz TA: Sertraline for the treatment of depression in Parkinson's disease. Mov Disord  1997; 12:756-759
[CrossRef] | [PubMed]
 
Tom T, Cummings JL: Depression in Parkinson's disease: pharmacological characteristics and treatment. Drugs and Aging  1998; 12:55-74
[CrossRef] | [PubMed]
 
Kasper S, Praschak-Rieder N, Tauscher J, et al: A risk-benefit assessment of mirtazapine in the treatment of depression. Drug Safety  1997; 17:251-264
[CrossRef] | [PubMed]
 
Fontaine R, Ontineros A, Elie R, et al: A double-blind comparison of nefazodone, imipramine, and placebo in major depression. J Clin Psychiatry  1994; 55:234-241
[PubMed]
 
Montgomery SA: Efficacy in long-term treatment of depression. J Clin Psychiatry 1996; 57(suppl 2):24-30
 
Marttila M, Jaaskelainen J, Jarvi R, et al: A double-blind study comparing the efficacy and tolerability of mirtazapine and doxepin in patients with major depression. Eur Neuropsychopharmacol  1995; 5:441-446
[PubMed]
 
Douyon R, Serby M, Klutehko B, et al: ECT and Parkinson's disease revisited: a "naturalistic" study. Am J Psychiatry 1989; 146:1451-  1455
 
Normann C, Hesslinger B, Frauenknecht S, et al: Psychosis during chronic levodopa therapy triggered by the new antidepressive drug mirtazapine. Pharmacopsychiatry  1997; 30:263-265
[CrossRef] | [PubMed]
 
Goetz G, Tanner C, Klawans H: Bupropion in Parkinson's disease. Neurology 1984; 45:1092-  1094
 
Benazzi F: Parkinson's disease worsened by nefazodone (letter). Int J Geriatr Psychiatry  1997; 12:1195
[CrossRef] | [PubMed]
 
Holcomb HH, Sternberg DE, Heninger GR: Effects of electroconvulsive therapy on mood, parkinsonism, and tardive dyskinesia in a depressed patient: ECT and dopamine systems. Biol Psychiatry  1983; 18:865-73
[PubMed]
 
Figiel GS, Hassen MA, Zorumski C, et al: ECT-induced delirium in depressed patients with Parkinson's disease. J Neuropsychiatry Clin Neurosci  1991; 3:405-411
[PubMed]
 
Yesavage J, Brink TL, Rose TL, et al: Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res  1983; 17:37-49
 
Fonda D: Parkinson's disease in the elderly: psychiatric manifestations. Geriatrics  1985; 40:109-114
 
Di Maio L, Squitieri F, Napolitano G, et al: Suicide risk in Huntington's disease. J Med Genet  1993; 30:293-295
[CrossRef] | [PubMed]
 
+

References

Parkinson J: An Essay on the Shaking Palsy. London, Neely and Jones, 1817
 
Coffey CE, Cummings JL: Parkinson's disease and parkinsonism, in Textbook of Geriatric Neuropsychiatry, edited by Coffey CE, Cummings JL. Washington DC, American Psychiatric Press, 1994, pp 434-456
 
Tandberg E, Larsen JP, Aarsland D, et al: The occurrence of depression in Parkinson's disease: a community-based study. Arch Neurol  1996; 53:175-179
[PubMed]
 
Dooneief G, Mirabello E, Bell K, et al: An estimation of the incidence of depression in idiopathic Parkinson's disease. Arch Neurol  1992; 49:305-307
[PubMed]
 
Cummings JL: Depression and Parkinson's disease: a review. Am J Psychiatry  1992; 149:443-454
[PubMed]
 
Santamaria J, Tolosa E, Valles A: Parkinson's disease with depression: a possible subgroup of idiopathic parkinsonism. Neurology 1986; 36:1130-  1133
 
Patrick HT, Levy DM: Parkinson's disease: a clinical study of one hundred and forty-six cases. Arch Neurol Psychiatry 1922; 711-720
 
Mjones H: Paralysis agitans: a clinical and genetic study. Acta Psychiatr Scand Suppl  1949; 54:1-95
 
Strang RR: Imipramine in treatment of parkinsonism: a double-blind placebo study. British Medical Journal  1965; 2:33-34
[CrossRef] | [PubMed]
 
Hoehn MM, Yahr MD: Parkinsonism: onset, progression, and mortality. Neurology  1967; 17:427-442
[PubMed]
 
Warburton JW: Depressive symptoms in Parkinson patients referred for thalamotomy. J Neurol Neurosurg Psychiatry  1967; 30:368-370
[CrossRef] | [PubMed]
 
Brown GL, Wilson WP: Parkinsonism and depression. South Med J  1972; 65:540-545
[CrossRef] | [PubMed]
 
Celesia GG, Wanamaker WM: Psychiatric disturbances in Parkinson's disease. Diseases of the Nervous System  1972; 33:577-583
[PubMed]
 
Bernheimer H, Birkmayer W, Hornykiewicz O, et al: Brain dopamine and the syndromes of Parkinson and Huntington: clinical, morphological and neurochemical correlations. J Neurol Sci  1973; 20:415-455
[CrossRef] | [PubMed]
 
Mindham RHS, Marsden CD, Parkes JD: Psychiatric symptoms during l-dopa therapy for Parkinson's disease and their relationship to physical disability. Psychol Med  1976; 6:23-33
[CrossRef] | [PubMed]
 
Lesser RP, Fahn S, Snider SR, et al: Analysis of the clinical problems in parkinsonism and the complications of long-term levodopa therapy. Neurology 1979; 29:1253-  1260
 
Lieberman A, Dziatolowski M, Kupersmith M, et al: Dementia in Parkinson disease. Ann Neurol  1979; 6:355-359
[CrossRef] | [PubMed]
 
Presthus J: Psychiatric side-effects occurring in parkinsonism during long-term treatment with levodopa alone and in combination with other drugs, in Parkinson's Disease: Current Progress, Problems and Management, edited by Rinne UK, Kingler M, Stamm G. Amsterdam, Elsevier, 1980, pp 255-270
 
Mayeux R, Stern Y, Rosen J, et al: Depression intellectual impairment, and Parkinson disease. Neurology  1981; 31:645-650
[PubMed]
 
Mayeux R, Williams JBW, Stern Y, et al: Depression and Parkinson's disease. Adv Neurol  1984; 40:241-250
[PubMed]
 
Mayeux R, Stern Y, Cote L, et al: Altered serotonin metabolism in depressed patients with Parkinson's disease. Neurology  1984; 34:642-646
[PubMed]
 
Rondot P, de Recondo J, Coignet A, et al: Mental disorders in Parkinson's disease after treatment with l-dopa. Adv Neurol  1984; 40:259-269
[PubMed]
 
Gotham AM, Brown RG, Marsden CD: Depression in Parkinson's disease: a quantitative and qualitative analysis. J Neurol Neurosurg Psychiatry  1986; 49:381-389
[CrossRef] | [PubMed]
 
Mayeux R, Stern Y, Williams JBW, et al: Clinical and biochemical features of depression in Parkinson's disease. Am J Psychiatry  1986; 142:756-759
 
Oyebode JR, Barker WA, Blessed G, et al: Cognitive functioning in Parkinson's disease: in relation to prevalence of dementia and psychiatric diagnosis. Br J Psychiatry  1986; 149:720-725
[CrossRef] | [PubMed]
 
Santamaria J, Tolosa ES, Valles A, et al: Mental depression in untreated Parkinson's disease of recent onset. Adv Neurol  1986; 45:443-446
 
Taylor A, Saint-Cyr JA, Lang AE, et al: Parkinson's disease and depression: a critical re-evaluation. Brain  1986; 109:279-292
[CrossRef] | [PubMed]
 
Kostic VS, Djuricic BM, Covickovic-Sternic N, et al: Depression and Parkinson's disease: possible role of serotonergic mechanisms. J Neurol  1987; 234:94-96
[CrossRef] | [PubMed]
 
Rogers D, Lees AJ, Smith E, et al: Bradyphrenia in Parkinson's disease and psychomotor retardation in depressive illness: an experimental study. Brain  1987; 110:761-776
[CrossRef] | [PubMed]
 
Brown RG, MacCarthy B, Gotham AM, et al: Depression and disability in Parkinson's disease: a follow-up of 132 cases. Psychol Med  1988; 18:49-55
[CrossRef] | [PubMed]
 
Huber SJ, Paulson GW, Shuttleworth EC: Depression in Parkinson's disease. Neuropsychiatry Neuropsychol Behav Neurol  1988; 1:47-51
 
Mayeux R, Stern Y, Rosenstein R, et al: An estimate of the prevalence of dementia in idiopathic Parkinson's disease. Arch Neurol  1988; 45:260-262
[PubMed]
 
Bieliauskas LA, Glantz RH: Depression type in Parkinson disease. J Clin Exp Neuropsychol  1989; 11:597-604
[CrossRef] | [PubMed]
 
Brown RG, MacCarthy B, Jahanshahi M, et al: Accuracy of self-reported disability in patients with parkinsonism. Arch Neurol  1989; 46:955-959
[PubMed]
 
Dakof G, Mendelsohn G: Patterns of adaptation to Parkinson's disease. Health Psychology  1989; 8:355-372
[CrossRef] | [PubMed]
 
MacCarthy B, Brown R: Psychosocial factors in Parkinson's disease. Br J Clin Psychology  1989; 28:41-52
[CrossRef]
 
Sano M, Stern Y, Williams J, et al: Coexisting dementia and depression in Parkinson's disease. Arch Neurol 1989; 46:1284-  1286
 
Starkstein SE, Berthier ML, Bolduc PL, et al: Depression in patients with early versus late onset of Parkinson's disease. Neurology 1989; 37:1441-  1445
 
Brown RG, MacCarthy B: Psychiatric morbidity in patients with Parkinson's disease. Psychol Med  1990; 20:77-87
[CrossRef] | [PubMed]
 
Ehman TS, Beninger RJ, Gawel MJ, et al: Depressive symptoms in Parkinson's disease: a comparison with disabled control subjects. J Geriatr Psychiatry Neurol  1990; 3:3-9
[CrossRef] | [PubMed]
 
Huber SJ, Freidenberg DL, Paulson GW, et al: The pattern of depressive symptoms varies with progression of Parkinson's disease. J Neurol Neurosurg Psychiatry  1990; 53:275-278
[CrossRef] | [PubMed]
 
Poewe W, Luef G, Kleedorfer B, Emre M: The premorbid personality of patients with Parkinson's disease: a comparative study with healthy controls and patients with essential tremor. Adv Neurol  1990; 53:339-342
[PubMed]
 
Paulus W, Jellinger K: The neuropathologic basis of different clinical subgroups of Parkinson's disease. J Neuropathol Exp Neurol  1991; 50:743-455
[CrossRef] | [PubMed]
 
Starkstein SE, Mayberg HS, Leiguarda R, et al: A prospective longitudinal study of depression, cognitive decline, and physical impairments in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry  1992; 55:377-382
[CrossRef] | [PubMed]
 
Stern Y, Marder K, Xi Tang M, et al: Antecedent clinical features associated with dementia in Parkinson's disease. Neurology 1993; 43:1692-  1692
 
Hantz P, Caradoc-Davies G, Caradoc-Davies T, et al: Depression in Parkinson's disease. Am J Psychiatry 1994; 151:1010-  1014
 
Kostic VS, Filipovic SR, Lecid D, et al: Effect of age at onset on frequency of depression in Parkinson's disease. J Neurol Neurosurg Psychiatry 1994; 57:1265-  1267
 
Cole SA, Woodard JL, Juncos JL, et al: Depression and disability in Parkinson's disease. J Neuropsychiatry Clin Neurosci  1996; 8:20-25
[PubMed]
 
Pilo L, Ring H, Quinn R, et al: Depression in multiple system atrophy and in idiopathic Parkinson's disease: a pilot comparative study. Biol Psychiatry  1996; 39:803-807
[CrossRef] | [PubMed]
 
Starkstein SE, Petracca G, Chemerinski E, et al: Depression in classic versus akinetic-rigid Parkinson's disease. Mov Disord  1998; 13:29-33
[CrossRef]
 
Brown RG, Marsden CD, Quinn N, et al: Alterations in cognitive performance and effect-arousal during fluctuations in motor function in Parkinson's disease. J Neurol Neurosurg Psychiatry  1984; 47:454-465
[CrossRef] | [PubMed]
 
Brown RG, Jahanshahi M, Marsden CD: Response choice in Parkinson's disease: the effects of uncertainty and stimulus-response compatibility. Brain  1993; 4:869-885
 
Starkstein SE, Preziosi TJ, Bolduc PL, et al: Depression in Parkinson's disease. J Nerv Ment Dis  1990; 178:27-31
[CrossRef] | [PubMed]
 
Stenager EN, Wermuth L, Stenager E, et al: Suicide in patients with Parkinson's disease: an epidemiological study. Acta Psychiatr Scand  1994; 90:70-72
[CrossRef] | [PubMed]
 
Rafal R: Mental disorders in Parkinson's disease. Rhode Island Medical Journal  1986; 69:323-326
[PubMed]
 
Hietanen M, Teravainen H: The effect of age and disease onset on neuropsychological performance in Parkinson's disease. J Neurol Neurosurg Psychiatry  1988; 51:244-249
[CrossRef] | [PubMed]
 
Lees AJ, Smith E: Cognitive deficits in the early stages of Parkinson's disease. Brain  1983; 106:257-270
[CrossRef] | [PubMed]
 
Folstein MF, Folstein SE, McHugh PF: "Mini-Mental State": a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res  1975; 12:189-198
[CrossRef] | [PubMed]
 
Todes CJ, Lees AJ: The pre-morbid personality of patients with Parkinson's disease. J Neurol Neurosurg Psychiatry  1985; 48:97-100
[CrossRef] | [PubMed]
 
Hubble JP, Koller WC: The parkinsonian personality. Adv Neurol  1995; 65:43-48
[PubMed]
 
Ward CD, Duvoisin RC, Ince SE, et al: Parkinson's disease in 65 pairs of twins and in a set of quadruplets. Neurology  1983; 33:815-825
[PubMed]
 
Menza MA, Forman NE, Goldstein HS, et al: Parkinson's disease, personality, and dopamine. J Neuropsychiatry Clin Neurosci  1990; 2:282-287
[PubMed]
 
Hubble JP, Venkatesch R, Hassanein RES, et al: Personality and depression in Parkinson's disease. J Nerv Ment Dis  1993; 181:657-662
[CrossRef] | [PubMed]
 
Eatough VM, Kempster PA, Stern GM, et al: Premorbid personality and idiopathic Parkinson's disease, in Parkinson's Disease: Anatomy, Pathology, and Therapy (Advances in Neurology, vol 53), edited by Streifler MB, Korczyn AD, Melamed E, et al. New York, Raven, 1990, pp 335-337
 
Menza MA, Golve LI, Cody RA, et al: Dopamine-related personality traits in Parkinson's disease. Neurology  1993; 43:505-508
[PubMed]
 
Gotham AM, Brown RG, Marsden CD: Depression in Parkinson's disease: a qualitative and quantitative analysis. J Neurol Neurosurg Psychiatry. 1986; 49:381-389
 
Ehmann TS, Beninger RJ, Gawel MJ, et al: Depressive symptoms in Parkinson's disease: a comparison with disabled control subjects. J Geriatr Psychiatry Neurol  1990; 2:3-9
 
Cantello R, Gilli M, Riccio A, et al: Mood changes associated with "end-of-dose deterioration" in Parkinson's disease: a controlled study. J Neurol Neurosurg Psychiatry 1986; 49:1182-  1190
 
Brown R, Jahanshahi M: Depression in Parkinson's disease: a psychosocial viewpoint. Adv Neurol  1995; 65:61-84
[PubMed]
 
Warburton JW: Depressive symptoms in Parkinson patients referred for thalamotomy. J Neurol Neurosurg Psychiatry  1967; 30:368-370
[CrossRef] | [PubMed]
 
Horn S: Some psychological factors in parkinsonism. J Neurol Neurosurg Psychiatry  1974; 37:27-31
[CrossRef] | [PubMed]
 
Brown A, Gershon S: Dopamine and depression. J Neural Transm  1993; 91:75-109
[CrossRef]
 
Mayberg H, Solomon D: Depression in Parkinson's disease: a biochemical and organic viewpoint, in Behavioral Neurology of Movement Disorders (Advances in Neurology, vol 65), edited by Weiner WJ, Lang AE. New York, Raven, 1995, pp 49-60
 
Chan-Palay V, Asan E: Quantitation of catecholamine neurons of the locus coeruleus in senile dementia of the Alzheimer type and in Parkinson's disease with and without dementia and depression. J Comp Neurol 1989; 287: 373-392
 
Chia L, Cheng L, Chuo L et al: Studies of dementia, depression, electrophysiology and cerebrospinal fluid monoamine metabolites in patients with Parkinson's disease. J. Neurol Sci 1995; 133: 73-78
 
Santamaria J, Tolosa E, Valles A: Parkinson's disease with depression: a possible subgroup of idiopathic parkinsonism. Neurology 1988; 36:1130-  1133
 
Klaassen T, Verhey FRJ, Sneijders G, et al: Treatment of depression in Parkinson's disease: a meta-analysis. J Neuropsychiatry Clin Neurosci  1995; 7:281-286
[PubMed]
 
Silver JM, Yudofsky SC: Drug treatment of depression in Parkinson's disease, in Parkinson's Disease: Neurobehavioral Aspects, edited by Huber SJ, Cummings JL. New York, Oxford University Press, 1992, pp 240-254
 
Drevets WC: Geriatric depression: brain imaging correlates and pharmacologic considerations. J Clin Psychiatry 1994; 55(suppl A):71-81
 
Preskorn SH: Recent pharmacologic advances in antidepressant therapy for the elderly. Am J Med 1993; 94(suppl 5A):2S-12S
 
Richard IH, Kurlan R: A survey of antidepressant drug use in Parkinson's disease. Neurology 1997; 49:1168-  1170
 
Stoudemire A: New antidepressant drugs and the treatment of depression in the medically ill patient. Psychiatr Clin North Am  1996; 19:495-514
[CrossRef] | [PubMed]
 
Olanow C, Warren MD: A 61 year-old man with Parkinson's disease. JAMA  1996; 275:716-722
[CrossRef] | [PubMed]
 
Richard IH, Kurlan R, Tanner C, et al: Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson's disease. Neurology 1997; 48:1070-  1077
 
Hauser RA, Zesieweicz TA: Sertraline for the treatment of depression in Parkinson's disease. Mov Disord  1997; 12:756-759
[CrossRef] | [PubMed]
 
Tom T, Cummings JL: Depression in Parkinson's disease: pharmacological characteristics and treatment. Drugs and Aging  1998; 12:55-74
[CrossRef] | [PubMed]
 
Kasper S, Praschak-Rieder N, Tauscher J, et al: A risk-benefit assessment of mirtazapine in the treatment of depression. Drug Safety  1997; 17:251-264
[CrossRef] | [PubMed]
 
Fontaine R, Ontineros A, Elie R, et al: A double-blind comparison of nefazodone, imipramine, and placebo in major depression. J Clin Psychiatry  1994; 55:234-241
[PubMed]
 
Montgomery SA: Efficacy in long-term treatment of depression. J Clin Psychiatry 1996; 57(suppl 2):24-30
 
Marttila M, Jaaskelainen J, Jarvi R, et al: A double-blind study comparing the efficacy and tolerability of mirtazapine and doxepin in patients with major depression. Eur Neuropsychopharmacol  1995; 5:441-446
[PubMed]
 
Douyon R, Serby M, Klutehko B, et al: ECT and Parkinson's disease revisited: a "naturalistic" study. Am J Psychiatry 1989; 146:1451-  1455
 
Normann C, Hesslinger B, Frauenknecht S, et al: Psychosis during chronic levodopa therapy triggered by the new antidepressive drug mirtazapine. Pharmacopsychiatry  1997; 30:263-265
[CrossRef] | [PubMed]
 
Goetz G, Tanner C, Klawans H: Bupropion in Parkinson's disease. Neurology 1984; 45:1092-  1094
 
Benazzi F: Parkinson's disease worsened by nefazodone (letter). Int J Geriatr Psychiatry  1997; 12:1195
[CrossRef] | [PubMed]
 
Holcomb HH, Sternberg DE, Heninger GR: Effects of electroconvulsive therapy on mood, parkinsonism, and tardive dyskinesia in a depressed patient: ECT and dopamine systems. Biol Psychiatry  1983; 18:865-73
[PubMed]
 
Figiel GS, Hassen MA, Zorumski C, et al: ECT-induced delirium in depressed patients with Parkinson's disease. J Neuropsychiatry Clin Neurosci  1991; 3:405-411
[PubMed]
 
Yesavage J, Brink TL, Rose TL, et al: Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res  1983; 17:37-49
 
Fonda D: Parkinson's disease in the elderly: psychiatric manifestations. Geriatrics  1985; 40:109-114
 
Di Maio L, Squitieri F, Napolitano G, et al: Suicide risk in Huntington's disease. J Med Genet  1993; 30:293-295
[CrossRef] | [PubMed]
 
+
+

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Web of Science® Times Cited: 127

Related Content
Articles
Books
The American Psychiatric Publishing Textbook of Geriatric Psychiatry, 4th Edition > Chapter 26.  >
The American Psychiatric Publishing Textbook of Psychiatry, 5th Edition > Chapter 26.  >
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 12.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 44.  >
APA Practice Guidelines > Chapter 0.  >
Topic Collections
Psychiatric News
APA Guidelines
PubMed Articles