Depression in PD

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Depression is the most common neuropsychiatric disturbance in IPD. A comprehensive review of the literature by Cummings (1992) found rates of depression to average 40% with the range being 4% to 70% depending on the specific population assessed and the rating scales used. Of these, approximately half met criteria for major depression and the other half had chronic dysthymia. Another recent literature review between 1922 and 1998 by Slaughter, Slaughter, Nichols, and Martens (2001) found an overall prevalence of depression of 31% in patients with IPD. Between 20% and 60% of patients with IPD experience affective changes sometime during the course of their illness. Santamaria and Valles (1986) found that in 50% of the cases, depression preceded the motor manifestations by an average of five years. In general, depressed patients had a younger age of onset and were less physically disabled. Starkstein (1992) found depression to be more common in IPD with onset before age 55. Depressed patients with IPD have greater frontal lobe dysfunction and greater involvement of dopaminergic and noradrenergic systems than nondepressed patients with PD (Cummings, 1992). Although depression is more common among those with greater cognitive impairment, depression is equally frequent in IPD patients with and without overt dementia. In a paper by Starkstein et al. (1996), the presence of affective symptoms was compared in patients with IPD and dementia and AD. Major depression in IPD with dementia was 30% as opposed to 6% of AD patients matched for dementia severity. Dysthymia, however, was found in 27% PDD and 27% AD.

Treatment of depression in IPD includes the use of a wide range of antidepressants, only a few of which have been shown to be effective in this population in controlled studies. Selection of which antidepressant to use should be based on side effect profile of the drug and potential drug interactions. Antidepressants with more anticholinergic properties such as amitriptyline can produce cognitive disturbances in the elderly and should generally be avoided. Tricyclic antidepressants with fewer anticholinergic properties and cardiovascular side effects such as nortryptiline are generally better tolerated in the elderly population. The serotonin reuptake inhibitors have little effect on the cholinergic system and only minor action on norepinephrine and dopamine. They have few side effects and may offer some advantage in the treatment of depression in this patient population. A few relatively small-scale studies have shown them to be effective in this patient population. In a recent study of paroxetine (Ceravolo et al., 2000), six months of treatment with 20 mg was found to be effective in treating depression without worsening the parkinsonian motor symptoms. Extrapyramidal side effects, however, have been described as adverse events, and worsening of PD

Table 3.3 Contrasting Features of the Subcortical Dementia of PD and AD

Feature

Language Memory Visuospatial Processing speed Executive skills Insight

Personality/mood

Aphasia

Amnestic

Severe

Normal

Proportionate

Lacks insight

Unconcerned

Motor speech problems Retrieval deficit Mild impairment Slowed

Greater difficulty

Preserved

Depression symptoms have been reported in a few cases. Moreover, there is the potential of developing a serotonin syndrome if these drugs are used in conjunction with selegiline, an MAO-B inhibitor commonly used in the treatment of PD. Although this has only rarely been described in the literature, concurrent administration of selegiline and a selective serotonin reuptake inhibitor should be avoided. Bupropion is an antidepressant with indirect dopamine agonist effects and, therefore, may offer some additional advantage when treating depression. Data on the newer class of combined serotonin and norepinephrine reuptake inhibitors in treating depression specifically in PD are not available. Klaassen et al. (1995) published a meta-analysis of treatment of depression in PD and found that despite the abundance of literature on PD and depression, there was a paucity of well-controlled studies on the treatment of depression in this population. Elec-troconvulsive therapy is effective treatment for major depression in PD patients. In the majority of cases, improvements are seen in both the depression and in the extrapyramidal motor symptoms (Burke et al., 1998). These improvements in motor symptoms tend to be short-lived but may persist for weeks in some cases (Table 3.3).

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