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Editorial accepted July 2011.
In the past 36 months, Dr. Black has received honoraria and travel funds from Merck and from Synosia for consultation on pharmacological imaging; he also received research support through contracts with Washington University from Synosia, Acadia, Bristol-Myers Squibb, the Tourette Syndrome Association, and the National Institutes of Health. Dr. Freedman has reviewed this editorial and found no evidence of influence from these relationships.
Address correspondence to Dr. Black (firstname.lastname@example.org).
Copyright © American Psychiatric Association
Parkinson's disease is the most common neurodegenerative disease after Alzheimer's disease, affecting 1%–4% of people by age 80 (1). Although it is defined by motor signs, the symptoms that most impair the lives of patients—and their caregivers—are psychological symptoms, including depressed mood (2). In clinical settings, about 25% of patients with Parkinson's disease have a major depressive syndrome, and about half have clinically important depressive symptoms (2, 3). (The terminology is awkward, because according to DSM-IV-TR, a major depressive episode cannot be diagnosed if the symptoms are directly caused by a nonpsychiatric illness such as Parkinson's disease, and there is substantial evidence that the Parkinson's disease process does directly cause at least some of the depression in these patients ).The increased rate of depression in Parkinson's disease begins before motor impairment is evident, and it is not explained by a psychological reaction to disability (2).
Depression in Parkinson's disease (4) is demonstrably different from ordinary major depression in terms of sex ratio, age, symptom profile, comorbidity, and chronicity. Pharmacotherapy for depression in Parkinson's disease entails special concerns related to side effects and drug-drug interactions. The cognitive deficits present in a substantial fraction of Parkinson's disease patients raise questions about psychotherapy efficacy. Thus, treatment studies on major depression in patients without Parkinson's disease cannot be assumed to apply in Parkinson's disease. Nevertheless, successful treatment of depression in Parkinson's disease improves quality of life and reduces disability (5).
Given this background, it is remarkable that less than a decade ago almost no empirical data existed to guide antidepressant treatment in Parkinson's disease. Most reports claiming antidepressant effects for dopamine agonists in Parkinson's disease are limited to changes in depression symptom scores in patients who were not assessed for the presence of a diagnosable depressive disorder. At present, only a handful of randomized controlled trials for depression in Parkinson's disease have been published, and they have focused on pharmacotherapy, despite the appearance decades ago of multicenter randomized controlled trials for psychotherapies in people with major depression but not Parkinson's disease. One controlled trial of group psychotherapy for patients with Parkinson's disease has been reported, but the published report did not reveal whether assignment to active treatment was random (6).
In this setting, Dobkin and colleagues (7) report a randomized controlled trial of cognitive-behavioral therapy adapted especially for depression in Parkinson's disease (8). This may be the largest randomized controlled trial of any treatment for depression in Parkinson's disease published to date. The study has several additional strengths, not least of which is the expertise of the authors in this area (5, 7–9). The inclusion and exclusion criteria were chosen wisely, as were the primary and secondary outcome measures. The authors included excellent control of treatment fidelity, which is necessary for important conclusions about psychotherapeutic benefits. The statistical analysis controlled for the number of comparisons. Furthermore, the 4-week follow-up period allowed an initial estimate of the duration of treatment benefit.
The results are strong, with a large effect size of 1.59 (Cohen's d) for the primary outcome measure. Half of the patients in the treatment group responded to treatment and maintained the response 4 weeks after the active treatment phase, compared to none of the patients in the control group. There were significant beneficial effects for most other outcomes, and it is interesting that one of these was parkinsonian motor signs.
One important parenthetical observation should be made here. In the diagnosis of major depressive disorder, the original semistandardized diagnostic interview adapted for this study followed DSM-IV-TR in requiring expert judgment as to whether a direct effect of Parkinson's disease was to blame for each symptom and for the syndrome. Dobkin et al. instead followed an expert panel's suggestion that researchers ignore these etiological rules in diagnosing depression in Parkinson's disease (4). Nevertheless, that decision is arbitrary and the results of this study apply equally to Parkinson's disease patients diagnosed clinically with major depressive disorder or with mood disorder due to Parkinson's disease.
These data are important for their quality, primacy, and clinical significance. However, as the authors point out, substantial work remains to be done on psychotherapy for depression in Parkinson's disease. The treatment group had much more attention during the study than the control group, so we do not know whether other psychotherapeutic options, such as interpersonal therapy, would work as well. It also remains to be shown what degree of therapist expertise is required for treatment success. However, the results are remarkably good compared to usual clinical care, and they are unlikely to be due to the placebo effect alone. In fact, the treatment group improved substantially more than did Parkinson's disease patients at the authors' own center who took placebo pills in a double-blind randomized controlled trial of antidepressant medications (9). More work will also be needed to clarify how widely these results generalize within the Parkinson's disease population.
Nevertheless, the report by Dobkin and colleagues (7) is an important step for the neuropsychiatry of Parkinson's disease, and these results should encourage an important "new" treatment option to be provided (and reimbursed) to a large number of Parkinson's disease patients.
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