Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the US [
17]. Affecting approximately 500,000 – 1 million people [
17], PD is a progressive illness that is associated with significant functional disability. Depression is the most frequently reported non-motor symptom in PD [
18] and may present as major depressive disorder, dysthymia, or subthreshold symptoms that do not meet formal DSM-IV criteria for a depressive disorder [
19], yet cause great distress and impairment. In addition, depression may co-occur with the motor “on-and-off” fluctuations frequently observed during dopaminergic treatment in PD patients. For example, some patients may experience mood fluctuations (i.e., brief periods of dysphoria or anxiety) in conjunction with motor fluctuations or “off time” (i.e., intermittent periods throughout the day when their motor symptoms are not well controlled by the anti-parkinson’s medications- usually resulting from long term use of levodopa) [
20,
21,
22].
While a wide range of statistics have been reported regarding the prevalence of depression in PD (i.e., depending on the type and setting of the assessment, definition of depression used), it has been suggested that some form of depression may affect up to 50% of patients [
23,
24,
25,
26]. Early-onset PD may be a risk factor for depression [
27] while research regarding the relationship between PD severity and depression has yielded mixed results [
27,
28,
29]. Depression in PD (dPD) may precede the onset of motor symptoms [
30], is often under-detected by medical professionals [
31], and warrants significant attention from clinicians as it is related to a faster progression of physical symptoms, greater cognitive decline, poorer quality of life, increased caregiver burden, and decreased ability to care for oneself [
32,
33,
34,
35,
36].
Despite these established pernicious effects, there is a dearth of well-designed research that can guide clinical care for these patients. Although some placebo-controlled studies have suggested that antidepressants may be beneficial for PD patients, conclusions have been weakened by methodological shortcomings [
37]. Limitations include small sample size, low power, inadequate dosing, use of assessment tools with undocumented reliability and validity, inclusion of medically unstable patients, and lack of consideration of symptom overlap between depression and PD. In addition, a recent meta-analysis of limited studies suggests that antidepressants may not be as helpful for PD patients as they are for the non-PD depressed aged [
38]. Several NIH sponsored clinical trials, including one at our site, are currently being conducted to further elucidate the efficacy of ADMs for dPD. Nevertheless, a paucity of empirical support regarding the efficacy and tolerability of antidepressant treatment in the PD population is currently available.
Similarly, there has been a paucity of investigations regarding non-pharmacological treatments for dPD. Deep brain stimulation (DBS) is often used as a late therapeutic option in the treatment of PD when motor symptoms can not be adequately controlled with medication alone [
39]. In addition to improving motor function, some studies have also found DBS to be associated with improvements in mood and depression [
40,
41,
42]. The results of these studies are equivocal, however, as some reports have demonstrated adverse reactions, including significant worsening of depressive symptoms and suicidal ideation [
41,
43,
44] and inducement of mania [
45,
46,
47]. In addition, a randomized, controlled trial of Qigong exercise showed decreases in depression scores in both the control and treatment group, although those in the treatment group did experience a greater improvement in motor symptoms [
48]. Two exploratory studies of bright light therapy for dPD, one of which was a randomized placebo-controlled double blind study, have demonstrated moderate improvement in depressive symptoms [
49,
50], but further research is necessary to replicate these findings.
The application of cognitive-behavioral therapy to the treatment of dPD has also received little experimental attention. To date, only one published pilot report (with a comparison condition) has examined the helpfulness of cognitive therapy for depressed PD patients. As participants were not randomly assigned to treatment condition, endorsed very mild depressive symptoms at baseline, and had comparison groups that were unequal in size, only very limited conclusions may be drawn from this study [
51]. An uncontrolled 15-patient pilot study [
52] and several case reports have also documented the feasibility of CBT for dPD [
53,
54]. Moreover, an eight-session group educational program for PD patients and their caregivers that introduced many of the skills covered in CBT, such as self-monitoring, stress management, dealing with negative thoughts, and appropriate use of social supports, was pilot tested with 36 participants [
55]. While the program yielded short-term improvements in global ratings of mood, no significant effects on depression or quality of life were observed and it is unclear if patients with formal diagnoses of depression were enrolled [
55]. Although educational programs have great merit, they are more diffuse by nature than individualized cognitive-behavioral therapy programs designed to treat patients with mood disorders.
This site is currently conducting a large study sponsored by the National Institutes of Health, to examine the impact of cognitive-behavioral therapy on major and minor depressive episodes, as well as dysthymia, in patients with Parkinson’s disease. Eighty PD patients without evidence of dementia, psychosis, or significant motor fluctuations (i.e., “off” greater than 50% of waking hours) will be randomized to receive either 10 weeks of CBT or 10 weeks of standard medical care under the supervision of their personal physicians. Secondary outcomes regarding anxiety, sleep, motor function, quality of life, appropriate use of social supports, coping, dysfunctional attitudes, and cognitive functioning will also be explored. Additional trials of this nature are also in progress at other academic medical centers. Further research support for a cognitive-behavioral intervention for depression in PD would not only provide clinicians with one additional treatment option for their patients, but it would also meet a significant need for people living with PD who have expressed an interest in alternative treatments to help them cope with the unique cognitive, physical, and psychosocial issues that they face [
101]. For example, in a recent psychosocial needs assessment, 65% of PD patients reported that they desired counseling to help them cope with their illness [
56]. In a separate study conducted in a multidisciplinary clinic, 95% of patients sampled requested to speak with a mental health professional in order to deal with PD related concerns [
57]. Empirically validated psychotherapies, such as CBT, are greatly needed to guide these efforts. The distinctive aspects of depression in Parkinson’s disease, including executive dysfunction, psychiatric complexity, and highly involved caregivers, as well as how CBT can best be tailored in order to meet these needs, are further addressed below.