The results of this first randomized controlled trial suggest that CBT may be a feasible and possibly efficacious approach to treating depression in Parkinson’s disease. Ninety-percent of the sample completed the study and 88% of patients randomized to CBT attended all 10 treatment sessions. CBT was associated with significant improvements on all clinician-rated and self-report measures of depression. Gains were observed by the end of treatment (week 10) and maintained during follow-up (week 14). Effect sizes were large for both the HAM-D (1.59) and BDI (1.1). Response rates favored CBT at weeks 10 (56% vs. 8%) and 14 (51% vs. 0%).
The CBT group also reported greater improvements in quality of life, coping, and anxiety, as well as less motor decline. These results underscore several points. First, CBT patients reported less avoidance of and greater enjoyment from social activities, as well as the use of positive reframing as a coping strategy in response to daily stress. Second, treatment effects may generalize to the negative thoughts and avoidance behaviors that maintain anxiety. Third, the incorporation of anxiety management strategies, such as worry control and relaxation, into a CBT program for primary depression in Parkinson’s disease may be useful. Lastly, consistent with previous findings, sub-optimally treated depression may accelerate Parkinson’s-related physical disability (7
While there was no significant group by time interaction on inferences, treatment responders exhibited larger decreases in negative thinking compared to nonresponders. Since negative thoughts are a primary target of CBT, it follows that people who did not “respond” to treatment would not exhibit changes in thinking patterns. Despite moderate effect sizes, the impact of CBT on problem-focused coping and perceptions of role-limitations and physical disability were no longer significant after controlling for multiple comparisons. CBT also had no substantial effects on sleep, social support, or caregiver burden.
There are no controlled trials of CBT for depression in Parkinson’s disease with which to compare these results. However, completion rates, response rates, and effect sizes are comparable to those observed in randomized trials of CBT in other populations (41
). For example, the literature suggests that the average effect size of CBT for depression vs. a similar comparison condition to the one utilized in this study (i.e., no new treatment) is .67 (41
). Thus, this initial randomized-controlled trial offers preliminary data to suggest that the beneficial effects of CBT observed in other patient groups might not be attenuated by the disease process (i.e., neurodegeneration, neurotransmitter changes, dysfunction in brain regions/pathways).
This study also has several limitations related to the interpretation of efficacy. First, the study design did not include an attention-matched control or alternative psychosocial intervention. Although the additive approach and comparison condition employed did control for threats to internal validity (i.e., time, spontaneous remission, regression to the mean, history, effects of repeated testing) and are appropriate for use in early phase psychotherapy trials (23
), the role of non-specific factors, such as the increased attention and social contact received by the CBT group, cannot be adequately explored. It is also not possible to isolate which aspects of the CBT package (e.g., caregiver sessions, exercise) were most helpful. Related to this, we cannot rule out the placebo effect as a partial explanation for differences between groups. However, several factors make this explanation less likely. Throughout the trial, it was emphasized that the impact of both study treatments (CBT and clinical monitoring) on depression in Parkinson’s disease was not yet known and that there may not be any personal benefit from participation. Additionally, the chronic nature of depression in the sample, progressive nature of Parkinson’s disease (i.e., not an acute stressor), durability of CBT gains exhibited over 14 weeks, changes in negative cognition that accompanied treatment response, minimal improvement observed in the clinical monitoring condition, and comparability of results to CBT trials in other populations suggests that the impact of CBT may be larger than that which can be explained by placebo response alone. Of note, a CBT effect size of .75 is obtained when comparing CBT data from this study to pill placebo data from our own recent double-blind placebo-controlled antidepressant trial for depression in Parkinson’s disease (10
Second, despite an average reduction of 7.35 points, the mean HAM-D score of 13.58 for the CBT group at week 10 still reflects moderate depressive symptoms. This finding may in part be due to the high rate of somatic complaints experienced by Parkinson’s patients, independent of depression, as well as the inclusive scoring approach employed (44
). For example, all reported symptoms were counted towards HAM-D ratings despite potential overlap with the physical symptoms of Parkinson’s disease (i.e., psychomotor slowing, fatigue). Importantly, the BDI emphasizes cognitive symptoms of depression (i.e., guilt, hopelessness) and the week 10 BDI score of 9.7 for the CBT group indicates minimal symptoms of depression. Third, given the psychiatric comorbidity in the sample and the inclusion of two anxiety management modules in the CBT package, it is possible that reduced anxiety could have influenced depression treatment response. Because the depression effect remained robust (P
when controlling for HAM-A change (exploratory analyses), it is unlikely that improved anxiety was a main mechanism of action. Fourth, motor functioning results warrant prudent interpretation. Although the group-by-time interaction on motor scores at week 10 was statistically significant, the effect size was small (.13) and may be an artifact of the sample.
It is also necessary to acknowledge that our results may not generalize to those with more advanced stage disease, severe depression, dementia, sub-optimal social supports, inability to travel to weekly therapy, and limited access to specialized mental health resources. In addition, we could not explore the longer-term durability of treatment gains because the follow-up period was limited to one-month for ethical reasons (protocol restrictions regarding changing depression treatment). Lastly, treatment side effects were not assessed prospectively. Collectively, these limitations suggest that the results should be viewed as a preliminary first step in the establishment of an evidence base for CBT in Parkinson’s disease.
The precise cause of depression in Parkinson’s disease is unclear, with both biological and psychosocial factors implicated in its onset and maintenance (45
). As a whole, the results of this trial suggest that cognitive behavior therapy for depression in patients with Parkinson’s disease may be beneficial, independent of etiology. Further research is needed to replicate and extend these findings.