This study assessed the course of clinically significant depressive symptoms in early PD subjects followed for 12–18 months. We used data from two clinical trials that were designed to evaluate progression of PD, controlling for treatment assignment and other covariates. Most subjects who screened positive on the GDS-15 had mild depressive symptoms that remained mild. Thirteen (11.4%) of the 114 subjects who screened positive for depression had moderate to severe symptoms. Nearly half of the subjects had remission of clinically significant depressive symptoms within 6 months as measured by the GDS-15. However, mild depressive symptoms were associated with a more than 6- fold increased risk of developing moderate to severe depressive symptoms compared with absence of depressive symptoms. Additionally, higher GDS-15 scores were associated with a lower likelihood of remission. Just a one point increase on the GDS-15 reduced the chances of remission by 17%.
There is little information about the course of depression in PD. One clinic-based study followed 187 PD subjects for a median of 14 months. Similar to our study in early PD, 27% of the cohort screened positive for depression using the Beck Depression Inventory.12
Only 15.9% of those who were depressed at baseline remained depressed at the final visit. Subjects who remain depressed had higher baseline BDI scores. Another study examining a range of PD subjects showed that after 1 year, 63% of subjects with minor depression were likely to be in remission, but only 11% of subjects who initially had major depression were in remission.13
Consistent with prior studies, we found that the majority of cases of depression in early PD were in remission by 6–9 months, but that greater depression severity was associated with a lower chance of remission.
We found a more than 6-fold increase in risk of more severe depressive symptoms among those who had minor symptoms. Similarly, findings in a community setting and general medical patients suggest that minor or subthreshold depression may predict subsequent major depression.14
Chronic illness has also been associated with an increased risk for conversion from subthreshold depression to major depression.15
While many of the community-based studies have had follow-up periods of one year, some have followed subjects for more than 10 years. Studies with longer follow-up will help to clarify the evolution of depressive symptoms during the course of PD and help inform treatment decisions. Our findings clearly indicate, however, that careful monitoring of depressive symptoms in PD is warranted.
We modeled remission of depressive symptoms in two ways to maximize the value of our data. The model including only baseline cases allowed us to include important covariates that were not measured at all visits, such as cognition (RBANS) and HY stage. The model using both baseline and incident cases provided a larger sample size but shorter follow-up period among incident compared with baseline cases. For baseline cases, in addition to more severe depression, older age and longer PD duration were associated with protracted depression. Prior studies support these findings and suggest that advanced age and longer disease duration may be risk factors for incident depression in PD.12, 13, 16–19
Higher HY stage was associated with a greater chance of remission, but total UPDRS score was not associated with the course of depressive symptoms. There is not a clear relationship between motor impairment and depressive symptoms in any stage of PD.20
All subjects started the study with HY stage of I-II. The emergence of postural instability and development of HY stage III can be highly variable in early PD when postural instability is measured by the pull test.21
Thus, this finding should be interpreted with caution. Similarly, the association with RBANS was modest and the RBANS showed little change (mean change –1.48, ± 10.8) during this study, suggesting either that cognition did not decline appreciably during the course of the study or that the RBANS may have been insensitive to progression of cognitive impairment in this cohort. The combined analysis using incident cases did not replicate these findings (data not shown). This may be due to the different variables in the model or differences between incident cases and baseline cases. Because of the small and inconsistent effects, these findings require replication.
The use of antidepressants was associated with a lower likelihood of remission of depressive symptoms. In this cohort, more severely depressed PD patients were more likely to be treated with antidepressants.5
Thus, this finding likely represents confounding by severity, such that those with a worse prognosis were more likely to be treated with antidepressants.22
Among the 114 subjects who screened positive for depression, 53 were treated with antidepressants; 33 received an SSRI, 1 received a TCA, and the remainder received other antidepressants alone or in combination with an SSRI. Two recently completed randomized, double-blinded, placebo-controlled clinical trials suggest that both SSRIs and TCAs may be effective for treating depression in PD.23, 24
Thus, there is no reason to believe that treatment with antidepressants would actually reduce the likelihood of remission of depressive symptoms.
The main limitation of this study is the absence of psychiatric diagnostic interviews for establishing depressive or other affective diagnoses.25
However, the GDS-15 is validated as a depression screening tool in the geriatric population and scores of ≥5 are predictive of clinically significant depressive disturbances in PD.3
The GDS-15 was not designed to measure response to therapy and may have over- or under-estimated rates of remission.
Additionally, we adjusted for important covariates, but did not eliminate the potential for bias inherent in an observational study, and we found evidence of confounding by symptom severity.
Mild depressive symptoms in PD are common, and single episodes of clinically significant symptoms appear to be limited to 6–9 months in duration for most subjects. However, greater symptom severity reduced the likelihood of remission and, for some subjects, these mild symptoms may portend development of more severe depressive symptoms.