Depression has been found repeatedly to be a primary determinant of QoL in patients with PD6
and their caregivers.22
In fact, several studies have suggested that up to 40% of the observed variance in QoL in PD is due to depression and that the impact of depression on QoL exceeds that of the movement disorder aspects of the illness.7,23,24
Thus, the study of depression and QoL is of great importance in this population.
Despite this clear association of depression and poor QoL in PD, there is a paucity of research that examines the effect of treating depression on this important outcome. The only previous work of which we are aware was a single blind study of sertraline and amitriptyline. In this study, sertraline treatment of depression was associated with significant improvements in the PDQ-39 scale.
In the present study, we found that patients who had improvement in depression, compared to those without improvement in depression, evidenced significant gains on both the PDQ-8 and the SF-36 measures of QoL and disability during the eight-week study. Furthermore, for the subset of patients who entered the extension phase, these gains were maintained throughout the 6-month study. It is important to note that we reported in our original publication of the efficacy results of the 8-week acute study9
that there were no differences in QoL measurements between treatments, that is no treatment (nortriptyline, paroxetine, or placebo) was significantly superior to any other on QoL. In this report, we examine the difference (regardless of treatment arm) between those whose depression had improved compared to those whose depression had not improved. This addresses the important question of whether or not successfully treating depression helps to improve QoL.
We found continued improvement using the PDQ-8, a PD-specific QoL measure, and the SF-36 a more generic QoL and disability instrument. These results are comparable with results from nonPD populations, in which treatment of depression leads to an improvement in QoL of similar magnitude.26
Although we believe that these data are important and are the first of their kind, the trial has a number of limitations and the conclusions must be seen as preliminary. The sample size was small and relatively few patients finished the entire 24 weeks of the study. Thus, there is a danger of generalizing from this small, possibly nonrepresentative, sample. Only 20% (4 of 20 patients) relapsed in the extension phase, so the comparisons between placebo and active drug treatment should be viewed with caution. In general, the treatments were well tolerated, but there were 13 of 52 patients (25%) who dropped out of the acute study for adverse events and 2 of 20 patients (10%) who dropped out of the extension study for tolerability reasons. Lastly, it is important to note that cardiac conduction needs to be monitored in patients on nortriptyline.
Of note, the improvements in QoL and disability were mostly limited to emotional and psychosocial aspects of QoL, whereas parallel improvements were not seen in the physical aspects of QoL. There were also no changes in measures of PD disease severity, suggesting that the improvement seen in QoL is not the result of any impact of the medications on the disease itself, but rather is an effect on the emotional distress.
In addition, we also found that individuals who were on active drug were less likely to relapse than those on placebo, suggesting that antidepressants have an ongoing positive impact on depressive symptoms in PD. The prevention of relapse is an important goal in the treatment of depression because of the potentially chronic and disabling nature of the disorder. There is no literature on PD depression relapse rates with which to compare these results. However, in a systematic review of the literature on depression relapse in non-PD patients, the average rate of relapse was 41% in people receiving placebo compared with 18% for those continuing antidepressant treatment.27
Thus, our results are comparable to those observed in the nonPD population and suggest that antidepressants not only can treat depression in patients with PD but that the effect is sustained through at least 6 months.
Furthermore, it appears that patients tolerated up to 6 months of paroxetine and nortriptyline are relatively well. There were no apparent cardiotoxic effects of nortriptyline, though one needs to be cautious of this in a geriatric population.
Given the observation that depression in patients with PD is under-recognized and under-treated in clinical practice,28,29
we believe, despite the limitations of the trial, that the findings are important for patients with PD and their families.