Contrary to our hypothesis, we found that the frequency and patterns of antidepressant prescribing for depressed patients with and without PD were similar, which is surprising given anecdotal experience that there are ongoing concerns among both clinicians and patients about the use of antidepressants in PD. These findings reflecting current VA clinical practice are supported by recent research suggesting that antidepressant treatment is safe and overall well-tolerated in PD. Specifically, a recent review and meta-analysis of antidepressant studies found that over 85% of PD patients enrolled in treatment studies were able to tolerate antidepressant treatment.13
In addition, concerns about the possible occurrence of serotonin syndrome in patients taking anti-Parkinson monoamine oxidase B inhibitor drugs (MAO B, eg, seligiline or rasagiline), together with an SSRI have been somewhat allayed by a large survey of clinicians, which found very low occurrence rates of both possible (0.24% [11/4568]) and definitive (0.04% [2/4568]) serotonin syndrome with this combination of medications.14
Nevertheless, caution is advised when combining an MAO B inhibitor and a SSRI or a tricyclic antidepressant.15
Our findings suggest that once depression is diagnosed in PD, the frequency and type of pharmacological treatment is not different from that received by elderly depressed patients without PD. Thus underrecognition, not patient or clinician concerns about antidepressant treatment, may be the main reason that a significant percentage of depressed PD patients do not receive pharmacological treatment for depression. Therefore, future interventions should strive to improve depression screening and diagnosis.
Regarding specific antidepressant use, in the decade prior to the collection of our data a substantial percentage of depressed PD patients were treated with a TCA.8
However, about two-thirds of depressed PD patients in our sample were prescribed an SSRI, suggesting that prescribing trends for PD have mirrored trends for the treatment of depression in general (ie, the shift from the use of non-SSRI antidepressants to the use of predominantly SSRIs).
The only statistically significant differences between the 2 groups in terms of antidepressant treatment were that PD patients were slightly less likely to take a TCA, and slightly more likely to take either venlafaxine or mirtazapine. The use of TCAs in PD is somewhat controversial, as their anticholinergic properties can improve motor symptoms but worsen autonomic symptoms and cognitive impairment, both of which are common in PD. Neither mirtazapine nor venlafaxine has been well studied in PD, but both affect multiple neurotransmitter systems, and there is evidence of both serotonergic and noradrenergic impairment in PD.3,16
It is important to state that although PD patients seen for depression were in general receiving similar treatment to that of depressed elderly patients without PD, this does not mean that the care being provided was optimal. For instance, the efficacy of SSRIs for depression in PD has not been established, and it is possible that they are not as effective in this population as in non-PD patients.13
In addition, there is evidence that once treatment for depression is initiated in PD, patients receive only a single antidepressant trial at submaximal dosages, even in the face of persistent depression.17
Therefore, clinical and research efforts should focus on optimizing treatment strategies for depressed PD patients who do not respond to an initial trial of an SSRI at a low to moderate dose.
Our study also revealed that with advancing age, PD is increasingly likely to be a comorbid condition in patients with depression; in our sample, PD was present in over 5% of depression cases in patients aged 75 years and older. This finding likely reflects the fact that increasing age is the primary risk factor for the development of PD. Regardless, it is important that clinicians are aware of the possibility of a comorbid PD diagnosis when formulating treatment strategies for depression in the elderly.
Our results should be interpreted with caution, given that all patients studied were male veterans. Thus, the findings cannot be generalized to nonveterans or females. Other limitations include the retrospective nature of the study and certain constraints imposed by the registry data that were used. For instance, we were not able to assess the accuracy of diagnoses or the use of antidepressants for purposes other than depression (eg, insomnia and chronic pain). Clearly, PD or non-PD patients with unrecognized depression cannot be identified using registry data, and because of diagnostic overlap, PD patients may be somewhat more likely than non-PD patients to have unrecognized depression. Finally, we were not able to assess antidepressant adherence, only whether a prescription was filled.
Our primary finding that a Parkinson’s disease diagnosis had minimal impact on the frequency and type of antidepressant treatment is important. Given that previous research suggests underrecognition and suboptimal treatment of depression in PD, future clinical interventions and research in this population should target depression screening and diagnosis, as well as establish the efficacy of different antidepressants and other depression treatment strategies in this population.