Use of antidepressants for depression in patients with Parkinson's disease

Bonuccelli et al. [1] conducted the first and largest study of the effectiveness and tolerability of duloxetine [serotonin--norepinephrine reuptake inhibitors (SNRIs)] for the treatment of depression in patients with Parkinson’s disease (PD). That study showed that a 12-week course of duloxetine 60 mg/day was well tolerated and effective for treating depression in patients with PD and that it had no detrimental effects on the signs and symptoms of PD. The use of antidepressants for PD patients has been a common practice not only in psychiatry but also in neurology and primary practice. Hence, clinical issues in the use of antidepressants in PD patients should be more addressed. Although the etiology of depression in patients with PD is not yet fully understood [2,3], it has consistently been proposed that alterations in neurotransmitters other than dopamine -such as serotonin, noradrenalin, glutamate and acetylcholine -are involved in the development of depression in this population [4]. According to a recent positron emission tomography (PET) study [5], PD patients with significant depressive symptoms showed significantly raised C-DASB binding in the amygdala, hypothalamus, caudal raphe nuclei and posterior cingulate cortex compared with those without these symptoms, whereas the C-DASB binding values in other regions were similarly decreased in depressed and non-depressed PD patients compared with healthy controls. These data are consistent with the fact that abnormal raphe and limbic areas may contribute, in part, to the pathophysiology of depression and PD as well as justify the use of serotonergic agents. Additionally, pramipexole, a dopamine D2/3 receptor agonist that preferentially affects brain activity in the prefrontal and limbic cortices according to a PET study [6], was also found to be efficacious and safe for the treatment of depression by a number of placebo-controlled clinical trials [7]. Thus, currently available PET studies support the existence of both serotonergic and dopaminergic deficits in the specific brain pathways of such patients. Based on currently available data [8], tricyclic antidepressants (TCAs) have been the most popular agents for the treatment of depression in PD patients, with efficacy that is superior to that of newer antidepressants, such as selective serotonin reuptake inhibitors (SSRIs). However, the significant tolerability issues of TCAs compared with those of SSRIs [8] should not be neglected in clinical practice, given that PD patients usually have comorbid medical conditions and are especially vulnerable to unwanted side effects due to polypharmacy [2,3,9-11]. SNRIs have weak effects on dopamine reuptake, whereas they have simultaneous effects on serotonin and norepinephrine 5-HT reuptake transporters, theoretically resulting in faster onset and relatively higher efficacy compared with SSRIs. However, the putative superiority of SNRIs over other antidepressants has not yet been confirmed. Indeed, duloxetine and venlafaxine were found to have lower acceptability and tolerability than SSRIs [12]. Thus, clinicians treating depression in PD patients must carefully