Depression is a frequent non-motor symptom of Parkinson’s disease (PD), and may even
precede the onset of motor symptoms of parkinsonism. Beyond its negative influence on mood,
depression in PD is frequently associated with other neuropsychiatric symptoms and with late-stage
complications such as dementia. Despite its profound impact on the quality of life and cognitive
functioning in PD, depression in PD is often under-recognized and poorly treated.
Pathophysiological studies demonstrated that depression in PD is associated with global dysfunction
of interactions between discrete brain areas rather than focal structural or functional abnormalities,
and that it is sustained by pathological changes of several neurotransmitter/receptor complexes.
In general, all traditional antidepressants and some dopamine agonists have been found to be safe
and well-tolerated to treat depressive symptoms in PD, despite initial warning on worsening of
parkinsonism. Available data suggest that the time-course of response differs among antidepressants.
Efficacy results from clinical trials with antidepressant in PD are, however, rather uncertain,
although pooled analysis suggests a moderate benefit. Several issues may critically impact the
results of clinical trials with antidepressants in PD, including the correct psychiatric diagnosis, the
overlap of symptoms between depression and PD, and the selection of appropriate end-points and