Depression is common in Parkinson's disease (PD) and is associated with several poor outcomes. However the literature regarding treatment with antidepressants in this population is controversial. The aim of this paper was to systematically review all randomized controlled trials that studied the efficacy of antidepressants for depression in PD (dPD). Studies were retrieved from PubMed (1966-July 2012), Cochrane Library (-July 2012, issue 7), Embase (1980-July 2012), PsycINFO (1980-July 2012), Lilacs (1982-July 2012), secondary references, clinical trials registries and a thesis database. Only double-blind, randomized controlled trials in which an antidepressant was given as the main treatment and compared with placebo and/or another antidepressant were included. Out of the 1438 studies retrieved, only six could be included. Taking into account the five placebo-controlled trials, the overall risk ratio (RR) for response was 1.36 (0.98, 1.87), indicating no statistically significant superiority of antidepressants over placebo. However, in the sensitivity analysis, the RR for response was 1.41 (1.01, 1.96) and 1.48 (1.05, 2.10) after exclusion of one study with questionable results, and when only studies with low risk of bias were considered, respectively. No specific antidepressant class was superior to placebo. In general antidepressant medications were well tolerated. The results suggest antidepressants may be efficacious in the treatment of dPD. However, the results were unstable. In fact, the small number of trials and methodological drawbacks preclude definitive conclusions about their efficacy and tolerability in dPD.