According to a recent update [60], Tricyclic Antidepressants (TCAs) can be considered “possibly useful” to treat depression. Evidence seems to be insufficient for the use of Amitriptyline, although a recent review has shown that it seems to be more effective than other antidepressants [67]. Treatment of PD patients with TCAs may result in psychosis, sedation, and daytime sleepiness as well as in cognitive dysfunction or delirium when used in patients with PDD. Regarding the use of Selective Serotonin Reuptake Inhibitors (SSRIs) and Selective Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), Venlafaxine seems to present the best effective profile, although other antidepressants such as Citalopram, Sertraline, Paroxetine, and Fluoxetine are considered possibly useful in clinical practice. As a result of conflicting efficacy data, there are still “insufficient evidence” for all SSRIs reviewed. SSRIs have been found to present an improved safety profile in comparison with TCAs in studies conducted in psychiatric populations. SSRIs may worsen PD tremors in up to 5% of patients and occasionally worsen other features of parkinsonism [68]. In addition, Citalopram, used in a daily dose of more than 20 mg, may cause a QT interval (QTc) prolongation in patients over 60 years [60]. Moreover, Serotonin syndrome may occur when SSRIs or SNRIs are used in association with Monoamine oxidase B inhibitors (MAO-BIs), such as Selegiline and Rasagiline [69]. PD-related depression may also be treated with second generation non-ergot Dopamine agonists (DA) such as Pramipexole [70]. A new study has evaluated Rotigotine with negative outcomes. Currently, insufficient evidence is present for the use of MAO-BIs [60].