Funding is insufficient.

Parkinson's disease (PD) is one of the most common neurological diseases manifested by movement disturbance. The concomitant psychiatric symptoms, especially depression, are often observed and have also great impact on patients' quality of life. The treatment of depressive symptoms in PD with antidepressants as the majority remains variable and inefficient, which complicates the disease prognosis. Transcranial direct current stimulation (tDCS) is a non-invasive brain modulation technique and has been demonstrated to improve psychiatric diseases such as major depression. In this study the investigators will assess the combined effects of tDCS on sertraline for the treatment of depression in PD. Ten sessions of tDCS in two weeks will be applied and the follow-up evaluation will continue bi-weekly for one month after completing all sessions. The efficacy of tDCS vs sertraline will be compared and evaluated with behavioral and cognitive outcome. In addition, the investigators will evaluate if the baseline dopaminergic activity in brain could predict the treatment outcome by using SPECT imaging. The investigators aim to establish the therapeutic parameters and safety criteria of tDCS as an add-on or alternative therapy, and further enhance the overall clinical efficacy in the treatment of depression in PD.

Study design

This study is a factorial randomized, placebo-control trial, including 2 groups: 'sertraline only' (sertraline + sham tDCS), and 'combined treatment' (sertraline + active tDCS). It is planned to recruit 20 subjects for each group, which results in all together 40 participants. Patients will take 12 tDCS sessions (30min for each session): first 10 consecutive sessions for two weeks (Monday to Friday), and then 2 follow-up sessions scheduled 2 and 4 weeks after the consecutive treatment. Both pharmacological and tDCS intervention will be started simultaneously on the first day of the treatment.

Inclusion Criteria:

1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3. Suffers from Parkinson's disease fulfill the Parkinson's Disease Society Brain Bank clinical criteria with insidious 2 or more PD symptoms (bradykinesia, tremor, or rigidity).
4. Suffers from "DSM-IV major depressive disorder, single episode" or "DSM-IV major depressive disorder, recurrent" according to Diagnostic & Statistical Manual of Mental Disorders, 4th Edition - Text Revision (DSM-IV-TR) criteria.
5. Reported duration of the current episode is ≥4 weeks and has not been treated with antidepressants.
6. Has a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥20 at the screening (baseline) visit.
7. Is a man or woman aged 18 to 75 years, inclusive.

Exclusion criteria:

1. Subjects known to have allergies to sertraline and pimozide.
2. Subjects showed any signs of substantial risk of suicide during the trial.
3. Subjects ever received electroconvulsive treatment.
4. Subjects co-morbid with other major mental disorders or with substance/alcohol dependence or abuse in the past 6 months per DSM-IV criteria.
5. Nursing women, pregnant women or patients suspected pregnant.
6. History or presence of clinically significant hepatic, cardiovascular or renal disease, or other serious medical disease that might compromise the study.
7. History of seizure disorder or need to taking medications that increase the risk of seizure.
8. History or presence of dementia and any previous history of brain tumor, brain arteriovenous malformation, encephalitis or meningitis.
9. Subjects ever received or plan to receive brain surgery during the trial.
10. Subjects with pacemaker or are contraindicated for MRI.

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