Editorial

Repetitive Transcranial Magnetic Stimulation as Treatmentfor Depression in Parkinson’s Disease

Robert Chen, MBBChir, MSc, FRCPC*

Department of Medicine, Division of Neurology, University of Toronto and Toronto Western Research Institute,University Health Network, Toronto, Ontario, Canada

While the classic features of Parkinson’s disease

(PD) are related to the motor symptoms and signs, the

importance of nonmotor symptoms is increasingly

being recognized.1,2 For many nonmotor symptoms,

there is no effective treatment. Depression is among

the commonest nonmotor symptoms in PD with

reported prevalence from 40% to more than 70%.2–4

While depression may partly be a reactive process,

there is evidence that depression is related to the neu-

rodegenerative process of PD.2,5

Both pharmacological and nonpharmacological

approaches are used to treat depression. Pharmacologi-

cal treatment may be ineffective or have intolerable

adverse effects in many PD patients. Therefore, non-

pharmacological approaches to the treatment of depres-

sion are needed. Transcranial magnetic stimulation

(TMS) is a safe and noninvasive way to stimulate the

human brain.6 High frequency repetitive TMS (rTMS)

increases cortical excitability while low frequency

rTMS decreases cortical excitability.7,8 High frequency

rTMS of the left dorsolateral prefrontal cortex

(DLPFC) is an approved treatment for medication re-

sistant depression in several countries, including the

United States and Canada. In PD, many studies exam-

ined the effects of rTMS on motor symptoms. Most

studies stimulated the motor cortex, but stimulations of

other motor-related areas and the DLPFC have also

been examined. While the previous studies are highly

variable in their study design and stimulus parameters

used, two recent meta-analyses suggested that high fre-

quency rTMS may improve motor symptoms in PD.9,10

However, there has not been a large double-blinded,

placebo-controlled study of rTMS in PD.

Only a few studies have examined the effects of

rTMS on depression in PD. In this issue, Pal et al.11

showed in a placebo-controlled trial of 22 PD patients

with mild-to-moderate depression that rTMS to the

left DLPFC improved depressive symptoms. After 10treatment sessions (one session per day), the antide-

pressant effect lasted for up to 30 days after treat-ment. These results are consistent with a previous

study showing that rTMS had similar antidepressant

effect as fluoxetine.12 Although the study sample sizeis relatively small, the findings provide promising evi-

dence that rTMS may be a useful treatment fordepression in PD.

Compared to the largest study to date of rTMS as

treatment of depression,13 the effect size of the current

study11 in PD appeared to be smaller. There are several

possible reasons for the differences. The stimulus

parameters are different and the present study used

lower stimulus intensities, frequencies, and number

of pulses. Moreover, the present study examined

mildly depressed patients where the previous study13

involved treatment resistant patients with major depres-

sion who had much higher baseline depression scores.

The response of PD patients may also be different

Potential conflict of interest: None.

*Correspondence to: Dr. Robert Chen, Toronto Western Hospital,McLaughlin Pavilion, 7th Floor Room 411, 399 Bathurst Street, To-ronto, Ontario, Canada M5T 2S8.E-mail: robert.chen@uhn.on.ca

Received 25 March 2010; Revised 18 April 2010; Accepted 30April 2010

Published online 24 August 2010 in Wiley Online Library(wileyonlinelibrary.com). DOI: 10.1002/mds.23266

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from patients without PD. The small sample size of

the present study may lead to less stable findings.

Interestingly, the present study showed a trend for

improvement in motor function in PD patients. This

finding has been previously reported12,14 and suggest

that rTMS of DLPFC may also improve motor func-

tions in PD.

Clearly, further studies are needed before rTMS

become an established treatment for PD. Much larger,

blinded, sham-controlled, multi-centered studies are

needed. Whether a combination of rTMS of different

cortical areas targeted to treat depression with DLPFC

stimulation and to treat motor symptoms with stimula-

tion of motor cortical areas would produce additive or

even synergistic benefits also needs to be studied. As

effective rTMS treatment likely requires multiple ses-

sions, this may be burdensome to some patients. It will

be an expensive treatment because, at a minimum, a

qualified technician is required to administer rTMS.

Therefore, even if further studies show positive results,

these limitations need to be considered in the adoption

of rTMS in routine clinical care.

Financial Disclosures: Dr. Chen received research grantsfrom the Canadian Institutes of Health Research, Michael J.Fox Foundation for Parkinson Research, Dystonia MedicalResearch Foundation and Medtronic Inc., honoraria fromAllergan, Medtronic, Merz, Novartis, Teva, and from experttestimony.

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12. Fregni F, Santos CM, Myczkowski ML, et al. Repetitive trans-cranial magnetic stimulation is as effective as fluoxetine in thetreatment of depression in patients with Parkinson’s disease.J Neurol Neurosurg Psychiatry 2004;75:1171–1174.

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