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Transcranial Magnetic Stimulation Helpful in Parkinsonian Depression

By Megan Brooks, Medscape Today

September 2, 2010 — Repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) exerts antidepressive effects in patients with Parkinson's disease (PD) and mild to moderate depression, confirm results of a randomized, double-blind, placebo-controlled study published online August 24 in the journal Movement Disorders.

"In our study, we also demonstrated that not only depression, but also some aspects of cognition improved by rTMS treatment," Norbert Kovacs, MD, PhD, of the Department of Neurology at the University of Pecs in Hungary, told Medscape Medical News. "Simultaneously, in the sham-treated group neither depression nor the cognitive functions improved," Dr. Kovacs noted.

Motor function also showed some improvement with active rTMS, they report.

There are several theories to explain the apparent effects of rTMS on cognition and motor function, Felipe Fregni, MD, PhD, director of the Laboratory of Neuromodulation at Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, noted in a telephone interview with Medscape.

It is possible, he explained, that by improving depressed mood, patients become more physically active, less nervous, and perhaps think more clearly.

"The area that is being stimulated is involved in depression but also cognitive function, so you have this dual advantage and effect," said Dr. Fregni, who was not involved in the current study, but who has studied rTMS in depressed PD patients (J Neurol Neurosurg Psychiatry. 2004;75:1171-1174).

Depression Common in PD

Depression is one of the most important nonmotor features of idiopathic PD, affecting 40% to 70% of patients, Dr. Kovacs and colleagues note in their report. Depressed mood may not only worsen the motor symptoms of PD, but it can also cause immense personal suffering.

"Because most antidepressants may worsen Parkinsonian symptoms (eg, sexual dysfunction, excessive sweating, tremor, sleep disturbances or fatigue), the pharmacological treatment of depression may be a challenge," Dr. Kovacs said. "Therefore, a distinct, noninvasive and well-tolerable antidepressive method is needed for treating depression in PD."

rTMS of the DLPFC is a US Food and Drug Administration–approved technique for drug-resistant major depression. Contradictory data on the efficacy of rTMS in Parkinsonian depression led Dr. Kovacs and colleagues to evaluate the antidepressive effects of rTMS over the left DLPFC in a randomized, double-blind, and placebo-controlled manner.

A total of 22 patients (mean ± SD age, 68.5 ± 7.9 years) with idiopathic PD fulfilling Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria for mild to moderate depression participated; 12 were randomly assigned to real rTMS (90% of resting motor threshold, 5 Hz, 600 pulses-a-day for 10 days) over the left DLPFC and 10 to sham rTMS. There were no significant differences between the 2 groups in baseline characteristics. All of the patients finished the study protocol.

 

Few Adverse Effects

Mirroring prior studies, rTMS was safe and well tolerated in the study population. Except for a mild transient headache in 2 patients, "no side effects occurred in the treated group," the investigators report.

"Fulfilling our expectations, we could demonstrate significant improvement in the severity of depression, which either lasted for at least 1 month after treatment ended or even showed a further improvement," Dr. Kovacs told Medscape Medical News.

Comparing the 1-day (short-term) results to baseline, scores on the Beck Depression Inventory (BDI) improved from 9 points to 5 points (median, 44.4% improvement; P < .05) and on the Montgomery-Asberg Depression Rating Scale (MADRS) decreased from 11.5 points to 10 points (13.0% improvement, P < .05).

These improvements were stable or even more pronounced at 30 days, the study authors say; the BDI score remained 5 points, whereas the MADRS score decreased to 8.5 points, a total improvement of 26.1% compared with baseline (P < .05). There were significantly more treatment responders in the real rTMS group (9 patients, 75%) than the sham rTMS group (2 patients, 20%).

Patients in the real rTMS also performed better on the Stroop test in both the short- and long-term (results improved from 78.1% to 90.6%, P < .01). However, results on the Trail-Making tests and the Mini-Mental State Examination did not change markedly after active rTMS.

In the sham rTMS group, none of the neuropsychological tests showed improvement that reached the level of significance.

Eleven of 12 patients in the real rTMS group reported subjective improvement after treatment; "they reported faster movement, cognition, and better sleep," the study authors report. However, several objective scales (ie, visual analog, Hoehn-Yahr, activities of daily living, and Epworth Sleepiness scales) failed to confirm these subjective feelings.

With real rTMS, there was a moderate but not statistically significant improvement on the Unified Parkinson's Disease Rating Scale III motor examination (7.5-point improvement, 31.9%; P = .06), the study authors note. In the sham rTMS group, none of these tests improved significantly.

Dr. Kovacs said further studies are needed to investigate the effects of rTMS on parkinsonian symptoms.

Limitations, Caveats

The study's single-center design and inclusion of only patients with mild to moderate depression are 2 limitations of the study, the study authors note. Because rTMS requires multiple treatment sessions and is unlikely to be available widely, its application might be limited to patients in whom conventional antidepressant therapy is not tolerable, they add.

"It's not a pill, so it is a bit more difficult," added Dr. Fregni.

It is also likely to be an expensive treatment option, Robert Chen, MBBChir, MSc, FRCPC, at the Department of Medicine, Division of Neurology, at the University of Toronto and Toronto Western Research Institute in Ontario, Canada, notes in a commentary published with the study.

"Clearly, further studies are needed before rTMS becomes an established treatment for PD," Dr. Chen concludes. Even if further studies show positive results, he adds, the limitations of rTMS "need to be considered in the adoption of rTMS in routine clinical practice."

Dr. Kovacs was supported by the government-based Bolyai Scholarship of the Hungarian Scientific Academy. Two other study authors were supported by a research grant from the Norwegian Financial Mechanism of European Union. No other financial disclosures were reported by the study team. Dr. Chen received research grants from the Canadian Institutes of Health Research, Michael J. Fox Foundation for Parkinson Research, Dystonia Medical Research Foundation, and Medtronic Inc and honoraria from Allergan, Medtronic, Merz, Novartis, Teva, and from expert testimony. Dr. Fregni has disclosed no relevant financial relationships.

Mov Disord. Published online August 24, 2010.