Temporary Interruption of Deep Brain Stimulation for Parkinson's Disease During Outpatient Electroconvulsive Therapy for Major Depression: A Novel Treatment Strategy

This 71-year-old married man was referred by his treating psychiatrist for ECT evaluation in August 2008. The patient, a retired university professor, had been diagnosed with idiopathic PD in 1989. He initially had a good response to L-dopa, but gradually developed a disabling, predominantly right-sided hand tremor. Therefore, a bilateral subthalamic DBS device was installed in 2003. The procedure was well-tolerated, and the clinical response was such that he was able to stop L-dopa medication and return to work. Batteries had to be replaced frequently because of the high voltage parameters (left: 7.0V, PW 90, 185 Hz, 3+1–0-; right: 2.3V, PW 60, 185Hz, 3+2–1-). The rest of his medical history was unremarkable.

The patient had a first major depressive episode in 1972. He was then on and off medication for many years, with limited clinical response. Although his father suffered from bipolar type I disorder and was successfully treated with ECT, the patient himself never experienced a manic episode. He had been treated with right-unilateral ECT in 1996 for a recurrent depression, with good clinical response and minimal side effects. He then had two other successful courses of bilateral ECT in 2000 and 2002, before the DBS surgery. In February 2008, he relapsed into a major depressive episode with anxious ruminations about the future. Over the next few months, he lost about 50 pounds, but never expressed any suicidal ideation. He did not respond to escitalopram, bupropion, and a 1-month course of pramipexole. He was also exhibiting mild executive-function problems that antedated the depressive relapse, probably secondary to his PD. The main DSM-IV diagnosis was major depressive disorder, recurrent and severe. Given the poor response to medication, the patient himself requested another ECT course. After neurological and medical evaluations, it was decided that ECT was indeed the treatment of choice.

With the DBS turned off, the patient's severe disabling tremor would recur within seconds. In that context, it was deemed that stopping the DBS for the complete duration of the ECT course was unacceptable. Therefore, we decided to turn off the DBS generator just before the ECT stimulus, and restart it in the recovery area before the patient regained full consciousness (about 2 minutes of DBS interruption). A modified bifrontal lead placement was chosen to avoid bitemporal placement, which is closer to the electrodes, while maximizing efficacy.¹⁶ He was initially treated as an outpatient at the McLean Hospital in October 2008 with 8 bilateral ECT treatments, 3 times per week. The stimulus was given with a MECTA machine at 0.8mA, PW 1ms, frequency 40Hz, and durations from 1.25 sec to 3.5 sec. The clinical response was adequate, and the patient was maintained on antidepressants.

In March 2010, a depressive relapse required another course of ECT. After discussion with the device manufacturer (Medtronic, Inc.), we decided to set the voltage to 0V just before the ECT stimulus, and adjust it back to the regular settings in the recovery area. This was different from the first ECT course, during which the DBS was simply turned off. Changing the voltage to 0V, as opposed to setting the device at Off, prevents the small theoretical risk that the electrical stimulus could inadvertently turn on the DBS generator during the treatment. With similar bilateral modified bifrontal placement (0.8mA, PW 1ms, frequency 40Hz, and duration up to 4.5 sec), he received 7 treatments, 3 times per week, with almost a complete remission of symptoms. The treatments were then gradually tapered down in frequency, and it was decided to continue maintenance ECT every 4 to 6 weeks. At this point, the patient has received a total of 17 treatments, which is the most reported in conjunction with DBS. There were no complications related to the DBS. The brief interruption of voltage proved to be safe, and the control of his tremor was sustained. The patient elected not to have post-ECT brain imaging; however, the lead position is almost certainly adequate, given that DBS remained effective for the tremor. The mild cognitive impairment that was present before the treatment remained stable.

The need for ECT in patients with DBS devices is likely to go up in the next few years, increasing the need for safety data. Although the safety of this procedure has not been formally established, six cases of ECT in patients with DBS for various pathologies have been reported, and all patients had good clinical outcomes, without any unexpected adverse events. Of note, the impact that potential ECT complications, such as prolonged seizures or repeated stimulations within one session because of inadequate seizures, might have on DBS electrodes has not been documented.¹⁷ On follow-up, involved physicians need to regularly verify stimulation parameters and impedance to ensure the absence of damage creating a short or an open circuit, as described in current consensus statements.¹⁸ Also, it is crucial before proceeding to ECT to make sure that depressive or other neuropsychiatric symptoms are not uniquely secondary to DBS, either in the postoperative period or due to voluntary or accidental changes in stimulation parameters.¹⁸

This patient is the first in whom the DBS system was turned off or put to 0V only for the brief moment of the acute ECT stimulus and restarted immediately after the convulsion. Although all previous cases reported that DBS was stopped for the complete ECT course, there is no clear theoretical rationale for this decision. In PD, the temporary improvement of neurological symptoms with ECT might alleviate the need for continuous DBS, but, clearly, not in all patients, as our case illustrates.¹⁹ In our opinion, there is no additional risk to a short-term interruption of DBS treatment, and there were no complications for this patient despite his high DBS voltage. The strategy of setting the generator at 0V instead of turning it off is theoretically safer, as it prevents undesired activation of the generator. However, this requires a programming device, as opposed to simply turning the DBS off with the patient's own access device. Importantly, the clinical response to both ECT for major depression and bilateral STN DBS for his PD were robust and sustained. Finally, this case provides evidence supporting the potential of safely administering outpatient ECT in a patient with DBS for PD.

In summary, although the safety of ECT in patients with DBS remains to be formally studied, all 6 patients reported on thus far have had good outcomes. The temporary interruption of the DBS device only during the ECT procedure itself might be a safe strategy that minimizes negative impacts on the underlying condition requiring DBS. This strategy could also be more potent in patients with DBS for major depression who might benefit from augmentation with ECT because of incomplete response or breakthrough episodes of depression. This treatment strategy will need further investigation, but it underscores the growing interest in the potential of combining different neurotherapeutic techniques in a single patient. In that context, there is a need to eventually develop guidelines on the use ECT in patients with DBS devices.

Dr. Ducharme, Dr. Flaherty, and Dr. Seiner have no disclosure or conflict of interest related to this topic. Dr. Dougherty's research has been funded by NIMH, NARSAD, TSA, and OCF. He has received honoraria, consultation fees, and/or royalties from Wyeth, Jazz Pharmaceuticals, Bristol-Myers Squibb, Medtronic, Eli Lilly, Northstar, McNeil, Brand Ideas, and Reed Elsevier. He has also participated in research funded by Medtronic, Cyberonics, Eli Lilly, McNeil and Northstar.

Dr. Morales is the inventor on a patent application owned by McLean Hospital that is related to the subject matter of this manuscript, but this application is still pending and is not licensed to any for-profit entity, and Dr. Morales receives no income or revenues attributable to that patent application. Dr. Morales is the PI on a clinical trial agreement that is not yet executed, but is under negotiation with Brainsway, Inc., and McLean Hospital.