Psychiatric, Motor, and Autonomic Effects of Bifrontal ECT in Depressed Parkinson’s Disease Patients

Our study was approved by the University of British Columbia (UBC) Research Ethics Board. Patients receiving ECT at St. Paul’s Hospital in Vancouver, British Columbia, from January 1, 2014, to December 31, 2018, were screened, and included provided they had a neurologist-confirmed diagnosis of idiopathic Parkinson’s disease, had a psychiatrist-confirmed diagnosis of a depressive disorder, and received at least six ECT sessions during the study period. No specific exclusion criteria were applied. Patients were referred for consideration of ECT from neurologists at the UBC Pacific Parkinson’s Research Centre and subsequently referred for the procedure following assessment by a consulting psychiatrist. As our study was deemed minimal risk given its retrospective nature, informed consent was waived in conformance with Tri-Council ethics and institutional review board guidance. All data were anonymized and stored on a single secure, encrypted electronic device.

Our primary outcome was clinical improvement in depressive symptoms, measured by the Clinical Global Impression-Severity (CGI-S) and Improvement (CGI-I) scales (22) and administered retrospectively by the primary treating psychiatrist. Secondary outcomes included changes in motor symptoms, as measured by Part III of the Unified Parkinson’s Disease Rating Scale, Movement Disorders Society revision (MDS-UPDRS) (23), administered as part of routine clinical care by neurologists formally trained in the use of this scale; changes in doses of levodopa and other dopaminergic medications; and autonomic response to ECT, as measured by blood pressure and heart rate readings during treatment sessions.

Response of depressive symptoms to ECT was defined as both a minimum of a 1-point decrease on the CGI-S and a score of 1 or 2 (“very much improved” or “much improved”) on the CGI-I. For motor symptoms, clinically important difference (CID) criteria (24) were applied to changes in the MDS-UPDRS motor score for each patient (minimal change, 3–5 points; moderate, 6–10 points; and large, 11 or more points). For dopaminergic medications, a total levodopa equivalent dose was calculated at baseline and end of treatment for each patient, using the equivalency calculations developed by Tomlinson et al. (25) (see also Table S1 in the online supplement).

ECT treatments were delivered at St. Paul’s Hospital in Vancouver. Written informed consent was obtained for all patients prior to the first treatment. Anticonvulsant and dopaminergic medications were held for 12 hours prior to the procedure. All patients received ECT using a Thymatron IV device. Bifrontal electrode placement was used for all patients throughout the treatment course, per site protocol using bifrontal as the standard initial electrode placement for index ECT. General anesthesia was provided with methohexital (1–1.5 mg/kg) for induction and succinylcholine (1 mg/kg) for neuromuscular blockade. Heart rate and blood pressure monitors were used during all treatments, and these data were systematically recorded.

Baseline demographic and clinical data were collected. Hoehn and Yahr stage (26) was assessed based on the “on” state at baseline. Medications and doses, including levodopa equivalent dose (25), were recorded at baseline and end of treatment. ECT treatment data collected included electrode placement, electrical dose, seizure duration, and completion or noncompletion of ECT course. Clinical outcome data included baseline and posttreatment CGI-S and CGI-I scores, depressive relapse in the first year post-ECT, baseline and posttreatment MDS-UPDRS motor scores, and autonomic data (heart rate and blood pressure measurements) recorded during ECT treatment.

Outcomes were examined as an overall group and within the subgroups of patients who completed a full course of ECT (completers) and those who discontinued ECT before undergoing a full course (noncompleters). Descriptive statistics (median, range) were calculated and reported for continuous demographic and clinical data points. Measures of autonomic response to ECT (blood pressure and heart rate) were reported using mean values and standard deviation, owing to the much larger number of data points and heterogeneity in size of dataset per patient.

Our retrospective study provides the first preliminary clinical evidence, to our knowledge, in support of the feasibility and effectiveness of bifrontal ECT in treating dPD. This placement has evidence for similar efficacy with fewer cognitive side effects versus bitemporal in the general population (14). Indeed, a much lower incidence of delirium was observed in our study (one event in more than 200 treatments) than other reports (11, 27). Postponement of treatments after concussion is emphasized, because the affected patient experienced a concussion 2 weeks prior to treatment. Factors potentially explaining the low incidence of post-ECT delirium include the use of a less invasive placement than conventional, and the fact that our patients were systematically asked to hold the night and morning dose of levodopa before ECT. Our sample included patients with baseline disease from stage 2 to 4, as rated on the Hoehn and Yahr scale. The only patient with stage 4 disease discontinued ECT before completion because of adverse effects, highlighting the potential limitations of this treatment in patients with advanced motor disease.

We observed a 75% response rate of depressive symptoms to ECT, including 83% of patients who completed an ECT course. This rate is comparable to prior observational data on ECT for dPD and to the general adult population (11). This highlights bifrontal placement as potentially useful in dPD. Additionally, the low relapse rate among patients who responded and subsequently received maintenance ECT (20%) suggests a role for long-term treatment as a strategy for relapse prevention.

Among patients with complete data on motor symptoms via the MDS-UPDRS motor subscale, three out of five patients demonstrated clinically significant improvement following ECT, including two with at least moderate improvement. The remaining two patients showed minimal to moderate worsening, to a degree consistent with estimates of typical motor symptom progression in the absence of treatment changes (28).

We also found a decrease in median levodopa equivalent dose among patients who completed a full course of ECT. Interestingly, of the three out of five patients who demonstrated MDS-UPDRS motor improvement, the two who completed a full course of ECT had larger score improvements and concomitant decreases in dopaminergic medication load. This suggests that ECT may lower the necessary dose of dopaminergic agents for some patients. Although medications were possibly decreased due to side effects, the apparent dose-response (levodopa/levodopa equivalent dose decrease only seen in ECT completers) supports the plausibility of a causal link. Of note, the two patients with decreases in both MDS-UPDRS motor and levodopa equivalent dose were the only patients in the sample not taking benzodiazepines, which are potential inhibitors of ECT effectiveness.

Possible mechanisms for the effect of ECT on PD motor symptoms may include enhancement of striatal dopamine release (20–22) or of the permeability of the blood-brain barrier to levodopa (29), the latter potentially related to our finding that ECT decreased dopaminergic medication requirement for some patients. This effect would be clinically useful, given the adverse effects of higher doses dopaminergic agents, including psychosis and impulse control disorders (30). The patients who demonstrated both motor improvement and decrease in levodopa equivalent dose may represent a subset of PD patients with particularly ECT-responsive motor pathology. Further study is necessary to determine whether ECT responsiveness relates to disease subtype or motor symptom pattern. Another potential contributor to the improvement in motor symptoms in our sample is amelioration of the psychomotor retardation commonly seen in depression, which may confound changes in motor symptoms, especially bradykinesia. Differentiating this effect from motor symptom improvement per se will require larger samples and likely component analysis of changes in symptom clusters on the UPDRS-MDS (i.e., bradykinesia versus rigidity) in response to ECT.

Aberrant autonomic responses to ECT may affect efficacy or tolerability. Given the autonomic dysfunction commonly associated with PD, these patients may be vulnerable, highlighting the importance of investigating autonomic response in our study, which was, to our knowledge, the first such attempt in patients with PD. Our data showed relatively typical autonomic responses following ECT stimulus, with gradually less pronounced sympathetic peaks over time (see Figure S1 in the online supplement). Additionally, no severe bradycardic (heart rate <40) or asystolic events were detected. Our data suggest that patients with PD can generally tolerate ECT from an autonomic perspective. The absence of severe bradycardia or asystole is consistent with the safety profile of bifrontal ECT compared with bitemporal (20, 21).

Chief among our study’s limitations are the relatively small sample size, lack of control group, and retrospective, unblinded approach to analysis. Additionally, quantification of the motor effects of ECT was constrained by the incomplete reporting of rating scales in our sample. In addition, we cannot judge the generalizability of our findings to other samples of patients with PD, as this is the first study of its kind examining bifrontal ECT in PD and was conducted at a single site. For these reasons, while we have observed an encouraging rate of response for both depressive and motor symptoms, we cannot make definitive conclusions about the effectiveness of bifrontal ECT for dPD or whether it offers any advantage to other placements based on our data. However, given the limited evidence available on this topic, our data provide support for important and testable hypotheses related to the clinical effectiveness and tolerability of ECT in depressed patients with PD.

Despite growing evidence for ECT’s effectiveness in dPD, concerns about adverse effects and stigma (31) may be limiting uptake. Determination of optimal electrode placement and identification of patients at higher risk for adverse events are important further areas of investigation, which may improve acceptability. More study of autonomic data is necessary to better understand the relationship between autonomic response and both tolerability and efficacy. Ultimately, randomized controlled studies are needed to establish the true efficacy and tolerability of this procedure in dPD, including the comparative performance of different electrode placements, and to investigate associations with autonomic response and neurocognitive effects.