1. Response Without Remission with Right Unilateral Ultrabrief Pulse ECT: Switch to Brief Pulse Unilateral ECT Can be Effective. A Report of Two Cases. Holly D. Dornan, MD, FRCPC* and Lisa McMurray, MD, FRCPC* *University of Ottawa, Royal Ottawa Mental Health Centre, Department of Geriatric Psychiatry, Ottawa, Ontario, Canada Objective: To examine a clinical strategy in the management of partial responders to right unilateral ultrabrief pulse ECT. Background: Electroconvulsive therapy (ECT) is one of the most effective treatments in psychiatry. New research involving different electrode placements and pulse widths has allowed us to be more precise in giving effective ECT while minimizing cognitive side effects. However, controversy exists in the ECT community over the preferred technique. Presently, there are relatively few randomized controlled trials to guide practitioners in their choices. 1 A landmark randomized controlled trial published in 2008 by Sackeim et al. demonstrated that right unilateral ultrabrief pulse (RUL-UB) was equally effective and had better cognitive outcomes than right unilateral brief pulse (RUL-B) and bilateral brief pulse ECT. 2 Consequently, many ECT practitioners are choosing RUL-UB as their electrode placement and pulse width of choice. However, if these parameters are not effective or only yield a partial response for an individual patient, what would be a reasonable next step? Method: We describe two cases of geriatric patients with major depressive disorder who achieved a response, but not remission with a course of right unilateral ultrabrief pulse (RUL-UB) ECT, as evidenced by a plateau in the depression scores (measured using the Montgomery-Åsberg Depression Rating Scale (MADRS)) after 10 and 12 treatments of RUL-UB ECT Figure 1. Montgomery-Asberg Depression Rating Scale (MADRS) scores for patient in Case 1. Figure 2. Montgomery-Asberg Depression Rating Scale (MADRS) scores for patient in Case 2. Ultrabrief Pulse width (0.3 ms) Brief Pulse width (1.0 ms) Case #1. 66 year old woman admitted to a specialized Geriatric Psychiatry inpatient unit with a diagnosis of major depressive disorder, recurrent, severe with psychotic features. Psychiatric medications included escitalopram 10 mg daily, quetiapine 25 mg at bedtime and trazodone 50 mg at bedtime. Three years prior to her admission she was treated for an episode of psychotic depression with 24 treatments of bilateral brief pulse width ECT. Following the 24 ECT treatments she did achieve remission, however she also experienced a profound subjective loss of autobiographical memory, which she described as being unable to recall a two year period of her life. Although she had concerns regarding the cognitive side effects of ECT, she agreed to a course of RUL-UB ECT in order to minimize the risk of memory impairment. A Montgomery-Åsberg Depression Rating Scale (MADRS) was used to monitor her response. Prior to the initiation of ECT her score was 50. Her Montreal Cognitive Assessment (MoCA) score prior to ECT was 28/30. She was initially treated with a series of ten treatments of RUL-UB ECT at a frequency of three times per week. A titration was performed using the MECTA spECTrum 5000 Q device and threshold was established at the following settings: pulse width 0.3 msec, duration 2 seconds, frequency 20 Hz and amplitude of 800 mA. Her subsequent treatments were administered at six times threshold. By her second week of ECT, her MADRS score had declined from 50 to 39. However, after this initial improvement, her MADRS scores remained at a plateau for the next two weeks (see Figure 1). Case 1. (con’t) After ten treatments a decision was made to switch her to right unilateral brief pulse width (1.0 msec) ECT. A new titration was performed and she received a stimulus dose at six times seizure threshold. Of note, the duration of seizure activity shortened with the change to brief pulse width, ranging from 18 to 54 seconds of EEG seizure activity. Inadequate duration of EEG seizure activity (<25 seconds) occurred on 2 out of the 7 RUL-B treatments. Following the switch, her MADRS scores began to decline steadily and reached a score of 1 (remission regarded as ≤6) after 8 treatments of RUL-B ECT (see Figure 1.) Her remission was sustained and she was discharged home. Her MoCA score following the completion of ECT was 29/30. She did not experience any subjective or objective memory loss during the course of the ECT. Case #2. The patient is a 74 year old male admitted to a specialized Geriatric Psychiatry inpatient unit with an eight month history of a major depressive episode and a diagnosis of major depressive disorder, recurrent, severe. This was his third lifetime episode of depression. He had previously failed five medication trials with antidepressants due to lack of efficacy (paroxetine, mirtazapine and venlafaxine) or intolerability (duloxetine and nortriptyline). He had received only two ECT treatments during a depressive episode over 20 years ago and had never received a full course of ECT prior to his current hospitalization. His MoCA was 27/30 and his MADRS score was 28 prior to the initiation of ECT. He consented to a course of RUL-UB ECT in order to minimize the risk of cognitive impairment. During the course of ECT he was taking venlafaxine XR 225 mg daily, quetiapine XR 100 mg at supper and lorazepam 0.5 mg in the morning and 1 mg at bedtime. He initially received a series of twelve treatments, administered three times per week, using an ultrabrief pulse width of 0.3 msec. A successful titration was performed and threshold was determined at the following parameters: pulse width 0.3 msec, duration 4 seconds, frequency 20 Hz and amplitude 800 mA. For subsequent treatments he received an electrical stimulus at six times seizure threshold. Clinically, he did show a response when ECT was started, however reached a plateau in his MADRS after the first five treatments (see Figure 2). After twelve treatments with RUL-UB, he continued to report a distressing level of anxiety and amotivation. A decision was made with the patient to change the treatment pulse width to right unilateral brief pulse (1.0 msec). He received an additional six treatments of RUL-B. Maximum settings on the machine were used as a result of his previous high threshold and short seizure duration. Immediately following the switch his scores resumed a downward trend and he reached remission with a MADRS score of 3 after five treatments with the brief pulse width (see Figure 2). His anxiety and dysphoria had completely resolved. His MoCA score after the completion of ECT was 28/30 and he denied any subjective memory impairment. Patients requiring ECT Non-urgent or significant concern of cognitive effects RUL-UB Non-urgent, but longer course undesirable RUL-B Urgent need for Rapid response Bitemporal If no remission Discussion: Some patients will only have a partial response to a particular form of ECT and may require a change in ECT technique in order to achieve complete remission. Numerous guidelines suggest a modification to the ECT technique if there is no significant clinical response after 6-10 treatments, including increasing the stimulus intensity and switching from RUL to bilateral or bifrontal placement. 4-6 These guidelines are not specific to patients who have failed RUL-UB ECT and do not comment on whether such patients could be rescued with a change to RUL-B. In addition, little guidance exists surrounding the decision to proceed with a switch in patients who have a partial response without remission. There is emerging evidence in the literature that RUL-UB may not be as effective as RUL-B. A recently published, prospective, double-blind, randomized trial comparing RUL-B and RUL-UB demonstrated that there was a statistically significant difference in the remission rates between the group receiving RUL-B and the group receiving RUL-UB among completers of the course of ECT (remission rates 68.4% and 49.0%, respectively). 7 In addition, the two groups were equivalent in terms of cognitive side effects. Interestingly, there was no statistically significant difference between the two groups in 50% response rate, defined as a reduction in MADRS score of at least 50% from baseline. These findings correspond to our observations that RUL-UB is equally effective in producing a response, but not remission. Discussion (con’t) In the two cases presented above, a switch to RUL-B was robustly and rapidly effective for both patients. A switch to bilateral ECT was unnecessary, therefore allowing both patients to achieve complete remission while preserving the cognitive advantages of the right unilateral electrode placement. According to our results, increasing the pulse width to a standard brief pulse is a feasible and practical management option that is effective and preserves cognitive function. We propose that this strategy can be considered an interim step before switching to a bilateral placement. We propose that an evidenced-based algorithm approach applied to an initial series of acute ECT could also lead to better patient outcomes and clinical care. For example, a patient with major depressive disorder in a non-urgent situation could be started on RUL-UB ECT to minimize cognitive toxicity. If the patient fails to improve or reaches a plateau, our cases illustrate that a switch to RUL-B ECT may allow the patient to achieve remission while still preserving the cognitive benefits of unilateral electrode placement. When a longer series of ECT is undesirable but the situation is not emergent,, RUL-B could be chosen as the initial electrode placement. Bilateral ECT would remain the treatment of choice when an urgent response is needed. (see below). This case series adds to an emerging literature surrounding the decreased efficacy of RUL-UB ECT. 3,7,8,9 This is of potential concern given the fact that RUL-UB is being used frequently and has even become a default form of ECT in some centres. Consequences of giving a less effective form of ECT include the increased burden of inadequately treated psychiatric illness, the elevated risk of serious medical complications associated with added treatments, as well as an increased use of resources and decreased cost effectiveness. Additional research regarding the effectiveness of RUL-UB is required in order to make more definitive recommendations to ECT practitioners. However, if personalized algorithms are utilized, there is a reduced risk that patients would fail to achieve an adequate remission. References: 1. Loo CK, Katalinic N, Martin D, et al. A review of ultrabrief pulse width electroconvulsive therapy. Ther Adv Chronic Dis. 2012;3(2):69–85. 2. Sackeim HA, Prudic J, Nobler MS, et al. Effects of pulse width and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy. Brain Stimulat.2008;1:71–83. 3. Loo CK, Sainsbury K, Sheehan P, et al. A comparison of RUL ultrabrief pulse (0.3 ms) ECT and standard RUL ECT. Int J Neuropsychopharmacol. 2008;11:883–890. 4. Kennedy SH, Lam RW, Parikh SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. IV. Neurostimulation therapies. J Affect Disord. 2009;117: S44–S53. 5. American Psychiatric Association (2001) The Practice of Electroconvulsive Therapy: Recommendations for Treatment, Training, and Privileging. 2nd edition. Washington, DC: American Psychiatric Publishing. 6. British Columbia Ministry of Health Services (2002). Electroconvulsive Therapy: Guidelines for Health Authorities in British Columbia. 8. Spaans HP, Verwijk E, Comijs HC, et al. Efficacy and Cognitive Side Effects After Brief Pulse and Ultrabrief Pulse Right Unilateral Electroconvulsive Therapy for Major Depression: A Randomized, Double- Blind, Controlled Study. J Clin Psychiatry. 2013;74(11):e1029–e1036. 9. McCormick LM, Brumm MC, Benede AK, et al. Relative Ineffectiveness of Ultrabrief Right Unilateral Versus Bilateral Electroconvulsive Therapy in Depression. J ECT. 2009;25:238-242. 11. Loo CK, Garfield JBB, Katalinic N, et al. Speed of response in ultrabrief and brief pulse width right unilateral ECT. Int J Neuropsychopharmacol. 2013;16:755–761.