Vagus Nerve Stimulation Modulates Inflammation in Treatment-Resistant Depression Patients: A Pilot Study.

Vagal neurostimulation (VNS) is used for the treatment of epilepsy and major medical-refractory depression. VNS has neuropsychiatric functions and systemic anti-inflammatory activity. The objective of this study is to measure the clinical efficacy and impact of VNS modulation in depressive patients. Six patients with refractory depression were enrolled. Depression symptoms were assessed with the Montgomery-Asberg Depression Rating, and anxiety symptoms with the Hamilton Anxiety Rating Scale. Plasmas were harvested prospectively before the implantation of VNS (baseline) and up to 4 years or more after continuous therapy. Forty soluble molecules were measured in the plasma by multiplex assays. Following VNS, the reduction in the mean depression severity score was 59.9% and the response rate was 87%. Anxiety levels were also greatly reduced. IL-7, CXCL8, CCL2, CCL13, CCL17, CCL22, Flt-1 and VEGFc levels were significantly lowered, whereas bFGF levels were increased (p values ranging from 0.004 to 0.02). This exploratory study is the first to focus on the long-term efficacy of VNS and its consequences on inflammatory biomarkers. VNS may modulate inflammation via an increase in blood-brain barrier integrity and a reduction in inflammatory cell recruitment. This opens the door to new pathways involved in the treatment of refractory depression.

Evaluating real-world effectiveness of accelerated transcranial magnetic stimulation for treatment-resistant depression in a tertiary referral center based in Quebec, Canada.

OBJECTIVE: To assess the effectiveness of accelerated transcranial magnetic stimulation (TMS) for treatment-resistant depression (TRD) in a tertiary referral center in Quebec, Canada, focusing on a real-world clinical setting. METHODS: We reviewed the data of 247 TRD patients treated between January 2012 and May 2022 who received accelerated TMS. Participants were adults diagnosed with unipolar or bipolar depression, resistant to at least two antidepressant trials, and assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Significant symptom reduction was found in the completer sample (N = 147), with 46.3 % of patients meeting post-treatment response criteria and 36.1 % achieving remission. Baseline severity of depression, age, and the number of antidepressant trials were key predictors of treatment outcomes. Patients who did not complete treatment had generally more severe depressive and anxious symptoms and greater treatment resistance. No significant differences in response rates were observed across different TMS coils. CONCLUSION: The study demonstrated the effectiveness and tolerability of accelerated TMS for TRD in a real-world clinical setting.

Listening to Cancer Patients' Narratives During Residency: A Pilot Study on a Communication Skills' Workshop Involving Patients-Partners.

The field of cancer care still lacks best practices in communication. Few postgraduate training programs offer formal training to develop such skills. The patient partnership has been used in medical education to increase the sensitivity of the subjective experiences of patients. In our Canadian center, residents and patient-partners participated in an educational workshop on communication focusing on patient's narrative. The aim of this pilot qualitative study was to explore the experiences of participants in the workshop. Using theoretical sampling, we recruited 6 residents and 6 patient-partners. Semi-structured interviews were conducted and transcribed. A thematic analysis was performed. From analysis, 4 themes emerged: (1) lack of communication skills training; (2) barriers to effective communication in cancer care; (3) the empathy of patient-partners towards the communication challenges faced by residents; and (4) the participants' reactions to the workshop. Based on our findings, our communication skills workshop centered on narrative medicine and involving patient-partners appears feasible. Future research could study its pedagogical value and the optimal learning environment required.

Intravenous ketamine for treatment-resistant depression patients who have failed to respond to transcranial magnetic stimulation: A case series.

BACKGROUND: For individuals with treatment-resistant depression (TRD), transcranial magnetic stimulation (TMS) has become a well-established approach. In the past decade, intravenous (IV) racemic ketamine has also emerged as a potential treatment for TRD. Currently, little data is available on the clinical effects of IV racemic ketamine in TRD patients who experienced TMS-failure. METHODS: Twenty-one (21) TRD patients who had failed to respond to a standard course of high-frequency left-dorsolateral prefrontal cortex TMS were subsequently scheduled to received IV racemic ketamine infusions. The IV racemic ketamine protocol consisted of 0,5 mg/kg infusions over 60 min, 3 times a week over 2 weeks. RESULTS: Treatment was safe with minimal side-effects. Mean baseline MADRS score was 27.6 ± 6.4 (moderate depression), decreasing down to 18.6 ± 8.9 (mild depression) post-treatment. Mean percent improvement was 34.5 % ± 21.1 from baseline to post-treatment. Paired sample t-test showed significant MADRS score decrease pre- to post-treatment [t(20) = 7.212, p < .001]. Overall, four (4) patients (19.0 %) responded and two (2) of those achieved remission (9.5 %). LIMITATIONS: Limitations of this case series include its retrospective and uncontrolled open-label nature, the lack of self-rating and standardized adverse events questionnaires, as well as follow-ups beyond the immediate treatment period. CONCLUSIONS: Novel ways to increase the clinical effects of ketamine are being explored. We discuss potential combination approaches of ketamine with other modalities to augment its effects. Given the global burden of TRD, novel approaches are needed to curb the current mental health epidemic around the world.

Improving Palliative Care and Medical Assistance in Dying Practice in Canada: How Patients-Partners Could Contribute to Continuing Medical Education.

Medical Assistance in Dying (MAiD) is still considered an evolving practice in Canada. Practitioners are facing the challenge of staying up to date and hence need efficient continuing medical education (CME). A patient-partner has been recently invited as a keynote speaker to CME activities in Canada to share her perspectives and views about patient engagement in palliative care and MAiD practice, calling for compassion. To our knowledge, few data exist on patient-partners' contribution to CME on these topics. Based on that experience, we discuss different issues on patient engagement's contribution in such CME events and call for further research.

Transcranial magnetic stimulation and intravenous ketamine combination therapy for treatment-resistant bipolar depression: A case report.

About a third of patients suffering from major depression develop treatment-resistant depression (TRD). Although repetitive transcranial magnetic stimulation (rTMS) and intravenous ketamine have proven effective for the management of TRD, many patients remain refractory to treatment. We present the case of a patient suffering from bipolar TRD. The patient was referred to us after failure to respond to first-and second-line pharmacotherapy and psychotherapy. After minimal response to both rTMS and ketamine alone, we attempted a combination rTMS and ketamine protocol, which led to complete and sustained remission. Various comparable and complimentary mechanisms of antidepressant action of ketamine and rTMS are discussed, which support further study of this combination therapy. Future research should focus on the feasibility, tolerability, and efficacy of this novel approach.

Learning about psychiatric aspects of medical assistance in dying: a pilot survey of self-perceived educational needs among assessors in a Canadian academic hospital.

BACKGROUND: Medical assistance in dying (MAiD) was legalized in Canada in 2016, although it has been accessible as an end-of-life option in the province of Quebec since 2015. Before its implementation in clinical settings, few physicians had received formal training on requests assessments. New data indicate MAiD requesters have high rates of psychiatric comorbidities. Hence, assessment and management of psychiatric and psychosocial issues among MAiD requesters are important competencies to develop for assessors, although few training programs address them. The aim of our study was to explore physicians' self-perceived educational needs on psychiatric aspects related to MAiD in the province of Quebec. METHODS: We conducted a cross-sectional online survey and used a non-probability sampling design in one academic tertiary care center. A descriptive analysis was performed, and responders were compared on different variables. RESULTS: From twenty-five physician assessors, nineteen responded anonymously to an online survey (n=19). The findings of our pilot study revealed that participants felt highly competent in most psychiatric aspects at end-of-life and related to MAiD practice, except for psychotherapy and psychopharmacology as well as depression identification. Most indicated strong interest in further training. No statistical differences were found among responders regarding previous experience or training in palliative care. CONCLUSIONS: Based on our study, MAiD assessors reported high level of competency in managing psychiatric issues among requesters, but that they also expressed a strong desire for additional education.

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series.

Intermittent theta burst stimulation (iTBS) using 600 pulses is an effective and FDA-cleared transcranial magnetic stimulation (TMS) protocol for major depressive disorder (MDD). Prolonged iTBS (piTBS) using 1,800 pulses could increase the effectiveness of TMS for MDD, but its real-world effectiveness is still debated. We assessed the safety, tolerability, and preliminary effectiveness of a 3x daily piTBS 1,800 pulses protocol delivered over 2 weeks in 27 participants. Only four participants (18.2%) achieved response, two of them achieving remission (9.1%). Five participants (18.5%) experienced tolerability issues. Future studies should focus on the neurophysiological effects of TBS protocols to determine optimal parameters.

Allostatic load as a predictor of response to repetitive transcranial magnetic stimulation in treatment resistant depression: Research protocol and hypotheses.

Treatment resistant depression is challenging because patients who fail their initial treatments often do not respond to subsequent trials and their course of illness is frequently marked by chronic depression. Repetitive transcranial magnetic stimulation (rTMS) is a well-established treatment alternative, but there are several limitations that decreases accessibility. Identifying biomarkers that can help clinicians to reliably predict response to rTMS is therefore necessary. Allostatic load (AL), which represents the 'wear and tear' on the body and brain which accumulates as an individual is exposed to chronic stress could be an interesting staging model for TRD and help predict rTMS treatment response. We propose an open study which aims to test whether patients with a lower pre-treatment AL will have a stronger antidepressant response to 4 week-rTMS treatment. We will also assess the relation between healthy lifestyle behaviors, AL, and rTMS treatment response. Blood samples for AL parameters will be collected before the treatment. The AL indices will summarize neuroendocrine (cortisol, Dehydroepiandrosterone), immune (CRP, fibrinogen, ferritin), metabolic (glycosylated hemoglobin, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, uric acid, body mass index, waist circumference), and cardiovascular (heart rate, systolic and diastolic blood pressure) functioning. Mood assessment (Montgomery-Åsberg Depression Rating Scale and Inventory of Depressive symptomatology) will be measured before the treatment and at two-week intervals up to 4 weeks. With the help of different lifestyle questionnaires, a healthy lifestyle index (i.e., a single score based on lifestyle factors) will be created. We will use linear and logistic regressions to assess AL in relation to changes in mood score. Hierarchical regression will be done in order to assess the association between AL, healthy lifestyle index and mood score. Long-lasting and unsuccessful antidepressant trials may increase the chance of not responding to future trials of antidepressants and it can therefore increase treatment resistance. It is essential to identify reliable biomarkers that can predict treatment responses.

"I Want to Help Others Like Me": A Pilot Qualitative Study on Patients' Participation in a Screening for Distress Program.

Screening for distress was implemented in our academic hospital with the engagement of patients as partners. Little is known about how they appreciate such participation. This pilot qualitative study aimed to explore their experience. Six participants completed a semi-structured interview, which was transcribed verbatim. Thematic analysis was performed on the transcripts. Four themes emerged: "opinions about their participation", "working with others", "role of patient partners", and "barriers encountered". Mean global satisfaction reported on a Likert scale reached 8.92 over 10. Our preliminary findings suggest that patients-as-partners appreciated their participation, and also identified barriers that should be explored in future quality improvement (QI) projects.

Optimized repetitive transcranial magnetic stimulation techniques for the treatment of major depression: A proof of concept study.

Although effective in major depressive disorder (MDD), repetitive transcranial magnetic stimulation (rTMS) is costly and complex, limiting accessibility. To address this, we tested the feasibility of novel rTMS techniques with cost-saving opportunities, such as an open-room setting, large non-focal parabolic coils, and custom-built coil arms. We employed a low-frequency (LF) 1 Hz stimulation protocol (360 pulses per session), delivered on the most affordable FDA-approved device. MDD participants received an initial accelerated rTMS course (arTMS) of 6 sessions/day over 5 days (30 total), followed by a tapering course of daily sessions (up to 25) to decrease the odds of relapse. The self-reported Beck Depression Inventory II (BDI-II) was used to measure severity of depression. Forty-eight (48) patients completed the arTMS course. No serious adverse events occurred, and all patients reported manageable pain levels. Response and remission rates were 35.4% and 27.1% on the BDI-II, respectively, at the end of the tapering course. Repeated measures ANOVA showed significant changes of BDI-II scores over time. Even though our protocol will require further improvements, some of the concepts we introduced here could help guide the design of future trials aiming at increasing accessibility to rTMS.

Vagus Nerve Stimulation for Treatment-Resistant Depression: a Case Series of Clinical Symptoms Associated with the End of Service Period.

BACKGROUND: This work describes the clinical symptoms associated with end of service (EOS) of the batteries of vagus nerve stimulation (VNS) generators in treatment-resistant depression (TRD). Because neurostimulator software may not provide reliable information on battery depletion, careful monitoring of clinical symptoms during the EOS period is an important concern in the follow-up of TRD patients treated with VNS therapy. METHODS: Twenty-six (26) patients were implanted and followed at the Centre Hospitalier de l'Université de Montréal. Fourteen (14) patients required battery replacement and we retrieved chart data up to 3 months before generator battery replacement. RESULTS: Our study demonstrated there might be a decrease or increase in VNS associated physical side effects, and possibly an increase in depressive symptoms during EOS. LIMITATIONS: Our observations are limited by the retrospective nature of this small case series, and larger prospective studies evaluating both VNS side effects and depressive symptoms are therefore needed to further validate those findings. CONCLUSION: Our study is the first to examine clinical symptoms associated with EOS of the batteries of VNS in TRD.

Electrocardiogram Corrected Q-T Interval Predicts Response to Vagus Nerve Stimulation in Depression.

INTRODUCTION: Recent studies have revealed a possible link between heart rate variability (HRV) and major depressive disorder (MDD), with decreased HRV in MDD compared with healthy subjects. Corrected Q-T interval (QTc) has been suggested to represent an indirect estimate of HRV, as QTc length is inversely correlated to parasympathetic activity in healthy subjects. This retrospective study assessed the ability of QTc length in predicting response to vagus nerve stimulation (VNS) treatment in refractory depression. METHODS: We measured QTc length in 19 patients suffering from refractory depression, selected to be implanted with VNS. Correlations were calculated between baseline QTc (preimplantation) and long-term mood response. RESULTS: Nineteen patients selected for VNS surgery were included in the study. Baseline 28-item Hamilton Depression Rating Scale scores were 28.5 ± 6.8 and decreased to 15.1 ± 9.5 at 12 months and 12.4 ± 10.4 at 24 months post-VNS. Among the 19 patients, 53% (10) were responders and 26% (5) were in remission at 12 months. Pretreatment QTc averaged 425.5 ± 22.0. Patients with longer baseline QTc displayed larger improvement, with a significant correlation between mood and QTc values after 12 months (r(18) = -0.526, P = 0.02) and also after 24 months of VNS therapy (r(17) = -0.573, P = 0.016). CONCLUSIONS: The presented analysis showed that increased QTc in patients with MDD might be used as a baseline biomarker for depressive episodes that might respond preferentially to VNS. The link between cardiovagal activity in depression and response to VNS treatment requires further investigation in larger cohorts and randomized controlled trials.