Effectiveness and Safety of Flumazenil Augmentation During Electroconvulsive Therapy.

INTRODUCTION: Benzodiazepines are considered to negatively affect seizure quality and duration during electroconvulsive therapy (ECT). Several researchers have advocated the use of flumazenil, a competitive benzodiazepine receptor antagonist, for patients treated with benzodiazepines during ECT. However, clinical evidence regarding flumazenil use in ECT remains sparse. The aim of this study is to investigate the effects of flumazenil on seizure duration and adverse effects. METHODS: All patients with depressive disorders, treated with flumazenil during a course of ECT in 2019 in a tertiary hospital, were identified through a retrospective chart review. Seizure duration was recorded before and after flumazenil administration. Effectiveness of ECT was assessed using the Inventory of Depressive Symptomatology and the Bush-Francis Catatonia Rating Scale. Postictal agitation was ascertained by identifying patients who received additional sedatives immediately after ECT or who needed physical restraint. RESULTS: Twenty-six patients were included, receiving a total of 363 treatments, of which 263 were augmented with flumazenil. Flumazenil administration increased electroencephalogram seizure duration on average with 10.5 seconds comparing ECT with or without flumazenil (P = 0.003). In 21.8% of the cases, no increase in seizure duration was observed. Postictal agitation occurred at least once in 34.6% of the patients receiving flumazenil during their course of ECT. CONCLUSION: Our results show that flumazenil increases seizure duration, albeit with limited clinical implications. Noteworthy, the prevalence of postictal agitation is high. When confronted with short seizures, clinicians should therefore deploy other available techniques to lower seizure threshold before considering flumazenil.

How are OCD patients and their families coping with the COVID-19 pandemic? A qualitative study.

Patients with obsessive-compulsive disorder (OCD) are likely to be affected by the COVID-19 crisis since fear of contamination is highly prevalent in this illness and disease reminders are omnipresent during this crisis. The current study aimed to investigate the impact of the pandemic and the lockdown on the mental health, well-being and coping abilities of OCD patients and their families in order to increase our understanding of the underlying mechanisms of the disorder. Twenty-two patients and 13 family members were interviewed one-to-one about their experiences and challenges caused by the pandemic and home-confinement directives. Verbatim transcripts of the interviews were analyzed using inductive thematic analysis. Five overarching themes were identified: (1) changing point of reference: confusion and legitimization of OCD behavior, (2) coping strategies were challenged: too much or too little exposure to obsessional concerns, (3) distress but also relief in some areas, (4) developing a new equilibrium within the family, (5) changes in accessibility and nature of therapy: perils and merits of online treatment. These findings make clear the importance of the accessibility of mental health services during this pandemic through direct patient contacts or in a remote format. In therapy therapists should focus on challenging the changing point of reference, providing practical advice on coping, stimulating to engage in exposure and encouraging patients to seek social support. Furthermore, it is important to involve family members in therapy to support and coach them to be validating, supportive and encouraging, without accommodating to the OCD behaviour.

How are OCD Patients and Family Members Dealing with the Waxing and Waning Pattern of the COVID-19 Pandemic? Results of a Longitudinal Observational Study.

The current study aimed to investigate the impact of the COVID-19 pandemic on the mental health of people with OCD and the degree of family accommodation (FA) by live-in family members across phases of the lockdown measures imposed by the Belgian government. Forty-nine OCD patients and 26 live-in family members participated in the study. We assessed OCD symptom severity and FA of the live-in family members, as well as depressive symptoms, anxiety and stress levels and COVID-19 related psychological distress of patients and family members at four different timepoints: one month after the start of the lockdown (T1), during the gradual relaxation (T2), between the two waves (T3) and during the second wave (T4). Results showed that although COVID-19 related stress increased and decreased in accordance with the waxing and waning pattern of the pandemic, OCD symptoms showed an initial slight increase followed by a decrease at T3 and again at T4. Changes in family members' accommodation of symptoms followed the same course as the OCD symptoms. Furthermore, OCD symptoms correlated with depressive symptoms, anxiety and stress levels and COVID-19 related distress at all timepoints. It is important to involve family members in the treatment of OCD even during a pandemic. Clinicians should also pay attention to symptoms of depression, anxiety and stress during OCD treatment. Further research is necessary to entangle the causal relationship between OCD symptoms, FA and symptoms of depression, anxiety and stress.

Discontinuation of Continuation or Maintenance Electroconvulsive Therapy Caused by the COVID-19 Pandemic: A Naturalistic Study Investigating Relapse in Patients With Major Depressive Disorder.

BACKGROUND: Continuation or maintenance electroconvulsive therapy (C/M-ECT) is recommended to reduce relapse rates of patients with major depressive disorder. During the ongoing COVID-19 pandemic, ECT services have come under pressure or needed to close because of redirected resources and safety reasons. We investigated the impact of C/M-ECT discontinuation on relapse in patients with unipolar depressive disorder in Flanders, Belgium. METHODS: Between March 30 and June 18, 2020, all patients receiving C/M-ECT in 2 ECT centers were included. Continuation or maintenance electroconvulsive therapy was discontinued in 33 patients and continued in 4 patients. Relapse was defined as the need to restart ECT or the need for hospitalization. Depressive symptoms were assessed every 3 weeks using the Patient Health Questionnaire, the Clinical Global Impression Scale, and 2 additional patient-rated questions. RESULTS: Relapse in the discontinuation group was 60.6%. All 4 patients who continued ECT remained remitted. Kaplan-Meier survival analysis showed significantly shorter relapse rates for patients receiving bitemporal and/or frequent C/M-ECT (1- to 2-week intervals). Patients older than 60 years showed longer survival rates. CONCLUSIONS: Our results confirm earlier prospective and retrospective data regarding the efficacy and importance of C/M-ECT as relapse prevention. After treatment discontinuation, close monitoring of early warning signs for relapse is crucial, especially in the first few months. With the COVID-19 pandemic continuing, our data provide an indication of the necessity to ensure adequate care and access to ECT not only for the acutely ill but also for the vulnerable patients who are depending on C/M-ECT.

Is twice daily LF-rTMS a viable treatment option for treatment-resistant OCD? Results from an open-label feasibility study.

Several reports point to the beneficial effects of repetitive transcranial magnetic stimulation (rTMS) in the treatment of resistant obsessive-compulsive disorder (OCD). This study aimed to evaluate the safety and efficacy of rTMS targeting the dmPFC in the treatment of treatment-resistant OCD patients. Twelve patients received 20 sessions of low-frequency (LF) rTMS (1 Hz, 1200 pulses) in a twice daily protocol during 10 weekdays. Y-BOCS and IDS scores modestly but significantly decreased after treatment and at follow-up and HADS anxiety improved at follow-up. LF rTMS may improve OCD, anxiety, and depressive symptoms in treatment-resistant OCD and was a safe and well-tolerated treatment.

Cognitive remediation following electroconvulsive therapy in patients with treatment resistant depression: randomized controlled trail of an intervention for relapse prevention - study protocol.

BACKGROUND: Major depressive episode (MDE) is worldwide one of the most prevalent and disabling mental health conditions. In cases of persistent non-response to treatment, electroconvulsive therapy (ECT) is a safe and effective treatment strategy with high response rates. Unfortunately, longitudinal data show low sustained response rates with 6-month relapse rates as high as 50% using existing relapse prevention strategies. Cognitive side effects of ECT, even though transient, might trigger mechanisms that increase relapse in patients who initially responded to ECT. Among these side effects, reduced cognitive control is an important neurobiological driven vulnerability factor for depression. As such, cognitive control training (CCT) holds promise as a non-pharmacological strategy to improve long-term effects of ECT (i.e., increase remission, and reduce depression relapse). METHOD/DESIGN: Eighty-eight patients aged between 18 and 70 years with MDE who start CCT will be included in this randomized controlled trial (RCT). Following (partial) response to ECT treatment (at least a 25% reduction of clinical symptoms), patients will be randomly assigned to a computer based CCT or active placebo control. A first aim of this RCT is to assess the effects of CCT compared to an active placebo condition on depression symptomatology, cognitive complaints, and quality of life. Secondly, we will monitor patients every 2 weeks for a period of 6 months following CCT/active placebo, allowing the detection of potential relapse of depression. Thirdly, we will assess patient evaluation of the addition of cognitive remediation to ECT using qualitative interview methods (satisfaction, acceptability and appropriateness). Finally, in order to further advance our understanding of the mechanisms underlying effects of CCT, exploratory analyses will be conducted using video footage collected during the CCT/active control phase of the study. DISCUSSION: Cognitive remediation will be performed following response to ECT, and an extensive follow-up period will be employed. Positive findings would not only benefit patients by decreasing relapse, but also by increasing acceptability of ECT, reducing the burden of cognitive side-effects. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov . Study ID: NCT04383509 Trial registration date: 12.05.2020.

Late-life depression: issues for the general practitioner.

Late-life depression (LLD) is both a prevalent and life-threatening disorder, affecting up to 13.3% of the elderly population. LLD can be difficult to identify because patients mainly consult their general practitioner (GP) for somatic complaints. Moreover, patients may be hesitant to express the problem to their GP. Increased vigilance on the part of the GP can only benefit older people with depression. To recognize the risk of LLD, screening tools are provided in addition to treatment options for LLD. This review aims to provide the GP with guidance in recognizing and treating LLD. It tries to connect mainstream etiologies of LLD (e.g., vascular, inflammation, hypothalamo-pituitary-adrenal axis) with risk factors and current therapies. Therefore, we provide a basis to the GP for decision-making when choosing an appropriate therapy for LLD.

Accelerated intermittent theta burst stimulation treatment in medication-resistant major depression: A fast road to remission?

Although accelerated repetitive Transcranial Magnetic Stimulation (rTMS) paradigms and intermittent Theta-burst Stimulation (iTBS) may have the potency to result in superior clinical outcomes in Treatment Resistant Depression (TRD), accelerated iTBS treatment has not yet been studied. In this registered randomized double-blind sham-controlled crossover study, spread over four successive days, 50 TRD patients received 20 iTBS sessions applied to the left dorsolateral prefrontal cortex (DLPFC). The accelerated iTBS treatment procedure was found to be safe and resulted in immediate statistically significant decreases in depressive symptoms regardless of order/type of stimulation (real/sham). While only 28% of the patients showed a 50% reduction of their initial Hamilton Depression Rating Scale score at the end of the two-week procedure, this response rate increased to 38% when assessed two weeks after the end of the sham-controlled iTBS protocol, indicating delayed clinical effects. Importantly, 30% of the responders were considered in clinical remission. We found no demographic predictors for response. Our findings indicate that only four days of accelerated iTBS treatment applied to the left DLPFC in TRD may lead to meaningful clinical responses within two weeks post stimulation.

Self-directedness: an indicator for clinical response to the HF-rTMS treatment in refractory melancholic depression.

Although well-defined predictors of response are still unclear, clinicians refer a variety of depressed patients for a repetitive Transcranial Magnetic Stimulation (rTMS) treatment. It has been suggested that personality features such as Harm Avoidance (HA) and self-directedness (SD) might provide some guidance for a classical antidepressant treatment outcome. However, to date no such research has been performed in rTMS treatment paradigms. In this open study, we wanted to examine whether these temperament and character scores in particular would predict clinical outcome in refractory unipolar depressed patients when a typical high-frequency (HF)-rTMS treatment protocol is applied. Thirty six unipolar right-handed antidepressant-free treatment resistant depressed (TRD) patients, all of the melancholic subtype, received 10 HF-rTMS sessions applied to the left dorsolateral prefrontal cortex (DLPFC). All patients were classified as at least stage III TRD and were assessed with the Temperament and Character Inventory (TCI) before a HF-rTMS treatment. Only the individual scores on SD predicted clinical outcome. No other personality scales were found to be a predictor of this kind of application. Our results suggest that refractory MDD patients who score higher on the character scale SD may be more responsive to the HF-rTMS treatment.