Home-administered transcranial direct current stimulation with asynchronous remote supervision in the treatment of depression: feasibility, tolerability, and clinical effectiveness.

Introduction Background: Depression is an often chronic condition, characterized by wide-ranging physical, cognitive and psychosocial symptoms that can lead to disability, premature mortality or suicide. It affects 350 million people globally, yet up to 30% do not respond to traditional treatment, creating an urgent need for novel non-pharmacological treatments. This open-label naturalistic study assesses the practical feasibility, tolerability, and clinical effectiveness of home-administered transcranial direct current stimulation (tDCS) with asynchronous remote supervision, in the treatment of depression. Method: Over the course of 3 weeks, 40 patients with depression received psychotherapy and half of this group also received daily bi-frontal tDCS stimulation of the dorsolateral prefrontal cortex. These patients received tDCS for 30 min per session with the anode placed over F3 and the cathode over F4, at an intensity of 2 mA for 21 consecutive days. We measured patients' level of depression symptoms at four time points using the Beck Depression Inventory, before treatment and at 1-week intervals throughout the treatment period. We monitored practical feasibility such as daily protocol compliance and tolerability including side effects, with the PlatoScience cloud-based remote supervision platform. Results: Of the 20 patients in the tDCS group, 90% were able to comply with the protocol by not missing more than three of their assigned sessions, and none dropped out of the study. No serious adverse events were reported, with only 14 instances of mild to moderate side effects and two instances of scalp pain rated as severe, out of a total of 420 stimulation sessions. Patients in the tDCS group showed a significantly greater reduction in depression symptoms after 3 weeks of treatment, compared to the treatment as usual (TAU) group [t(57.2) = 2.268, p = 0.027]. The tDCS group also showed greater treatment response (50%) and depression remission rates (75%) compared to the TAU group (5 and 30%, respectively). Discussion Conclusion: These findings provide a possible indication of the clinical effectiveness of home-administered tDCS for the treatment of depression, and its feasibility and tolerability in combination with asynchronous supervision.

A New Treatment Protocol of Combined High-Dose Levothyroxine and Repetitive Transcranial Magnetic Stimulation for the Treatment of Rapid-Cycling Bipolar Spectrum Disorders: A Cohort Evaluation of 55 Patients.

Background: Bipolar spectrum disorders (BSD) are highly disabling, with rapid cycling being treatment resistant. High-dose levothyroxine (HDT) has been reported to be effective. Diagnosis is associated with mutations in thyroid-activating enzymes and cerebral transporter protein carrier. Repetitive transcranial magnetic stimulation (rTMS) has neuroplastic effects. Methods: We report data on 55 severely symptomatic patients with rapid-cycling BSD treated with a combination protocol of HDT and rTMS. Of the patients, 31 patients (56.4%) were female and 40 (72.7%) had at least one additional diagnosis. Results: Patients were evaluated at three monthly intervals after acute treatment. Remission was measured using the Sheehan Disability Scale (SDS). The average number of medications prescribed was 1.8, with 32 patients (58.2%) needing only levothyroxine. The average dose of levothyroxine was 303.7 mcg (50 mcg−1000 mcg). A total of 53 patients were in remission (96.4%), with an average duration of 2.0 years. The SDS scores decreased significantly (Cohen's d = 2.61 (95% C.I. 1.81 to 2.83, p < 0.001). One patient had reversible side effects. A total of 52 (94.3%) patients had Deiodinase 1 and 2 (DiO1/DiO2) or SLCO1C1 protein carrier gene mutations. Conclusion: The data support the safety and acceptability of combined HDT/rTMS. Patients achieved long remissions with substantial improvements in quality of life.

A Different rTMS Protocol for a Different Type of Depression: 20.000 rTMS Pulses for the Treatment of Bipolar Depression Type II.

In this open-label naturalistic study, we assess the feasibility, tolerability, and effectiveness of a repetitive transcranial magnetic stimulation protocol with a reduced total pulse number for treating patients suffering from bipolar disorder type II. All patients received one rTMS treatment session of 1000 pulses for 20 consecutive working days, accumulating to 20.000 rTMS pulses applied over 4 weeks. We measured the patients' symptoms before the start, halfway through, directly after, and one month after treatment. We quantified the depression symptoms using both the Beck depression inventory scale and the symptom checklist-90 depression subscale. Patients showed a significant reduction in depression symptoms directly after treatment and an even further reduction one month after treatment. The remission rates were at 26% halfway through treatment (after the 10th session), 61% directly after treatment (after the 20th session), and increased to 78% at the 1-month follow-up. Importantly, the protocol proved to be feasible and highly tolerable in this patient population, with no adverse effects being reported. Considering these positive results, further research should focus on replicating these findings in larger clinical samples with control groups and longer follow-up periods, while potentially adding maintenance sessions to optimize the treatment effect and stability for bipolar disorder type II patients.

Association between Neuropathic Pain and Depression: Focusing on the Transcranial Magnetic Stimulation As a Promising Treatment Approach.

BACKGROUND: Neuropathic pain (NP) affects approximately 7% of the general population and is often accompanied by depressive symptoms with up to 85% of NP patients are suffering from comorbid depression (CD). The noninvasive neuromodulation technique of transcranial magnetic stimulation (TMS) is an established proven clinically effective nonpharmacological treatment for depression, and considered a highly promising option also for reducing the burden of NP by relieving pain perception and increasing patients' quality of life. In this article, we systematically review the various clinical protocols used in TMS treatments in patients suffering from NP and comorbid depression. SUBJECTS AND METHODS: Using Scopus, Elsevier, and PubMed databases, our keyword search identified 639 articles, of which 22 were selected for detailed analysis based on the inclusion criteria and in consideration of the heterogeneous study design of the majority of small trials. We evaluated the clinical efficacy in NP and comorbid depression, in relation to various TMS protocol parameters including coil type, target brain area, locus of increased evoked motor potential, amplitude of stimulation, duration of session, number of sessions per day/month, as well as inter-session-intervals, number and frequency of trains, and number and frequency of pulses. RESULTS: The most effective TMS protocols for treating comorbid NP and depression, as marked by decreased pain and depression scores proved to entail figure-of-8 coils targeting the primary motor area (M1), and applying at least ten daily rTMS sessions using high frequency stimulation (10-20 Hz) with a sub threshold intensity of 80-90% RMT and a total number of pulses of at least 1500 per session. Performing an additional maintenance phase after the acute treatment phase may strengthen and prolong the therapeutic effects of rTMS. CONCLUSIONS: Our database analysis suggests that a specific combination of TMS parameters is most effective for treating NP and comorbid depression. Although results are promising, the heterogeneity within the literature is such that many underpowered studies contribute rather little to the outcome, as evident by our inclusion / exclusion analysis. Moreover, we see a need for consensus on clinical protocols and inclusion of much larger clinical samples. Furthermore, we conclude that future research should entail advanced TMS procedures with multiple brain region stimulation (sequential or concurrent), and address issues of TMS maintenance and improved coil engineering for targeting deeper structures.

Preliminary Assessment of Pre-Electroconvulsive Therapy Evaluation Practices in European Countries: The Need for Guidelines.

OBJECTIVES: Pre-electroconvulsive therapy (ECT) evaluation is an essential part of ECT preparation, a standard treatment in the psychiatric field. However, no routine pre-ECT evaluation has been published so far. This preliminary study aimed to explore different practices in pre-ECT evaluation across European countries. METHODS: The data were collected as a snowball sample approach using an online survey from September 2019 to April 2020. The final analysis included data from 18 clinics placed in 16 European countries. RESULTS: Regulations on the pre-ECT evaluation were found in 9 countries. All clinics reported doing complete blood count, serum electrolytes, and renal function analysis as a part of regular laboratory testing, alongside with a cardiovascular assessment. Ten clinics reported using psychiatric scales. Six clinics reported doing a cognitive assessment, of which all had regulations on the pre-ECT evaluation. Not one evaluation had the same sets of procedures and diagnostics. CONCLUSIONS: The differences in assessment approaches mirror high variability of the pre-ECT evaluation practice across Europe. Cognitive assessment and objectification of psychiatric symptoms should be a regular part of the pre-ECT evaluation because of the monitoring of the most common adverse effect and observing the clinical response to ECT. Standardization of the pre-ECT evaluation and ECT in general would remove criticisms and opposition to the treatment, make it based on the best of our knowledge, and provide a method respectful of patients' best interests and rights.

Advances in transcranial magnetic stimulation (TMS) and its applications in resistant depression.

Transcranial magnetic stimulation (TMS) is a non-invasive method of brain stimulation that is receiving increasingly attentionTranscranial magnetic stimulation (TMS) is a non-invasive method of brain stimulation that is receiving increasingly attentionfor new clinical applications. Through electromagnetic induction cortical activity can be modulated and therapeuticeffects can be achieved in a variety of psychiatric and neurological conditions. According to the World Health Organization(WHO) depression is the most disabling disease in the world and 350 million people suffer from depression globally. Majordepression is the most common disorder to be treated with TMS and the first mental disorder for which TMS received approvalfrom the US Food and Drug Administration (FDA). We here introduce the basic principles of TMS, discuss the latestdata on safety and side effects, and present various TMS treatment protocols as well as treatment response predictors inmajor depressive disorder.