Treating depression at home with transcranial direct current stimulation: a feasibility study.

Introduction: Treating major depressive disorder (MDD) with transcranial direct current stimulation (tDCS) devices at home has various logistic advantages compared to tDCS treatment in the clinic. However, preliminary (controlled) studies showed side effects such as skin lesions and difficulties in the implementation of home-based tDCS. Thus, more data are needed regarding the feasibility and possible disadvantages of home-based tDCS. Methods: Ten outpatients (23-69 years) with an acute depressive episode were included for this one-arm feasibility study testing home-based tDCS. All patients self-administered prefrontal tDCS (2 mA, 20 min, anodal left, cathodal right) at home on 30 consecutive working days supported by video consultations. Correct implementation of the home-based treatment was analyzed with tDCS recordings. Feasibility was examined by treatment compliance. For additional analyses of effectiveness, three depression scores were used: Hamilton depression rating scale (HDRS-21), Major Depression Inventory (MDI), and the subscale depression of the Depression-Anxiety-Stress Scale (DASS). Furthermore, usability was measured with the user experience questionnaire (UEQ). Tolerability was analyzed by the number of reported adverse events (AEs). Results: Eight patients did not stick to the protocol. AEs were minimal. Four patients responded to the home treatment according to the MDI. Usability was judged positive by the patients. Conclusions: Regular video consultations or other safety concepts are recommended regardless of the number of video sessions actually conducted. Home-based tDCS seems to be safe and handy in our feasibility study, warranting further investigation.

Effectiveness of Repetitive Transcranial Magnetic Stimulation in the Treatment of Depression in the Elderly: A Retrospective Natural Analysis.

INTRODUCTION: Depression in the elderly is an understudied condition. Psychopharmacological and psychotherapeutic approaches suffer from specific difficulties with this patient group. Brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) offer a therapeutic alternative. rTMS remains understudied in this age group when compared with younger patients. METHODS: A cohort of 505 patients with depression was analyzed in retrospect concerning their response to rTMS treatment. A total of 15.5% were 60 years old or older, defined as the elderly group of depressed patients. The majority of these were treated with high-frequency protocols over the left dorsolateral prefrontal cortex (DLPFC). For group comparisons, we used Student t-tests or chi-square-tests, depending on the scales of measurement. As measures for effect size, we used Cohen's d for the relative and absolute change in the HDRS total score. RESULTS: Groups did not differ significantly with respect to baseline depression severity or treatment parameters. In the group of elderly patients, a higher number of females were present. Groups did not differ significantly with respect to treatment efficacy, as indicated by the absolute and relative changes in the HDRS-21 sum score. Elderly patients tended to take higher numbers of mood stabilizers. Elderly patients showed a significantly superior reduction for the item "appetite" and a superior reduction tending towards significance for the item "work and interests". CONCLUSIONS: Antidepressant rTMS treatment showed comparable efficacy for patients above 60 years to that in younger patients. Differences between the age groups concerning amelioration of distinct HDRS single items deserve further investigation.

Cognitive Behavioral Group Therapy for Chronic Tinnitus in a German Tertiary Clinical Real-World Setting.

Cognitive behavioral therapy (CBT) was shown to be effective in reducing tinnitus-related distress in numerous controlled trials. Real-world data from tinnitus treatment centers are an important addition to controlled trials for demonstrating the ecological validity of the results from the randomized controlled trials. Thus, we provided the real-world data of 52 patients participating in CBT group therapies during the time period from 2010 to 2019. The groups consisted of five to eight patients with typical CBT content such as counseling, relaxation, cognitive restructuring, attention training, etc. applied through 10-12 weekly sessions. The mini tinnitus questionnaire, different tinnitus numeric rating scales and the clinical global impression were assessed in a standardized way and were analyzed retrospectively. All outcome variables showed clinically relevant changes from before to after the group therapy, which were still evident in the follow-up visit after three months. Amelioration of distress was correlated to all numeric rating scales, including tinnitus loudness but not annoyance. The observed positive effects were in a similar range as effects of controlled and uncontrolled studies. Somewhat unexpected was the observed reduction in loudness, which was associated with distress and the missing association of changes in distress with annoyance as it is generally assumed that standard CBT concepts reduce annoyance and distress, but not tinnitus loudness. Apart from confirming the therapeutic effectiveness of CBT in real-world settings, our results highlight the need for a clear definition/operationalization of outcome measures when investigating psychological interventions of tinnitus.

Activate & fire: a feasibility study in combining acoustic stimulation and continuous theta burst stimulation in chronic tinnitus.

BACKGROUND: Low frequency repetitive transcranial magnetic stimulation (rTMS) is commonly used to inhibit pathological hyperactivity of the auditory cortex in tinnitus. Novel and supposedly superior and faster inhibitory protocols such as continuous theta burst stimulation (cTBS) were examined as well, but so far there is not sufficient evidence for a treatment application in chronic tinnitus. rTMS effects in general are dependent on the brain state immediate before stimulation. This feasibility study was designed based on the concept to shift the pathological intrinsic brain state of tinnitus patients via acoustic stimulation ("activate") and induce inhibitory effects via cTBS ("fire"). METHODS: Seven tinnitus patients with response in residual inhibition received 10 consecutive daily sessions of a combinatory treatment comprised of 3-minute acoustic stimulation with white noise followed by 600 pulses of cTBS over the left temporo-parietal cortex (activate & fire). A control group of 5 patients was treated parallel to the activate & fire data collection with 10 sessions á 3000 pulses of 1 Hz rTMS over the left temporo-parietal cortex. RESULTS: The activate & fire protocol was well tolerated except in one patient with tinnitus loudness increase. This patient was excluded from analyses. No statistical superiority of the activate & fire treatment approach in alleviating tinnitus-related symptoms was evident. Power calculations showed an effect size of 0.706 and a needed sample size of 66 for statistical significant group differences. On a descriptive level the activate & fire group demonstrated a stronger decrease in tinnitus-related symptoms. CONCLUSION: The present feasibility study showed that combining acoustic stimulation with magnetic brain stimulation may be well-tolerable in the majority of patients and represents a promising treatment approach for tinnitus by hypothetically alter the intrinsic state prior to brain stimulation.

One way or another: Treatment effects of 1 Hz rTMS using different current directions in a small sample of tinnitus patients.

INTRODUCTION: So far studies on the efficacy of repetitive transcranial magnetic stimulation (rTMS) as a treatment for tinnitus are inconclusive. Two large scale placebo-controlled randomized clinical trials (RCT) examined the efficacy of low frequency temporal cortex rTMS and report different findings. As the used TMS devices differ in their used primary current direction by default, this technical parameter was speculated as a potential reason for the observed incongruences in tinnitus-related outcomes. The aim of the present pilot study was to investigate the treatment effect of 1 Hz rTMS using two different current flows. MATERIALS AND METHODS: Nine tinnitus patients were treated in two different groups each comprised of 10 treatment sessions á 3000 biphasic pulses of 1 Hz rTMS applied over the left temporo-parietal cortex using either an anterior-posterior to posterior-anterior (AP-PA) or posterior-anterior to anterior-posterior (PA-AP) induced current flow. RESULTS: 1 Hz rTMS with a primary posterior-anterior to anterior-posterior (PA-AP) current flow caused a superior reduction in tinnitus-related symptoms, particularly tinnitus unpleasantness, loudness and tinnitus-related distress. CONCLUSIONS: The present pilot study demonstrated that the technical TMS parameter current direction might be essential for the efficacy of rTMS as a treatment for tinnitus. Systematic investigations of technical TMS parameters like current direction in larger samples of tinnitus patients are highly needed.

Low Sleep Satisfaction Is Related to High Disease Burden in Tinnitus.

Previous studies have shown a high prevalence of sleep disturbances in tinnitus patients. However, no study has yet evaluated subjective sleep satisfaction. The present study aimed to investigate associations of self-reported sleep satisfaction with sociodemographic factors, tinnitus-related distress, depression, and self-reported quality of life. This is a retrospective analysis of 2344 outpatients with tinnitus presenting at a tertiary German tinnitus clinic from 2010 to 2020. Patients who filled in five questionnaires (Tinnitus Handicap Inventory (THI), Tinnitus Questionnaire (TQ), Major Depression Inventory (MDI), Tinnitus Sample Case History Questionnaire (TSCHQ), and the World Health Organization Quality of Life Brief Version (WHOQOL-Bref)) were included. Based on the question about sleep satisfaction in the WHOQOL-Bref, group classification into (I) sleep-satisfied, (II) neither satisfied or dissatisfied, and (III) sleep-dissatisfied patients was performed. Associations between sleep satisfaction and quality of life, depression, tinnitus distress, and tinnitus characteristics were analyzed by group differences and a multinomial regression model with elastic net penalization. A total of 42.38% of patients were satisfied or very satisfied with sleep, whereas 40.91% of patients were dissatisfied or very dissatisfied with sleep. The remaining patients reported being neither satisfied nor dissatisfied with sleep. Sleep-dissatisfied patients were significantly more burdened in questionnaires on depressive symptoms (MDI), tinnitus distress (TQ, THI), and quality of life (WHOQOL-Bref). In addition, they suffered significantly more often from comorbidities such as headache, neck pain, or temporomandibular joint disorder (TMJ). The elastic net regression based on sum scores of THI, TQ, MDI, the four domains of WHOQOL-Bref, as well as all individual questions from the TSCHQ was able to classify patients satisfied with their sleep with an accuracy of 79%, 87.8% sensitivity, and 70.4% specificity. The model could not identify patients indifferent with the quality of their sleep (neither satisfied nor dissatisfied) (sensitivity: 0%; specificity: 100%). The accuracy of the model to predict patients dissatisfied with their sleep was 80.7%, with 83% sensitivity and 78.4% specificity. Poor physical and mental health (Domain I/II WHOQOL-Bref) as well as tinnitus distress were the strongest predictors of sleep dissatisfaction. Conversely, for sleep satisfaction, good physical and mental health as well as low tinnitus distress were the strongest predictors. The division into sleep-satisfied and sleep-dissatisfied tinnitus patients allows a very good discrimination regarding disease burden as indicated by depression, tinnitus distress, quality of life, and pain-related comorbidities. Physical and mental health as well as tinnitus distress seem to be strongly related to sleep satisfaction underscoring the concept of "tinnitus" versus "tinnitus disorder", but also the importance of sleep satisfaction as a global health indicator. Moreover, these data indicate the relevance of addressing sleep disorders in the therapeutic management of chronic tinnitus patients.

Restless Legs Syndrome Prevalence and Clinical Correlates Among Psychiatric Inpatients: A Multicenter Study.

Background: There are only limited reports on the prevalence of restless legs syndrome (RLS) in patients with psychiatric disorders. The present study aimed to evaluate the prevalence and clinical correlates in psychiatric inpatients in Germany and Switzerland. Methods: This is a multicenter cross-sectional study of psychiatric inpatients with an age above 18 years that were diagnosed and evaluated face-to-face using the International RLS Study Group criteria (IRLSSG) and the International RLS severity scale (IRLS). In addition to sociodemographic and biometric data, sleep quality and mood were assessed using the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), the Epworth Sleepiness Scale (ESS), and the Patient Health Questionnaire (PHQ-9). In addition to univariate statistics used to describe and statistically analyze differences in variables of interest between patients with and without RLS, a logistic model was employed to identify predictors for the occurrence of RLS. Results: The prevalence of RLS in a sample of 317 psychiatric inpatients was 16.4%, and 76.9% of these were diagnosed with RLS for the first time. RLS severity was moderate to severe (IRLS ± SD: 20.3 ± 8.4). The prevalences in women (p = 0.0036) and in first-degree relatives with RLS (p = 0.0108) as well as the body mass index (BMI, p = 0.0161) were significantly higher among patients with RLS, while alcohol consumption was significantly lower in the RLS group. With the exception of atypical antipsychotics, treatment with psychotropic drugs was not associated with RLS symptoms. Regarding subjective sleep quality and mood, scores of the PSQI (p = 0.0007), ISI (p = 0.0003), and ESS (p = 0.0005) were higher in patients with RLS, while PHQ-9 scores were not different. A logistic regression analysis identified gender (OR 2.67; 95% CI [1.25; 5.72]), first-degree relatives with RLS (OR 3.29; 95% CI [1.11; 9.73], ESS score (OR 1.09; 95% CI [1.01; 1.17]), and rare alcohol consumption (OR 0.45; 95% CI [0.22; 0.94] as predictors for RLS. Conclusions: Clinically significant RLS had a high prevalence in psychiatric patients. RLS was associated with higher BMI, impaired sleep quality, and lower alcohol consumption. A systematic assessment of restless legs symptoms might contribute to improve the treatment of psychiatric patients.

Effectiveness of Repetitive Transcranial Magnetic Stimulation in the Treatment of Bipolar Disorder in Comparison to the Treatment of Unipolar Depression in a Naturalistic Setting.

Repetitive transcranial magnetic stimulation (rTMS) is effective in the treatment of depression. However, for the subset of patients with bipolar disorder, less data is available and overall strength of evidence is weaker than for its use in unipolar depression. A cohort of 505 patients (of which 46 had a diagnosis of bipolar disorder) with depression who were treated with rTMS were analyzed retrospectively with regards to their response to several weeks of treatment. Hamilton Depression Rating Scale (HDRS) was assessed as main outcome. Unipolar and bipolar patients with depression did not differ significantly in baseline demographic variables or severity of depression. Both groups did not differ significantly in their response to treatment as indicated by absolute and relative changes in the HDRS and response and remission rates. On HDRS subitem-analysis, bipolar patients showed superior amelioration of the symptom "paranoid symptoms" in a statistically significant manner. In conclusion, depressed patients with a diagnosis of bipolar disorder benefit from rTMS in a similar fashion as patients with unipolar depression in a naturalistic setting. rTMS might be more effective in reducing paranoia in bipolar than in unipolar patients.

The Many Faces of Sleep Disorders in Post-Traumatic Stress Disorder: An Update on Clinical Features and Treatment.

Sleep disorders and nightmares are core symptoms of post-traumatic stress disorder (PTSD). The relationship seems to be bidirectional, and persistent disturbed sleep may influence the course of the disorder. With regard to sleep quality, insomnia and nocturnal anxiety symptoms, as well as nightmares and stressful dreams, are the most prominent sleep symptoms. Polysomnographic measurements reveal alterations of the sleep architecture and fragmentation of rapid eye movement sleep. In addition, sleep disorders, such as sleep-related breathing disorders and parasomnias are frequent comorbid conditions. The complex etiology and symptomatology of trauma-related sleep disorders with frequent psychiatric comorbidity require the application of multimodal treatment concepts, including psychological and pharmacological interventions. However, there is little empirical evidence on the effectiveness of long-term drug treatment for insomnia and nightmares. For nondrug interventions, challenges arise from the current lack of PTSD-treatment concepts integrating sleep- and trauma-focused therapies. Effective therapy for sleep disturbances may consequently also improve well-being during the day and probably even the course of PTSD. Whether early sleep interventions exert a preventive effect on the development of PTSD remains to be clarified in future studies.

A direct comparison of neuronavigated and non-neuronavigated intermittent theta burst stimulation in the treatment of depression.

OBJECTIVE: To investigate whether a four-week course of neuronavigated intermittent theta burst stimulation (iTBS) of the left dorsolateral prefrontal cortex is superior to the non-neuronavigated F3-EEG method of positioning. METHODS: We conducted a single-center, two-arm, randomized and double-blinded study (clinicaltrials.gov NCT03953521). 37 inpatients with an at least moderate depressive episode were randomized to receive either neuronavigated or 10-20-EEG-system based F3 guided iTBS. Both groups received twenty week daily sessions of iTBS while continuing to receive standard-of-care treatment by their ward physicians. For navigated iTBS, we used magnetic resonance imaging to target the border between the anterior and middle third of the middle frontal gyrus considered to represent the left dorsolateral prefrontal cortex (lDLPFC). Differences in the treatment arms were blinded by completely mimicking the procedures of the respective other treatment group. Rating physicians were not involved in the treatment procedure. Primary outcome was defined as the change of the 21-item version of the Hamilton Depression Score (HAMD) from baseline to end of treatment at week 4. Secondary outcomes included HAMD score during the treatment, Patient Health Questionnaire-9, WHO Quality of Life-BREF and Clinical Global Impression. For primary outcome, we used a planned group comparison for the absolute change in the HAMD. For secondary outcome measures we calculated analyses of variance (ANOVAs) with the within-subjects factor time (primary: baseline vs. week 4; secondary: all visits) and the between-subjects factor group (navigated vs. F3 guided group). We also did planned contrasts between both groups for all variables and all treatment and follow-up visits with the aim not to oversee any group differences. For group contrasts we used Student T-tests for metric and chi-square tests for categorial variables. Significance threshold was set to 5% uncorrected for multiple comparisons. RESULTS: Enrolment of 80 patients with interim analysis was planned. Interim analysis was performed after 37 patients (intention to treat). 6 patients dropped out, leaving 31 for analysis. With respect to primary outcome criteria, absolute change in the HAMD did not differ significantly between groups. In accordance, relative change and number of responders and remitters were not significantly different. Overall number of responders was 53% and of remitters was 60%. On a descriptive level, the results favor the clinical effects of the F3 group for the absolute and relative change in the HAMD and the number of responders. Number of remitters were exactly the same for both groups. Therefore, we decided to stop the trial due to the added burden of magnetic resonance imaging and neuronavigated treatment in relation to the effect. Secondary outcomes did also not differ significantly between groups. Patients did not differ in their baseline characteristics nor with respect to intake of medication during the trial period and all had access to the same therapeutic interventions. CONCLUSION: We noticed a high antidepressive effect of add-on iTBS treatment to standard inpatient treatment but failed to demonstrate a clinical superiority of neuronavigated localization. The non-navigated, F3 guided iTBS treatment used as a control group may be sophisticated enough to dilute potential added benefits, and the difference between the localization approaches is either negligible or too small to justify the additional efforts of navigation. The effects of concomitant treatment may mask effects, but our patient population reflects clinical reality in an inpatient setting. Further prospective studies are warranted to compare neuronavigated with surface-based approaches.

Sleep Disturbances and Suicidality in Posttraumatic Stress Disorder: An Overview of the Literature.

A causal relationship between sleep disturbances and suicidal behavior has been previously reported. Insomnia and nightmares are considered as hallmarks of posttraumatic stress disorder (PTSD). In addition, patients with PTSD have an increased risk for suicidality. The present article gives an overview about the existing literature on the relationship between sleep disturbances and suicidality in the context of PTSD. It aims to demonstrate that diagnosing and treating sleep problems as still underestimated target symptoms may provide preventive strategies with respect to suicidality. However, heterogeneous study designs, different samples and diverse outcome parameters hinder a direct comparison of studies and a causal relationship cannot be shown. More research is necessary to clarify this complex relationship and to tackle the value of treatment of sleep disturbances for suicide prevention in PTSD.