The Ghent Psychotherapy Study: A Pragmatic, Stratified, Randomized Parallel Trial into the Differential Efficacy of Psychodynamic and Cognitive-Behavioral Interventions in Dependent and Self-Critical Depressive Patients.

INTRODUCTION: Different types of psychotherapy are effective for treating major depressive disorder across groups yet show large within-group differences. Patient personality style is considered a potentially useful variable for treatment matching. OBJECTIVE: This study is the first experimental test of the interaction between therapeutic approach and patients' dependent versus self-critical personality styles. METHODS: A pragmatic stratified parallel trial was carried out with 100 adult patients diagnosed with DSM-IV-TR major depressive disorder. They were randomly assigned to short-term (16-20 sessions) cognitive behavioral therapy (CBT) or short-term psychodynamic psychotherapy (STPP). Patients were assessed at baseline, during therapy, post-therapy, and at 3- and 6-month follow-up. Primary outcome is depression severity measured by the Hamilton Rating Scale for Depression posttreatment. Primary analysis was by intention to treat. This trial is registered with the ISRCTN registry (www.isrctn.com), number ISRCTN17130982. RESULTS: The intention-to-treat sample consisted of 100 participants; 40 with self-critical and 60 with dependent personality styles were randomized to either CBT (n = 50) or STPP (n = 50). We observed no interaction effect (-0.34 [-6.14, 5.46]) between therapy and personality style and found no evidence for a difference in effectiveness between the treatments in general in terms of symptom reduction and maintained benefits at 6-month follow-up. CONCLUSION: We found no evidence that dependent versus self-critical personality styles moderate the relation between treatment and outcome in depression. Research using individual patient data could gain further insight into why specific therapeutic approaches work better for specific patients.

Precision targeting in prediction for rTMS clinical outcome in depression: what about sgACC lateralization, metabolic connectivity, and the potential role of the cerebellum?

Predicting clinical response to repetitive transcranial magnetic stimulation (rTMS) in medication-resistant depression (MRD) has gained great importance in recent years. Mainly, the right subgenual anterior cingulate cortex (sgACC) functional connectivity has been put forward as biomarker in relation to rTMS clinical outcome. Even though the left and right sgACC may have different neurobiological functions, little is known about the possible lateralized predictive role of the sgACC in rTMS clinical outcome. In 43 right-handed antidepressant-free MRD patients, we applied a searchlight-based interregional covariance connectivity approach using the baseline 18FDG-PET scan-collected from two previous high-frequency (HF)-rTMS treatment studies delivering stimulation to the left dorsolateral prefrontal cortex (DLPFC)-and investigated whether unilateral or bilateral sgACC glucose metabolism at baseline would result in different predictive metabolic connectivity patterns. Regardless of sgACC lateralization, the weaker the sgACC seed-based baseline metabolic functional connections with the (left anterior) cerebellar areas, the significantly better the clinical outcome. However, the seed diameter seems to be crucial. Similar significant findings on sgACC metabolic connectivity with the left anterior cerebellum, also unrelated to sgACC lateralization, in relation to clinical outcome were observed when using the HCPex atlas. Although we could not substantiate that specifically right sgACC metabolic connectivity would predict HF-rTMS clinical outcome, our findings suggest considering the entire sgACC in functional connectivity predictions. Given that the interregional covariance connectivity results were significant only when using the Beck Depression Inventory (BDI-II) and not with the Hamilton Depression Rating Scale (HDRS), our sgACC metabolic connectivity observations also suggest the possible involvement of the (left) anterior cerebellum involved in higher-order cognitive processing as part of this predictive value.

Accelerated Repetitive Transcranial Magnetic Stimulation to Treat Major Depression: The Past, Present, and Future.

Repetitive transcranial magnetic stimulation (rTMS) is an effective and evidence-based therapy for treatment-resistant major depressive disorder. A conventional course of rTMS applies 20-30 daily sessions over 4-6 weeks. The schedule of rTMS delivery can be accelerated by applying multiple stimulation sessions per day, which reduces the duration of a treatment course with a predefined number of sessions. Accelerated rTMS reduces time demands, improves clinical efficiency, and potentially induces faster onset of antidepressant effects. However, considerable heterogeneity exists across study designs. Stimulation protocols vary in parameters such as the stimulation target, frequency, intensity, number of pulses applied per session or over a course of treatment, and duration of intersession intervals. In this article, clinician-researchers and neuroscientists who have extensive research experience in accelerated rTMS synthesize a consensus based on two decades of investigation and development, from early studies ("Past") to contemporaneous theta burst stimulation, a time-efficient form of rTMS gaining acceptance in clinical settings ("Present"). We propose descriptive nomenclature for accelerated rTMS, recommend avenues to optimize therapeutic and efficiency potential, and suggest using neuroimaging and electrophysiological biomarkers to individualize treatment protocols ("Future"). Overall, empirical studies show that accelerated rTMS protocols are well tolerated and not associated with serious adverse effects. Importantly, the antidepressant efficacy of accelerated rTMS appears comparable to conventional, once daily rTMS protocols. Whether accelerated rTMS induces antidepressant effects more quickly remains uncertain. On present evidence, treatment protocols incorporating high pulse dose and multiple treatments per day show promise and improved efficacy.

Combining transcranial direct current stimulation with group cognitive behavioral therapy developed to treat rumination: a clinical pilot study.

Background: As part of repetitive negative thinking (RNT), rumination is a maladaptive cognitive response style to stress or negative mood which can increase the risk of depression and may prohibit complete recovery. Cognitive behavioral therapy (CBT) and transcranial direct current stimulation (tDCS) both proved to be effective in decreasing rumination. However, the combined effects of tDCS and CBT interventions on rumination have not yet been explored. The first aim of this pilot study is to investigate whether the combination of tDCS and CBT has an accumulating positive effect on modulating state rumination. The second aim is to assess the feasibility and safety profile of the proposed combined approach. Method: Seventeen adults aged 32-60 years, suffering from RNT, were referred by their primary care professional to participate in an 8-week group intervention for RNT ("Drop It") comprising 8 sessions of CBT. Before each CBT session, patients underwent one double-blinded prefrontal active (2 mA for 20 min) or sham tDCS (anode over F3, cathode over the right supraorbital region) combined with an internal cognitive attention task focused on individual RNT, i.e., online tDCS priming. During each session, the Brief State Rumination Inventory was used to assess state rumination. Results: A mixed effects model analysis revealed no significant differences between the stimulation conditions, weekly sessions, or their interaction in terms of state rumination scores. Conclusion: Overall, the combination of online tDCS priming followed by group CBT was found to be safe and feasible. On the other hand, no significant additional effects of this combined approach on state rumination were established. Although our pilot study may have been too small to find significant clinical effects, future larger RCT studies on combined tDCS-CBT treatment protocols may reevaluate the selection of internal cognitive attention tasks and more objective neurophysiological measurements, consider the optimal timing of the combination (concurrently or sequentially), or may add additional tDCS sessions when following CBT.

The current perspective of neuromodulation techniques in the treatment of alcohol addiction: a systematic review.

BACKGROUND: Alcohol dependency can be considered as a chronic mental disorder characterized by frequent relapses even when treated with appropriate medical or psychotherapeutic interventions. Here, the efficacy of different neuromodulation techniques in alcohol addiction, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS), vagal nerve stimulation (VNS) and electroconvulsive therapy (ECT) is critically evaluated. METHODS: A broad literature search on electronic databases such as NCBI PubMed, the Web of Knowledge, the Cochrane Library was conducted. Additionally, we searched recent handbooks on neuromodulation and/or addiction. RESULTS: Studies investigating these neuromodulation techniques in alcohol addiction remain to date rather limited and especially tDCS and rTMS applications have been investigated. Overall, the clinical effects seem modest. The use of VNS and ECT has yet to be investigated in alcohol dependent patients. CONCLUSIONS: Neuromodulation techniques have only recently been subject to investigation in alcohol addiction and methodological differences between the few studies restrict clear-cut conclusions. Nevertheless, the scarce results encourage further investigation in alcohol addiction.

Acute effects of repetitive transcranial magnetic stimulation on attentional control are related to antidepressant outcomes.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) applied over the dorsolateral prefrontal cortex (DLPFC) is a new treatment procedure that holds promise of more insight into the pathophysiology of depression because the DLPFC may play an important role in the interplay between emotional and attentional information processing. We sought to investigate whether acute neurocognitive effects of rTMS are related to antidepressant outcomes. METHODS: Between January 2005 and May 2007, we examined the effects of a single session compared with 2 weeks of rTMS over the left DLPFC on cognition and mood in therapy-resistant patients with depression. We used a crossover placebo-controlled double-blind design and differentiated rTMS treatment responders and nonresponders. We used a task-switching paradigm to measure cognitive function. RESULTS: After 2 weeks of high-frequency rTMS over the left DLPFC, depressive symptoms improved in more than half (53%) of our therapy-resistant population. After a single session, mood did not improve but attentional control was increased solely within our group of treatment responders. LIMITATIONS: Our results should be interpreted as preliminary because our sample was small and because the cognitive task we used has not been tested for validity and reliability. In addition, despite minimal stimulation of the DLPFC during sham stimulation, it is possible that the stimulation was partially active. Finally, benzodiazepines may have had impairing effects on the attentional task. CONCLUSION: Cognitive reactivity after a single session of rTMS may hold promise as a predictor of beneficial treatment outcomes. Moreover, within the group of responders, attentional control appears to play an important role in the progress of mood disorders.

Repetitive transcranial magnetic stimulation treatment for depressive disorders: current knowledge and future directions.

PURPOSE OF REVIEW: After three decades of clinical research on repetitive transcranial magnetic stimulation (rTMS), major depressive disorder (MDD) has proven to be the primary field of application. MDD poses a major challenge for health systems worldwide, emphasizing the need for improving clinical efficacy of existing rTMS applications and promoting the development of novel evidence-based rTMS treatment approaches. RECENT FINDINGS: Several promising new avenues have been proposed: novel stimulation patterns, targets, and coils; combinatory treatments and maintenance; and personalization and stratification of rTMS parameters, and treatment of subpopulations. SUMMARY: This opinion review summarizes current knowledge in the field and addresses the future direction of rTMS treatment in MDD, facilitating the establishment of this clinical intervention method as a standard treatment option and continuing to improve response and remission rates, and take the necessary steps to personalize rTMS-based treatment approaches.

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.