Clinician treatment choices for post-traumatic stress disorder: ambassadors survey of psychiatrists in 39 European countries.

BACKGROUND: Considering the recently growing number of potentially traumatic events in Europe, the European Psychiatric Association undertook a study to investigate clinicians' treatment choices for post-traumatic stress disorder (PTSD). METHODS: The case-based analysis included 611 participants, who correctly classified the vignette as a case of PTSD, from Central/ Eastern Europe (CEE) (n = 279), Southern Europe (SE) (n = 92), Northern Europe (NE) (n = 92), and Western Europe (WE) (N = 148). RESULTS: About 82% woulduse antidepressants (sertraline being the most preferred one). Benzodiazepines and antipsychotics were significantly more frequently recommended by participants from CEE (33 and 4%, respectively), compared to participants from NE (11 and 0%) and SE (9% and 3%). About 52% of clinicians recommended trauma-focused cognitive behavior therapy and 35% psychoeducation, irrespective of their origin. In the latent class analysis, we identified four distinct "profiles" of clinicians. In Class 1 (N = 367), psychiatrists would less often recommend any antidepressants. In Class 2 (N = 51), clinicians would recommend trazodone and prolonged exposure therapy. In Class 3 (N = 65), they propose mirtazapine and eye movement desensitization reprocessing therapy. In Class 4 (N = 128), clinicians propose different types of medications and cognitive processing therapy. About 50.1% of participants in each region stated they do not adhere to recognized treatment guidelines. CONCLUSIONS: Clinicians' decisions for PTSD are broadly similar among European psychiatrists, but regional differences suggest the need for more dialogue and education to harmonize practice across Europe and promote the use of guidelines.

[On the Admission of Patients with Borderline Personality Disorder to Outpatient Psychotherapy]. / Zur Aufnahme von Patient*innen mit Borderline Persönlichkeitsstörung in die ambulante Psychotherapie.

BACKGROUND: Patients with borderline personality disorder (BPD) present difficulties in self-regulation and interaction, which is a challenge for psychotherapists that is also addressed in BPD-specific interventions. Against this background, outpatient psychotherapists were surveyed about the factors playing a decisive role in their treatment offer for patients with BPD. METHODS: Psychotherapists for adults were contacted via their email address published on the website of the Kassenärztliche Vereinigung (Association of Statutory Health Insurance Physicians), 231 of whom answered an online questionnaire. The results were analysed descriptively and examined inferentially with regard to the psychotherapists' admission behaviour. RESULTS: Almost 90% reported that they would generally accept patients with BPD in therapy. However, of those, 85% did not have a therapy slot available. The psychotherapists' learned approach of treatment was not a decisive factor in determining whether they were willing to provide treatment. Most of the psychotherapists (85%) recommended a BPD disorder-specific therapy such as Dialectical Behavior Therapy (DBT), Mentalization-Based Treatment (MBT), Transference-Focused Psychotherapy (TFP) or Schema Therapy (ST). However, only just under 7% were certified in such a disorder-specific approach. Significant individual stress factors described by the psychotherapists were suicidal risk (70%) and potential other-directed aggression (59%). In addition, it was shown that it played a role whether the psychotherapists were trained in an additional therapy approach (with at least 16 teaching units) or not. CONCLUSION: The care situation for people with BPD seeking an outpatient psychotherapy place is clearly in need of improvement. This is mainly due to a general lack of available therapy places as well as various fears and anxieties, such as increased suicidality, which in turn can have a negative impact on the provision of outpatient therapy. Psychotherapists who have undergone disorder-specific further training feel less burdened by suicidal behaviour. However, since only a small number of them are able to offer BPD-specific therapies, it is essential to expand and (financially) support specific training programmes. In order to meet the demand for care, professional changes are urgently needed.

EMDR therapy vs. supportive therapy as adjunctive treatment in trauma-exposed bipolar patients: A randomised controlled trial.

INTRODUCTION: Patients with bipolar disorder (BD) are frequently exposed to traumatic events which worsen disease course, but this study is the first multicentre randomised controlled trial to test the efficacy of a trauma-focused adjunctive psychotherapy in reducing BD affective relapse rates. MATERIALS AND METHODS: This multicentre randomised controlled trial included 77 patients with BD and current trauma-related symptoms. Participants were randomised to either 20 sessions of trauma-focused Eye Movement Desensitization and Reprocessing (EMDR) therapy for BD, or 20 sessions of supportive therapy (ST). The primary outcome was relapse rates over 24-months, and secondary outcomes were improvements in affective and trauma symptoms, general functioning, and cognitive impairment, assessed at baseline, post-treatment, and at 12- and 24-month follow-up. The trial was registered prior to starting enrolment in clinical trials (NCT02634372) and carried out in accordance with CONSORT guidelines. RESULTS: There was no significant difference between treatment conditions in terms of relapse rates either with or without hospitalisation. EMDR was significantly superior to ST at the 12-month follow up in terms of reducing depressive symptoms (p=0.0006, d=0.969), manic symptoms (p=0.027, d=0.513), and improving functioning (p=0.038, d=0.486). There was no significant difference in dropout between treatment arms. CONCLUSIONS: Although the primary efficacy criterion was not met in the current study, trauma-focused EMDR was superior to ST in reducing of affective symptoms and improvement of functioning, with benefits maintained at six months following the end of treatment. Both EMDR and ST reduced trauma symptoms as compared to baseline, possibly due to a shared benefit of psychotherapy. Importantly, focusing on traumatic events did not increase relapses or dropouts, suggesting psychological trauma can safely be addressed in a BD population using this protocol.

[Inpatient Treatment of Complex PTSD Following Childhood Abuse: Effectiveness and Predictors of Treatment Outcome]. / Stationäre Therapie der komplexen PTBS in Folge körperlicher oder sexualisierter Gewalt in der Kindheit: Wirksamkeit und Prädiktoren des Behandlungsverlaufs.

BACKGROUND: There is a lack of studies investigating the effectiveness of inpatient trauma-focused psychotherapy of complex post-traumatic stress disorder. The first aim of this retrospective investigation was to analyze the course of PTSD. Second, possible predictors of treatment response were investigated. METHODS: 150 inpatients of Clinic St. Irmingard with complex PTSD following childhood physical and childhood sexual abuse were assessed regarding childhood abuse, PTSD symptomatology, mindfulness, dissociation and general psychopathology. Differences in pre and post scores were analyzed using regression analyses. A classification tree was used to identify predictors of response. RESULTS: The significant reduction of PTSD symptoms corresponded to a large effect (d=1.8) and a reponse rate of 52% according to the reliable change index (p<0.05). Effect sizes for other symptoms were medium to large (0.5

Serum levels of brain-derived neurotrophic factor are unchanged after transcranial direct current stimulation in treatment-resistant depression.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays an important role in differentiation and repair of neurons in the adult brain. BDNF serum levels have been found to be lower in depressed patients than in healthy subjects. In a couple of studies, effective antidepressant treatment including electroconvulsive therapy led to an increase in BDNF serum levels. As transcranial direct current stimulation (tDCS) is currently discussed as novel therapeutic intervention in major depression, we investigated BDNF serum levels during tDCS in therapy-resistant depression. METHODS: Twenty-two patients with a major depressive episode participated in a double-blind placebo-controlled trial and received randomized cross over treatment with 2 weeks active and 2 weeks sham tDCS (1 or 2 mA for 20 min, anode over the left dorsolateral prefrontal cortex, cathode right supraorbital cortex). RESULTS: Clinical assessment only showed a modest and non-significant improvement in HAMD, BDI and CGI in both groups. BDNF serum levels were measured at baseline, after 2 and after 4 weeks. There was neither a significant change of BDNF levels following active tDCS, nor were severity of depressive symptoms and BDNF levels correlated. LIMITATIONS: The small sample size, its heterogeneity, the short observation period and a cross-over design without an interval between both conditions. CONCLUSIONS: tDCS did not change BDNF serum levels unlike other established antidepressant interventions in this treatment resistant sample. However, larger studies are needed.

Evaluation of sham transcranial direct current stimulation for randomized, placebo-controlled clinical trials.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been investigated as therapeutic intervention in various psychiatric and neurologic disorders. As placebo responses to technical interventions may be pronounced in many clinical conditions, it is important to thoroughly develop placebo conditions which meet the requirements for application in randomized double-blind controlled trials. OBJECTIVE: The two-part experiment reported here aims at evaluating a new sham tDCS condition in healthy subjects and device operators. Sham or active tDCS is delivered after entering a number code to the device and allows blinding of the operator before and during tDCS. The sham mode has no short stimulation period. METHODS: The experimental sequence was as follows: 1) Evaluation of successful blinding by comparing placebo to active stimulation at prefrontal sites based on the rating of subjects undergoing tDCS, 2) Evaluation of successful blinding by comparing placebo to active stimulation at prefrontal sites based on the operator/observer ratings. RESULTS: Subjects were not able to distinguish between active and sham tDCS for prefrontal stimulation. Overall there was no relevant discomfort and tDCS was well tolerated. Operators/observers were able to identify sham stimulation based on skin reddening after active, but not after sham tDCS. CONCLUSIONS: The tDCS sham condition investigated here may be suitable for placebo-controlled trials keeping subjects blind to treatment conditions. However, operators can easily be aware of the condition applied and they should not get involved in rating outcome measures during the course of high standard placebo-controlled trials.

Two-year outcome of vagus nerve stimulation in treatment-resistant depression.

One of the major goals of antidepressant treatment is a sustained response and remission of depressive symptoms. Some of the previous studies of vagus nerve stimulation (VNS) have suggested antidepressant effects. Our naturalistic study assessed the efficacy and the safety of VNS in 74 European patients with therapy-resistant major depressive disorder. Psychometric measures were obtained after 3, 12, and 24 months of VNS. Mixed-model repeated-measures analysis of variance revealed a significant reduction (P < or = 0.05) at all the 3 time points in the 28-item Hamilton Rating Scale for Depression (HRSD28) score, the primary outcome measure. After 2 years, 53.1% (26/49) of the patients fulfilled the response criteria (> or =50% reduction in the HRSD28 scores from baseline) and 38.9% (19/49) fulfilled the remission criteria (HRSD28 scores < or = 10). The proportion of patients who fulfilled the remission criteria remained constant as the duration of VNS treatment increased. Voice alteration, cough, and pain were the most frequently reported adverse effects. Two patients committed suicide during the study; no other deaths were reported. No statistically significant differences were seen in the number of concomitant antidepressant medications. The results of this 2-year open-label trial suggest a clinical response and a comparatively benign adverse effect profile among patients with treatment-resistant depression.

Transcranial direct current stimulation in a patient with therapy-resistant major depression.

Transcranial direct current stimulation (tDCS) of the prefrontal cortex (PFC) has been reported to exert significant antidepressant effects in patients with major depression. Several recent studies found an improvement of depressive symptoms in drug-free patients. Here we report the case of a 66-year-old female patient suffering from recurrent major depressive episodes who underwent anodal tDCS of the left dorsolateral PFC over 4 weeks as an add-on treatment to a stable antidepressant medication. Only a modest improvement of depressive symptoms was observed after tDCS, i.e. reduction of the baseline scores in the Hamilton Depression Rating Scale from 23 to 19 and in the Beck Depression Inventory from 27 to 20. However, there was an increase from 52 to 90% in the Regensburg Verbal Fluency Test. In addition, EEG was used to assess the acute effects of tDCS. Low resolution brain electromagnetic tomography (LORETA) showed a left unilateral focal effect (25-40% reduced power) in the delta, theta and alpha frequency bands. The same effect appeared in the surface analysis of the EEG. The absolute, as well as the relative power decreased significantly in the delta, theta and alpha bands after a comparison of the spectral analysis. Though tDCS over 4 weeks did not exert clinically meaningful antidepressant effects in this case of therapy-resistant depression, the findings for cognitive measures and EEG suggest that beneficial effects may occur in depressed subjects and future studies need to further explore this approach also in therapy-resistant major depression.

Controversy: Repetitive transcranial magnetic stimulation or transcranial direct current stimulation shows efficacy in treating psychiatric diseases (depression, mania, schizophrenia, obsessive-complusive disorder, panic, posttraumatic stress disorder).

Brain imaging studies performed over the past 20 years have generated new knowledge about the specific brain regions involved in the brain diseases that have been classically labeled as psychiatric. These include the mood and anxiety disorders, and the schizophrenias. As a natural next step, clinical researchers have investigated whether the minimally invasive brain stimulation technologies (transcranial magnetic stimulation [TMS] or transcranial direct current stimulation [tDCS]) might potentially treat these disorders. In this review, we critically review the research studies that have examined TMS or tDCS as putative treatments for depression, mania, obsessive-complusive disorder, posttraumatic stress disorder, panic disorder, or schizophrenia. (Separate controversy articles deal with using TMS or tDCS to treat pain or tinnitus. We will not review here the large number of studies using TMS or tDCS as research probes to understand disease mechanisms of psychiatric disorders.) Although there is an extensive body of randomized controlled trials showing antidepressant effects of daily prefrontal repetitive TMS, the magnitude or durability of this effect remains controversial. US Food and Drug Administration approval of TMS for depression was recently granted. There is much less data in all other diseases, and therapeutic effects in other psychiatric conditions, if any, are still controversial. Several issues and problems extend across all psychiatric TMS studies, including the optimal method for a sham control, appropriate coil location, best device parameters (intensity, frequency, dosage, and dosing schedule) and refining what subjects should be doing during treatment (activating pathologic circuits or not). In general, TMS or tDCS as a treatment for most psychiatric disorders remains exciting but controversial, other than prefrontal TMS for depression.

White and gray matter abnormalities in the brain of patients with fibromyalgia: a diffusion-tensor and volumetric imaging study.

OBJECTIVE: To use a combination of magnetic resonance diffusion-tensor imaging (MR-DTI) and MR imaging of voxel-based morphometry (MR-VBM) in patients with fibromyalgia syndrome (FMS) to determine microstructural and volume changes in the central neuronal networks involved in the sensory-discriminative and affective-motivational characteristics of pain, anxiety, memory, and regulation of the stress response. METHODS: Thirty female patients with FMS and 30 healthy female control subjects were studied. Predefined areas of the brain were measured for volume of gray matter by MR-VBM and for diffusivity and fractional anisotropy (FA) by MR-DTI. Higher FA values and reduced diffusivity are thought to reflect increased complexity of brain-tissue microstructure. RESULTS: MR-VBM and MR-DTI demonstrated a striking pattern of changes in brain morphology in patients with FMS. Both thalami, the thalamocortical tracts, and both insular regions showed significant decreases in FA. In contrast, increases in FA and decreases in gray matter volume were seen in the postcentral gyri, amygdalae, hippocampi, superior frontal gyri, and anterior cingulate gyri. Increased pain intensity scores were correlated with changes in MR-DTI measurements in the right superior frontal gyrus. Increased fatigue was correlated with changes in the left superior frontal and left anterior cingulate gyrus, and self-perceived physical impairment was correlated with changes in the left postcentral gyrus. Higher intensity scores for stress symptoms were correlated negatively with diffusivity in the thalamus and FA in the left insular cortex. No relationship was found between MR-VBM measurements and symptom intensity scores. CONCLUSION: MR-DTI allows the visualization of microstructural changes in the brain of patients with FMS, appears to be more sensitive than MR-VBM, and may serve as an additional diagnostic technique in FMS and probably other dysfunctional pain syndromes.

Repetitive transcranial magnetic stimulation : does it have potential in the treatment of depression?

Transcranial magnetic stimulation (TMS) has become a major research tool in experimental clinical neurophysiology as a result of its potential to noninvasively and focally stimulate cortical brain regions. Currently, studies are being conducted to investigate whether repetitive TMS (rTMS)-mediated modulation of cortical function may also provide a therapeutic approach in neurological and psychiatric disorders. Preclinical findings have shown that prefrontal rTMS can modulate the function of fronto-limbic circuits, which is reversibly altered in major depression. rTMS has also been found to exert effects on neurotransmitter systems involved in the pathophysiology of major depression (e.g. stimulates subcortical dopamine release and acts on the hypothalamic pituitary adrenal axis, which is dysregulated in depression). To date, numerous open and controlled clinical trials with widely differing stimulation parameters have explored the antidepressant potential of rTMS. Though conducted with small sample sizes, the majority of the controlled trials demonstrated significant antidepressant effects of active rTMS compared with a sham condition. Effect sizes, however, varied from modest to substantial, and the patient selection focused on therapy-resistant cases. Moreover, the average treatment duration was approximately 2 weeks, which is short compared with other antidepressant interventions. Larger multicentre trials, which would be mandatory to demonstrate the antidepressant effectiveness of rTMS, have not been conducted to date.A putative future application of rTMS may be the treatment of patients who did not tolerate or did not respond to antidepressant pharmacotherapy before trying more invasive strategies such as electroconvulsive therapy and vagus nerve stimulation. Theoretically, rTMS may be also applied early in the course of disease in order to speed up and increase the effects of antidepressant pharmacotherapy. However, this application has not been a focus of clinical trials to date. Research efforts should be intensified to further investigate the effectiveness of rTMS as an antidepressant intervention and to test specific applications of the technique in the treatment of depressive episodes.

Occurrence of delusions during repetitive transcranial magnetic stimulation (rTMS) in major depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been suggested as a potentially useful treatment for major depression. Nonpsychotic depressed patients appear to have a better outcome than those with psychotic symptoms. METHODS: We report findings in a patient suffering from recurrent, nonpsychotic major depression (DSM-IV) who had 13 daily sessions of rTMS monotherapy within a 3 week period. RESULTS: During rTMS treatment, the patient developed recurrent severe delusions, which he had never experienced before. Psychotic symptoms remitted quickly with neuroleptic medication. CONCLUSIONS: In light of preclinical findings showing increased dopaminergic activity after rTMS treatment, occurrence of psychotic symptoms should be considered a potential side effect of rTMS treatment.

Relation between responses to repetitive transcranial magnetic stimulation and partial sleep deprivation in major depression.

Repetitive transcranial magnetic stimulation (rTMS) has been found to ameliorate symptoms in major depression. However, its mechanism of action has to be further elucidated and the relationship between responses to rTMS and other antidepressant interventions except electroconvulsive therapy has not been investigated to date. Here we studied in an open trial whether the response to partial sleep deprivation may predict the clinical outcome of rTMS treatment. Thirty-three drug-free patients suffering from a major depressive episode underwent a partial sleep deprivation at least 5 days prior to rTMS and subsequently received 10 sessions of 10 Hz rTMS of the left prefrontal cortex. After rTMS a significant overall improvement of 32% on the Hamilton Rating Scale for Depression was observed. Forty-two percent of patients showed an antidepressant response after rTMS. Amelioration of depression after partial sleep deprivation was inversely correlated with improvement after rTMS. There was no clinically applicable predictive value of the response to partial sleep deprivation for the outcome after rTMS. Apparently, different subgroups of depressed patients respond to both interventions. Further studies are needed to characterize the response to rTMS by means of clinical and biological parameters.