Midpalatal miniscrew insertion: The accuracy of digital planning and surgical placement.

INTRODUCTION: The objective of this study was to investigate the accuracy of palatal miniscrew insertion, evaluating the effect of guide fabrication and surgical placement. METHODS: Guided insertion of bilateral paramedian palatal miniscrews was undertaken using Appliance Designer software (3Shape, Copenhagen, Denmark). A resin surgical guide (P Pro Surgical Guide; Straumann AG, Basel, Switzerland) was used. Superimposition of the miniscrew position relative to the digital design was undertaken using bespoke software (Inspect 3D module, OnyxCeph; Image Instruments GmbH, Chemnitz, Germany) to assess surgical inaccuracy. Miniscrew position relative to the surgical guide was also assessed to isolate the effect of planning inaccuracies. Both horizontal and vertical discrepancies were evaluated at both implant locations. RESULTS: Twenty-seven patients having bilateral palatal insertions were examined. Mean discrepancies were <0.5 mm, both in the horizontal and vertical planes. The mean overall horizontal and vertical discrepancy between the digital design and final miniscrew position on the left side was 0.32 ± 0.15 mm and 0.34 ± 0.17 mm, respectively. The maximum horizontal discrepancy observed was 0.72 mm. No significant differences were observed in relation to the accuracy of mini-implant positioning on the basis of sidedness, either for horizontal (P = 0.29) or vertical (P = 0.86) discrepancy. CONCLUSIONS: High levels of accuracy associated with guided insertion of paramedian palatal implants were recorded with mean discrepancies of less than 0.5 mm both in the horizontal and vertical planes. No difference in accuracy was noted between the left and right sides. Very minor levels of inaccuracy associated both with surgical techniques and surgical guide fabrication were recorded.

Bilateral accessory middle turbinate presenting as double middle turbinate: A unique case report.

Many anatomical variations of the middle turbinate (MT), including pneumatized, paradoxically curved, bifurcate, trifurcate, secondary, and accessory, have been described. The most common is pneumatized MT (concha bullosa), but other less common variations may also impact the outcome of clinical management. Anatomical variations of the MT, particularly with a concomitant deviated nasal septum, tend to obstruct the middle meatus leading to disruption of the normal sinus drainage and worsening the symptoms of rhinosinusitis. By recognizing the unique anatomical variant by endoscopy or imaging will help us to improve the management. We report an endoscopic presentation of a rare accessory MT.

Effect of PET/CT standardized uptake values on complete response to treatment before definitive chemoradiotherapy in stage III non-small cell lung cancer.

PURPOSE: The standard treatment for patients with stage III non-small cell lung cancer (NSCLC), unsuitable for resection and with good performance, is definitive radiotherapy with cisplatin-based chemotherapy. Our aim is to evaluate the effect of the maximum value of standardized uptake values (SUVmax) of the primary tumor in positron emission tomography-computed tomography (PET/CT) before treatment on complete response (CR) and overall survival. METHODS: The data of 73 stage III NSCLC patients treated with concurrent definitive chemoradiotherapy (CRT) between 2008 and 2017 and had PET/CT staging in the pretreatment period were evaluated. ROC curve analysis was performed to determine the ideal cut-off value of pretreatment SUVmax to predict CR. RESULTS: Median age was 58 years (range 27-83 years) and 66 patients were male (90.4%). Median follow-up time was 18 months (range 3-98 months); median survival was 23 months. 1-year overall survival (OS) rate and 5-year OS rate were 72 and 19%, respectively. Median progression-free survival (PFS) was 9 months; 1-year PFS rate and 5-year PFS rate were 38 and 19%, respectively. The ideal cut-off value of pretreatment SUVmax that predicted the complete response of CRT was 12 in the ROC analysis [AUC 0.699 (0.550-0.833)/P < 0.01] with a sensitivity of 83%, and specificity of 55%. In patients with SUVmax < 12, CR rate was 60%, while, in patients with SUV ≥ 12, it was only 19% (P = 0.002). Median OS was 26 months in patients with pretreatment SUVmax < 12, and 21 months in patients with SUVmax ≥ 12 (HR = 2.93; 95% CI 17.24-28.75; P = 0.087). CR rate of the whole patient population was 26%, and it was the only factor that showed a significant benefit on survival in both univariate and multivariate analyses. CONCLUSION: Pretreatment SUVmax of the primary tumor in PET/CT may predict CR in stage III NSCLC patients who were treated with definitive CRT. Having clinical CR is the only positive predictive factor for prolonged survival.

Discharge management strategies and post-discharge care interventions for depression - Systematic review and meta-analysis.

BACKGROUND: Patients with depression require treatment continuity when discharged from inpatient care. Interventions aimed at optimizing transition into outpatient care may be effective in preventing symptom deterioration and readmission. We aimed to evaluate the effectiveness of care transition interventions for patients with depression after psychiatric hospitalization. METHODS: Systematic review and random-effects meta-analysis of controlled trials. Primary outcomes were readmissions and symptoms of depression. The control condition was treatment as usual. RESULTS: We included 16 publications reporting the results of 13 different studies. Studies were heterogeneous concerning patient selection and interventional approach. Effects on readmissions and depression symptoms were non-significant in meta-analysis of 8 studies/710 patients and 7 studies/592 patients, respectively. Overall risk ratio for readmission during follow-up was 0.65 (95% CI [0.42;1.01], p=0.06), standardized mean difference for depression symptoms was -0.09 (95% CI [-0.37;0.19], p=0.53). Subgroup analyses indicated no preference for a specific interventional strategy. Data point to considerable risk for selection and publication bias. LIMITATIONS: Included studies are heterogeneous; subgroups are often small and may not attain the power to detect effects. Reasonable classification of interventions into groups of comparable approaches was a challenge and may be arbitrary in some cases. CONCLUSIONS: This systematic review and meta-analysis could not identify any convincingly effective interventional transition approach for patients with depression after psychiatric hospitalization. Current evidence regarding discharge management for depression is limited, heterogeneous and potentially prone to bias. Interventions might be more appropriate for patients with other diagnoses than depression. Further high-quality randomized studies are required.

[Depression and epilepsy : Two clinical pictures with common causes?]. / Depression und Epilepsie : Zwei Krankheitsbilder mit gemeinsamen Ursachen?

BACKGROUND: Epilepsy and depressive disorders show a high rate of comorbidity. Thus, neurobiological similarities and a bidirectional relationship in terms of pathogenesis have been suggested. OBJECTIVES: The aim of this article is to present the common neurobiological features of both disorders, to characterize the bidirectional relationship and to provide an overview of therapeutic consequences. MATERIAL AND METHODS: A review of the current literature and evaluation of studies on the topics of depression and epilepsy are presented. RESULTS: Epilepsy and depression share common neurobiological features. In epileptic patients depression should be diagnosed early and reliably as the successful treatment has a great influence on the prognosis, quality of life and suicide risk in these individuals. In therapeutic doses, antidepressive medication with noradrenergic and specific serotonergic antidepressants (NaSSA) or selective serotonin reuptake inhibitors (SSRI) imparts no clinically relevant epileptogenic potential; however, it increases the quality of life and could have anticonvulsant effects in patients with epilepsy. Clomipramine, bupropion and maprotiline, however, should not be administered to patients with epilepsy as they are known to lower the seizure threshold.

Levothyroxine effects on depressive symptoms and limbic glucose metabolism in bipolar disorder: a randomized, placebo-controlled positron emission tomography study.

Adding supraphysiologic doses of levothyroxine (L-T4) to standard treatment for bipolar depression shows promise, but the mechanisms underlying clinical improvement are unknown. In a previous pilot study, L-T4 treatment reduced depression scores and activity within the anterior limbic network. Here we extended this work in a randomized, double-blind, placebo-controlled study of patients with bipolar depression. Cerebral glucose metabolism was assessed with positron emission tomography and [F-18]fluorodeoxyglucose before and after 6 weeks of treatment with L-T4 (n=15) or placebo (n=10) in 12 volumes of interest (VOIs): the bilateral thalamus, amygdala, hippocampus, dorsal striatum and ventral striatum, and midline cerebellar vermis and subgenual cingulate cortex. Radioactivity in the VOIs, normalized to whole-brain radioactivity was taken as a surrogate index of glucose metabolism, and markers of thyroid function were assayed. Changes in brain activity and their association with clinical response were assessed using statistical parametric mapping. Adjunctive L-T4 treatment produced a significant decline in depression scores during the 6-week treatment. In patients treated with L-T4, we found a significant decrease in regional activity at P<0.05 after Bonferroni correction in the left thalamus, right amygdala, right hippocampus, left ventral striatum and the right dorsal striatum. Decreases in the left thalamus, left dorsal striatum and the subgenual cingulate were correlated with a reduction in depression scores (P<0.05 after Bonferroni correction). Placebo treatment was associated with a significant decrease in activity only in the right amygdala, and no region had a change in activity that was correlated with change in depression scores. The groups differed significantly in the relationship between the changes in depression scores and in activity in the thalamus bilaterally and the left ventral striatum. The findings provide evidence that administration of supraphysiologic thyroid hormone improves depressive symptoms in patients with bipolar disorder by modulating function in components of the anterior limbic network.

Prediction of antidepressant response to venlafaxine by a combination of early response assessment and therapeutic drug monitoring.

INTRODUCTION: Early assessment of a therapeutic response is a central goal in antidepressant treatment. The present study examined the potential for therapeutic drug monitoring and symptom rating to predict venlafaxine treatment efficacy (measured by overall patient response and remission). METHODS: 88 patients were uptitrated homogenously to 225 mg/day venlafaxine. Serum concentrations of venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODV) were measured at week 2. Continuous psychopathometric ratings were measured for up to 6 weeks by independent study raters. RESULTS: An early improvement was significantly more common in venlafaxine responders than non-responders (χ(2); p=0.007). While ODV serum levels were significantly higher in responders (t test; p=0.006), VEN serum levels, sum level of VEN+ODV and the ratio of ODV/VEN levels were not. Moreover, patients who showed an early response combined with an ODV serum level above the median of 222 ng/mL were significantly more likely to achieve full response (binary logistic model; p<0.01). Sensitivity (84% for early response) and specificity (81% for combination of early response and therapeutic drug monitoring) were sufficient to qualify as a reasonable screening instrument. CONCLUSION: Our results indicate that early improvement and ODV serum concentration are predictive of therapeutic outcome and can thus be used to guide use of the antidepressant venlafaxine.

Hormone receptor and HER2 status in patients with breast cancer by races in southeastern Turkey.

PURPOSE: Hormone receptor (HR) status is a prognostic factor in women with breast cancer and differs among different ethnic groups. HR status among Turkish, Kurdish and Arabic women with breast cancer living in Turkey is unknown and in this study we investigated the relationship between HR and HER2 status and race. METHODS: FA total of 648 women with breast cancer (Turkish 438, Kurdish 174, Arabic 35 and Armenian 1) living in southeastern Turkey and referred to the Department of Radiation Oncology between July 2006-July 2012 were included in the study. Patients were categorized into 4 groups according to their HR status. Estrogen receptor (ER) and progesterone receptor (PR) positive (ER+/PR+), ER positive and PR negative (ER+/PR-), ER negative and PR positive (ER-/PR+) and ER and PR negative (ER-/PR-). Human epidermal growth factor receptor 2 (HER2) status was recorded immunohistochemically (IHC) as negative (0 and 1+), and positive (3+). Statistical analysis included ER, PR, HER2, triple subtypes (combination of ER, PR and HER2), and race. RESULTS: The median age at diagnosis was 48 years (range 20-83). ER+, PR+ and HER2+ patients were 453 (70%), 470 (72.6%) and 206 (32.1%), respectively. ER+/PR+ rates among Turkish and Arabic patients were similar, but were higher than Kurdish patients (p<0.002). Triple-negative (ER-/PR-/HER2-) rates among Kurdish and Arabic patients were similar, but were higher than Turkish patients (p=0.04). CONCLUSION: Turkish, Kurdish and Arabic women with breast cancer in southeastern Turkey differed by HR status. Compared to Turkish and Arabic patients, Kurdish patients had more unfavorable prognostic factors.

Depression with psychotic features is influenced by the polymorphism of the serotonin transporter gene.

INTRODUCTION: Current diagnostic classifications regard psychotic symptoms during depressive episodes as indicators of depression severity. However, growing evidence suggests that depression with psychotic symptoms (MDP) may represent a distinct subtype of depression. In the course of the search for discriminating factors we tested the hypothesis that the serotonin transporter gene (5-HTTLPR) may interact with the manifestation of psychotic symptoms in acute depression. METHODS: 112 inpatients (61 female) with a depressive episode (16 bipolar, 86 unipolar) at admission were genotyped for 5-HTTLPR variants. Psychotic symptoms und general psychopathology were evaluated comprehensively using the Manual of the Association for Methodology and Documentation in Psychiatry (Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie, 1981). For statistical analysis a chi-square test and a logistic regression model was used. RESULTS: 16 (14.3%) out of 112 patients were currently presenting with psychotic symptoms. The primary finding of our study was the higher prevalence of the s-allele of the 5-HTTLPR within the group of MDP patients (Pearson χ²=7.87; df=2; p<0.03). Secondly, in a logistic regression model, 5-HTTLPR was found to significantly contribute to the diagnosis of MDP (χ²=6.5; df=1; p=0.01). This effect was even more pronounced upon comparing only severely depressed patients with MDP patients. From a psychopathological perspective, MDP patients showed higher AMDP hostility and apathy scores but equal AMDP depression scores. DISCUSSION: This is the first study to show an influence of 5-HTTLPR on psychotic symptoms in acutely depressed patients. LIMITATIONS: The lack of a control group and the relatively small sample size limits the present study's findings, thus replication in a larger sample is necessary.

The validity of self-rated psychotic symptoms in depressed inpatients.

BACKGROUND: Self-ratings of psychotic experiences might be biased by depressive symptoms. METHOD: Data from a large naturalistic multicentre trial on depressed inpatients (n=488) who were assessed on a biweekly basis until discharge were analyzed. Self-rated psychotic symptoms as assessed with the 90-Item Symptom Checklist (SCL-90) were correlated with the SCL-90 total score, the SCL-90 depression score, the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale 21 item (HAMD-21) total score, the Montgomery Åsberg Depression Rating Scale (MADRS) total score and the clinician-rated paranoid-hallucinatory score of the Association for Methodology and Documentation in Psychiatry (AMDP) scale. RESULTS: At discharge the SCL-90 psychosis score correlated highest with the SCL-90 depression score (0.78, P<0.001) and with the BDI total score (0.64, P<0.001). Moderate correlations were found for the MADRS (0.34, P<0.001), HAMD (0.37, P<0.001) and AMDP depression score (0.33, P<0.001). Only a weak correlation was found between the SCL-90 psychosis score and the AMDP paranoid-hallucinatory syndrome score (0.15, P<0.001). Linear regression showed that change in self-rated psychotic symptoms over the treatment course was best explained by a change in the SCL-90 depression score (P<0.001). The change in clinician-rated AMDP paranoid-hallucinatory score had lesser influence (P=0.02). CONCLUSIONS: In depressed patients self-rated psychotic symptoms correlate poorly with clinician-rated psychotic symptoms. Caution is warranted when interpreting results from epidemiological surveys using self-rated psychotic symptom questionnaires as indicators of psychotic symptoms. Depressive symptoms which are highly prevalent in the general population might influence such self-ratings.

Access of emotional information to visual awareness in patients with major depressive disorder.

BACKGROUND: According to cognitive theories of depression, negative biases affect most cognitive processes including perception. Such depressive perception may result not only from biased cognitive appraisal but also from automatic processing biases that influence the access of sensory information to awareness. METHOD: Twenty patients with major depressive disorder (MDD) and 20 healthy control participants underwent behavioural testing with a variant of binocular rivalry, continuous flash suppression (CFS), to investigate the potency of emotional visual stimuli to gain access to awareness. While a neutral, fearful, happy or sad emotional face was presented to one eye, high-contrast dynamic patterns were presented to the other eye, resulting in initial suppression of the face from awareness. Participants indicated the location of the face with a key press as soon as it became visible. The modulation of suppression time by emotional expression was taken as an index of unconscious emotion processing. RESULTS: We found a significant difference in the emotional modulation of suppression time between MDD patients and controls. This difference was due to relatively shorter suppression of sad faces and, to a lesser degree, to longer suppression of happy faces in MDD. Suppression time modulation by sad expression correlated with change in self-reported severity of depression after 4 weeks. CONCLUSIONS: Our finding of preferential access to awareness for mood-congruent stimuli supports the notion that depressive perception may be related to altered sensory information processing even at automatic processing stages. Such perceptual biases towards mood-congruent information may reinforce depressed mood and contribute to negative cognitive biases.

Relationship between baseline severity of depression and antidepressant treatment outcome.

INTRODUCTION: Assessment of depression severity is of key importance, since several clinical guidelines recommend choice of treatment dependent on the depression severity grade. Using different tools to assess baseline severity may result in different outcomes. METHODS: This paper describes the results of a multicentre, naturalistic study investigating the relationship between depression symptom severity (using 4 different measures of symptom severity) and clinical outcome among patients hospitalised for depression (N=1 014). Moreover, the impact of differences between methods of measuring depression severity has been investigated. Statistical analyses (univariate measurements, logistic regression models) were conducted to detect coherences and differences between the various methods of severity categorisation. RESULTS: Results revealed different associations between outcome and classification methods. Response or remission rates varied if baseline severity was assessed by different instruments. Moreover, the number of responders increased with higher baseline severity grades of depression, whereas the number of remitters decreased. Additional analyses dependent on outcome criteria using continuous instead of categorical data revealed similar results. DISCUSSION: Baseline severity may be only one of many other important clinical variables that mediate clinical outcome, but it is surely an important one deserving further research and consideration.

[Molecular biological aspects of neuroplasticity: approaches for treating tinnitus and hearing disorders]. / Molekularbiologische Aspekte der Neuroplastizität: Ansätze für die Therapie bei Tinnitus und Hörstörungen.

Peripheral and central structures are involved in the onset of tinnitus. Neuronal plasticity is of special importance for the occurrence of central tinnitus and its persistent form. Neuronal plasticity is the ability of the brain to adapt its own structure (synapses, nerve cells, or even whole areas of the brain) and its organization to modified biological requirements. Neuroplasticity is an ongoing dynamic process. Generally speaking, there are two types of plasticity: synaptic and cortical. Cortical plasticity involves activity-dependent changes in size, connectivity, or in the activation pattern of cortical networks. Synaptic plasticity refers to the activity-dependent change in the strength of synaptic transmission and can affect both the morphology and physiology of the synapse. The stimulation of afferent fibers leads to long-lasting changes in synaptic transmission. This phenomenon is called long-term potentiation (LTP) or long-term depression (LTD). From the perspective of molecular biology, synaptic plasticity is of particular importance for the development of tinnitus and its persistence. Ultimately, the damage to the hair cells, auditory nerve, and excitotoxicity results in an imbalance between LTP and LTD and thus in changes of synaptic plasticity. After excessive acoustic stimulation, LTP can be induced by the increase of afferent inputs, whereas decreased afferent inputs generate LTD. The imbalance between LTP and LTD leads to changes in gene expression and involves changes in neurotransmission, in the expression of the receptors, ion channels, regulatory enzymes, and in direct changes on the synapses. This causes an increase of activity on the cellular level. As a result, the imbalance can lead to hyperactivity in the dorsal cochlear nucleus, inferior colliculus, and in the auditory cortex and, later on, to changes in cortical plasticity leading to tinnitus.

Reduction of irradiated small bowel volume with Trendelenburg position in gynecologic pelvic radiotherapy.

The aim of this study was to assess the effect of Trendelenburg position in comparison to prone position on small bowel volume and treatment dose in gynecologic pelvic external beam radiotherapy using three-dimensional conformal treatment plans. Eight patients with gynecologic cancers, treated with definitive or postoperative pelvic radiotherapy were investigated. Pelvic computerized tomography (CT) scans for treatment planning were performed in prone and 25 degree Trendelenburg positions for each patient. The dose-volume histograms of small bowel within the treatment fields were obtained and compared for both positions. The clinical target volume (CTV) and the planning target volume (PTV) were also defined and evaluated in the subjects. Treatment dose was 5040 cGy to PTV with 180 cGy daily fraction doses in both techniques for all patients. The average irradiated small bowel volume was 726 cc for prone position and 458 cc for the Trendelenburg position. The average irradiated small bowel volume reduction in the Trendelenburg position was 38.0% (95% CI 19.5 +/- 38%) compared with the prone position. The average small bowel percent dose was 25.4% (1280 cGy) for Trendelenburg position and 39.9% (2010 cGy) for prone position. PTV doses were similar in both techniques. The results of this dosimetric study suggest that gynecologic pelvic radiotherapy in the Trendelenburg position decreases the volume of irradiated small bowel compared to prone position and may decrease treatment related small bowel morbidity. Clinical benefit of this position should be evaluated in further clinical studies.

[The significance of stress: its role in the auditory system and the pathogenesis of tinnitus]. / Bedeutung von Stress : Seine Rolle im auditorischen System und bei der Tinnitusentstehung.

Emotional stress is often associated with auditory phenomena such as hyperacusis, tinnitus, Ménière's disease and vertigo. Stress develops as a result of a person's attempts to come to terms with the increased or unexpected demands of his or her environment. Stress serves to protect one from physical danger and to temporarily increase one's performance in order to increase the probability of survival. Sleep and appetite are particularly reduced, while anxiety increases. The mental changes induced by stress may contribute to the onset or exacerbation of tinnitus. The following links exist between the auditory and stress systems: the limbic system, which regulates instinctive behavior and emotions, is linked to the auditory system via the medial geniculate body (amygdala). The hypothalamus, which is the integrative center of the endocrine and autonomic systems, is linked to the auditory system via the inferior colliculus. The reticular system, which is focused on the behavior pattern of attention and excitement, projects serotonergic fibers to all pathways of the auditory system, ranging from the cochlea to the auditory cortex.

Effect of bladder distention on bladder base dose in gynaecological intracavitary high dose rate brachytherapy.

The purpose of this study was to assess the impact of bladder volume on bladder base doses during gynaecological intracavitary high dose rate (HDR) brachytherapy. 42 different intracavitary HDR brachytherapy applications (tandem and ovoid, 25; ovoid, 17) were performed in 41 patients treated for cervical (n = 29) and endometrial (n = 12) cancer. The International Commission on Radiation Units and Measurements (ICRU) bladder reference point (BRP) dose and doses of 17 points selected on the bladder base were calculated using planning orthogonal radiographs taken after applicator placement with 100 ml and 270 ml bladder volumes. The effect of bladder volume on ICRU BRP and bladder base maximum point (BBMP) doses were analysed for both types of applications. Median ICRU BRP doses (in percentage of prescription dose) were 36.2% (18.2-69.8%) and 40.0% (21.0-61.8%) for ovoid applications (p = 0.13) and 34.9% (15.7-81.0%) and 33.8% (16.5-88.1%) for tandem and ovoid applications (p = 0.48) in 100 ml and 270 ml bladder volumes, respectively. Median BBMP doses were 75.1% (33.8-141.0%) and 104.0% (62.8-223.0%) for ovoid applications (p<0.001) and 116% (51.2-242.0%) and 124.0% (62.0-326%) for tandem and ovoid applications (p = 0.018) in 100 ml and 270 ml bladder volumes, respectively. Although the BBMP dose significantly increases, the ICRU BRP dose does not change with increasing bladder volume in gynaecological intracavitary HDR brachytherapy. Increasing bladder volume increases bladder base maximum dose in intracavitary gynaecological brachytherapy.

Safety of high-intensity treatment with the irreversible monoamine oxidase inhibitor tranylcypromine in patients with treatment-resistant depression.

INTRODUCTION: Because the irreversible monoamine oxidase inhibitor tranylcypromine (TCP) was introduced nearly 50 years ago, only few studies exist on today's clinical prescribing practice together with 2nd and 3rd generation psychotropic drugs. METHODS: We performed a practice-based observational study of patients with depression treated with TCP in two psychiatric departments in Berlin to assess side effects, effectiveness, comedication and acceptance of the low-tyramine diet. RESULTS: We identified thirty-two patients treated with TCP at a mean dose of 51.9 mg/day after an average of 3.3 pre-treatments in the current episode. Dosing of TCP and the use of multiple psychotropic comedications indicate a high-intensity treatment. The most frequent side effects resulted from arterial hypotonia (28%). Dietary restrictions were mainly rated as moderate. 59% of patients remitted (HAMD- (21)<9 or CGI-I=1) and 22% responded (HAMD- (21) reduction >50% or CGI-I=2). DISCUSSION: A high-intensity treatment of inpatients with TCP is clinically feasible, i.e., the use of high doses and multiple comedications with a good benefit-risk-ratio. Prospective data aiming at comparisons with modern antidepressants and clarifying further safety issues are warranted.

[Clinical standing of valproate treatment of bipolar disorders]. / Klinischer Stellenwert der Valproat-Therapie bei bipolaren Störungen.

During recent years valproate has been established as a cornerstone for the drug-treatment of bipolar disorder. In Germany, valproate was licensed both for the treatment of acute mania and for maintenance treatment in summer 2005. At this occasion, this review summarises the scientific evidence and clinical experience of well-known experts with valproate-treatment. It was concluded that valproate will continue to be of high clinical significance despite the recent increase of treatment alternatives, both in monotherapy and combination treatment of acute mania, mixed states and maintenance treatment.