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Intermediate-high risk acute pulmonary embolism (PE) remains associated with substantial mortality despite anticoagulation therapy.The aim of this randomised pilot study was to compare catheter-directed thrombolysis to standard anticoagulation therapy.Intermediate-high risk acute PE patients were admitted to a tertiary care centre (November 2019 to April 2021) and randomised in a 1:1 ratio to catheter-directed thrombolysis (CDT) or standard anticoagulation. Two catheters were used for the infusion of alteplase (1 mg/hr/catheter; total dose 20 mg) in the CDT group. The primary efficacy endpoint targeted improvement of right ventricular (RV) function, a decrease in pulmonary pressure, and a reduction of thrombus burden.Twenty-three patients were included (12 in the CDT group and 11 in the standard care group). The primary efficacy endpoint was achieved more frequently in the CDT group than in the standard care group (7 of 12 patients vs 1 of 11 patients, p=0.0004). An RV/left ventricular ratio reduction ≥25% (evident on computed tomography angiography) was achieved in 7 of 12 patients in the CDT group vs 2 of 11 patients in the standard care group (p=0.03). A systolic pulmonary artery pressure decrease of ≥30% or normotension at 24 hrs after randomisation was present in 10 of 12 patients in the CDT group vs 2 of 11 patients in the standard care group (p=0.001). There was no intracranial or life-threatening bleeding (type 5 or 3c bleeding, according to the Bleeding Academic Research Consortium classification).CDT for intermediate-high risk acute PE appears to be safe and effective. Further research is warranted to assess clinical endpoints.

Silexan is a proprietary active substance produced from Lavandula angustifolia, with proven anxiolytic efficacy in subthreshold and generalized anxiety disorder as well as in mixed anxiety and depressive disorder with beneficial impact on anxiety-related sleep disturbances. The pharmacological profile and clinical observations suggest that Silexan may also have an antidepressant effect. To investigate the effect of Silexan on co-occurring depressive symptoms, we present a meta-analysis of the five placebo-controlled clinical trials hitherto performed with Silexan in subthreshold anxiety (n = 3) and anxiety disorders (n = 2). Patients of all trials received Silexan 1 × 80 mg/day or placebo for 10 weeks according to random assignment. Assessment of the antidepressant effect was based on item ‘depressed mood’ from the Hamilton Anxiety Rating Scale (HAMA) administered in all trials and on the total scores of the Montgomery Åsberg Depression Rating Scale (MADRS) or the Hamilton Depression Rating Scale (HAMD) used in three trials. After 10-week treatment, patients receiving Silexan showed significantly more pronounced score reduction for HAMA item ‘depressed mood’ than those in the placebo group (p = 0.01). Significant superiority of Silexan over placebo could also be shown for mean MADRS or HAMD total score reduction (three studies; p

ZusammenfassungDie unipolare Depression zählt weltweit zu den häufigsten psychischen Erkrankungen und ist mit einer enormen Krankheitslast assoziiert. Trotz Verfügbarkeit von zahlreichen effektiven und gut verträglichen antidepressiv wirksamen Psychopharmakotherapeutika erreicht nur etwa ein Drittel unserer Patientinnen und Patienten auf eine etablierte antidepressive „First-line-Therapie“ eine vollständige Remission. Im Gegensatz dazu spricht ein weiteres Drittel aller Betroffenen auf zwei konsekutive, adäquate antidepressive Therapien mit gleich oder unterschiedlich wirkenden Antidepressiva, die ausreichend hoch dosiert und genügend lange verabreicht wurden, nur unzureichend an und erfüllt somit die Kriterien einer therapieresistenten Depression (TRD). Das Vorhandensein einer TRD stellt für Behandler häufig eine sehr anspruchsvolle, klinische Herausforderung dar. Der folgende Artikel unterstreicht die Wichtigkeit der therapeutischen Beziehung und effektiver, transparenter Kommunikation sowie die absolute Notwendigkeit, das therapeutische Vorgehen strikt nach bestehenden Leitlinien auszurichten, um einen optimalen Therapieerfolg zu gewährleisten. Ein Fallbericht skizziert eine erfolgreiche Anwendung von Esketamin-Nasenspray als höchst effektive neu zugelassene Behandlungsoption.

Introduction Due to favorable antidepressant (AD) efficacy and tolerability, selective-serotonin reuptake inhibitors (SSRIs) are consistently recommended as substances of first choice for the treatment of major depressive disorder (MDD) in international guidelines. However, little is known about the real-world clinical correlates of patients primarily prescribed SSRIs in contrast to those receiving alternative first-line ADs. Methods These secondary analyses are based on a naturalistic, multinational cross-sectional study conducted by the European Group for the Study of Resistant Depression at ten research sites. We compared the socio-demographic and clinical characteristics of 1410 patients with primary MDD, who were either prescribed SSRIs or alternative substances as first-line AD treatment, using chi-squared tests, analyses of covariance, and logistic regression analyses. Results SSRIs were prescribed in 52.1% of MDD patients who showed lower odds for unemployment, current severity of depressive symptoms, melancholic features, suicidality, as well as current inpatient treatment compared to patients receiving alternative first-line ADs. Furthermore, patients prescribed SSRIs less likely received add-on therapies including AD combination and augmentation with antipsychotics, and exhibited a trend towards higher response rates. Conclusion A more favorable socio-demographic and clinical profile associated with SSRIs in contrast to alternative first-line ADs may have guided European psychiatrists’ treatment choice for SSRIs, rather than any relevant pharmacological differences in mechanisms of action of the investigated ADs. Our results must be cautiously interpreted in light of predictable biases resulting from the open treatment selection, the possible allocation of less severely ill patients to SSRIs as well as the cross-sectional study design that does not allow to ascertain any causal conclusions.

Background We aimed to investigate the prescription pattern of pregabalin augmentation of antidepressants in major depressive disorder (MDD) and to explore variables associated with add-on pregabalin treatment. Methods 1410 MDD patients participated in this naturalistic European multicenter study with retrospective assessment of treatment response. Analyses of covariance, chi-squared tests, and binary logistic regressions were accomplished to determine differences in socio-demographic and clinical characteristics between MDD patients with and without pregabalin augmentation. Results Add-on pregabalin was established in 102 (7.23%) MDD patients. Compared to those without receiving pregabalin, pregabalin-treated patients were characterized by a significantly higher likelihood for older age (mean: 54.74 ± 13.08 vs 49.93 ± 14.13 years), unemployment (78.43% vs 51.23%), melancholic features (83.33% vs 58.94%), inpatient treatment (72.55% vs 31.65%), previous psychiatric hospitalizations (13.52 ± 24.82 vs 4.96 ± 19.93 weeks), any somatic comorbidity (68.63% vs 44.57%), comorbid hypertension (37.25% vs 17.51%), more severe depressive symptom severity at the onset of the current episode (mean MADRS: 37.55 ± 9.00 vs 33.79 ± 7.52), receiving augmentation/combination treatment strategies in general (mean number of psychotropic drugs: 3.64 ± 0.92 vs 2.07 ± 1.17), and with antidepressants (50.00% vs 27.91%) and antipsychotics (46.08% vs 24.08%) in particular. Limitations Due to its observational cross-sectional study design, our patient sample might not be fully representative for MDD patients in primary care settings. Conclusions Our findings suggest that add-on pregabalin is particularly administered in more severe/difficult-to-treat MDD conditions, whereas no association between the prescription of adjunctive pregabalin and comorbid anxiety symptoms could be determined.

Introduction We report on a meta-analysis of Silexan, a proprietary active substance produced from Lavandula angustifolia, in subthreshold anxiety, mixed anxiety and depressive disorder (MADD), and generalized anxiety disorder (GAD). Methods The present analyses are based on all currently completed 5 double-blind, randomized, placebo-controlled trials investigating Silexan in adult out-patients who received Silexan 1 × 80 mg/day or placebo for ten weeks according to random assignment (n = 1213). Efficacy was assessed based on the Hamilton Anxiety Rating Scale (HAMA), several anxiety self-rating scales, the Clinical Global Impression (CGI) scale, and the Short Form-36 (SF-36) health status questionnaire. Results After ten weeks’ treatment, Silexan was significantly superior to placebo in reducing the HAMA total score (including the psychic and somatic anxiety sub-scores) and self-rated anxiety. Based on a ≥ 50% HAMA total score reduction, the responder rate ratio was 1.34 favoring Silexan, and the rate ratio of subjects much or very much improved according to the CGI was 1.51. Silexan was also significantly superior in improving the physical and mental health summary scores of the SF-36. There were no significant between-group differences concerning the occurrence of adverse events (AEs), serious AEs, and premature withdrawal due to AEs. Conclusions This meta-analysis demonstrates that Silexan exerts significant anxiolytic effects in subthreshold anxiety, GAD and MADD that were consistently reflected in investigator ratings and patient-reported outcomes, including improvement of health-related life-quality, while showing favorable tolerability and safety.

Contains fulltext : 292377.pdf (Publisher’s version ) (Open Access) BACKGROUND: Serotonin-norepinephrine reuptake inhibitors (SNRIs) are among the most frequently prescribed antidepressants (ADs) for major depressive disorder (MDD), with an increasing trend in the last decade. Given the relative dearth of information regarding rationales for their preferred use as first-line ADs in the broad clinical routine, the present study systematically investigated real-world characteristics of MDD patients prescribed either SNRIs or other AD substances across different countries and treatment settings. METHODS: In the present secondary analyses based on a large European, multi-site, naturalistic and cross-sectional investigation with a retrospective assessment of treatment outcome, we firstly defined the proportion of MDD patients receiving SNRIs as first-line AD psychopharmacotherapy and secondly compared their sociodemographic and clinical characteristics to those patients prescribed alternative first-line ADs during their current major depressive episode (MDE). RESULTS: Within the total sample of 1410 MDD patients, 336 (23.8 %) received first-line SNRIs. Compared to other ADs, SNRIs were significantly associated with inpatient care, suicidality and treatment resistance during the current MDE, and a longer lifetime duration of psychiatric hospitalizations. Moreover, greater severity of depressive symptoms at study entry, higher daily doses of the administered ADs, as well as more frequent prescriptions of psychopharmacotherapeutic add-on strategies in general and antipsychotic augmentation in particular, were significantly related to first-line SNRIs. CONCLUSIONS: Considering the limitations of a cross-sectional and retrospective study design, our data point towards a preferred use of first-line SNRIs in a generally more severely ill MDD patients, although they did not lead to superior treatment outcomes compared to alternative ADs.

Background: Sex-related effects on the evolution and phenotype of major depressive disorder (MDD) were reported previously. Methods: This European multicenter cross-sectional study compared sociodemographic, clinical, and treatment patterns between males and females in a real-world sample of 1410 in- and outpatients with current MDD. Results: Male MDD patients (33.1%) were rather inpatients, suffered from moderate to high suicidality levels, received noradrenergicand specific serotonergic antidepressants (ADs) as first-line AD treatment, generally higher mean AD daily doses, and showed a trend towards a more frequent administration of add-on treatments. Female MDD patients (66.9%) were rather outpatients, experienced lower suicidality levels, comorbid thyroid dysfunction, migraine, asthma, and a trend towards earlier disease onset. Conclusions: The identified divergencies may contribute to the concept of maleand female depressive syndromes and serve as predictors of disease severity and course, as they reflect phenomena that were repeatedly related to treatment-resistant depression (TRD). Especially the greater necessity of inpatient treatment and more complex psychopharmacotherapy in men may reflect increased therapeutic efforts undertaken to treat suicidality and to avoid TRD. Hence, considering sex may guide the diagnostic and treatment processes towards targeting challenging clinical manifestations including comorbidities and suicidality, and prevention of TRD and chronicity.

Background While the association between relationship status and the development of depressive symptoms in the general population were reported previously, its relation to the severity and the course of major depressive disorder (MDD) as well as the treatment patterns and response rates needs to be elucidated. Methods The present international multicenter cross-sectional study performed by the European Group for the Study of Resistant Depression (GSRD) investigated socio-demographic and clinical patterns of relationship status in a real-world sample of 1410 adult in- and outpatients with MDD as primary diagnosis. Results While 49.9% of all MDD patients were partnered, 25.4% were separated, and 24.8% were single. Single relationship status was linked to younger mean age, earlier mean age of onset, and current suicidal risk. Being separated was related to older mean age, unemployment, greater symptom severity, current suicidal risk, and add-on treatment strategies. Partnered relationship status was associated with less frequent current suicidal risk. Limitations The retrospective assessment of treatment response that was exclusively based on psychopharmacotherapeutic strategies should be critically considered and weighed while interpreting the present results providing novel insights into the complex interaction of relationship status with the clinical phenotype of MDD. Conclusions Although MDD patients living in relationships do not seem to be omitted from the evolution of MDD, they may be spared from chronicity and suicidality. Hence, being aware of the current relationship status might support clinicians in the diagnostic and therapeutic process towards optimized management of such challenging clinical phenomena and their negative consequences.

ZusammenfassungEinschränkungen der Bewegungsfreiheit psychiatrischer Patienten im Sinne einer mechanischen Fixierung sind in Österreich im Rahmen des Unterbringungsgesetzes zur Abwehr von Selbst- und Fremdgefährdung zulässig, sofern deren Anwendung verhältnismäßig ist. Neben rechtlichen Aspekten sind im Rahmen von Bewegungseinschränkungen auf das Krankenbett ethische Aspekte in Zusammenhang mit einem sorgfältigen klinischen Management unentbehrlich. International gibt es Bestrebungen, Zwangsmaßnahmen dieser Art in der Psychiatrie zu reduzieren. Breiter Konsensus besteht darüber, dass deren Anwendung als Ultima-Ratio-Intervention zu sehen ist, die ausschließlich in Situationen eingesetzt werden soll, die nicht durch gelindere Maßnahmen zu bewältigen sind. Die vorgestellten Fallvignetten aus der psychiatrischen Intermediate Care Station der Wiener Universitätsklinik sollen dies verdeutlichen.

Objectives Predictors for unfavorable treatment outcome in major depressive disorder (MDD) applicable for treatment selection are still lacking. The database of a longitudinal multicenter study on 1079 acutely depressed patients, performed by the German research network on depression (GRND), allows supervised and unsupervised learning to further elucidate the interplay of clinical and psycho‐sociodemographic variables and their predictive impact on treatment outcome phenotypes. Experimental Procedures Treatment response was defined by a change of HAM‐D 17‐item baseline score ≥50% and remission by the established threshold of ≤7, respectively, after up to eight weeks of inpatient treatment. After hierarchical symptom clustering and stratification by treatment subtypes (serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotic, and lithium augmentation), prediction models for different outcome phenotypes were computed with random forest in a cross‐center validation design. In total, 88 predictors were implemented. Results Clustering revealed four distinct HAM‐D subscores related to emotional, anxious, sleep, and appetite symptoms, respectively. After feature selection, classification models reached moderate to high accuracies up to 0.85. Highest accuracies were observed for the SSRI and TCA subgroups and for sleep and appetite symptoms, while anxious symptoms showed poor predictability. Conclusion Our results support a decisive role for machine learning in the management of antidepressant treatment. Treatment‐ and symptom‐specific algorithms may increase accuracies by reducing heterogeneity. Especially, predictors related to duration of illness, baseline depression severity, anxiety and somatic symptoms, and personality traits moderate treatment success. However, prospectives application of machine learning models will be necessary to prove their value for the clinic.

Objective: To discuss the impact of depression on work and how depression-related sick leave duration could be a potential indicator and outcome for measuring functionality in depression. Methods: Our review was based on a literature search and expert opinion that emerged during a virtual meeting of European psychiatrists that was convened to discuss this topic. Results: Current evidence demonstrates that depression-related sick leave duration is influenced by multiple disease-, patient- and work-related factors, together with societal attitudes towards depression and socioeconomic conditions. A wide variety of pharmacological and non-pharmacological treatments and work-based interventions are effective in reducing depression-related sick leave duration and/or facilitating return to work. Recent real-world evidence showed that patients treated with antidepressant monotherapy appear to recover their working life faster than those receiving combination therapy. Although depression-related sick leave duration was found to correlate with severity of depressive symptoms, it cannot be used alone as a viable marker for disease severity. Conclusions: Given its multifactorial nature, depression-related sick leave duration is not on its own a viable outcome measure of depression severity but could be used as a secondary outcome alongside more formal severity measures and may also represent a useful measure of functionality in depression. Key points Depression in the working population and depression-related sick leave have a profound economic impact on society Depression-related sick leave duration is influenced by multiple disease-, patient- and work-related factors, together with societal attitudes towards depression and socioeconomic conditions A wide variety of pharmacological and non-pharmacological treatments and work-based interventions have been shown to be effective in reducing depression-related sick leave duration and/or facilitating return to work In terms of pharmacological intervention, recent real-world evidence has shown that patients treated with antidepressant monotherapy are able to recover their working life faster than those treated with combination therapy Although depression-related sick leave duration has been shown to correlate with severity of depressive symptoms, it is not a viable outcome measure of depression severity on its own, but could be used as secondary outcome alongside more formal clinician- and patient-rated severity measures Depression-related sick leave duration may, however, represent a viable outcome for measuring functionality in depression.

BACKGROUND: The present multicenter study aimed at defining the clinical profile of patients with major depressive disorder (MDD) and comorbid migraine. METHODS: Demographic and clinical information for 1410 MDD patients with vs without concurrent migraine were compared by descriptive statistics, analyses of covariance, and binary logistic regression analyses. RESULTS: The point prevalence rate for comorbid migraine was 13.5% for female and 6.2% for male patients. MDD + migraine patients were significantly younger, heavier, more likely female, of non-Caucasian origin, outpatient, and suffering from asthma. The presence of MDD + migraine resulted in a significantly higher functional disability. First-line antidepressant treatment strategy revealed a trend towards agomelatine. Second-generation antipsychotics were significantly less often administered for augmentation treatment in migraineurs. Overall, MDD + migraine patients tended to respond worse to their pharmacotherapy. CONCLUSION: Treatment guidelines for comorbid depression and migraine are warranted to ensure optimal efficacy and avoid possible pitfalls in psychopharmacotherapy, including serotonin syndrome., SCOPUS: ar.j, DecretOANoAutActif, info:eu-repo/semantics/published

In this meta-analysis, we aimed to estimate and compare the efficacy of add-on treatment of antidepressants with esketamine nasal spray and second-generation antipsychotics in patients with nonpsychotic major depressive disorder and inadequate response to antidepressants. Searching for acute-phase, double-blind, placebo-controlled, randomized trials, we found 22 second-generation antipsychotic (n = 8363) and 3 intranasal esketamine (n = 641) studies. Mean change in the Montgomery Åsberg Depression Rating Scale total score served as outcome. We determined a higher mean difference (vs placebo) for the pooled esketamine nasal spray trials (mean difference = 4.09, 95% confidence interval: 2.01 to 6.17) than for the pooled second-generation antipsychotic augmentation trials (mean difference = 2.05, 95% confidence interval: 1.51 to 2.59). Thus, the effect size for intranasal esketamine was nearly twice as high as those for the second-generation antipsychotics. This indicates high efficacy of add-on esketamine nasal spray in treatment-resistant major depressive disorder compared with other well-established, evidence-based pharmacological options such as augmentation with second-generation antipsychotics.

Background Augmentation with second-generation antipsychotics (SGAs) represents an evidence-based psychopharmacotherapeutic strategy recommended in case of insufficient response to the first-line antidepressant (AD) treatment in major depressive disorder (MDD). Comparative evidence regarding efficacy and prescription preferences of the individual SGAs is scarce. Methods In the scope of this European, multi-site, naturalistic cross-sectional investigation with retrospective assessment of treatment outcome, we compared sociodemographic and clinical characteristics of 187 MDD patients receiving either quetiapine (n = 150) or aripiprazole (n = 37) as augmentation of their first-line AD psychopharmacotherapy. Results Comorbid posttraumatic stress disorder and diabetes were significantly associated with aripiprazole augmentation in our primary and post-hoc binary logistic regression analyses. Furthermore, we identified an association between aripiprazole co-administration and the presence of additional psychotic features, higher rates of AD combination treatment, and a longer duration of psychiatric hospitalizations during the lifetime, which, however, lost significance after correcting for multiple comparisons. Regarding treatment outcome, we found a trend of higher response rates and greater reductions in severity of depressive symptoms in MDD patients dispensed quetiapine. Conclusions Factors associated with a more chronic and severe profile of MDD seem to encourage clinicians to choose aripiprazole over quetiapine, that was, however, administered in the majority of our MDD patients, which might reflect the current approval situation allowing to prescribe exclusively quetiapine as on-label augmentation in MDD in Europe. Given the retrospective assessment of treatment response, the markedly smaller proportion of patients receiving aripiprazole augmentation generally showing an unfavorable disease profile, and the partially heterogeneous statistical robustness of our findings, further studies are required to elaborate on our observation and to generate unambiguous recommendations regarding the choice of first-line SGA augmentation in MDD.

About two thirds of the patients with major depressive disorder (MDD) do not sufficiently respond to monotherapy with antidepressants (ADs) which makes them reliant on further treatment approaches. Hereby, combination of different ADs and augmentation with second-generation antipsychotics (SGAs) are widely used and recommended psychopharmacotherapeutic strategies. The present secondary analyses are based on an international, naturalistic, cross-sectional multicenter study conducted by the European Group for the Study of Resistant Depression. Comparing socio-demographic and clinical characteristics of 436 adult MDD patients receiving either SGAs (N = 191, 43.8%) or ADs (N = 245, 56.2%), that were additionally administered to their first-line AD psychopharmacotherapy, we aimed to identify possible trajectories of decision-making for clinicians regarding which treatment option to prefer in individual patients. Our most robust findings represent an association of SGA augmentation with the presence of psychotic symptoms, longer mean duration of lifetime psychiatric hospitalizations, employment of further augmentation strategies with mood-stabilizers and benzodiazepines, and a trend towards higher mean daily dosages of their first-line ADs and current suicidal risk. Treatment outcome was not significantly different between patients receiving either SGA augmentation or AD combination. Being aware of limitations inherent to the cross-sectional study design and the lack of randomization, more severe and rather chronic conditions in MDD seemed to encourage clinicians to choose SGA augmentation over AD combination. The fact that mood-stabilizers and/or benzodiazepines were more frequently co-administered with SGAs may represent a requirement of an overall refined psychopharmacotherapy including additional fast-acting agents with potent AD, tranquilizing and anti-suicidal effects in MDD patients experiencing challenging clinical manifestations. New glutamatergic substances seem to be promising in this regard.

Since selective serotonin reuptake inhibitors, that are recommended as first-line antidepressant psychopharmacotherapy for major depressive disorder (MDD), may not be the optimal choice for every patient, antidepressants with different modes of action exerting a distinct set of expectant effects, represent a valuable alternative. Despite the previously observed increased prescription rates of noradrenergic and specific serotonergic antidepressants (NaSSAs) particularly mirtazapine in Europe, the individual profiles of patients primarily prescribed NaSSAs in real-world settings have not been systematically investigated yet. In this secondary analysis based on a European, cross-sectional, naturalistic, multicenter study involving 1410 adult males and females with primary MDD, sociodemographic and clinical variables were compared between patients dispensed NaSSAs and those with alternative first-line antidepressants. Hereby, NaSSAs were administered in 8.6 % of the sample (mirtazapine: n = 114, mianserin: n = 7). We detected associations with older mean age, male sex, unemployment, as well as additional melancholic and catatonic features, inpatient treatment, lower mean daily dosages of the administered antidepressants but higher rates of augmentation with low-potency antipsychotics, and greater mean reductions of depressive symptoms during their current major depressive episodes. Although the study design is unsuitable to draw any causal conclusions, our findings provide a realistic picture of patients eligible for first-line antidepressant treatment with NaSSAs, especially mirtazapine, and underscore the role of this AD substance class in severe MDD. Further, they may represent a promising basis for future systematic research focusing on precision diagnostics and treatment in MDD, that would ideally result in faster responses and better outcomes, especially in the so-called difficult-to-treat conditions including treatment resistant depression.

The promise of machine learning has fueled the hope for developing diagnostic tools for psychiatry. Initial studies showed high accuracy for the identification of major depressive disorder (MDD) with resting-state connectivity, but progress has been hampered by the absence of large datasets. Here we used regular machine learning and advanced deep learning algorithms to differentiate patients with MDD from healthy controls and identify neurophysiological signatures of depression in two of the largest resting-state datasets for MDD. Resting-state functional magnetic resonance imaging data were obtained from the REST-meta-MDD (N=2338) and PsyMRI (N=1039) consortia. Classification of functional connectivity matrices was done using support vector machines (SVM) and graph convolutional neural networks (GCN) and performance was evaluated using 5-fold cross-validation. Results were visualized using GCN-Explainer, an ablation study and univariate t-testing.Mean classification accuracy was 61% for MDD versus controls. Mean accuracy for classifying (non-)medicated subgroups was 62%. Visualization of the results showed that classifications were driven by stronger thalamic connections in both datasets, while nearly all other connections were weaker with small univariate effect sizes.Whole brain resting-state connectivity is a reliable though poor biomarker for MDD, presumably due to disease heterogeneity. Deep learning revealed thalamic hyperconnectivity as a prominent neurophysiological signature of depression in both multicenter studies, which may guide the development of biomarkers in future studies.

The objective of the present multicenter study was to elucidate relevant associations between major depressive disorder (MDD) and comorbid hypertension that are known for their frequent co-occurrence and interaction with regard to functional disability. Demographic and clinical information of altogether 1410 patients were retrieved cross-sectionally. Consecutively, a comparison of patient characteristics between MDD subjects with and without comorbid hypertension were conducted by descriptive statistics, analyses of covariance (ANCOVA) and binary logistic regression analyses. The point prevalence rate for comorbid hypertension was 18.9%. Patients with MDD+comorbid hypertension were significantly older, heavier, more likely to be in a relationship, inpatient and diagnosed with further comorbid chronic somatic diseases including heart disease, diabetes and thyroid dysfunction. In addition, individuals with MDD and comorbid hypertension exhibited a higher score at the Montgomery and Åsberg Depression Rating Scale (MADRS) at onset of the current depressive episode. Melancholic features of depression showed a higher probability. The first line antidepressant treatment did not differ significantly between MDD subjects with versus without comorbid hypertension. Augmentation with pregabalin and combination with one additional antidepressant, however, were more common in the MDD+hypertension group. In conclusion, high blood pressure may influence illness severity and is associated with a distinct psychopathology in MDD patients. Patients with MDD and comorbid hypertension, that seems to be underdiagnosed in MDD patients compared to the general population, are subject to additional somatic diseases in almost 100 percent of the cases and hence, need to be screened and treated accordingly.

The aim of the present study was to estimate the number of patients with a seasonal prescription pattern of antidepressants, which might be taken as a surrogate marker for medicated patients with seasonal affective disorder (SAD). Furthermore, we examined the time course of sick leaves for patients with seasonal and non-seasonal prescriptions of antidepressants. A retrospective analysis of prescription data of all patients insured by the Sickness Fund Burgenland (BGKK) between 2005 and 2016 was performed. Patients with treatment initiation of an antidepressant in the last and first quarter of the year for at least two consecutive years were selected (SAD-med). Patients with continuation treatment in the third quarter and patients with initiation of antidepressant medication in the second and third quarter of the year were excluded. The mean yearly prescription rate for antidepressants was 9.6% in the insured population. 3.0% of patients treated with antidepressants and 0.9% of insured cases satisfied the definition of SAD-med. The mean number of yearly sick leave days was similar for SAD-med patients and those with non-seasonal prescriptions. Time series analysis showed that sick leaves in SAD-med were influenced by seasonal fluctuations for several years after the first antidepressant prescription. Our study sheds light on antidepressant prescription and sick leave patterns in the general population. Compared to the prevalence of SAD, the estimated rate of SAD-med is substantial. Sick leaves appear to be closely linked to antidepressant prescriptions, and show a characteristic time course before and after the initial prescription.

This cross-sectional European multicenter study with retrospective assessment of treatment response sought to determine variables associated with the administration of augmentation strategies with second-generation antipsychotics (SGAs) and lithium in the pharmacotherapy of major depressive disorder (MDD). In 349 DSM-IV-TR MDD patients, differences in socio-demographic, clinical, treatment, and pharmacological features between participants receiving add-on treatment of their antidepressants with either SGAs (n = 318) or lithium (n = 31) were investigated using analyses of covariance, chi-squared tests, and binary logistic regression analyses. As only significant between-group difference, we found SGA augmentation (compared with lithium augmentation) to be associated with high depressive symptom severity expressed by a higher mean Montgomery and Åsberg Depression Rating (MADRS) total score (27.19 ± 11.35 vs 18.87 ± 12.88, F = 14.82, p = .0001) and a higher mean 21-item Hamilton Rating Scale for Depression (HAM-D) total score (21.27 ± 9.30 vs 13.74 ± 9.11, F = 18.60, p = .0001). No significant differences for socio-demographic features, psychotic symptoms, suicidality, psychiatric and somatic comorbidities, antidepressant pharmacotherapy, and other add-on medications could be seen. Even if there was no significant superiority of one augmentation strategy with regard to treatment response pattern, a trend whereupon adjunctive SGAs were more likely dispensed in treatment-resistant and difficult-to-treat MDD conditions could be observed. In terms of the prescription pattern, we could demonstrate that lithium is less frequently used than SGAs in the clinical routine care which may reflect the need of continuous plasma level determinations and the anticipation of adverse effects.

Despite plenty of effective antidepressant (AD) treatments, the outcome of major depressive disorder (MDD) is often unsatisfactory, probably due to improvable exploitation of available therapies. This European, cross-sectional, naturalistic multicenter study investigated the frequency of additional psychotherapy in terms of a manual-driven psychotherapy (MDP) in 1410 adult in- and outpatients with MDD, who were primarily treated with AD psychopharmacotherapy. Socio-demographic and clinical patterns were compared between patients receiving both treatments and those lacking concomitant MDP. In a total of 1279 MDD patients (90.7%) with known status of additional MDP, those undergoing a psychopharmacotherapy-MDP combination (31.2%) were younger, higher educated, more often employed and less severely ill with lower odds for suicidality as compared to patients receiving exclusively psychopharmacotherapy (68.8%). They experienced an earlier mean age of MDD onset, melancholic features, comorbid asthma and migraine and received lower daily doses of their first-line ADs. While agomelatine was more often established in these patients, MDD patients without MDP received selective serotonin reuptake inhibitors more frequently. These two patient groups did not differ in terms of response, non-response and treatment resistant depression (TRD). Accordingly, the employment of additional MDP could not be related to better treatment outcomes in MDD. The fact that MDP was applied in a minority of patients with rather beneficial socio-demographic and clinical characteristics might reflect inferior accessibility of these psychotherapeutic techniques for socially and economically disadvantaged populations., SCOPUS: ar.j, info:eu-repo/semantics/published

Seasonal fluctuations in mood, drive, energy, sleeping- and eating behavior, weight, as well as further important mental and physical functions, and the utilization of light as an effective treatment option were already described by Hippocrates of Kos and Araeteus, the Cappadocian. The concept of the so-called seasonal affective disorder (SAD) as a disruption of the circadian rhythm precipitated by a deficiency of environmental light during darker seasons was first described in the 1980s. Furthermore, chronobiological and hormonal dysregulation in SAD patients was repeatedly shown to be accompanied by alterations on a neuroreceptor and neurotransmitter level and to normalize after remission. Hence, SAD represents one of the most important models of a chronobiological disorder with over 1000 international publications on its aetiology and treatment options, whereby their underpinnings could be elucidated on a clinical as well as molecular level. The present article summarizes the current understanding of etiological mechanisms of SAD and provides an overview of diagnostic and therapeutic strategies, which are based on available international evidence including clinical trials, systematic reviews, and meta-analyses. According to current recommendations of international guidelines, promising treatment options as bright light therapy, psychopharmacotherapy, therapeutic sleep deprivation, and their underlying mechanisms of action are presented.

Highlights • Disturbed glycemic control is an intrinsic feature of schizophrenia. • The neurotransmitter dopamine has a key role in regulating glucose homeostasis. • We studied brain dopamine and blood glucose levels in first episode psychosis. • The relationship between glucose and brain dopamine is altered in schizophrenia., An elemental function of brain dopamine is to coordinate cognitive and motor resources for successful exploitation of environmental energy sources. Dopamine transmission, goal-directed behavior, and glucose homeostasis are altered in schizophrenia patients prior to and after initiation of pharmacological treatment. Thus, we investigated the relationship between blood glucose levels and brain dopamine signaling in drug-naïve patients with first-episode psychosis. We quantified blood glucose levels and binding of the dopamine D2/3 receptor agonist radioligand (+)-[11C]-PHNO in 15 medication-naïve patients and 27 healthy volunteers employing positron emission tomography. Whole-brain voxel-wise linear model analysis identified two clusters of significant interaction between blood glucose levels and diagnosis on (+)-[11C]-PHNO binding-potential values. We observed positive relationships between blood glucose levels and binding-potential values in healthy volunteers but negative ones in patients with first episode psychosis in a cluster surviving rigorous multiple testing correction located in the in the right ventral tegmental area. Another cluster of homologous behavior, however at a lower level of statistical significance, comprised the ventral striatum and pallidum. Extracellular dopamine levels are a major determinant of (+)-[11C]-PHNO binding in the brain. In line with the concept that increased dopamine signaling occurs when goal-directed behavior is needed for restoring energy supply, our data indicate that in healthy volunteers, extracellular dopamine levels are high when blood glucose levels are low and vice-versa. This relationship is reversed in patients with first-episode psychosis, possibly reflecting an underlying pathogenic alteration that links two seemingly unrelated aspects of the illness: altered dopamine signaling and dysfunctional glucose homeostasis.

There is still a debate, if melancholic symptoms can be seen rather as a more severe subtype of major depressive disorder (MDD) or as a separate diagnostic entity. The present European multicenter study comprising altogether 1410 MDD in- and outpatients sought to investigate the influence of the presence of melancholic features in MDD patients. Analyses of covariance, chi-squared tests, and binary logistic regression analyses were accomplished to determine differences in socio-demographic and clinical variables between MDD patients with and without melancholia. We found a prevalence rate of 60.71% for melancholic features in MDD. Compared to non-melancholic MDD patients, they were characterized by a significantly higher likelihood for higher weight, unemployment, psychotic features, suicide risk, inpatient treatment, severe depressive symptoms, receiving add-on medication strategies in general, and adjunctive treatment with antidepressants, antipsychotics, benzodiazepine (BZD)/BZD-like drugs, low-potency antipsychotics, and pregabalin in particular. With regard to the antidepressant pharmacotherapy, we found a less frequent prescription of selective serotonin reuptake inhibitors (SSRIs) in melancholic MDD. No significant between-group differences were found for treatment response, non-response, and resistance. In summary, we explored primarily variables to be associated with melancholia which can be regarded as parameters for the presence of severe/difficult-to treat MDD conditions. Even if there is no evidence to realize any specific treatment strategy in melancholic MDD patients, their prescribed medication strategies were different from those for patients without melancholia.

Since many patients with major depressive disorder (MDD) do not satisfactorily respond to initial antidepressant monotherapy, add-on treatment strategies with other psychiatric compounds are often established. The present European multicenter cross-sectional study comprising 1410 MDD in- and outpatients investigated the prescription pattern of benzodiazepines as add-on treatment in the psychopharmacotherapy of MDD. Analyses of variance, chi-squared tests, and logistic regression analyses were conducted to examine differences in socio-demographic, clinical, and treatment characteristics between benzodiazepine users and non-users. The prescription rate for adjunctive benzodiazepine treatment amounted to 31.35%. The most often administered benzodiazepines were lorazepam (11.13%), clonazepam (6.74%), and alprazolam (6.60%). Benzodiazepine users exhibited more severe depressive symptoms expressed by a higher mean Montgomery and Åsberg Depression Rating Scale total score at study entry (26.92 ± 11.07 vs 23.55 ± 11.23, p

Introduction: An elemental function of brain dopamine is to coordinate cognitive and motor resources for successful exploitation of environmental energy sources. Dopamine transmission, goal-directed behaviour, and glucose homeostasis are altered in schizophrenia patients prior to and after initiation of pharmacological treatment. Thus, we investigated the relationship between blood glucose levels and brain dopamine signalling in drug-naive patients with first-episode psychosis. Methods: We quantified blood glucose levels and binding of the D 3 preferring dopamine D 2/3 receptor agonist radioligand (+)-[11C]-PHNO in 15 medication-naive patients and 27 healthy volunteers employing positron emission tomography. Results: Whole-brain voxel-wise linear model analysis identified two clusters of significant interaction between blood glucose levels and diagnosis on (+)-[11C]-PHNO binding-potential values. One cluster was located in the ventral striatum and pallidum, the other one in the right ventral tegmental area. We observed positive correlations between blood glucose levels and binding-potential values in healthy volunteers but negative correlations in patients with first episode psychosis. Interpretation: Extracellular dopamine levels are a major determinant of (+)-[11C]-PHNO binding in the brain. In line with the concept that increased dopamine signalling occurs when goal-directed behaviour is needed for restoring energy supply, our data indicate that in healthy volunteers, extracellular dopamine levels are low, when blood glucose levels are high and vice-versa. This relationship is reversed in patients with first-episode psychosis, possibly reflecting a pathogenic alteration underlying two seemingly unrelated aspects of the illness: dysfunctional dopamine signalling and glucose homeostasis. Trial Registration: Clinical Trial Registry:EUDRACT 2010-019586-29 Funding: Vienna Science and Technology Fund; Austrian Science Fund; Medical Scientific Fund of the Mayor of the City of Vienna Declaration of Interests: Without relevance to this work, M. Willeit declares to having received speaker honoraria and consulting fees from Janssen-Cilag Pharma GmbH, Austria. Without relevance to this work, W. Wadsak declares to having received speaker honoraria from GE Healthcare, research grants from Ipsen Pharma, Eckert-Ziegler AG, Scintomics and ITG. WW is a part time eployee ofCBmed Ltd (Center for Biomarker Research in Medicine, Graz, Austria). and is a member of advisory boards of Amgen, Chieri and Sanofi-Aventis. M. Hacker received consulting fees and/or honoraria from Bayer Healthcare BMS, Eli Lilly, EZAG, GE Healthcare, Ipsen, ITM, Janssen, Roche, Siemens Healthineers. R. Lanzenberger received travel grants and/or conference speaker honoraria within the last three years from Bruker BioSpin MR, Heel, and support from Siemens Healthcare regarding clinical research using PET/MR. He is a shareholder of the start-up company BM Health GmbH since 2019. S. Kasper received grants/research support, consulting fees and/or honoraria within the last three years from Angelini, AOP Orphan Pharmaceuticals AG, Celegne GmbH, Eli Lilly, Janssen-Cilag Pharma GmbH,KRKA-Pharma, Lundbeck A/S, Mundipharma, Neuraxpharm, Pfizer, Sanofi,Schwabe, Servier, Shire, Sumitomo Dainippon Pharma Co. Ltd. and Takeda. U. Sauerzopf, A. Weidenauer, I. Dajic, M. Bauer, L. Bartova, B. Meyer, L. Nics, C. Philippe, S. Pfaff, V. Pichler, M. Mitterhauser, L. Pezawas and N. Praschak-Rieder have no conflict of interest to declare Ethics Approval Statement: This study was approved by the Ethics-Committee of the Medical University of Vienna and Austrian federal regulatory authorities. All subjects signed an informed consent form.

Objectives: Clinical variables were investigated in the ‘treatment resistant depression (TRD)- III’ sample to replicate earlier findings by the European research consortium ‘Group for the Study of Resistant Depression’ (GSRD) and enable cross-sample prediction of treatment outcome in TRD. Experimental procedures: TRD was defined by a Montgomery and Åsberg Depression Rating Scale (MADRS) score ≥22 after at least two antidepressive trials. Response was defined by a decline in MADRS score by ≥50% and below a threshold of 22. Logistic regression was applied to replicate predictors for TRD among 16 clinical variables in 916 patients. Elastic net regression was applied for prediction of treatment outcome. Results: Symptom severity (odds ratio (OR) = 3.31), psychotic symptoms (OR = 2.52), suicidal risk (OR = 1.74), generalized anxiety disorder (OR = 1.68), inpatient status (OR = 1.65), higher number of antidepressants administered previously (OR = 1.23), and lifetime depressive episodes (OR = 1.15) as well as longer duration of the current episode (OR = 1.022) increased the risk of TRD. Prediction of TRD reached an accuracy of 0.86 in the independent validation set, TRD-I. Conclusion: Symptom severity, suicidal risk, higher number of lifetime depressive episodes, and comorbid anxiety disorder were replicated as the most prominent risk factors for TRD. Significant predictors in TRD-III enabled robust prediction of treatment outcome in TRD-I., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: This European multicenter study aimed to elucidate suicidality in major depressive disorder. Previous surveys suggest a prevalence of suicidality in major depressive disorder of ≥50%, but little is known about the association of different degrees of suicidality with socio-demographic, psychosocial, and clinical characteristics. Methods: We stratified 1410 major depressive disorder patients into 3 categories of suicidality based on the Hamilton Rating Scale for Depression item 3 (suicidality) ratings (0 = no suicidality; 1–2 = mild/moderate suicidality; 3–4 = severe suicidality). Chi-squared tests, analyses of covariance, and Spearman correlation analyses were applied for the data analyses. Results: The prevalence rate of suicidality in major depressive disorder amounted to 46.67% (Hamilton Rating Scale for Depression item 3 score ≥1). 53.33% were allocated into the no, 38.44% into the mild/moderate, and 8.23% into the severe suicidality patient group. Due to the stratification of our major depressive disorder patient sample according to different levels of suicidality, we identified some socio-demographic, psychosocial, and clinical variables differentiating from the patient group without suicidality already in presence of mild/moderate suicidality (depressive symptom severity, treatment resistance, psychotic features, add-on medications in general), whereas others separated only when severe suicidality was manifest (inpatient treatment, augmentation with antipsychotics and benzodiazepines, melancholic features, somatic comorbidities). Conclusions: As even mild/moderate suicidality is associated with a failure of achieving treatment response, adequate recognition of this condition should be ensured in the clinical practice., SCOPUS: ar.j, info:eu-repo/semantics/published

Background Valproic acid (VPA) has been increasingly shown to trigger hyperammonemic encephalopathies in patients suffering from urea cycle defects and in those receiving polypharmacy. Methods We report on two cases of psychiatric inpatients with regular VPA intake who showed severe cognitive impairment due to non-cirrhotic hyperammonaemia without VPA overdosing. Results In the first case, OTC deficiency appeared to be the underlying cause of a comatose state in a middle-aged bipolar female patient. Besides hyperammonemia, we identified increased plasma levels of glutamine and alanine, decreased plasma levels of arginine and urea, as well as increased urinary levels of orotate. In the second case, we observed severe cognitive impairment in a younger male patient with a current psychotic episode with predominant affective symptoms who we treated with polypharmacy including VPA and topiramate. Limitations As this case series focused on individual patients, the results should be interpreted with caution and cannot be generalized. Conclusions In patients receiving VPA, considering urea cycle deficiencies and potential drug interactions seems crucial for avoiding potential life-threatening symptoms.

This international, multicenter, cross-sectional study comprising 1346 adult in- and outpatients with major depressive disorder (MDD) investigated the association between MDD as primary diagnosis and comorbid post-traumatic stress disorder (PTSD). In a cross-sectional data collection process, the presence of comorbid PTSD was determined by the Mini International Neuropsychiatric Interview (MINI) and the patients’ socio-demographic, clinical, psychopharmacological, and response information were obtained. Clinical features between MDD with and without concurrent PTSD were compared using descriptive statistics, analyses of covariance (ANCOVA), and binary logistic regression analyses. 1.49% of the MDD patients suffered from comorbid PTSD. Significantly more MDD + comorbid PTSD patients exhibited atypical features, comorbid anxiety disorders (any comorbid anxiety disorder, panic disorder, agoraphobia, and social phobia), comorbid bulimia nervosa, current suicide risk, and augmentation treatment with low-dose antipsychotic drugs. In the binary logistic regression analyses, the presence of atypical features (odds ratio (OR) = 4.49, 95%CI:1.01–20.12; p≤.05), any comorbid anxiety disorder (OR = 3.89, 95%CI:1.60-9.44; p = .003), comorbid panic disorder (OR = 6.45, 95%CI:2.52–16.51; p = .001), comorbid agoraphobia (OR = 6.51, 95%CI:2.54-16.68; p≤.001), comorbid social phobia (OR = 6.16, 95%CI:1.71–22.17; p≤.001), comorbid bulimia nervosa (OR = 10.39, 95%CI:1.21–88.64; p = .03), current suicide risk (OR = 3.58, 95%CI:1.30–9.91; p = .01), and augmentation with low-potency antipsychotics (OR = 6.66, 95%CI:2.50–17.77; p

Background: As many patients with unipolar depression do not respond sufficiently to initial antidepressant monotherapy, a dose increase of the current administered antidepressant (dose escalation, high-dose treatment) is frequently carried out as next treatment measure. Methods: We conducted a meta-analysis which included all double-blind randomized controlled trials (RCTs) comparing a dose increase of antidepressants directly to continuation of standard-dose treatment in unipolar depressive patients who were non- responders to standard-dose pharmacotherapy. A mean change in the Hamilton Rating Scale for Depression (HAM-D) total score was the primary outcome. Secondary outcomes were response rates and discontinuation rates due to any reason, inefficacy, and adverse effects. Hedges g and risk ratios were calculated as effect sizes. Results: Seven double-blind RCTs (8 study arms) representing 1,208 participants were included. Fluoxetine (N [number of studies] = 2, n [number of patients] = 448), sertraline (N = 2, n = 272), paroxetine (N = 2, n = 146), duloxetine (N = 1, n = 255), and maprotiline (N = 1, n = 87) were investigated. Dose escalation was not more efficacious in HAM-D total score reduction than maintaining standard-dose treatment, neither for the pooled antidepressant group (N = 7, n = 999; Hedges g = -0.04, 95% CI: -0.20 to 0.12; p = 0.63) nor the individual antidepressants. No differences could be determined for response rates, all-cause discontinuation, and drop-outs due to inefficacy. Significantly more patients in the dose escalation group dropped out due to adverse effects than in the standard-dose continuation group. The metaregressions indicate no influence of baseline symptom severity or amounts of dose increments on effect sizes. Conclusions: According to our meta-analytic findings, dose escalation after initial non-response to standard-dose pharmacotherapy cannot be regarded as general evidence-based treatment option in unipolar depression.

Rapid anti-suicidal and antidepressant effects of ketamine have repeatedly been confirmed in unipolar and bipolar depression. Although meaningful antidepressant efficacy of ketamine has also been shown in depressed patients with a history of psychotic symptoms, its administration in psychotic disorders has largely been neglected due to its potential to exacerbate dissociative or psychotic symptoms. Presenting a case of a young female inpatient suffering from schizophrenia with a severe post-psychotic depression, we demonstrate a robust anti-suicidal and antidepressant effect of S-ketamine infusions administered thrice weekly for 3 weeks in total. Importantly, no relevant psychotic or dissociative symptoms occurred during the whole augmentation treatment period leading to a sustained remission of depressive symptoms and suicidality. Our safe and effective experience with intravenous S-ketamine might encourage researchers and clinicians to widen its administration range beyond the diagnosis of depression to enrich the current knowledge of ketamine effects in psychotic disorders.

Objectives: The overview outlines two decades of research from the European Group for the Study of Resistant Depression (GSRD) that fundamentally impacted evidence-based algorithms for diagnostics and psychopharmacotherapy of treatment-resistant depression (TRD). Methods: The GSRD staging model characterising response, non-response and resistance to antidepressant (AD) treatment was applied to 2762 patients in eight European countries. Results: In case of non-response, dose escalation and switching between different AD classes did not show superiority over continuation of original AD treatment. Predictors for TRD were symptom severity, duration of the current major depressive episode (MDE), suicidality, psychotic and melancholic features, comorbid anxiety and personality disorders, add-on treatment, non-response to the first AD, adverse effects, high occupational level, recurrent disease course, previous hospitalisations, positive family history of MDD, early age of onset and novel associations of single nucleoid polymorphisms (SNPs) within the PPP3CC, ST8SIA2, CHL1, GAP43 and ITGB3 genes and gene pathways associated with neuroplasticity, intracellular signalling and chromatin silencing. A prediction model reaching accuracy of above 0.7 highlighted symptom severity, suicidality, comorbid anxiety and lifetime MDEs as the most informative predictors for TRD. Applying machine-learning algorithms, a signature of three SNPs of the BDNF, PPP3CC and HTR2A genes and lacking melancholia predicted treatment response. Conclusions: The GSRD findings offer a unique and balanced perspective on TRD representing foundation for further research elaborating on specific clinical and genetic hypotheses and treatment strategies within appropriate study-designs, especially interaction-based models and randomized controlled trials.

Due to lacking predictors of depression recovery, successful treatment of major depressive disorder (MDD) is frequently only achieved after therapeutic optimization leading to a prolonged suffering of patients. This study aimed to determine neural prognostic predictors identifying non-remitters prior or early after treatment initiation. Moreover, it intended to detect time-sensitive neural mediators indicating depression recovery. This longitudinal, interventional, single-arm, open-label, phase IV, pharmacological functional magnetic resonance imaging (fMRI) study comprised four scans at important stages prior (day 0) and after escitalopram treatment initiation (day 1, 28, and 56). Totally, 22 treatment-free MDD patients (age mean ± SD: 31.5 ± 7.7; females: 50%) suffering from a concurrent major depressive episode without any comorbid DSM-IV axis I diagnosis completed the study protocol. Primary outcome were neural prognostic predictors of depression recovery. Enhanced de-activation of anterior medial prefrontal cortex (amPFC, single neural mediator) indicated depression recovery correlating with MADRS score and working memory improvements. Strong dorsolateral PFC (dlPFC) activation and weak dlPFC-amPFC, dlPFC-posterior cingulate cortex (PCC), dlPFC-parietal lobe (PL) coupling (three prognostic predictors) hinted at depression recovery at day 0 and 1. Preresponse prediction of continuous (dlPFC-PL: R2day1 = 55.9%, 95% CI: 22.6–79%, P day1 = 0.91/0.82) recovery definitions remained significant after leave-one-out cross-validation. Identified prefrontal neural predictors might propel the future development of fMRI markers for clinical decision making, which could lead to increased response rates and adherence during acute phase treatment periods. Moreover, this study underscores the importance of the amPFC in depression recovery.