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The influence of baseline severity on the efficacy of Silexan, a proprietary essential oil from Lavandula angustifolia, in anxiety disorders has not been investigated in a pooled dataset. We report on an individual patient data analysis of all five double-blind, randomized, placebo-controlled trials with Silexan in anxiety disorders. Eligible participants received Silexan 80 mg/d or placebo for 10 weeks. Analyses were based on the Hamilton Anxiety Rating Scale (HAMA), its psychic and somatic anxiety subscores, and the Clinical Global Impressions (CGI) scale. To correlate baseline severity with outcome, patients were segregated into mild, moderate, and severe cases. Altogether 1,172 patients (Silexan, n = 587; placebo, n = 585) were analyzed. For the HAMA total score, we found a significant association between the score at baseline and the treatment effect of Silexan versus placebo at week 10 (p

The second-generation anticonvulsant lamotrigine is widely used in the psychiatric field as a mood stabilizer or antidepressant augmentation therapy. Although particularly older anticonvulsants are known for their potential to cause hypersensitivity syndromes, newer antiepileptic drugs do hold a certain risk as well. Presenting a case of a 32-year-old male inpatient of African ethnicity suffering from a primary severe depressive episode in the course of a recurrent major depressive disorder, we report the occurrence of a rapid-onset drug-induced pneumonitis. Herewith, the interstitial pneumonitis occurred after the initiation of 25 mg lamotrigine as an augmentation therapy. Except for the clear temporal correlation between the administration of lamotrigine and the onset of pneumonitis, we did not reveal any further potentially causal diagnostic hints. Importantly, no relevant genetic variations of metabolizing enzymes or drug interactions resulting in lamotrigine overdosage as a potential cause of toxicity were identified. Our experience with a potentially life-threatening adverse drug reaction shortly after the initiation of the largely well-tolerated lamotrigine suggests a potential side effect under the second-generation anticonvulsant although similar adverse events are deemed to be very rare.

The non-benzodiazepine hypnotic zolpidem is frequently administered as a short term psychopharmacotherapy for insomnia. Although it is well-established in a broad clinical routine and often well-tolerated, severe delirium and complex sleep behavior were reported in rare cases. Hereby, it remains unclear whether zolpidem's potential for delirium might be enhanced when combined with further psychopharmacotherapeutics. The present case report portrays a young male Caucasian inpatient with schizoaffective disorder, who was admitted due to severe hyperactive delirium after a single dose of zolpidem 10 mg that was administered in addition to already established psychopharmacotherapy including clozapine 200 mg/day, aripiprazole 15 mg/day and cariprazine 4.5 mg/day. In detail, disorientation, agitation, confabulations, bizarre behavior, and anterograde amnesia occurred shortly after ingestion of zolpidem and gained in intensity within a couple of hours. Once zolpidem was discontinued, the abovementioned symptoms subsided completely and did not reoccur. Since a clear temporal association could be drawn between the intake of zolpidem and the onset of hyperactive delirium, the present clinical experience should serve as a cautionary note for combining potent sedative-hypnotics and substances with anticholinergic properties, even in young adults in a good general condition. Moreover, our case argues for the necessity of further research into the pathomechanism of the interaction potential of non-benzodiazepines as zolpidem, especially with substances exerting anticholinergic properties, which are known for their potential to precipitate delirium. Therefore, the metabolic pathways of the concurrently administered substances should be further taken into account.

Abstract Background Treatment-resistant depression (TRD) is an important clinical challenge and may present differently between age groups. Methods A total of 893 depressed patients recruited within the framework of the European research consortium “Group for the Studies of Resistant Depression” were assessed by generalized linear models regarding age effects (both as numerical and factorial predictors) on treatment outcome, number of lifetime depressive episodes, hospitalization time, and duration of the current episode. Effects of age as numerical predictor on the severity of common depressive symptoms, measured with Montgomery–Åsberg Depression Rating Scale (MADRS) for two-time points, were assessed by linear mixed models, respectively, for patients showing TRD and treatment response. A corrected p threshold of 0.001 was applied. Results Overall symptom load reflected by MADRS (p 4) for these items both before and after treatment (all p ≤ 0.001). Conclusions In this naturalistic sample of severely ill depressed patients, antidepressant treatment protocols were equally effective in addressing TRD in old age. However, specific symptoms such as sadness, appetite, and concentration showed an age-dependent presentation, impacting residual symptoms in severely affected TRD patients and calling for a precision approach by a better integration of age profiles in treatment recommendations.

Abstract Major depressive disorder (MDD) is associated with abnormal neural circuitry. It can be measured by assessing functional connectivity (FC) at resting-state functional MRI, that may help identifying neural markers of MDD and provide further efficient diagnosis and monitor treatment outcomes. The main aim of the present study is to investigate, in an unbiased way, functional alterations in patients with MDD using a large multi-center dataset from the PsyMRI consortium including 1546 participants from 19 centers ( www.psymri.com ). After applying strict exclusion criteria, the final sample consisted of 606 MDD patients (age: 35.8 ± 11.9 y.o.; females: 60.7%) and 476 healthy participants (age: 33.3 ± 11.0 y.o.; females: 56.7%). We found significant relative hypoconnectivity within somatosensory motor (SMN), salience (SN) networks and between SMN, SN, dorsal attention (DAN), and visual (VN) networks in MDD patients. No significant differences were detected within the default mode (DMN) and frontoparietal networks (FPN). In addition, alterations in network organization were observed in terms of significantly lower network segregation of SMN in MDD patients. Although medicated patients showed significantly lower FC within DMN, FPN, and SN than unmedicated patients, there were no differences between medicated and unmedicated groups in terms of network organization in SMN. We conclude that the network organization of cortical networks, involved in processing of sensory information, might be a more stable neuroimaging marker for MDD than previously assumed alterations in higher-order neural networks like DMN and FPN.

QT interval prolongation and ventricular tachyarrhythmia are potential adverse effects of antidepressant (AD) and antipsychotic- (AP) agents, especially when overdosed. Since AD and AP agents are often prescribed to patients suffering from suicidal intentions, it is essential to estimate these risks in the context of intoxications. This retrospective and naturalistic one-year registry study included 105 patients treated for oral intoxication at the University Department of Emergency Medicine in Vienna, Austria. AD/AP intoxications were present in 26 patients, while in the control group (n = 79) non-AD/AP drugs (n = 54) and exclusively alcohol (n = 25) were the toxic agents. QT intervals, the necessity of intubation, the extent of conscious state, and the subsequent discharge management were compared. The mean age was 34.94 ± 14.6 years, 62 patients (59%) were female. There were no significant between-group differences regarding QT prolongation >470 ms using Bazett’s correction (p = 0.178), or >440 ms using Fridericia’s correction (p = 0.760). No significant group differences concerning the need for intubation were observed (p = 0.747). The AD/AP and the control group did not significantly differ regarding Glasgow Coma Scale scores (p = 0.439). Patients with AD/AP intoxication were significantly more often transferred to the psychiatric department, while discharge to home was more likely in the control group (p = 0.002). These results suggest that the risk of a potentially life-threatening outcome in cases of intoxication with AD/AP is not substantially higher than in other easily available toxic agents, in line with the advantageous risk/benefit ratio of newer ADs and APs.

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.

Abstract Background Seasonal affective disorder (SAD) is a seasonally recurrent type of major depression that has detrimental effects on patients’ lives during winter. Little is known about how it affects patients during summer and about patients’ and physicians’ perspectives on preventive SAD treatment. The aim of our study was to explore how SAD patients experience summers, what type of preventive treatment patients implement, which preventive treatment methods, if any, physicians recommend, and what factors facilitate or hinder implementation/recommendation of SAD prevention. Methods We conducted 15 semi-structured interviews, ten with adult patients with a history of SAD and five with physicians. Transcripts were analyzed by two researchers using an inductive thematic analysis approach. Results One group of patients was able to enjoy summer and ignore thoughts of the upcoming winter. The other group feared the impending depressive episode in winter, and this fear negatively impacted these patients’ well-being during the summer. Preventive treatment was a relevant issue for all patients, and all but one person implemented SAD prevention during summer. We identified six factors that influenced patient use of preventive treatment of SAD. Four factors occur on an individual level (knowledge about disease and preventive treatment options, experience with treatment in acute phase, acceptability of intervention, willingness to take responsibility for oneself), one on an interpersonal level (social and work environment), and one on a structural level (healthcare system). All psychiatrists recommended some kind of preventive intervention, most commonly, lifestyle changes. Four factors influenced psychiatrists in recommending prevention of SAD (patient expectations, disease history and stability, risk/benefit ratio, lack of evidence). Conclusions Success in the implementation of SAD prevention does not solely depend on the willingness of the patients, but is also influenced by external factors. Raising awareness of SAD among general practitioners and low-level access to mental-health support could help patients find appropriate help sooner. To better guide the optimal treatment choice, comparative effectiveness research on treatments to prevent a new onset in patients with a history of SAD and clinical practice guidelines on SAD are needed.

The diagnosis of parkinsonian syndromes in patients with severe depression may be challenging due to overlapping clinical phenomena, especially regarding psychomotor and affective symptoms. [123I]FP-CIT-SPECT is a useful method to detect degenerative parkinsonian disorders. However, some drugs may influence the tracer binding and thus alter the result. We present a case of 56-year-old female inpatient with difficult-to-treat late-onset depression. Since the current major depressive episode (MDE) was accompanied by psychotic features including delusions and hallucinations as well as hypokinesia, stooped posture and hypomimia, underlying degenerative parkinsonism was suspected. The pathologic [123I]FP-CIT-SPECT scan under ongoing antidepressant therapy with bupropion 300 mg/die (serum level of bupropion 43 ng/ml and hydroxybupropion 2,332 ng/ml) showed reduced [123I]FP-CIT binding throughout the striatum. The scan normalized upon a wash-out phase of four half-time periods (serum level of bupropion was 0.4 ng/ml and for hydroxybupropion 80.5 ng/ml). Our report should serve as a cautionary note for use of [123I]FP-CIT in depressed patients, particularly in those treated with drugs interfering with the dopamine transporter. Furthermore, our case argues for a need of consultation of a movement disorder specialist prior to dopamine transporter imaging.

In order to assess whole-brain resting-state fluctuations at a wide range of frequencies, resting-state fMRI data of 20 healthy subjects were acquired using a multiband EPI sequence with a low TR (354 ms) and compared to 20 resting-state datasets from standard, high-TR (1800 ms) EPI scans. The spatial distribution of fluctuations in various frequency ranges are analyzed along with the spectra of the time-series in voxels from different regions of interest. Functional connectivity specific to different frequency ranges (

The serotonin transporter (5-HTT) is abundantly expressed in humans by the serotonin transporter gene SLC6A4 and removes serotonin (5-HT) from extracellular space. A blood-brain relationship between platelet and synaptosomal 5-HT reuptake has been suggested, but it is unknown today, if platelet 5-HT uptake can predict neural activation of human brain networks that are known to be under serotonergic influence.A functional magnetic resonance study was performed in 48 healthy subjects and maximal 5-HT uptake velocity (Vmax) was assessed in blood platelets. We used a mixed-effects multilevel analysis technique (MEMA) to test for linear relationships between whole-brain, blood-oxygen-level dependent (BOLD) activity and platelet Vmax.The present study demonstrates that increases in platelet Vmax significantly predict default-mode network (DMN) suppression in healthy subjects independent of genetic variation within SLC6A4. Furthermore, functional connectivity analyses indicate that platelet Vmax is related to global DMN activation and not intrinsic DMN connectivity.This study provides evidence that platelet Vmax predicts global DMN activation changes in healthy subjects. Given previous reports on platelet-synaptosomal Vmax coupling, results further suggest an important role of neuronal 5-HT reuptake in DMN regulation.