Oral prolonged-release ketamine in treatment-resistant depression - A double-blind randomized placebo-controlled multicentre trial of KET01, a novel ketamine formulation - Clinical and safety results.

INTRODUCTION: We investigated the antidepressant effects of a novel oral prolonged-release formulation of racemic ketamine (KET01) in patients suffering from treatment-resistant depression (TRD) as add-on therapy. MATERIAL AND METHODS: Patients were randomized to an additional 160 mg/day or 240 mg/day KET01 or placebo for 14 days. The primary endpoint was change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline to day 15. For treatment group comparisons, we used ANOVA with pairwise least squares mean difference tests in a mixed model repeated measures analysis. RESULTS: Twenty-seven patients completed the double-blind protocol before trial premature termination due to poor recruitment during the COVID-19 pandemic. Mean (SD) MADRS scores on day 15 were 23 (10.32) in placebo, 25 (8.28) with 160 mg/day and 17 (10.32) with 240 mg/day KET01. MADRS change was numerically larger but statistically non-significant in the 240 mg/day KET01 group vs placebo on day 7 (-5.67; p = 00.106) and day 15 was (difference: 4.99; p = 00.15). In exploratory analysis, baseline leukocyte count correlated with response to KET01 (p = 00.01). Distribution of adverse event rates were comparable between the treatment arms. Safety analysis did not identify increased risk of suicidality, dissociation, hear rate, systolic and diastolic blood pressure associated with trial treatment. DISCUSSION: Our results suggest that adjunctive oral administration of prolonged-release ketamine at a dose of 240 mg/day shows a positive, although statistically non-significant, trend towards antidepressant efficacy, however, the benefit could not be confirmed due to premature trial termination. Given its ease of use and low side effects, further trials are warranted to investigate this route of ketamine administration as a promising potential treatment of TRD.

[Unemployment and Addiction: The SUNRISE Project]. / Arbeitslosigkeit und Sucht ­ Das SUNRISE-Projekt.

OBJECTIVES: In the SUNRISE-project, the unemployment benefit office refers long-term unemployed clients (25-49 years old) to medical and psychological specialists of an addiction clinic, if substance-related problems are suspected as an obstacle for job placement. The present study aims at characterizing these clients with respect to educational qualifications, vocational training, diagnosed addictive disorders, and other mental disorders. Of special interest is the temporal sequence of unemployment and addictive disorders. METHOD: Officials referred clients to medical examination if substance abuse was suspected. The examination was based on Europ-ASI, diagnosis of mental disorders based on SCID-I and SCID-II. RESULTS: In 87 out of the first 100 examined persons, an addictive disorder was diagnosed, most frequently alcohol-related disorders, and often multiple addictive disorders. These 87 clients were on average 40 years old (SD 8.5), and mostly male (73 out of 87 clients). About one-third had very low school qualification, and 55.2% had not completed vocational training. An additional psychiatric diagnosis was made in 51.7%. Addictive disorders had commenced during adolescence or early adulthood in most cases. The longest duration of continuous employment was 3 years (median). In only a few cases (7.4%), the current period of unemployment had started before regular substance use. CONCLUSION: Many long-term unemployed clients examined here showed deficits in schooling and vocational training, early onset of regular substance use, and additional mental disorders. In most cases, the addictive disorder did not emerge as a consequence of unemployment, but had existed before. Programs combining the efforts of unemployment benefit offices and the healthcare system are needed for these clients to help them gain access to the regular job market.

[Psychiatric interventions for the unemployed]. / Psychiatrische Interventionen für Arbeitslose.

Unemployment is related to a higher risk for psychological distress and mental disorders, which cause individual suffering and socioeconomic costs for society in general. This selective review surveys the relationship between unemployment and psychological well-being and mental disorders. The most important programs for the improvement of the mental health of the unemployed are summarized: 1. Interventions for the unemployed with the aim of improving coping strategies reduce the risk of developing depressive symptoms. 2. The SUPPORT liaison outpatient unit collaborates closely with the unemployment agency and offers a low-threshold screening for mental disorders for unemployed subjects as well as counseling for those in need of treatment. 3. A group training based on cognitive behavioral therapy improves the psychological well-being of unemployed participants. 4. Supported employment is an effective means of placing severely mentally ill patients in a work-place accompanied by an extensive professional support.

Markers of coagulation activation for evaluation of the antithrombotic efficacy of heparin: a prospective study in acute deep venous thrombosis.

The potential value of measurements of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complexes (TAT) and D-dimer for the assessment of antithrombotic efficacy of heparin in acute deep venous thrombosis (DVT) was prospectively investigated. These variables were determined at presentation and subsequently once daily during a course of seven days heparin therapy. Heparin doses were adjusted according to the activated partial thromboplastin time (APTT). Compression ultrasonography was performed at presentation and on day 7 to determine the extent of thrombosis according to a predefined score. Out of a total of 50 patients accrued to the study 44 patients had reduced or unchanged extent of thrombosis, whereas in six patients an extension was documented. Although thrombin generation was significantly inhibited after initiation of heparin therapy as reflected by a decrease in F1 + 2 and TAT levels, these markers were not useful for the detection of patients with DVT extension. In contrast, anti-factor-Xa activities but not APTT measurements were significantly lower in the group of patients with propagation of DVT (median: 0.22 U/ml versus 0.38 U/ml, interquartile range: 0.1-0.33 U/ml versus 0.19-0.55 U/ml; P = 0.001). D-dimer decreased within the first days of heparin therapy but failed to indicate DVT progression. These data suggest that plasma anti-factor-Xa activity correlates better with the antithrombotic efficacy of heparin than APTT measurements and markers of coagulation or fibrinolysis activation.