Intranasal esketamine as therapeutic option: a case report of an adolescent with treatment resistant depression.

Depression is among the most common mental health disorders worldwide and treatment resistant depression (TRD) represents a major challenge for both patients and clinicians. In recent years ketamine has received attention as an antidepressant agent, demonstrating promising results in TRD in adults. To date, few attempts have been made in treating adolescent TRD with ketamine and none have used intranasal application. This paper discusses a case of a 17-year-old female adolescent suffering from TRD who underwent treatment with intranasal esketamine application (Spravato 28 mg). As symptoms showed clinically insignificant improvement despite modest gains in objective assessments (GAF, CGI, MADRS), treatment was prematurely discontinued. However, the treatment was tolerable and side effects were scarce and mild. Although this case report does not demonstrate clinical effectiveness, ketamine may nonetheless be a promising substance in treating TRD in other adolescents. Questions regarding the safety of ketamine use in the rapidly developing brains of adolescents still remain unanswered. To further explore the potential benefits of this treatment method a short term RCTs for adolescents with TRD is recommended.

Conspiracy beliefs and COVID-19 guideline adherence in adolescent psychiatric outpatients: the predictive role of adverse childhood experiences.

BACKGROUND: Conspiracy beliefs have become widespread throughout the COVID-19 pandemic. Previous studies have shown that endorsing conspiracy beliefs leads to lower protective guideline adherence (i.e., wearing face masks), posing a threat to public health measures. The current study expands this research across the lifespan, i.e., in a sample of adolescents with mental health problems. Here, we investigated the association between conspiracy beliefs and guideline adherence while also exploring the predictors of conspiracy beliefs. METHODS: N = 93 adolescent psychiatric outpatients (57% female, mean age: 15.8) were assessed using anonymous paper-pencil questionnaires. Endorsement of generic and COVID-19 conspiracy beliefs was assessed, in addition to items measuring adherence to protective guidelines and mental health (stress, depressive symptoms, emotional/behavioral problems, and adverse childhood experiences). Multiple regressions and supervised machine learning (conditional random forests) were used for analyses. RESULTS: Fourteen percent of our sample fully endorsed at least one COVID-19 conspiracy theory, while protective guidelines adherence was relatively high (M = 4.92, on a scale from 1 to 7). The endorsement of COVID-19 conspiracy beliefs-but not of generic conspiracy beliefs-was associated with lower guideline adherence (ß = - 0.32, 95% CI - 0.53 to - 0.11, p < .001). Conditional random forests suggested that adverse childhood experiences and peer and conduct problems were relevant predictors of both conspiracy belief categories. CONCLUSION: While a significant proportion of our sample of adolescents in psychiatric treatment endorsed conspiracy beliefs, the majority did not. Furthermore, and to some degree, contrary to public perception, we found that adolescents show relatively good adherence to public health measures-even while experiencing a high degree of mental distress. The predictive value of adverse childhood experiences and peer/conduct problems for conspiracy beliefs might be explained by compensatory mechanisms to ensure the safety, structure, and inclusion that conspiracies provide.

Survey to identify depth of penetration of critical incident reporting systems in Austrian healthcare facilities.

Incident reporting systems or so-called critical incident reporting systems (CIRS) were first recommended for use in health care more than 15 years ago. The uses of these CIRS are highly variable among countries, ranging from being used to report critical incidents, falls, or sentinel events resulting in death. In Austria, CIRS have only been introduced to the health care sector relatively recently. The goal of this work, therefore, was to determine whether and specifically how CIRS are used in Austria. A working group from the Austrian Society for Quality and Safety in Healthcare (ASQS) developed a survey on the topic of CIRS to collect information on penetration of CIRS in general and on how CIRS reports are used to increase patient safety. Three hundred seventy-one health care professionals from 274 health care facilities were contacted via e-mail. Seventy-eight respondents (21.0%) completed the online survey, thereof 66 from hospitals and 12 from other facilities (outpatient clinics, nursing homes). In all, 64.1% of the respondents indicated that CIRS were used in the entire health care facility; 20.6% had not yet introduced CIRS and 15.4% used CIRS only in particular areas. Most often, critical incidents without any harm to patients were reported (76.9%); however, some health care facilities also use their CIRS to report patient falls (16.7%), needle stick injuries (17.9%), technical problems (51.3%), or critical incidents involving health care professionals. CIRS are not yet extensively or homogeneously used in Austria. Inconsistencies exist with respect to which events are reported as well as how they are followed up and reported to health care professionals. Further recommendations for general use are needed to support the dissemination in Austrian health care environments.

Clinical study results from a randomized controlled trial of cognitive behavioural guided self-help in patients with partially remitted depressive disorder.

OBJECTIVES: Cognitive behavioural guided self-help has been shown to be effective in mild and moderate depressive disorder. It is not known, however, if it is effective in individuals with partially remitted depressive disorder, which is a serious clinical problem in up to 50-60% of treated patients. This study is the first one to examine the clinical benefit of this intervention in this patient population. DESIGN: For the purpose of this study, a single-blind, randomized controlled design was used. METHOD: We randomized 90 individuals with partially remitted depressive disorder either to cognitive behavioural guided self-help plus psychopharmacotherapy (n = 49) or psychopharmacotherapy alone (n = 41). They were clinically assessed at regular intervals with ratings of depressive symptoms and stress-coping strategies over a 3-week run-in period and a 6-week treatment period. RESULTS: After 6 weeks, intention-to-treat analysis (n = 90) showed that patients treated with cognitive behavioural guided self-help plus psychopharmacotherapy did not have significantly lower scores on the Hamilton Rating Scale of Depression (17-item version; HRSD-17) and on the Beck Depression Inventory (BDI) compared to patients treated with psychopharmacotherapy alone. When negative stress-coping strategies were considered, there was a significant difference between the two groups at the end of treatment with respect to the BDI but not to the HRSD-17. CONCLUSIONS: Guided self-help did not lead to a significant reduction in symptom severity in patients with partially remitted depressive disorder after a 6-week intervention. However, the intervention leads to a reduction of negative stress-coping strategies. PRACTITIONER POINTS: Cognitive behavioural guided self-help did not significantly improve depressive symptoms measured with the Hamilton Rating Scale of Depression (17-item version; HRSD-17) in patients with partially remitted depressive disorder. Improvements were found in reducing negative stress-coping strategies for those allocated to the cognitive behavioural guided self-help, which significantly improved Beck Depression Inventory but not HRSD-17. These findings suggest that cognitive behavioural guided self-help may offer some assistance in managing negative stress-coping strategies.

Migraine in patients with eating disorders: a study using a sister-pair comparison design.

OBJECTIVE: To evaluate the relationship between migraine and eating disorders by applying a special study design. BACKGROUND: To date, only a few studies have assessed eating disorders and eating behavior in patients with migraine. METHODS: The distinctive feature of this design is the comparison of sister pairs with one sister suffering from an eating disorder according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition and the other being free of such disease. RESULTS: We investigated 120 female patients with a median age of 24 years (interquartile range 20-31) as well as their non-eating-disordered sisters with a median age of 24 (20-31) years. Headache was diagnosed according to the International Classification of Headache Disorders, Second Edition. Thirteen sister pairs were concordant for the presence of migraine, 67 were concordant for the absence of migraine and 40 were discordant. Among the latter, 21 patients and 19 controls had migraine. The prevalence of migraine was virtually identical in patients (28%) and controls (27%). CONCLUSION: This clinic-based controlled study using a sister-pair comparison design showed no evidence of an increased prevalence of migraine among patients with eating disorder.

Influence of peak and trough levels of opioid maintenance therapy on driving aptitude.

To evaluate driving aptitude and traffic-relevant performance at peak and trough medication levels in opioid-dependent patients receiving maintenance therapy with either buprenorphine (mean: 13.4 mg) or methadone (52.7 mg) and a medication-free control group, the Addiction Clinic at Medical University Vienna conducted a prospective, open-label trial where 40 opioid-dependent patients maintained either on buprenorphine or methadone were assessed regarding their traffic-relevant performance. Using the standardized Act and React Testsystem (ART) 2020 Standard test battery, traffic-relevant performance was analysed 1.5 h (peak level) and 20 h (trough level) after administration of opioid maintenance therapy. Results showed that patients at trough level had a significantly higher percentage of incorrect reactions (p = 0.03) and more simple errors (p = 0.02) than patients at peak level as well as methadone-maintained patients at peak level tended to perform less well than buprenorphine-maintained patients in some of the test items, e.g. methadone-maintained patients at trough level had a higher number of delayed reactions in the RST3 phase 2 test (p = 0.09) and answered fewer questions correctly in the visual structuring ability test (p = 0.04). This investigation indicates that opioid-maintained patients did not differ significantly at peak vs.trough level in the majority of the investigated items and that both substances do not appear to affect traffic-relevant performance dimensions when given as a maintenance therapy in a population where concomitant consumption would be excluded.

[Cocaine abuse in Vienna and European cities--a multi-center study]. / Kokainmissbrauch in Wien und in europäischen Metropolen--eine multizentrische Studie.

INTRODUCTION: As cocaine consumption seems to have increased over the last decades, the EU has funded this multi-center, cross-sectional survey to investigate cocaine consumption in three different target groups. The study was conducted by the Addiction Clinic, Department of Psychiatry, Medical University Vienna and other nine European cities. METHODS: Data were collected by structured face-to-face interviews. The sample was composed of 211 cocaine abusers out of three target groups: (1) treatment group undergoing opioid maintenance therapy, (2) marginalized scene group and (3) integrated party group. Sociodemographic data such as age, education, employment, monthly expenses on cocaine/crack, data on consumption patterns, physical and mental health and personal needs regarding cocaine consumption were evaluated. Urine toxicology results for cocaine in the treatment group completed the analysis. RESULTS: The marginalized scene group was the oldest with a mean age of 29.35 years, with the highest unemployment rate (mean 25.11 days) and the longest duration of cocaine consumption (mean 5.80 years). They had the highest cocaine consumption pattern with a mean of 22.32 days within the last month. On average 1969 Euros/months was spent for their addiction. The treatment group had the lowest school education with a mean of 10.36 years, but showed a sufficient insight in their cocaine problem. However, the party group (with the lowest mean age, 25.64 years) highly underestimated their drug problem, the mean amount of money they spent for their addiction was 588.99 Euro/months. Structured urine toxicology between 1996 and 2002 in patients undergoing opioid maintenance therapy ("treatment group") revealed a significant increase of concomitant cocaine consumption (1996: 33.1%; 2002: 40.2%; p = 0.044). DISCUSSION: The European trend of increased cocaine use could also be observed in Vienna. One of the greatest barriers for establishing adequate treatment settings for this target group is the difficulty to reach this population. In addition, multiple substance abuse seems to be one of the predominating patterns of cocaine consumption and this aspect should be integrated within treatment (in the treatment and scene groups additional heroin and benzodiapzepines abuse is observed, in the party group intensive alcohol consumption). The Viennese results are in line with those of the other European cities; however, it could not be confirmed that consumption of crack cocaine and binge play a similarly significant role as in cities such as Hamburg or London.

Opioid plasma concentrations in methadone-and buprenorphine-maintained patients.

This is the first trial to compare the relationship of opioid plasma concentrations in methadone-versus buprenorphine-maintained subjects. Sixty subjects (19 females and 41 males) seeking treatment who met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for opioid dependence were recruited and treated at the Drug Addiction Outpatient Clinic at the University of Vienna. Of these, 44 (11 female and 33 male) were included in the analyses of plasma concentrations. Subjects received either daily sublingual buprenorphine (2 mg or 8 mg tablets; maximum daily dose: 8 mg) or oral methadone (racemic R-/S-methadone) and were maintained on a stable dose after an induction period of 2 weeks. Mean dose and mean plasma concentrations were correlated on an individual and collective basis. Correlation was 0.51 for buprenorphine, whereas the score for methadone was 0.69. Intra-individual variation was much higher for buprenorphine (p<0.0001), while the concentration-to-dose ratio was very small. Based on the differences of the pharmacokinetics of blood plasma of the two agents, we tried to explain the differences in the acceptance of treatment, which was significantly lower in the buprenorphine-maintained group. No such differences could be evaluated between completers and dropouts in buprenorphine-maintained subjects, neither concerning withdrawal scores nor dose, plasma concentration, concentration-to-dose ratios or intra-individual variation.

Use of slow-release oral morphine for the treatment of opioid dependence.

AIMS: In addition to methadone, other synthetic opioids are now available for the treatment of opioid dependence. The study investigated the treatment satisfaction of oral slow-release morphine for maintenance therapy in opioid-dependent patients in an open-label 3-week study. DESIGN: We evaluated the treatment satisfaction of oral slow-release morphine hydrochloride for 3 weeks in 110 patients meeting the diagnosis of opioid dependence (DSM-IV 304.0) or polysubstance dependence (DSM-IV 304.9). MEASUREMENTS: Primary outcome measures were the study retention rate, urinalysis for additional illicit consumption other than heroin, cravings and withdrawal symptoms 24 h after the last intake of the medication (duration of action of treatment). FINDINGS: In total, 103 patients completed the study, representing a retention rate of 94%. Patients reported significant improvements in somatic complaints, as well as significant reductions in heroin and cocaine cravings (p < 0.0001) and in additional consumption of cocaine in supervised urinalysis (p = 0.0083). Additional illicit consumption of benzodiazepines remained unchanged. CONCLUSIONS: The high study retention rate implies a good acceptance of slow-release acting oral morphine. However, randomised, double-blind, double-dummy studies with a longer investigational period are needed to meet criteria for evidence-based medicine.

Comparative study of the effectiveness of slow-release morphine and methadone for opioid maintenance therapy.

AIMS: Slow-release morphine may represent a much-needed new pharmacological treatment for opioid dependence. DESIGN: In a 14-week randomized, double-blind, double-dummy, cross-over study oral slow-release morphine was compared with methadone as a treatment for opioid dependency. During two study periods, each consisting of a 1-week titration and a 6-week fixed-dose treatment phase, medication was administered daily under supervised conditions. SETTING: The study was carried out at the Addiction Clinic, Department of Psychiatry, Medical University Vienna. PARTICIPANTS: Sixty-four subjects (56 males, eight females) with opioid dependence participated in the trial. MEASUREMENTS: Efficacy was evaluated on the basis of retention, use of illicit substances based on urinalysis, extent of drug cravings, withdrawal symptoms and general wellbeing. Safety was assessed on the basis of adverse events and clinical and physical examination. Demographic and baseline characteristics were assessed using the European Addiction Severity Index. FINDINGS: Fifty-five patients (86%) completed the study, with a mean methadone dose of 85 mg and a mean slow-release morphine dose of 680 mg. No significant differences in retention or use of illicit substances (opioids, benzodiazepines, cocaine) were observed, irrespective of treatment group or medication. However, patients receiving slow-release morphine had significantly lower depression (P < 0.001) and anxiety scores (P = 0.008) and fewer physical complaints (P < 0.001). CONCLUSIONS: Oral slow-release morphine is as effective as methadone in the treatment of opioid dependency, with comparable safety and tolerability and a greater benefit on patient wellbeing. Greater pharmaceutical diversity represents a modern development in mainstream medicine. Slow-release morphine might represent a future treatment option that will improve long-term outcomes for this target group.

Maintenance therapy with synthetic opioids and driving aptitude.

AIMS: To assess the influence of methadone and buprenorphine maintenance treatment on the driving aptitude of opioid-dependent patients. DESIGN: Prospective, open label, outpatient maintenance, single-blind (investigator) study. PARTICIPANTS AND SETTING: Thirty opioid-dependent patients maintained on either methadone or buprenorphine were recruited from the drug-addiction outpatient clinic in Vienna. MEASUREMENTS: The traffic-relevant performance dimensions of the participants were assessed 22 h after receiving synthetic opioid maintenance therapy, by a series of seven tests constituting the Act & React Test System (ART) 2020 Standard test battery, developed by the Austrian Road Safety Board (ARSB). To test for additional consumption of illicit substances, blood and urine samples were taken at the beginning of the tests. FINDINGS: The patient group only differed from control subjects in two of the ART 2020 Standard tests. During a task to test the subject's attention under monotonous circumstances (Q1 test), patients had a significantly greater number of reactions (p = 0.027) and a significantly higher percentage of incorrect reactions than control subjects. When driving in a dynamic environment (DR2 test) patients had a significantly longer mean decision time (p = 0.029) and mean reaction time (p = 0.009) compared with control subjects. Interestingly, when separated into treatment groups, the mean decision and reaction times of buprenorphine-maintained patients in the DR2 test did not differ from controls, whereas patients maintained on methadone showed significantly prolonged mean decision (p = 0.009) and reaction times (p = 0.004). In this same test, patients who had consumed additional illicit drugs had a longer mean reaction time compared with control subjects (p = 0.036). CONCLUSION: The synthetic opioid-maintained subjects investigated in the current study did not differ significantly in comparison to healthy controls in the majority of the ART 2020 Standard tests.

Neonatal outcome following buprenorphine maintenance during conception and throughout pregnancy.

AIMS: To assess the effects of maternal buprenorphine treatment at conception and during pregnancy on neonates in terms of birth outcomes and neonatal abstinence syndrome (NAS). DESIGN AND SETTING: Prospective, open-label, out-patient maintenance, case report study, conducted at the drug addiction out-patient clinic at the University Hospital Vienna. PARTICIPANTS: Two buprenorphine-maintained pregnant women who had conceived during buprenorphine treatment. Both patients had previously given birth to healthy neonates following induction on to buprenorphine maintenance therapy in the second trimester. MEASUREMENTS: Mothers: urinalysis. Neonates: gestational age at delivery, Apgar scores, birth weight, length and NAS (Finnegan Scale). FINDINGS: Urinalyses were negative for both women for 25 and 38 months, respectively, during the pregnancy period. There were no complications during the course of the pregnancy. The newborns delivered by both women were healthy, birth outcomes were within normal ranges and there were no NAS symptoms requiring treatment. CONCLUSIONS: To our knowledge this is the first report detailing the pregnancies of women treated with buprenorphine at the time of conception and investigated in a prospective study. The NAS noted in neonates born to buprenorphine-maintained mothers appears to be less severe than the NAS observed in neonates born to methadone-maintained mothers. These preliminary data indicate that, in our patient cohort, buprenorphine maintenance at the time of conception and during pregnancy did not seem to affect birth outcome measurements such as pregnancy complications, week of delivery, birth weight, length, umbilical pH or neurodevelopmental progress. Future prospective studies with larger study populations are warranted.

[Slow-release morphine hydrochloride for maintenance therapy of opioid dependence]. / Retardiertes Morphinhydrochlorid in der Erhaltungstherapie Opioidabhängiger.

INTRODUCTION: In Austria, methadone, buprenorphine as well as oral slow-release morphine are used for the treatment of opioid dependence. This controlled examination marks the first time that oral slow-release morphine hydrochloride is applied for maintenance therapy in opioid dependent subjects. METHODS: In order to evaluate the effectiveness of this psychopharmacological medication, we examined patients over a three-week period. Outcome measures were retention rate, additional consumption and the evaluation of opioid withdrawal 24 hours after the last oral medication. RESULTS: Sixty-seven patients were included; sixty-four patients completed the study, representing a retention rate of 94%. During the three-week period, a significant improvement in well-being and a significant reduction in heroin, cocaine and benzodiazepine craving (p < 0.0001) was evaluated. Furthermore, there was a significant reduction of additional consumption of benzodiazepines in supervised urinalysis. Additional consumption of cocaine remained unchanged. Laboratory results showed a significant reduction of CK over the course of investigation. DISCUSSION: The high retention rate of 94% implies a good acceptance and efficacy of the substance. The reduced CK is consistent with a reduction in intravenous application of illegal substances. However, randomized double-blind, double-dummy studies with oral slow-release morphine are needed in order to meet criteria for evidence based medicine.