Dear Doctor Letters regarding citalopram and escitalopram: guidelines vs real-world data.

Dear Doctor Letters (DDLs, Direct Healthcare Professional Communications) from 2011 provided guidance regarding QTc-prolonging effects with risk of torsade de pointes during treatment with citalopram and escitalopram. This study examines the DDLs' effects on prescription behavior. Data from 8842 inpatients treated with citalopram or escitalopram with a primary diagnosis of major depressive disorder (MDD) were derived from a European pharmacovigilance study (Arzneimittelsicherheit in der Psychiatrie, AMSP) from 2001 to 2017. It was examined to what extent new maximum doses were adhered to and newly contraindicated combinations with QTc-prolonging drugs were avoided. In addition, the prescriptions of psychotropic drugs before and after DDLs were compared in all 43,480 inpatients with MDD in the data set. The proportion of patients dosed above the new limit decreased from 8 to 1% in patients ≤ 65 years and from 46 to 23% in patients > 65 years old for citalopram versus 14-5% and 47-31% for escitalopram. Combinations of es-/citalopram with other QTc-prolonging psychotropic drugs reduced only insignificantly (from 35.9 to 30.9%). However, the proportion of patients with doses of quetiapine > 150 mg/day substantially decreased within the combinations of quetiapine and es-/citalopram (from 53 to 35%). After the DDLs, prescription of citalopram decreased and of sertraline increased. The DDLs' recommendations were not entirely adhered to, particularly in the elderly and concerning combination treatments. This might partly be due to therapeutic requirements of the included population. Official warnings should consider clinical needs.

A two-center pilot study on the effects of clinical ethics support on coercive measures in psychiatry.

BACKGROUND: The use of formal coercion such as seclusion, mechanical restraint, and forced medication is one of the most challenging and complex issues in mental health care, on the clinical, the legal, and the ethical level. Clinical ethics support aims at assisting healthcare practitioners in determining the morally most justifiable course of action in these situations. However, the effectiveness of clinical ethics support has hardly been studied so far. METHODS: Monthly moral case deliberation (MCD) was implemented in two acute wards of two different psychiatric hospitals in Switzerland. Frequency and intensity of coercion was measured on ward level (npatients = 405), and the Moral Attentiveness Scale, Knowledge on Coercion Scale, and Staff Attitudes towards Coercion Scale were applied on healthcare practitioner level (nHP = 46). Pre-post-comparisons were conducted using multi-level modeling where appropriate. RESULTS: After implementation of MCD, formal coercion was less frequent (particularly seclusion, small effect size; 9.6 vs. 16.7%, p = .034, Cramér's V = .105) and less intense (particularly mechanical restraint, large effect size; 86.8 ± 45.3 vs. 14.5 ± 12.1 h, exact p = .019, r = -.74), and approval for coercive measures among healthcare practitioners was lower when controlling for the number of MCD sessions attended. CONCLUSIONS: Clinical ethics support such as MCD may be a hitherto underutilized service for the reduction of coercion, complementing existing strategies and programs. Implementing clinical ethics support may help improve quality of care for persons suffering from severe mental illness.

Monitoring the effects of therapeutic interventions in depression through self-assessments.

The treatment of major psychiatric disorders is an arduous and thorny path for the patients concerned, characterized by polypharmacy, massive adverse side effects, modest prospects of success, and constantly declining response rates. The more important is the early detection of psychiatric disorders prior to the development of clinically relevant symptoms, so that people can benefit from early interventions. A well-proven approach to monitoring mental health relies on voice analysis. This method has been successfully used with psychiatric patients to 'objectively' document the progress of improvement or the onset of relapse. The studies with psychiatric patients over 2-4 weeks demonstrated that daily voice assessments have a notable therapeutic effect in themselves. Therefore, daily voice assessments appear to be a lowthreshold form of therapeutic means that may be realized through self-assessments. To evaluate performance and reliability of this approach, we have carried out a longitudinal study on 82 university students in 3 different countries with daily assessments over 2 weeks. The sample included 41 males (mean age 24.2±3.83 years) and 41 females (mean age 21.6±2.05 years). Unlike other research in the field, this study was not concerned with the classification of individuals in terms of diagnostic categories. The focus lay on the monitoring aspect and the extent to which the effects of therapeutic interventions or of behavioural changes are visible in the results of self-assessment voice analyses. The test persons showed an over-proportionally good adherence to the daily voice analysis scheme. The accumulated data were of generally high quality: sufficiently high signal levels, a very limited number of movement artifacts, and little to no interfering background noise. The method was sufficiently sensitive to detect: i) habituation effects when test persons became used to the daily procedure; and ii) short-term fluctuations that exceeded prespecified thresholds and reached significance. Results are directly interpretable and provide information about what is going well, what is going less well, and where there is a need for action. The proposed self-assessment approach was found to be well-suited to serve as a health-monitoring tool for subjects with an elevated vulnerability to psychiatric disorders or to stress-induced mental health problems. Daily voice assessments are in fact a low-threshold form of therapeutic means that can be realized through selfassessments, that requires only little effort, can be carried out in the test person's own home, and has the potential to strengthen resilience and to induce positive behavioural changes.

The new remuneration system TARPSY in Swiss psychiatric hospitals: effects on length of stay and readmissions?

BACKGROUND: In 2018, Switzerland introduced a nationwide case-based prospective remuneration system (TARPSY), with decreasing daily rates for reimbursement of inpatient care in mental health facilities. Initially, there were concerns that declining daily rates could result in early discharges and increased readmission rates. METHODS: We compared length of stay (LOS) and readmission rates for patients in adult and geriatric psychiatry treatment at four psychiatric hospitals between 2017 (the last year with the traditional remuneration system) and 2018 (the first year with TARPSY). RESULTS: A total of 26,324 treatment episodes of 15,464 patients were analysed. The reduction of average LOS was not statistically significant in the first year after the implementation of TARPSY, neither in adult (mean –0.6 days, 95% confidence interval [CI] –1.6 to 0.4; p = 0.226) nor in geriatric psychiatry (mean −1.6 days, 95% CI −3.8 to 0.7; p = 0.178). When compared with the traditional remuneration system with fixed daily rates, the readmission risk was statistically significantly reduced by −9.1% (95% CI −4.9 to −13.1%; p <0.001) in adult psychiatry but not in geriatric psychiatry (−6.8%, 95% CI −19.2 to 7.4%; p = 0.329). CONCLUSIONS: If being evident at all, the effects of the new remuneration system TARPSY on LOS and readmission rates seem to be small. Concerns that declining daily rates in TARPSY would result in early discharges and increased readmission rates did not prove true in adult and geriatric psychiatry.  .

[Acceptance of Psychiatric and Somatic Advance Directives: A Comparison in Psychiatric Patients and Professionals]. / Akzeptanz von psychiatrischen und somatischen Patientenverfügungen: ein Vergleich unter psychiatrischen Patienten und Fachpersonen.

OBJECTIVE: Assessment of the attitudes towards somatic and psychiatric advance directives in the German speaking part of Switzerland. METHODS: Questionnaire for psychiatric patients, psychiatrists, psychologists, psychiatric nurses and peers assessing the attitudes towards three exemplary advance directives. RESULTS: The attitudes were mainly positive in all participating groups. Compared to professionals (79-100 %), the somatic advance directive found approval in significantly less patients (46 %). There were no significant group differences regarding the psychiatric advance directives, but patients (58 % and 84 %) were slightly more agreeing compared to professionals (31-50 % and 62-70 %). CONCLUSION: Psychiatric advance directives seem to be broadly accepted. The development of campaigns might help to raise the awareness about these instruments and increase their usage in clinical practice.

Psychiatric advance directives in Switzerland: Knowledge and attitudes in patients compared to professionals and usage in clinical practice.

BACKGROUND: Psychiatric advance directives (PAD) were shown to be effective in the reduction of coercion and strengthening of the patients` autonomy. Therefore, the Swiss legislation was revised and stipulates that PAD must be taken into account during involuntary hospitalization. This study aimed to analyze knowledge on and attitudes towards this instrument in patients and healthcare practitioners and their usage in clinical practice. METHODS: We developed a structured questionnaire and included patients (n = 110), psychiatrists (n = 205), psychologists (n = 85), nurses (n = 268) and peers (n = 16) to rate their knowledge on and attitudes towards PAD. We registered the existing PAD in patients and peers. The response rate varied between 17% (nurses), 19% (psychologists) 21% (psychiatrists), 33% (peers) and 56% (patients). RESULTS: Only 7% of the participating patients had a PAD. Compared to the other groups, patients had the least knowledge on PAD. Psychiatrists were significantly more critical towards PAD. Concerns that PAD impede necessary and adequate treatment, restrict professionals and result in conflicts between patients and HCP were most frequently named as reason for critical attitudes. CONCLUSIONS: Although being explicitly mentioned in the Swiss legislation the usage of PAD is small. Proactive information and training of psychiatrists might be helpful for a reduction of skeptical attitudes. This might improve the attitudes and lead to active support of patients during the preparation of PAD.

Early Detection of the Risk of Developing Psychiatric Disorders: A Study of 461 Chinese University Students under Chronic Stress.

Chronic stress, a characteristic of modern time, has a significant impact on general health. In the context of psychiatric disorders, insufficient coping behavior under chronic stress has been linked to higher rates of (1) depressive symptoms among subjects of the general population, (2) relapse among patients under treatment for clinical depression, and (3) negative symptoms among subjects with an elevated vulnerability to psychosis. In this normative study we assessed basic coping behavior among 461 Chinese freshman university students along with their consumption behavior and general health in terms of regular exercises, physical health, psychosomatic disturbances, and mental health. The assessments relied on two instruments that have already demonstrated their capability of (1) reliably detecting insufficient coping behavior under chronic stress and (2) reliably quantifying the interrelation between coping behavior and mental health in the Western world. Thus, we aimed to complement existing data and to develop a generally available, socioculturally independent tool that can be used for the early detection of subjects with an elevated risk of mental health problems. Structural analyses yielded essentially the same scales "activity" and "defeatism" as previous studies on 2,500 students from Switzerland, Italy, Spain, the USA, and Argentina. These scales explained 74.3% of the observed variance in coping behavior among the 461 Chinese students. We found highly significant correlations (p < 0.0001) between the "defeatism" scale on the one hand, and the scales "regular use of medicine," "psychosomatic disturbances," and "impaired mental health" on the other. Particularly intriguing was the finding that a neural net classifier could be constructed to identify students with the highest contributions to the interrelation between "coping behavior" and "mental health," yielding a correlation coefficient as high as r = 0.597 for the respective subgroup. Based on the normative data, an online tool for risk assessments was developed with immediate feedback to users. This study provided another piece of evidence regarding the close link between basic coping behavior and mental health, across cultures and ethnicities. In consequence, our approach to quantifying basic coping behavior, along with other risk factors, can be expected to clear the way for an "early" detection of students with an elevated risk of stress-related mental health problems, nota bene prior to the development of clinically relevant symptoms. The socioeconomic impact of the potential prevention of depressive -disorders, and psychiatric disorders in general, may be enormous.

Cutaneous adverse drug reactions to psychotropic drugs and their risk factors - a case-control study.

Cutaneous adverse drug reactions (CADRs) in patients with psychotropic drugs are common. Large studies on the relevant drugs and other risk factors are still scarce. 594 cases of severe CADRs ("cases") were compared with 8085 cases of other adverse drug reactions ("non-cases") documented in a pharmacovigilance program in psychiatry (AMSP) from 1993 to 2014. Logistic regression was carried out to determine risk factors and between-drug differences. CADRs were relatively more prevalent in patients treated with clomipramine, maprotiline, carbamazepine, lamotrigine, acamprosate, clomethiazole and disulfiram as well as with antidepressants and anticonvulsants as drug classes (p < 0.01). For these drugs, significantly more women were found in patients using maprotiline, lamotrigine (not carbamazepine) and in the groups of antidepressants, tricyclics and anticonvulsants (p < 0.01). Women were more vulnerable to CADRs (67% in cases and 56% in non-cases, p < 0.01). The significantly higher rate of CADRs in women was mainly observed under age of 50 years, i.e. during female reproductive years. In a multivariate logistic regression, female sex, the diagnostic group ICD F1 (substance abuse), maprotiline, carbamazepine, lamotrigine and clomethiazole were identified as risk factors of CADRs. The case/non-case approach allowed to identify risk factors based on empirical data rather than experts' evaluations. The new findings of substance abuse and clomethiazole as risk factors for CADRs have to be confirmed in further studies. Since CADRs can be life-threatening, it is important to be aware of risk factors, especially women during their reproductive period and with lamotrigine treatment.

Inflammatory processes and schizophrenia: two independent lines of evidence from a study of twins discordant and concordant for schizophrenic disorders.

The concept of twin concordance involves quantifying the resemblance between co-twins in an "objective" and reproducible way. Yet, quantifying resemblance in the case of complex psychiatric traits like schizophrenic disorders leads to methodological problems, as the yes-no dichotomy of diagnostic schemata does not allow one to assess between-subject differences in psychopathology patterns sufficiently accurately. Therefore, we relied on a multidimensional, quantitative concordance measure that provided a high resolution and differentiation when assessing the resemblance of psychopathology patterns. This concordance measure was central to our investigations into the potential link between schizophrenic disorders and aberrancies of the inflammatory response system. Specifically, we aimed to determine the extent to which (1) the observed variation of between-subject psychopathology concordance among 100 schizophrenic patients and (2) the observed variation of within-pair psychopathology concordance among 71 twin pairs can be explained by immunoglobulin M (IgM) levels. To accomplish this goal, we had to "gauge" in a first step the concordance measure's performance by (1) comparing the psychopathology patterns of 269 index cases suffering from functional psychoses with the respective patterns of the 350 "affecteds" among their first-degree relatives; (2) systematically comparing the psychopathology patterns of 100 unrelated patients with a diagnosis of schizophrenic disorders with each other; and (3) detailing the within-pair concordance of elementary traits among 2734 healthy twin pairs. As to the role of active immune processes in the context of schizophrenic disorders, we found that there exists a 20-30% subgroup of patients for whom aberrancies of the inflammatory response system, as quantified through IgM levels, appeared to be linked to the pathogenesis of schizophrenic disorders (r = 0.7515/0.8184, p < 0.0001). The variation of within-pair psychopathology concordance among twins with schizophrenic disorders was found to be "explainable" in part by chronically elevated IgM levels (24.5% of observed phenotypic variance; p = 0.0434), thus suggesting that monozygotic twins concordant for schizophrenic disorders may possess a less "robust" variant of the inflammatory response system which can more easily be triggered by exogenous factors than the more "robust" variants of discordant pairs. Though the underlying biological mechanisms remain to be detected, our data have cleared the way for an early identification of patients with schizophrenic disorders for whom the inflammatory response system may be a target for therapeutic intervention. Moreover, our results will likely lead to new treatment strategies that involve elements of personalized medicine.

Assessing Chronic Stress, Coping Skills, and Mood Disorders through Speech Analysis: A Self-Assessment 'Voice App' for Laptops, Tablets, and Smartphones.

BACKGROUND: Computerized speech analysis (CSA) is a powerful method that allows one to assess stress-induced mood disturbances and affective disorders through repeated measurements of speaking behavior and voice sound characteristics. Over the past decades CSA has been successfully used in the clinical context to monitor the transition from 'affectively disturbed' to 'normal' among psychiatric patients under treatment. This project, by contrast, aimed to extend the CSA method in such a way that the transition from 'normal' to 'affected' can be detected among subjects of the general population through 10-20 self-assessments. METHODS: Central to the project was a normative speech study of 5 major languages (English, French, German, Italian, and Spanish). Each language comprised 120 subjects stratified according to gender, age, and education with repeated assessments at 14-day intervals (total n = 697). In a first step, we developed a multivariate model to assess affective state and stress-induced bodily reactions through speaking behavior and voice sound characteristics. Secondly, we determined language-, gender-, and age-specific thresholds that draw a line between 'natural fluctuations' and 'significant changes'. Thirdly, we implemented the model along with the underlying methods and normative data in a self-assessment 'voice app' for laptops, tablets, and smartphones. Finally, a longitudinal self-assessment study of 36 subjects was carried out over 14 days to test the performance of the CSA method in home environments. RESULTS: The data showed that speaking behavior and voice sound characteristics can be quantified in a reproducible and language-independent way. Gender and age explained 15-35% of the observed variance, whereas the educational level had a relatively small effect in the range of 1-3%. The self-assessment 'voice app' was realized in modular form so that additional languages can simply be 'plugged in' once the respective normative data become available. Results of the longitudinal self-assessment study in home environments demonstrated that CSA methods work well under most circumstances. CONCLUSIONS: We have successfully developed and tested a self-assessment CSA method that can monitor transitions from 'normal' to 'affected' in subjects of the general population in the broader context of mood disorders. Our easy-to-use 'voice app' evaluates sequences of 10-20 repeated assessments and watches for affect- and stress-induced deviations from baseline that exceed language-, gender-, and age-specific thresholds. Specifically, the 'voice app' provides users with stress-related 'biofeedback' and can help to identify that 10-15% subgroup of the general population that exhibits insufficient coping skills under chronic stress and may benefit from early detection and intervention prior to developing clinically relevant symptoms.

Quantifying insufficient coping behavior under chronic stress: a cross-cultural study of 1,303 students from Italy, Spain and Argentina.

The question of how to quantify insufficient coping behavior under chronic stress is of major clinical relevance. In fact, chronic stress increasingly dominates modern work conditions and can affect nearly every system of the human body, as suggested by physical, cognitive, affective and behavioral symptoms. Since freshmen students experience constantly high levels of stress due to tight schedules and frequent examinations, we carried out a 3-center study of 1,303 students from Italy, Spain and Argentina in order to develop socioculturally independent means for quantifying coping behavior. The data analysis relied on 2 self-report questionnaires: the Coping Strategies Inventory (COPE) for the assessment of coping behavior and the Zurich Health Questionnaire which assesses consumption behavior and general health dimensions. A neural network approach was used to determine the structural properties inherent in the COPE instrument. Our analyses revealed 2 highly stable, socioculturally independent scales that reflected basic coping behavior in terms of the personality traits activity-passivity and defeatism-resilience. This replicated previous results based on Swiss and US-American data. The percentage of students exhibiting insufficient coping behavior was very similar across the study sites (11.5-18.0%). Given their stability and validity, the newly developed scales enable the quantification of basic coping behavior in a cost-efficient and reliable way, thus clearing the way for the early detection of subjects with insufficient coping skills under chronic stress who may be at risk of physical or mental health problems.

Psychopharmacological treatment of 2195 in-patients with borderline personality disorder: A comparison with other psychiatric disorders.

Patients with borderline personality disorder (BPD) are usually prescribed a variety of psychotropic drugs; however, none is recommended in the guidelines nor has any been approved for this indication. As data on drug prescriptions for BPD are sparse, cross-sectional data from the European Drug Safety Project AMSP were used to analyse drug prescriptions of 2195 in-patients with BPD between 2001 and 2011, and the mean values, confidence intervals and regression analyses were calculated. 70% of all BPD patients were medicated with antipsychotics and/or antidepressants, 33% with anticonvulsants, 30% with benzodiazepines, and 4% with lithium; 90% received at least one, 80%≥2, and 54%≥3 psychotropic drugs concomitantly (mean: 2.8). Prescription rates for quetiapine, the single drug most often used in BPD (22%), increased significantly over time. In view of the high percentage of young females with BPD, 18-40 year-old female patients with BPD were compared with patients of the same age but with depression (unipolar and bipolar) and schizophrenia. Typical sedative antipsychotics and anticonvulsants were prescribed more often in BPD than in the other diagnostic groups, with the exception of bipolar depression; this was true for the single substances quetiapine, levomepromazine, chlorprothixene, carbamazepine, and valproate. A limitation of the study was the use of clinical data without verifying the diagnoses by structured interviews. Contrary to the guidelines, about 90% of in-patients with BPD received psychotropic drugs. Polypharmacy was common, and antipsychotics with sedative profiles such as quetiapine and mood-stabilizing anticonvulsants such as valproate appear to be preferred.

Affective state and voice: cross-cultural assessment of speaking behavior and voice sound characteristics--a normative multicenter study of 577 + 36 healthy subjects.

BACKGROUND: Human speech is greatly influenced by the speakers' affective state, such as sadness, happiness, grief, guilt, fear, anger, aggression, faintheartedness, shame, sexual arousal, love, amongst others. Attentive listeners discover a lot about the affective state of their dialog partners with no great effort, and without having to talk about it explicitly during a conversation or on the phone. On the other hand, speech dysfunctions, such as slow, delayed or monotonous speech, are prominent features of affective disorders. METHODS: This project was comprised of four studies with healthy volunteers from Bristol (English: n = 117), Lausanne (French: n = 128), Zurich (German: n = 208), and Valencia (Spanish: n = 124). All samples were stratified according to gender, age, and education. The specific study design with different types of spoken text along with repeated assessments at 14-day intervals allowed us to estimate the 'natural' variation of speech parameters over time, and to analyze the sensitivity of speech parameters with respect to form and content of spoken text. Additionally, our project included a longitudinal self-assessment study with university students from Zurich (n = 18) and unemployed adults from Valencia (n = 18) in order to test the feasibility of the speech analysis method in home environments. RESULTS: The normative data showed that speaking behavior and voice sound characteristics can be quantified in a reproducible and language-independent way. The high resolution of the method was verified by a computerized assignment of speech parameter patterns to languages at a success rate of 90%, while the correct assignment to texts was 70%. In the longitudinal self-assessment study we calculated individual 'baselines' for each test person along with deviations thereof. The significance of such deviations was assessed through the normative reference data. CONCLUSIONS: Our data provided gender-, age-, and language-specific thresholds that allow one to reliably distinguish between 'natural fluctuations' and 'significant changes'. The longitudinal self-assessment study with repeated assessments at 1-day intervals over 14 days demonstrated the feasibility and efficiency of the speech analysis method in home environments, thus clearing the way to a broader range of applications in psychiatry.

Efficacy of Coming Out Proud to reduce stigma's impact among people with mental illness: pilot randomised controlled trial.

BACKGROUND: Facing frequent stigma and discrimination, many people with mental illness have to choose between secrecy and disclosure in different settings. Coming Out Proud (COP), a 3-week peer-led group intervention, offers support in this domain in order to reduce stigma's negative impact. AIMS: To examine COP's efficacy to reduce negative stigma-related outcomes and to promote adaptive coping styles (Current Controlled Trials number: ISRCTN43516734). METHOD: In a pilot randomised controlled trial, 100 participants with mental illness were assigned to COP or a treatment-as-usual control condition. Outcomes included self-stigma, empowerment, stigma stress, secrecy and perceived benefits of disclosure. RESULTS: Intention-to-treat analyses found no effect of COP on self-stigma or empowerment, but positive effects on stigma stress, disclosure-related distress, secrecy and perceived benefits of disclosure. Some effects diminished during the 3-week follow-up period. CONCLUSIONS: Coming Out Proud has immediate positive effects on disclosure- and stigma stress-related variables and may thus alleviate stigma's negative impact.

Insufficient coping behavior under chronic stress and vulnerability to psychiatric disorders.

BACKGROUND: Epidemiological data indicate that 75% of subjects with major psychiatric disorders have their onset of illness in the age range of 17-24 years. An estimated 35-50% of college and university students drop out prematurely due to insufficient coping skills under chronic stress, while 85% of students receiving a psychiatric diagnosis withdraw from college/university prior to the completion of their education. In this study, we aimed at developing standardized means of identifying students with insufficient coping skills under chronic stress and at risk for mental health problems. SAMPLING AND METHODS: A sample of 1,217 college students from 3 different sites in the USA and Switzerland completed 2 self-report questionnaires: the Coping Strategies Inventory (COPE) and the Zurich Health Questionnaire (ZHQ), which assesses 'regular exercises', 'consumption behavior', 'impaired physical health', 'psychosomatic disturbances' and 'impaired mental health'. The data were subjected to structure analyses by means of a neural network approach. We found 2 highly stable and reproducible COPE scales that explained the observed interindividual variation in coping behavior sufficiently well and in a socioculturally independent way. The scales reflected basic coping behavior in terms of 'activity-passivity' and 'defeatism-resilience', and in the sense of stable, socioculturally independent personality traits. RESULTS: Correlation analyses carried out for external validation revealed a close relationship between high scores on the defeatism scale and impaired physical and mental health. This underlined the role of insufficient coping behavior as a risk factor for physical and mental health problems. CONCLUSION: The combined COPE and ZHQ instruments appear to constitute powerful screening tools for insufficient coping skills under chronic stress and for risks of mental health problems.