Optimizing subjective wellbeing with amisulpride in first episode schizophrenia or related disorders.

BACKGROUND: Subjective response (SR) to antipsychotic medication is relevant for quality of life, adherence and recovery. Here, we evaluate (1) the extent of variation in SR in patients using a single antipsychotic; (2) the association between subjective and symptomatic response; and (3) predictors of SR. METHODS: Open-label, single treatment condition with amisulpride in 339 patients with a first episode of a schizophrenia spectrum disorder, at most minimally treated before inclusion. Patients were evaluated at baseline, before start with amisulpride and after four weeks of treatment with the Subjective Wellbeing under Neuroleptic scale, the Positive and Negative Syndrome Scale, and the Calgary Depression Scale for Schizophrenia. RESULTS: (1) 26.8% of the patients had a substantial favorable SR, and 12.4% of the patients experienced a substantial dysphoric SR during treatment with amisulpride. (2) Modest positive associations were found between SR and 4 weeks change on symptom subscales (r = 0.268-0.390, p values < 0.001). (3) Baseline affective symptoms contributed to the prediction of subjective remission, demographic characteristics did not. Lower start dosage of amisulpride was associated with a more favorable SR (r = -0.215, p < 0.001). CONCLUSIONS: We conclude that variation in individual proneness for an unfavorable SR is substantial and only modestly associated with symptomatic response. We need earlier identification of those most at risk for unfavorable SR and research into interventions to improve SR to antipsychotic medication in those at risk.

Measuring process indicators and adverse events to assess the quality of care for inpatients with psychosis.

BACKGROUND: Research into the quality of care in psychiatry is scarce. Data collection is falling behind that for other fields of medicine and therefore the opportunity to improve care is missed. AIMS: In this medical record study we aim to determine: (i) whether or not patients' physical health indicators are assessed and pharmacological and behavioural treatment interventions applied; (ii) the incidence and nature of adverse events in psychotic inpatients. METHODS: Medical records of inpatients with psychosis admitted to psychiatric wards at Amsterdam UMC, location AMC, Department of psychiatry, were screened with a previously developed and tested two-step patient safety tool. RESULTS: Data of 299 admissions were included. Physical health indicators were not assessed in one-third of cases. Fifty-five percent of the patients were smokers but only 1% received an intervention. The family was actively involved in 43% of the cases. During 11,403 admission days, 235 adverse events had been recorded. The most frequent adverse event was adverse drug reactions (40%), which were mostly related to antipsychotic medication. CONCLUSIONS: In conclusion, quality of care auditing is useful to prioritize areas that need improvement. Future research should focus on interventions to improve the quality of psychiatric care.

Neuropsychological profile of psychogenic jerky movement disorders: importance of evaluating non-credible cognitive performance and psychopathology.

BACKGROUND: Psychogenic movement disorders are disorders of movements that cannot be explained by a known neurological disorder and are assumed to be associated with psychiatric symptoms such as depression and anxiety. OBJECTIVE: To examine the neuropsychological profile of patients with psychogenic movement disorders. METHODS: We examined cognitive functioning using neuropsychological tests in 26 patients with clinically established psychogenic jerky movement disorders (PMD). We included 16 patients with Gilles de la Tourette syndrome (GTS) who served as a patient control group, in addition to 22 healthy control subjects. Non-credible test performance was detected using a Symptom Validity Test (SVT). Psychopathology was also assessed. RESULTS: Apart from a worse performance on a verbal memory task, no evidence of neuropsychological impairments was found in our PMD sample. Interestingly however, patients with PMD reported more cognitive complaints in daily life and performed worse on the SVT than the two other groups. Patients with GTS did not report, or show, cognitive impairments. In patients with PMD, we found associations between verbal learning, SVT performance and severity of depression and anxiety complaints. CONCLUSIONS: We conclude that some patients with PMD show non-credible cognitive symptoms. In contrast, no evident cognitive impairments were present in patients with PMD or GTS. Our study underlines the importance of assessment of non-credible response in patients with PMD. Additionally, non-credible response might aid in the differentiation of PMD from other movement disorders.

Cognition and psychopathology in myoclonus-dystonia.

OBJECTIVE: (1) To study the neuropsychological and psychopathological profile in myoclonus-dystonia (M-D) patients with and without a mutation in the DYT11 gene. (2) To explore whether cognitive and psychiatric impairments are related to severity and duration of motor symptoms. Herewith, this study may help to clarify whether neuropsychological and psychiatric symptoms are associated with the DYT11 mutation or are secondary to the burden of motor impairments that originated in early childhood. METHODS: Extensive batteries of neuropsychological tests and psychiatric questionnaires were administered to DYT11 gene mutation-carrying (MC) M-D patients (n=31), non-mutation-carrying (NMC) M-D patients (n=20) and a healthy control group (n=36). RESULTS: MC M-D patients demonstrated mild impairments in executive functions. On the contrary, with the exception of one type of verbal fluency, no evident cognitive impairments were found in NMC M-D patients. Further, increased rates of anxiety disorders were found only in MC M-D patients, whereas increased rates of depressive symptoms were observed in both M-D groups. Correlation analyses yielded modest associations between severity of myoclonus and executive functions. No relationships were found between neuropsychological test performance and scores on the psychiatric assessments. CONCLUSIONS: The findings of this study suggest that anxiety disorders and executive dysfunctions may be part of the phenotype of M-D patients with a DYT11 mutation, whereas depressive symptoms and semantic fluency impairments may be secondary to suffering from a chronic movement disorder, regardless of DYT11 gene mutation.

The bumpy road to achieve reliability of clinical profile characteristics in psychosis and related disorders.

OBJECTIVES: Profile characteristics are factors that are relevant for diagnosis, prognosis or treatment. The present study aims to develop a set of clinically relevant profile characteristics. Moreover, our goal is to determine the inter-rater reliability (IRR) of the selected profile characteristics. METHODS: Potential profile characteristics were determined by literature review. Assessment of IRR was done by comparing scores on profile characteristics determined by two researchers. We conducted three subsequent studies: (1) assessment of pre-training IRR, (2) IRR following implementation of an instruction manual, (3) IRR after optimizing scoring methods. IRR was measured with the Intraclass Correlation Coefficient (ICC). RESULTS: IRR scores of profile characteristic Illegal activities were high across the three studies (ICC ≥ 0.75). Following training procedures in study 2 and 3, reliability estimates remained low to moderate (ICC < 0.75) for the profile characteristics Support of relatives, Aggression recent and lifetime, substance use and insight recent. IRR scores of the other eight profile characteristics varied from low, moderate to high across studies. CONCLUSION: IRR scores of profile characteristics were highly variable, and mostly inadequate in all three studies. Consequently, further research should focus on specification of severity scores of profile characteristics, optimizing scoring methods and re-evaluation of IRR.

Impaired emotion recognition in music in Parkinson's disease.

Music has the potential to evoke strong emotions and plays a significant role in the lives of many people. Music might therefore be an ideal medium to assess emotion recognition. We investigated emotion recognition in music in 20 patients with idiopathic Parkinson's disease (PD) and 20 matched healthy volunteers. The role of cognitive dysfunction and other disease characteristics in emotion recognition was also evaluated. We used 32 musical excerpts that expressed happiness, sadness, fear or anger. PD patients were impaired in recognizing fear and anger in music. Fear recognition was associated with executive functions in PD patients and in healthy controls, but the emotion recognition impairments of PD patients persisted after adjusting for executive functioning. We found no differences in the recognition of happy or sad music. Emotion recognition was not related to depressive symptoms, disease duration or severity of motor symptoms. We conclude that PD patients are impaired in recognizing complex emotions in music. Although this impairment is related to executive dysfunction, our findings most likely reflect an additional primary deficit in emotional processing.

An old but still burning problem: Inter-rater reliability in clinical trials with antidepressant medication.

BACKGROUND: Antidepressant trials are criticized due to potential methodological flaws. Root causes of failing methodology can be found in insufficient inter-rater reliability (IRR) and training practices, leading to higher placebo response and reduced study-power. However, it is unknown to what extent reliability estimates or training procedures are currently included in antidepressant reports. Therefore, we aimed to determine the proportion of publications concerning double-blind randomized controlled antidepressant trials that report on IRR coefficients and training procedures. METHODS: We extracted all double-blind randomized clinical trials (RCTs) from the meta-analysis of Cipriani et al. (2018) concerning the period from 2000 until January 2016. Further, we conducted a Medline-search for double-blind RCTs from January 2016 until January 2020 for additional reports. We identified IRR coefficients and training procedures in these publications. RESULTS: In total we identified 179 double-blind RCTs. Only 4.5% reported an IRR coefficient whereas 27.9% reported training procedures. LIMITATIONS: We did not contact individual authors for additional information regarding implementation of training procedures or inter-rater reliability assessment. CONCLUSIONS: There is a substantial lack of reporting IRR coefficients and training procedures in RCTs with antidepressant medication. Considering the large implications of insufficient reliability, we urge researchers to conduct and report training procedures and reliability estimations.

Staging and profiling for schizophrenia spectrum disorders: Inter-rater reliability after a short training course.

OBJECTIVE: Clinical staging and profiling have been proposed as a new approach in order to refine the diagnostic assessment of schizophrenia spectrum disorders. However, only limited evidence is available for the inter-rater reliability of the clinical staging and profiling model. The aim of the present study was therefore to determine the inter-rater reliability of the clinical staging and profiling model for schizophrenia spectrum disorders, and to investigate whether a short course can improve inter-rater reliability. METHODS: Consecutively recruited inpatients with schizophrenia spectrum disorders were included between January 2015 and January 2016 (study 1), and between March 2018 and October 2018 (study 2). By contrast with the assessors in study 1, all the assessors in study 2 were trained in clinical staging and profiling. We used the clinical staging model proposed by McGorry and identified profile characteristics. Inter-rater reliability was measured using the Intraclass Correlation Coefficient (ICC). RESULTS: The ICC score for clinical staging in study 1 was moderate (0.578). It improved considerably in study 2 (0.757). In general, the ICC scores for the profile characteristics in studies 1 and 2 ranged from poor to sufficient (0.123-0.781). CONCLUSION: This study demonstrated that inter-rater reliability in clinical staging was sufficient after training. However, inter-rater reliability for clinical profile characteristics was highly variable. The general implementation of the clinical staging model for schizophrenia spectrum disorders is therefore feasible but clinical profile characteristics should be used with caution.

Smoking, symptoms, and quality of life in patients with psychosis, siblings, and healthy controls: a prospective, longitudinal cohort study.

BACKGROUND: The self-medication hypothesis postulates that the high prevalence of smoking in patients with psychosis can be explained by the ameliorating effect of smoking on symptoms. However, there are few large prospective studies testing this hypothesis. We aimed to examine the multi-cross-sectional and prospective associations of changes in smoking behaviour with symptoms and quality of life. METHODS: In this prospective cohort study we recruited patients with a non-affective psychosis (n=1094), unaffected siblings (n=1047), and healthy controls (n=579). Patients aged between 16 and 50 years and diagnosed with a non-affective psychosis according to DSM-IV were recruited by clinicians from four university medical centres and 36 associated mental health-care institutions in the Netherlands and Belgium between Jan 13, 2004, and March 6, 2014. Smoking status and number of cigarettes per day were assessed at baseline, and at 3-year and 6-year follow-up using the Composite International Diagnostic Interview (CIDI). Symptom frequency was self-rated with the Community Assessment of Psychotic Experience (CAPE), and quality of life was assessed by the WHO Quality of Life (WHOQOL) schedule. Multiple linear mixed-effects regression analyses were done accounting for multiple confounders. FINDINGS: At baseline, 729 (67%) of 1094 of patients smoked (mean 17·5 cigarettes per day, SD 8·8) compared with 401 (38%) of 1047 siblings and 145 (25%) of 579 healthy controls. Multi-cross-sectional results of linear mixed-effects analyses showed that smoking in patients and siblings was associated with more frequent positive symptoms (estimate 0·14, SE 0·02, p<0·0001 in patients; 0·03, 0·01, p=0·0019 in siblings), negative symptoms (0·15, 0·03, p<0·0001 in patients; 0·09, 0·02, p<0·0001 in siblings), and depressive symptoms (0·12, 0·03 p<0·0001 in patients; 0·08, 0·02 p<0·0001 in siblings) and lower quality of life (-0·59, 0·11, p<0·0001 in patients; -0·31, 0·09, p=0·0002 in siblings) than non-smokers. In controls, smoking was associated with significantly higher frequency of subclinical positive symptoms (0·03, 0·01, p=0·0016) and depressive symptoms (0·05, 0·03, p=0·0432) than in participants who did not smoke. Patients who started to smoke during follow-up showed a significant increase in self-reported symptoms, particularly positive symptoms (0·161, 0·077, p=0·0381), whereas smoking cessation was not associated with changes in symptoms or quality of life compared with those who showed no change in smoking behaviour. Similar results were obtained for the changes in the number of cigarettes smoked. INTERPRETATION: Our findings do not empirically support the self-medication hypothesis. The absence of long-term symptomatic relief from smoking should encourage clinicians to help patients with psychosis to quit smoking. FUNDING: Dutch Health Research Council, Lundbeck, AstraZeneca, Eli Lilly, Janssen Cilag, Academic Psychiatric Center of the Academic Medical Center, GGZ inGeest, Arkin, Dijk en Duin, GGZ Rivierduinen, Erasmus Medical Center Amsterdam, GGZ Noord Holland Noord, University Medical Center Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Dimence, Mediant, GGNet Warnsveld, Yulius Dordrecht, Parnassia Psycho-medical Center, Maastricht University Medical Center, GGzE, GGZ Breburg, GGZ Oost-Brabant, Vincent van Gogh voor Geestelijke Gezondheid, Mondriaan, Virenze riagg, Zuyderland GGZ, MET GGZ, Universitair Centrum Sint-Jozef Kortenberg, CAPRI University of Antwerp, PC Ziekeren Sint-Truiden, PZ Sancta Maria Sint-Truiden, GGZ Overpelt, OPZ Rekem, University Medical Center Utrecht, Altrecht, GGZ Centraal, and Delta.

Correction: The use and helpfulness of self-management strategies for depression: The experiences of patients.

[This corrects the article DOI: 10.1371/journal.pone.0206262.].

The use and helpfulness of self-management strategies for depression: The experiences of patients.

OBJECTIVE: To explore which of 50 self-management strategies are actually used and which are perceived as most helpful by patients in their day-to-day management of depression, in order to empower patients and promote active engagement in their own care. METHODS: Retrospective study using an online self-report survey to assess the use and perceived helpfulness of 50 previously identified self-management strategies in 193 participants who recently recovered from a major depressive episode. RESULTS: Forty-five of the 50 strategies were used by at least half of all participants and about one third of all participants perceived almost 50% of all strategies as (very) helpful. The most used strategies, such as 'finding strategies to create pleasurable distractions', 'engaging in leisure activities' or 'identifying the cause of the depression', were not always perceived as most helpful. In addition, the perceived most helpful strategies, such as 'completing treatment' and 'leaving the house regularly' were not always the most used ones. CONCLUSIONS: Patients use and perceive a wide range of self-management strategies as helpful to recover from their depression. Patients use and perceive strategies about engagement in treatment and physical activities as being most helpful. These finding may contribute to the further development and implementation of self-management programs for the prevention or the rehabilitation of depression.

Association Between Smoking Behavior and Cognitive Functioning in Patients With Psychosis, Siblings, and Healthy Control Subjects: Results From a Prospective 6-Year Follow-Up Study.

OBJECTIVE: The high prevalence of smoking and cognitive deficits in schizophrenia patients is well known, but findings regarding the association between the two are contradictory, and longitudinal studies are lacking. The authors sought to examine the multi-cross-sectional association between smoking behavior and performance in specific cognitive domains and the longitudinal association between change in smoking behavior and change in cognitive functioning in a large prospective study. METHOD: The authors conducted a cohort study of patients with nonaffective psychosis (N=1,094), their siblings (N=1,047), and healthy control subjects (N=579). At baseline and at 3- and 6-year follow-ups, smoking behavior was assessed with the Composite International Diagnostic Interview and cognitive functioning with a test battery. Multivariate linear mixed-effects regression analyses were conducted to assess associations between smoking and cognitive domains while adjusting for variation in demographic factors, psychopathology, medication, and substance use. Bonferroni correction for multiple testing was applied. RESULTS: At baseline, 66.6% of the patients smoked, compared with 38.3% of the siblings and 25.2% of the control subjects. Significant multi-cross-sectional associations were found between smoking and lower processing speed in the patient and control groups compared with the nonsmoking patient group (estimate=-2.38, SE=0.84) and the nonsmoking control group (estimate=-3.13, SE=1.06). In siblings, smoking was significantly associated with lower performance in working memory and reasoning and problem solving compared with nonsmoking. Also, the number of cigarettes smoked per day was negatively associated with these domains. Patients, but not siblings and control subjects, who quit smoking showed a significant improvement in processing speed (estimate=4.90, SE=1.73). CONCLUSIONS: The study findings indicate that smoking is associated with poorer cognitive performance in patients, their siblings, and healthy control subjects compared with nonsmoking. Smoking cessation may improve processing speed in patients.

Predictors of Adverse Events and Medical Errors Among Adult Inpatients of Psychiatric Units of Acute Care General Hospitals.

OBJECTIVE: The aim of this study was to identify factors associated with the occurrence of adverse events (AEs) or medical errors (MEs) during inpatient psychiatric hospitalizations. METHODS: A full-probability random sample of 4,371 charts from 14 inpatient psychiatric units at acute care general hospitals in Pennsylvania were reviewed in a two-stage process that comprised screening and flagging by nurses followed by review by psychiatrists. AE and ME rates were calculated overall and then stratified by patient and hospital factors. Unadjusted and adjusted logistic regression models examined predictors of AEs and MEs. RESULTS: An AE was identified in 14.5% of hospitalizations (95% confidence interval [CI]=11.7-17.9), and an ME was identified in 9.0% (CI=7.5-11.0). In adjusted analyses, patients with a longer length of stay and older patients had higher odds of experiencing an AE or an ME. Patients ages 31-42 (compared with ages 18-30), with commercial insurance (compared with Medicare or Medicaid or uninsured), or treated at high-volume hospitals (compared with low, medium, or very high) had lower odds of an AE. Patients age 54 or older (compared with ages 18-30), admitted during the weekend, admitted to rural hospitals (compared with urban), or treated at very-high-volume hospitals (compared with high) were more likely to experience an ME. CONCLUSIONS: This study provides insight into factors that put patients and hospitals at increased risk of patient safety events. This information can be used to tailor improvement strategies that enhance the safety of patients treated on general hospital psychiatric units.

Preliminary validation of a clinical staging model in schizophrenia and related disorders.

Clinical staging for schizophrenia and related disorders might provide an ideal means to overcome some limitations of the current diagnostic system and to facilitate early intervention. This study aims to retrospectively explore 1) the validity of a staging model 2) the stability of staging over time, and 3) the clinical factors associated with transition to more chronic stages. Data were derived from the Genetic Risk and Outcome of Psychosis study, a large cohort study of patients with a schizophrenia spectrum disorder. We assigned patients to a clinical stage, according to methods described by McGorry in 2010, using PANSS and GAF measures at baseline and three-year follow-up. Distinction between the stages was best explained by worse symptomatic, social and neurocognitive functioning in the first ('First Episode of Psychosis'), and last stage ('Severe/Persisting illness') as compared to the intermediate stages. Approximately half of the participants changed stages over time. Transition to more chronic stages was associated with worse premorbid functioning, higher levels of hostility and depressive symptoms and lower quality of life at baseline. We conclude that the clinical staging model was applicable in our sample. However, distinction between the intermediate stages and their prognostic validity could be improved.

Dopamine D2-receptor affinity of antipsychotics in relation to subjective well-being in patients with a psychotic disorder.

Dopamine D2-receptor blockade by antipsychotic medication reduces psychotic symptoms, but may reduce subjective well-being. The current study aims to further explore the relation between dopamine D2-receptor affinity and subjective well-being within a large sample of patients with psychotic disorders. Patients participated in a longitudinal naturalistic cohort study: the Genetic Risk and Outcome of Psychosis (GROUP) study. Three groups of antipsychotic medication were created on the basis of their affinity for the D2-receptor: (i) loose or partial agonistic binding, (ii) moderate binding, and (iii) tight binding. Subjective well-being was assessed using the Subjective Well-being under Neuroleptics scale (SWN) at baseline and the 3-year follow-up. In addition, we compared changes in SWN scores when switching to a more 'loose or partial agonistic' binding agent or to a 'tighter' binding agent between baseline and the 3-year follow-up. The final group included 388 patients at baseline and 290 at the 3-year follow-up. No significant differences in the SWN scores were found between the three affinity groups at baseline and the 3-year follow-up. In addition, analyses yielded no significant changes in SWN scores after switching to a more 'loose or partial agonistic' or more 'tight' binding antipsychotic agent. We did not find further support for the hypothesis that subjective well-being is associated with antipsychotics affinity for dopamine D2-receptors. This might imply that the effect of antipsychotic D2-receptors binding on subjective well-being is not large enough to be detected in this cross-sectional study. Other factors besides dopamine antagonism are probably more relevant for subjective well-being.

Efficacy and safety of high-dose baclofen for the treatment of alcohol dependence: A multicentre, randomised, double-blind controlled trial.

Previous randomised placebo-controlled trials with low-to-medium doses of baclofen (30-60mg) showed inconsistent results, but case studies suggested a dose-response effect and positive outcomes in patients on high doses of baclofen (up to 270mg). Its prescription was temporary permitted for the treatment of alcohol dependence (AD) in France, and baclofen is now widely prescribed. Recently, a small RCT found a strong effect of a mean dose of 180mg baclofen. In the present study the efficacy and safety of high doses of baclofen was examined in a multicentre, double-blind, placebo-controlled trial. 151 patients were randomly assigned to either six weeks titration and ten weeks high-dose baclofen (N=58; up to 150mg), low-dose baclofen (N=31; 30mg), or placebo (N=62). The primary outcome measure was time to first relapse. Nine of the 58 patients (15.5%) in the high-dose group reached 150mg and the mean baclofen dose in this group was 93.6mg (SD=40.3). No differences between the survival distributions for the three groups were found in the time to first relapse during the ten-weeks high-dose phase (χ2=0.41; p=0.813) or the 16-weeks complete medication period (χ2=0.04; p=0.982). There were frequent dose-related adverse events in terms of fatigue, sleepiness, and dry mouth. One medication related serious adverse event occurred in the high-dose baclofen group. Neither low nor high doses of baclofen were effective in the treatment of AD. Adverse events were frequent, although generally mild and transient. Therefore, large-scale prescription of baclofen for the treatment of AD seems premature and should be reconsidered.

Qualitative and quantitative aspects of information processing in first psychosis: latent class analyses in patients, at-risk subjects, and controls.

We aimed to determine profiles of information processing deficits in the pathway to first psychosis. Sixty-one subjects at ultrahigh risk (UHR) for psychosis were assessed, of whom 18 converted to a first episode of psychosis (FEP) within the follow-up period. Additionally, 47 FEP and 30 control subjects were included. Using 10 neurophysiological parameters associated with information processing, latent class analyses yielded three classes at baseline. Class membership was related to group status. Within the UHR sample, two classes were found. Transition to psychosis was nominally associated with class membership. Neurophysiological profiles were unstable over time, but associations between specific neurophysiological components at baseline and follow-up were found. We conclude that certain constellations of neurophysiological variables aid in the differentiation between controls and patients in the prodrome and after first psychosis.

Sensory gating in subjects at ultra high risk for developing a psychosis before and after a first psychotic episode.

OBJECTIVES: To explore sensory gating deficits in subjects at Ultra High Risk (UHR) for psychosis before and after transition to a first psychotic episode. METHODS: Sensory gating was assessed with the paired click paradigm in 61 UHR subjects, of whom 18 (30%) made a transition to psychosis (UHR + T) over a 3-year follow-up period and 28 matched healthy controls. Subjects were assessed at inclusion and again after approximately 18 months. P50, N100 (N1) and P200 (P2) sensory gating was established using the amplitude on the first (S1) and second (S2) click, the ratio- (S2/S1) and the difference score (S1-S2). Psychopathology was also assessed. RESULTS: At baseline, UHR + T subjects presented smaller N1 difference scores compared to UHR + NT subjects and controls. The N1 difference score contributed modestly to the prediction of a first psychotic episode. Repeated measure analyses revealed smaller N1 and P2 S1 amplitudes, smaller P2 difference scores and larger P2 ratio's at follow-up compared to baseline in UHR + T subjects. CONCLUSION: The N1 difference score may be helpful in predicting a first psychosis. N1 and P2 sensory gating measures also showed alterations between the prodromal phase and the first psychosis, suggesting that these changes may relate to the onset of a frank psychotic episode.