[Dangerous or in need of care? Professional judgements of individuals with confused behavior]. / Gevaarlijk of hulpbehoevend? Professionele oordelen over personen met onbegrepen gedrag.

BACKGROUND: The number of police reports about nuisance caused by ‘confused persons’ in the Netherlands has been increasing for years. Psychological problems are suspected in a significant amount of the persons concerned. Stigmatization of these persons as dangerous and violent can influence the decision to send someone into mental healthcare or the judicial system. AIM: To investigate initial judgment of a person with confused behavior in a public place by police officers and mental healthcare providers. METHOD: Police officers (n = 53) and mental healthcare providers (n = 78) were presented footage of a person with agitated, hallucinatory and unpredictable behavior in a park. They were asked to answer a number of questions about this person on an online platform. RESULTS: Both groups of professionals considered deployment of mental health care more suitable than deployment of the police. Both groups found the person more needy than dangerous. There were no significant differences between the two groups. No relationship was found between judgment and initial decision. CONCLUSION: Police officers and healthcare providers seem consentient with regard to their first estimation and the approach of the person with confused behavior portrayed by us. Recommendations are made for daily practice and future scientific research.

Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders.

Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p = 1.03 × 10-3; R2 = 1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p = 0.01; R2 = 0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p = 6.84×10-4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p = 8.44×10-3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p = 3.78×10-7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia.

Renal concentrating ability and glomerular filtration rate in lithium-treated patients.

BACKGROUND: Lithium is the most effective drug for mood stabilization in bipolar disorder. However, lithium exposure has been associated with an impaired renal concentrating ability (RCA) and glomerular filtration rate (GFR). We examined RCA and estimated GFR in a cohort of patients treated with lithium. METHODS: 134 patients (≥ 18 years of age) with a mood disorder treated with lithium were screened; 100 patients were included. Demographic and clinical characteristics and blood and urine samples were collected. Additionally, a dDAVP-test was performed to determine maximal RCA. RESULTS: A dDAVP-test was performed in 98 patients (37 males, 61 females). Mean age was 51 years (SD: 12), median duration of lithium therapy 7 years (IQR: 4-15), mean maximal urine osmolality (Uosmol) 725 mOsmol/kg (SD: 153), and median eGFR 84 ml/min/1.73 m2 (IQR: 68-95). Fifty patients (51%) had an impaired RCA and 17 patients (17%) had nephrogenic diabetes insipidus (Uosmol 600-800 and < 600 mOsmol/kg, respectively). Notably, clinical symptoms did not predict an impaired RCA. Nineteen patients (19%) had an eGFR ≤ 60 ml/min/ 1.73 m2. Multivariable regression analysis showed a significant association between the duration of lithium treatment and maximal Uosmol (B = -6.1, 95%-CI: -9.4, -2.9, p < 0.001) and eGFR (B = -0.6, 95%-CI: 0.2, -3.3; p < 0.01). CONCLUSIONS: RCA is impaired in the majority of lithium-treated patients. Both RCA and eGFR are inversely associated with the duration of lithium therapy. Prospective follow-up will enable us to evaluate if abnormalities in RCA can be used to predict the development of lithium-induced chronic kidney disease.

['You tell me, you are the doctor'; patients on long-term psychiatric residences about their medication]. / 'Zegt u het maar, u bent de dokter'; patiënten op langdurige psychiatrische verblijfsafdelingen over hun medicatie.

BACKGROUND: In an era of patient centered care, the question rises whether practitioners of these patients are sufficiently aware of their treatment preferences.
AIM: To study the opinion and knowledge of older, long-term psychiatric patients about their medication and health priorities.
METHOD: Patients were interviewed with the Patient's Attitudes Towards Deprescribing questionnaire. Furthermore patients were asked to name their medication by heart, their health priorities and preferences in medication changes. These preferences were compared with those of their practitioners.
RESULTS: 47 patients (median age 67 years, median 11 drugs) were interviewed. The mean percentage of spontaneously recalled drugs was 37%. Though 64% believed all used drugs were necessary, 77% would like to deprescribe if the doctor said it was possible. Preferences in deprescribing of patients and doctors didn't correspond in about 80%.
CONCLUSION: Most of old psychiatric patients are willing to deprescribe, but await initiative of their doctor. They can recall little of their currently used drugs. Preferences in deprescribing of the patient and doctor do often not match. We recommend to include a patient interview about the need for education and treatment preferences in the annual medication reviews in order to deprescribe and deliver more patient centered care.

['How harmful is your mania to you or others?' Sharing decisions about antidepressant treatment in bipolar depression]. / 'Hoe schadelijk is uw manie voor u en uw naasten?' Gedeelde besluitvorming over antidepressiva bij bipolaire depressie.

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[Burn-out, commitment, personality and experiences during work and training; survey among psychiatry residents]. / Bevlogenheid en burn-out in relatie tot persoonlijkheid en context bij aiossen psychiatrie: een verkennend onderzoek.

BACKGROUND: In the last few years international studies have reported on increase in burn-out and depressive symptoms among psychiatry residents. In the field of research, however, commitment and dedication are now being mentioned more frequently as positive factors that counterbalance burn-out. AIM: To find out how a group of Dutch psychiatry residents feel about their work, to discover their degree of burn-out and commitment and to clarify the various factors involved. METHOD: 59 psychiatry residents from four teaching hospitals were asked to complete questionnaires concerning burn-out (U-BOS-C), commitment (UWES-15) and personality (BFI-NL). Respondents were also asked to describe how they felt about their experiences during their work and to give their views on the instruction and training they were receiving. RESULTS: In the U-BOS-C section only four trainees (almost 7%) met the criteria for burn-out. In the BFI-NL section the psychiatry residents obtained significantly lower scores on neuroticism and higher scores on empathy than did a comparable norm group of a similar age. The scores of the psychiatry residents indicated that the term 'being proud of your work' was significantly related to a feeling of commitment and particularly to all subscales that reflected commitment. CONCLUSION: In our study the percentage of psychiatry residents with burn-out is significantly lower than the percentage reported elsewhere in the literature. In fact, our results demonstrate that the psychiatry residents who were the subject of our study regarded themselves as being emotionally stable, friendly and committed to their work.

Ziprasidone vs olanzapine in recent-onset schizophrenia and schizoaffective disorder: results of an 8-week double-blind randomized controlled trial.

INTRODUCTION: Head-to-head comparisons of antipsychotics have predominantly included patients with chronic conditions. The aim of the present study was to compare the efficacy and tolerability of ziprasidone and olanzapine in patients with recent-onset schizophrenia. METHODS: The study was an 8-week, double-blind, parallel-group, randomized, controlled multicenter trial (NCT00145444). Seventy-six patients with schizophreniform disorder, schizophrenia or schizoaffective disorder (diagnosis < 5 y), and a maximum lifetime antipsychotic treatment < 16 weeks participated in the study. Efficacy of ziprasidone (80-160 mg/d) and olanzapine 10-20 mg was measured using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression (CGI) Scale, the Calgary Depression Scale for Schizophrenia (CDSS), and the Heinrich Quality of Life Scale (HQLS); tolerability assessments included laboratory assessments, body weight, and electroencephalogram. RESULTS: Olanzapine (n = 34) and ziprasidone (n = 39) showed equal efficacy as measured by the PANSS, CDSS, CGI, and HQLS. However, mean weight gain was significantly higher in the olanzapine group (6.8 vs 0.1 kg, P < .001). Ziprasidone was associated with decreasing levels of triglycerides, cholesterol, and transaminases, while these parameters increased in the olanzapine group (all P values < .05). There were no significant differences in fasting glucose and prolactin levels or in cardiac or sexual side effects. Patients on ziprasidone used biperiden for extrapyramidal side effects more frequently (P < .05). DISCUSSION: The results of this study indicate that ziprasidone and olanzapine have comparable therapeutic efficacy but differ in their side effect profile. However, there is a risk of a type II error with this sample size. Clinically significant weight gain and laboratory abnormalities appear early after initiating treatment and are more prominent with olanzapine, while more patients on ziprasidone received anticholinergic drugs to treat extrapyramidal symptoms.

Effects on cognitive functioning after olanzapine-ziprasidone crossover in recent-onset schizophrenia.

INTRODUCTION: To enhance functional outcome in schizophrenia improvement of cognitive symptoms is crucial. EXPERIMENTAL PROCEDURES: Using a comprehensive test battery, this follow-up examines cognitive effects in patients with recent-onset schizophrenia after a change of medication following insufficient clinical response and intolerance. RESULTS: After eight weeks cognitive outcomes had not improved in the patients having switched from olanzapine to ziprasidone (n=11; mean dose 136 mg) nor in those having switched from ziprasidone to olanzapine (n=10; mean 16 mg), while the symptoms of patients maintaining olanzapine (n=18; mean 10.9 mg) or ziprasidone (n=18; mean 88.9 mg) treatment had not improved further. DISCUSSION: The findings suggest that also in early-stage schizophrenia the antipsychotics tested affect cognitive symptoms similarly.

Effect of apomorphine on cognitive performance and sensorimotor gating in humans.

INTRODUCTION: Dysfunction of brain dopamine systems is involved in various neuropsychiatric disorders. Challenge studies with dopamine receptor agonists have been performed to assess dopamine receptor functioning, classically using the release of growth hormone (GH) from the hindbrain as primary outcome measure. The objective of the current study was to assess dopamine receptor functioning at the forebrain level. METHODS: Fifteen healthy male volunteers received apomorphine sublingually (2 mg), subcutaneously (0.005 mg/kg), and placebo in a balanced, double-blind, cross-over design. Outcome measures were plasma GH levels, performance on an AX continuous performance test, and prepulse inhibition of the acoustic startle. The relation between central outcome measures and apomorphine levels observed in plasma and calculated in the brain was modeled using a two-compartmental pharmacokinetic-pharmacodynamic analysis. RESULTS: After administration of apomorphine, plasma GH increased and performance on the AX continuous performance test deteriorated, particularly in participants with low baseline performance. Apomorphine disrupted prepulse inhibition (PPI) on high-intensity (85 dB) prepulse trials and improved PPI on low intensity (75 dB) prepulse trials, particularly in participants with low baseline PPI. High cognitive performance at baseline was associated with reduced baseline sensorimotor gating. Neurophysiological measures correlated best with calculated brain apomorphine levels after subcutaneous administration. CONCLUSION: The apomorphine challenge test appears a useful tool to assess dopamine receptor functioning at the forebrain level. Modulation of the effect of apomorphine by baseline performance levels may be explained by an inverted U-shape relation between prefrontal dopamine functioning and cognitive performance, and mesolimbic dopamine functioning and sensorimotor gating. Future apomorphine challenge tests preferentially use multiple outcome measures, after subcutaneous administration of apomorphine.

Emerging evidence for the use of atypical antipsychotics in borderline personality disorder.

BACKGROUND: The availability of new atypical antipsychotics provides new opportunities for the treatment of borderline personality disorder (BPD). METHODS: Original papers on this topic were sought. Our study reviewed and discussed 14 papers. RESULTS: 2 RCTs, 4 non-controlled open-label studies and 8 case reports. The patient populations studied were highly diverse and the dropout rate after a long follow-up period was high. All of the articles reported positive effects of olanzapine, clozapine, quetiapine and risperidone. CONCLUSION: BPD patients with psychotic-like, impulsive or suicidal symptoms might benefit from atypical antipsychotics. Since the methodological quality of the reviewed articles is poor, further randomised placebo-controlled studies with longer follow-ups are needed before any firm conclusions can be drawn.

[Increased number of systematic reviews in the Netherlands in the period 1991-2000]. / Toename van het aantal Nederlandse systematische reviews in de periode 1991-2000.

OBJECTIVE: To survey systematic reviews (SRs) as publication type in the Netherlands, with emphasis on differences between Cochrane reviews and SRs in printed journals. DESIGN: Bibliometric study. METHOD: A systematic search was carried out in Medline, EMBASE and the Cochrane Library for published systematic reviews of Dutch origin in the period 1991-2000. For each SR, the year of publication, the number of original articles included, the subject matter and the impact factor of the journal were identified. RESULTS: A total of 289 SRs were retrieved, of which 12% were Cochrane reviews. The number of SRs increased exponentially during this decade. The majority (56%) of the SRs concerned a therapeutic intervention. SRs were published in journals with a moderate to good impact factor (median impact factor 2.59). On average, compared to SRs published in the Cochrane Library, the SRs published in the general medical literature included significantly more original articles (28.8 versus 13.7; p < 0.05). This may be caused by the fact that the clinical questions for Cochrane reviews are more focused as compared with non-Cochrane SRs or by the fact that Cochrane review groups may have more stringent quality requirements for inclusion of an article in a review. CONCLUSIONS: The SR as a publication type showed a rapid growth in one decade and was published in important medical journals. Cochrane reviews represented a substantial proportion of the overall number of SRs in the Netherlands.