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The aim was to explore weight and body mass index (BMI) changes by baseline BMI in patients completing three years of monotherapy with various first- and second-generation antipsychotics in a large cohort in a post hoc analysis of three-year observational data.Data were analyzed by antipsychotic and three baseline BMI bands: underweight/normal weight (BMI <25 kg/m2), overweight (25–30 kg/m2) and obese (>30 kg/m2).Baseline BMI was associated with subsequent weight change irrespective of the antipsychotic given. Specifically, a smaller proportion of patients gained ≥7% baseline bodyweight, and a greater proportion of patients lost ≥7% baseline bodyweight with increasing baseline BMI. For olanzapine (the antipsychotic associated with highest mean weight gain in the total drug cohort), the percentage of patients gaining ≥7% baseline weight was 45% (95% CI: 43–48) in the underweight/normal weight BMI cohort and 20% (95% CI: 15–27) in the obese BMI cohort; 7% (95% CI: 6–8) of the underweight/normal cohort and 19% (95% CI: 13–27) of the obese cohort lost ≥7% baseline weight.BMI has an association with the likelihood of weight gain or loss and should be considered in analyses of antipsychotic weight change. [ABSTRACT FROM AUTHOR]

Background: Patients with severe mental illness (SMI) experience distress and disabilities in several aspects of life, and they have a higher risk of somatic co-morbidity. Both patients and their family members need the support of an easily accessible primary care system. The willingness of general practitioners and the impeding factors for them to participate in providing care for patients with severe mental illness in the acute and the chronic or residual phase were explored. Methods: A questionnaire survey of a sample of Dutch general practitioners spread over the Netherlands was carried out. This comprised 20 questions on the GP's 'Opinion and Task Perspective', 19 questions on 'Treatment and Experiences', and 27 questions on 'Characteristics of the General Practitioner and the Practice Organisation'. Results: 186 general practitioners distributed over urban areas (49%), urbanised rural areas (38%) and rural areas (15%) of the Netherlands participated. The findings were as follows: GPs currently considered themselves as the first contact in the acute psychotic phase. In the chronic or residual phase GPs saw their core task as to diagnose and treat somatic co-morbidity. A majority would be willing to monitor the general health of these patients as well. It appeared that GP trainers and GPs with a smaller practice setting made follow-up appointments and were willing to monitor the self-care of patients with SMI more often than GPs with larger practices. GPs also saw their role as giving support and information to the patient's family. However, they felt a need for recognition of their competencies when working with mental health care specialists. Conclusion: GPs were willing to participate in providing care for patients with SMI. They considered themselves responsible for psychotic emergency cases, for monitoring physical health in the chronic phase, and for supporting the relatives of psychotic patients. [ABSTRACT FROM AUTHOR]

Background: In primary care, GPs usually provide care for patients with chronic diseases according to professional guidelines. However, such guidelines are not available in the Netherlands for patients with recurring psychoses. It seems that the specific difficulties that GPs experience in providing care for these patients hinder the development and implementation of such guidelines. This study aims to explore the chances and problems GPs meet when providing care for patients susceptible for recurring psychoses, including schizophrenia and related disorders, bipolar disorder, and psychotic depression. Methods: A qualitative study of focus group discussions with practising GPs in both town and rural areas. Transcripts from three focus groups with 19 GPs were analysed with the computer program 'Kwalitan'. Theoretical saturation was achieved after these three groups. Results: Analysis showed that eight categories of factors influenced the GPs' care for psychotic patients: patient presentation (acute vs. chronic phase), emotional impact, expertise, professional attitude, patient related factors, patient's family, practice organization, and collaboration with psychiatric specialists. Conclusion: Current primary care for psychotic patients depends very much on personal characteristics of the GP and the quality of local collaboration with the Mental Health Service. A quantitative study among GPs using a questionnaire based on the eight categories mentioned above would determine the extent of the problems and limitations experienced with this type of care. From the results of this quantitative study, new realistic guidelines could be developed to improve the quality of care for psychotic patients. [ABSTRACT FROM AUTHOR]

Tardive dyskinesia (TD) may occur in never-medicated patients with psychotic illness, indicating the existence of non-medication, possibly disease-related, causes. We tested the hypothesis that, independent of the antipsychotic-induced rise in prolactin, the incidence of TD would be associated with the incidence of prolactin-related sexual disturbances (PRSD), which would be suggestive of a common pathology involving multiple dopamine tracts. Simple, global measures of TD and PRSD (loss of libido, amenorrhea, gynaecomastia, impotence, and galactorrhea) were rated in a prospective, observational European Health Outcomes Study (SOHO). New onset of TD and new onset of PRSD at 3, 6, and 12 months was analyzed in a risk set of 4263 patients using a Cox proportional hazard model yielding adjusted hazard ratios (aHR). Incidence of TD was significantly and linearly comorbid with the incidence of PRSD in both men and women. Compared to those with no PRSD, the risk for TD was 2.0 (95% CI: 1.1, 3.7) with one PRSD, 2.4 (95% CI: 1.3, 4.5) with two PRSD, and 3.6 (95% CI: 1.1, 11.8) with three PRSD. Associations were stronger in those who only had received prolactin-sparing medications (aHR per unit PRSD increase=2.0, 95% CI: 1.2, 3.3) than in those who only had received prolactin-raising medications (aHR=1.3, 95% CI: 0.9, 1.9). In people with schizophrenia, TD and PRSD show comorbidities that are independent of antipsychotic-induced alterations in plasma prolactin. This may suggest a shared, pandopaminergic pathological mechanism associated with schizophrenia itself, rather than only a medication effect.Neuropsychopharmacology (2006) 31, 1832–1837. doi:10.1038/sj.npp.1301044; published online 15 February 2006 [ABSTRACT FROM AUTHOR]

Objetivos: Este estudio examinó si los síntomas extrapiramidales pronosticaban la incidencia de discinesia tardía al cabo de 1 año. Método: Se utilizaron medidas globales sencillas para evaluar los síntomas extrapiramidales y la discinesia tardía en un estudio prospectivo observacional de los desenlaces clínicos. Se analizaron los datos de la evaluación inicial y a los 3, 6 y 12 meses en 9.298 pacientes utilizando el modelo de riesgo proporcional de Cox. Se examinó el inicio de discinesia tardía en dos grupos: 1) ausencia de discinesia tardía en la evaluación inicial (grupo de riesgo alto) y 2) ausencia de discinesia tardía en la evaluación inicial y a los 3 meses (grupo de riesgo bajo). Resultados: Los síntomas extrapiramidales basales pronosticaron el desarrollo posterior de discinesia tardía (grupo de riesgo alto: índice de riesgo = 2,0; grupo de riesgo bajo: índice de riesgo = 1,6). En los análisis ajustados a la edad, el sexo y la exposición a fármacos, no disminuyó el tamaño de efecto. Aproximadamente la mitad de los pacientes que desarrollaron discinesia tardía había experimentado, con anterioridad, síntomas extrapiramidales. Conclusiones: Aunque existe una relación estrecha entre la discinesia tardía y los síntomas extrapiramidales, éstos no identifican de forma concluyente a los individuos con un riesgo elevado de desarrollar discinesia tardía. No obstante, los regímenes farmacoterapéuticos y los procesos patológicos que acentúan los síntomas extrapiramidales aumentan, probablemente, el riesgo de discinesia tardía. [ABSTRACT FROM AUTHOR]

Objective: This study examined whether extrapyramidal symptoms predict incidence of tardive dyskinesia 1 year later. Method: Simple, global measures were used to rate extrapyramidal symptoms and tardive dyskinesia in a prospective, observational health outcomes study. Baseline and 3-, 6-, and 12-month data on 9,298 patients were analyzed by using a Cox proportional-hazard model. Onset of tardive dyskinesia was examined in two groups: 1) no tardive dyskinesia at baseline (broad risk set) and 21 no tardive dyskinesia at baseline and 3 months (narrow risk set). Results: Baseline extrapyramidal symptoms predicted later onset of tardive dyskinesia (broad risk set: hazard ratio=2.0, narrow risk set: hazard ratio=1.6). In analyses adjusted for age, gender, and medication exposure, this effect size was not reduced. About half of patients who developed tardive dyskinesia had earlier extrapyramidal symptoms. Conclusions: Although the association of tardive dyskinesia and extrapyramidal symptoms is significant, extrapyramidal symptoms do )lot robustly identify individuals at high risk for tardive dyskinesia. However, drug regimens and disease processes that increase extrapyramidal symptoms are likely to result in increased risk of tardive dyskinesia.p [ABSTRACT FROM AUTHOR]

Altered emotional experiences in response to antipsychotics may increase the burden of disease in patients with schizophrenia. In a large cross-sectional study, patients with schizophrenia completed the Subjects Reaction to Antipsychotics questionnaire (SRA) to assess whether they attributed altered emotional experiences (flattened affect or depressive symptoms) to their antipsychotics. Association with antipsychotic D 2 receptor affinity and occupancy was examined using logistic regression. We compared antipsychotic-attributed emotional experiences between patients using antipsychotic monotherapy and combination therapy. Of the 1298 included patients, 23% attributed flattened affect to their antipsychotics and 16% attributed depressive symptoms to their antipsychotics, based on the SRA. No differences were observed between antipsychotics in patients on monotherapy. We discuss that within these patients’ relatively low dose range, altered emotional experiences did not appear to relate to the level of D 2 receptor affinity of antipsychotic monotherapy. Patients using antipsychotic combination therapy (22%) were more likely to attribute depressive symptoms to their antipsychotics than patients using antipsychotic monotherapy (OR [95%CI]=1.443 [1.033–2.015]); possibly due to higher D 2 receptor occupancies as estimated by dose equivalents. [ABSTRACT FROM AUTHOR]

Abstract: Background: Monitoring patients' experiences with antipsychotics may help to improve medication adherence and outcome. We aimed to develop a shorter version of a comprehensive 74-item self-report questionnaire suitable for routine monitoring of desired and undesired effects of antipsychotics. Methods: Included were patients with psychotic disorders from seven mental health care organizations in The Netherlands, using antipsychotic medication, who completed the Subjects' Response to Antipsychotics (SRA-74). Exploratory factor analysis (EFA) and similarity analysis based on mutual information were used to identify the latent factor structure of the SRA. Items were reduced according to their metric properties and clinical relevance upon consensus by an expert panel, using a Delphi procedure of three rounds. We determined the internal consistency of the shorter version using Cronbach's alpha. Results: SRA data of N=1478 patients (mean age of 40years, 31% females) were eligible for analysis. EFA extracted thirteen factors from the SRA-74, including four factors for desired effects (e.g. recovery of psychosis, cognition and social functioning) and nine factors for undesired effects (e.g. weight gain, flattened affect and increased sleep). Based on this solution 12 items were eliminated for statistical reasons. The expert panel eliminated another 28 items with redundant content, resulting in a 34-item version. The SRA-34 includes 10 desired and 24 clinically relevant undesired effects. Both the subscales for desired and undesired effects have a Cronbach's alpha coefficient of 0.82. Conclusions: The SRA-34 can be used to evaluate desired and undesired effects of antipsychotics in routine clinical practice and research. [Copyright &y& Elsevier]

Background: Patients suffering from psychotic disorders have an increased risk of comorbid somatic diseases such as cardiovascular disorders and diabetes mellitus. Doctor-related factors, such as unfamiliarity with these patients, as well as patient-related factors, such as cognitive disturbance and negative symptoms, contribute to suboptimal health care for these patients. General practitioners (GPs) could play a key role in diagnosing and treating this somatic comorbidity as in the Netherlands, almost all residents are registered at a general practice. This study aims to find out whether there are any differences between the levels of health care provided by GPs to patients with psychotic disorders, compared to other types of patients. Methods: A cohort of patients with an ICPC code of psychosis and two matched control groups, one consisting of patients with other mental problems and the other one of patients without any mental problems, were followed over a period of 5 years. Results: Patients with psychotic disorders (N = 734) contacted the GP practice more often than patients in the control groups. These patients, both adults (p = 0.051) and the elderly (p < 0.005), received more home visits from their GPs. In the adult group (16 to 65 years old inclusive), the number of consultations was significantly higher among both psychosis patients and the group of patients with other mental problems (p < 0.0005). The number of telephone consultations was significantly higher in both age categories, adult group (p < 0.0005), and > 65 years old (p = 0.007). With regard to chronic illnesses, elderly psychosis patients had fewer contacts related to cardiovascular diseases or chronic lung diseases. Conclusion: Patients with psychotic disorders contact the GP practice more frequently than other types of patients. Adult psychosis patients with diabetes mellitus, cardiovascular diseases or chronic lung diseases receive the same amount of health care for these diseases as other primary care patients. The finding that older patients with psychotic disorders are diagnosed with cardiovascular diseases and obstructive lung diseases less frequently than other types of elderly patients requires further study. [ABSTRACT FROM AUTHOR]

Background: Neuroimaging findings implicate bilateral superior temporal regions in the genesis of auditory-verbal hallucinations (AVH). This study aimed to investigate whether 1 Hz repetitive transcranial magnetic stimulation (rTMS) of the bilateral temporo-parietal region would lead to increased effectiveness in the management of AVH, compared to left rTMS or placebo.Methods: 38 patients with schizophrenia (DSM-IV) and medication-resistant AVH were randomly assigned to 1 Hz rTMS treatment of the left temporo-parietal region, bilateral temporo-parietal regions, or placebo. Stimulation was conducted over 6 days, twice daily for 20 min, at 90% of the motor threshold. Effect measures included the Auditory Hallucination Rating Scale (AHRS), Positive and Negative Affect Scale (PANAS), and a score for hallucination severity obtained from the Positive and Negative Syndrome Scale (PANSS).Results: All groups showed some improvement on the total AHRS. Hallucination frequency was significantly reduced in the left rTMS group only. The bilateral rTMS group demonstrated the most remarkable reduction in self-reported affective responsiveness to AVH. A modest, but significant decrease on the PANSS hallucination item was observed in the combined rTMS treatment group, whereas no change occurred in the placebo group. The left rTMS group showed a significant reduction on the general psychopathology subscale.Conclusion: Compared to bilateral or sham stimulation, rTMS of the left temporo-parietal region appears most effective in reducing auditory hallucinations, and additionally may have an effect on general psychopathology. Placebo effects should however not be ruled out, since sham stimulation also led to improvement on a number of AVH parameters. [ABSTRACT FROM AUTHOR]

Abstract: Background: Neuroimaging findings implicate bilateral superior temporal regions in the genesis of auditory–verbal hallucinations (AVH). This study aimed to investigate whether 1Hz repetitive transcranial magnetic stimulation (rTMS) of the bilateral temporo-parietal region would lead to increased effectiveness in the management of AVH, compared to left rTMS or placebo. Methods: 38 patients with schizophrenia (DSM-IV) and medication-resistant AVH were randomly assigned to 1Hz rTMS treatment of the left temporo-parietal region, bilateral temporo-parietal regions, or placebo. Stimulation was conducted over 6days, twice daily for 20min, at 90% of the motor threshold. Effect measures included the Auditory Hallucination Rating Scale (AHRS), Positive and Negative Affect Scale (PANAS), and a score for hallucination severity obtained from the Positive and Negative Syndrome Scale (PANSS). Results: All groups showed some improvement on the total AHRS. Hallucination frequency was significantly reduced in the left rTMS group only. The bilateral rTMS group demonstrated the most remarkable reduction in self-reported affective responsiveness to AVH. A modest, but significant decrease on the PANSS hallucination item was observed in the combined rTMS treatment group, whereas no change occurred in the placebo group. The left rTMS group showed a significant reduction on the general psychopathology subscale. Conclusion: Compared to bilateral or sham stimulation, rTMS of the left temporo-parietal region appears most effective in reducing auditory hallucinations, and additionally may have an effect on general psychopathology. Placebo effects should however not be ruled out, since sham stimulation also led to improvement on a number of AVH parameters. [Copyright &y& Elsevier]

Cognitive dysfunction in schizophrenia has well-known functional consequences. The ability to learn (learning potential) may be an important mediator. This study examines the relationship between learning and functional status in schizophrenia patients before and after participation in a rehabilitation program. We reasoned that learning is a broad construct, encompassing controlled, effortful as well as automatic (learning by doing) mechanisms, called explicit and implicit learning, respectively. Both types of learning ability are important in daily life. The study included 44 medicated schizophrenia patients and 79 healthy controls. We included measures of implicit and explicit learning as well as measures of the cognitive domains for which significant relationships with functional outcome have been established: immediate and secondary verbal memory, card sorting and vigilance. Learning potential and the patient''s ‘learner status’ were also assessed. The results show that learning, as assessed by measures of explicit and implicit learning and learning potential, was not associated with social functioning or rehabilitation outcome. The highest correlations between cognitive functioning and social functioning were found for more or less ‘static’ performance measures when they were assessed for a second time with or without instructions on how to do the test. Optimized cognitive performance (i.e. performance after instruction or training) seems to be a better predictor of complex domains of functioning than naive or everyday performance. [Copyright &y& Elsevier]