The anxiolytic potential and psychotropic side effects of an echinacea preparation in laboratory animals and healthy volunteers.

We investigated the toxicity, psychotropic side effects and anxiolytic potential of an Echinacea angustifolia extract that produced promising effects in laboratory tests performed earlier. Rats were studied in the elevated plus-maze, conditioned fear, open-field, object recognition and conditioned place preference tests. Toxicity was studied in rats after intragastric administration. The preparation decreased anxiety in the elevated plus-maze and ameliorated contextual conditioned fear. No lethality or behavioural signs of discomfort were noticed in rats treated with 1000 and 3000 mg/kg Echinacea angustifolia. The extract was without effect in tests of locomotion (open-field), memory (object recognition) and rewarding potential (conditioned place preference) within a wide dose range. A pharmacological formulation based on the same E. angustifolia extract was tested in human subjects. One or two tablets per day were administered for 1 week to healthy volunteers scoring high on the State-Trait Anxiety Inventory (STAI). The tablets contained 20 mg of the plant extract. Data were collected using a structured self-assessment diary technique. The high dose (2 tablets per day) decreased STAI scores within 3 days in human subjects, an effect that remained stable for the duration of the treatment (7 days) and for the 2 weeks that followed treatment. The lower dose (1 tablet per day) did not affect anxiety significantly.

[Switching patients with schizophrenia to ziprasidone from conventional or other atypical antipsychotics]. / Váltás ziprasidonra hagyományos vagy más atípusos antipszichotikumokról szkizofréniában szenvedö betegekben.

OBJECTIVES: The aim of the study was to assess the efficacy, tolerability and safety of ziprasidone in patients with schizophrenia who were already treated with conventional or other atypical antipsychotics that had to be switched due the lack of efficacy or bad tolerance. METHODS: The study was a 12-week, open label, multicenter, non comparative trial on oral ziprasidone. 106 patients with DSM-IV schizophrenia were switched to ziprasidone from their previous antipsychotic without a washout phase. The study required fixed dosing with ziprasidone. For the first week the patient received 80 mg of study drug daily, followed for 3 weeks 120 mg/day. Subsequently for 8 weeks either 80 mg, or 120 mg, or 160 mg total daily dose could be given at the discretion of the investigator. Baseline and outcome assessment included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Severity of Illness Subscale (CGI-S) and Global Improvement Subscale (CGI-I), Calgary Depression Scale (CAD), Hamilton Depression Scale (HAMD), Drug Attitude Inventory (DAI), Simpson Angus Extrapyramidal Symptoms Rating Scale (SAS) and Barnes Akathisia Rating Scale (BARS). Changes in overall body weight were also evaluated. RESULTS: After 12 weeks on ziprasidone therapy, significant improvements were observed on all major symptoms measures and subscales. 34 (51,5%) patients (ITT) were rated much or very much improved on CGI-I at week 12. The mean SAS score significantly reduced during the ziprasidone treatment period (p<0.001). In the DAI ziprasidone treatment was also favorable rated. During treatment with ziprasidone for 12 weeks the body weight of the patients was significantly reduced (mean: 1,2 kg, SD=3,79, p=0.002). 58 adverse events occurred in 41 subjects (38.7%), of whom 7 patients (6.6%) encountered 9 severe adverse events. The adverse events were mainly mild and moderate. 15 patients (14.2%) were discontinued from the study due to adverse events. The reason for discontinuation in 4 cases was mainly insufficient clinical response. CONCLUSION: Switching patients from their previous antipsychotic to ziprasidone without a washout phase was generally well tolerated and was associated with symptoms improvements 12 weeks later. At least 50% of patients who needed to be switched because of unsatisfactory efficacy or poor tolerance were significantly improved on ziprasidone therapy. The favorable safety profile of ziprasidone treatment was consistent with that seen in other clinical trials. KEYWORDS: switching, ziprasidone, schizophrenia.

Predictors for 2-year outcome of major depressive episode.

In this 2-year prospective study, we searched for predictive factors influencing the 2-year outcome of major depressive episodes. Demographic characteristics (age, gender, education, employment), illness-related variables (severity, age at onset, number and duration of previous episodes), personality characteristics (DSM-IV personality disorders, trait anxiety, coping style), life context factors (life events before and during the depressive episode, social support, social adjustment), and biological markers (dexamethasone suppression test, thyroid stimulating hormone levels) of 117 inpatients with major depressive episode were assessed. A structural equation model was used to test the proposed correlational structure of the relevant variables. The non-remission of the depressive symptoms by the end of a 6-week acute treatment phase was found to be the most relevant factor predicting sustained non-remission at the end of a 2-year follow-up period. At the end of the sixth week, the severity of depression depended on the level of social support and on the severity of depression at baseline. Among the baseline variables, anxious personality traits and a lower level of education predicted a high level of depressive symptoms at the end of the 2-year follow-up. Life events before and during the depressive episode, and the biological markers at baseline had no direct effect on the outcome. The rapid remission of the depressive symptoms is the most important predictor for the favorable long-term outcome of a depressive episode. Personality characteristics, social support and level of education,--interacting with each other--also play a significant role.

Olanzapine versus clozapine in treatment-resistant or treatment-intolerant schizophrenia.

Clozapine has been the gold standard for treatment of patients with refractory schizophrenia but is associated with serious safety liabilities. This has prompted the search for therapeutic alternatives for treatment-resistant schizophrenia. The objective of this study was to compare the efficacy and safety of olanzapine versus clozapine in schizophrenic patients who failed to respond adequately to antipsychotic medication or who experienced intolerable adverse effects associated with the medication. This 18-week, randomized, double-blind, parallel study compared treatment with either olanzapine (5-25 mg/day, n=75) or clozapine (100-500 mg/day, n=72) in patients with schizophrenia who were nonresponsive to, or intolerant of, standard acceptable antipsychotic therapy. At the 18-week endpoint, no statistically significant differences were found between olanzapine and clozapine in any efficacy measure used: Positive and Negative Syndrome Scale (PANSS) total, positive, negative, or general psychopathology or Clinical Global Impression severity (CGI-S). Response rates based on the criteria of Kane et al. [Arch. Gen. Psychiatry 45 (1988) 789] were also not significantly different between olanzapine-treated (57.9%) and clozapine-treated patients (60.8%). There were no significant differences in measurements of extrapyramidal symptoms or electrocardiography, and no clinically and statistically significant changes were seen in vital signs or laboratory measures in either group. Both treatments were well tolerated. Olanzapine demonstrated similar efficacy to clozapine in patients who had failed previous treatment because of lack of efficacy (treatment resistance) or intolerable side effects (treatment intolerance). Olanzapine therefore presents a safe alternative in the treatment of refractory schizophrenia.

Anxiety and mood disorders in primary care practice.

Anxiety and mood disorders are common conditions in primary health care service. Primary care physicians (PCPs) have a privileged role in the early recognition of these conditions. In this study, the prevalence rates of threshold and subthreshold mood and anxiety disorders were surveyed among 1815 primary care attendees in 12 PCPs' offices in Budapest, using the Diagnostic Interview Schedule (DIS). The 1-year prevalence of DIS/DSM-III-R anxiety and/or mood disorders was 16.8%, and the 1-month prevalence was 12.5%. The occurrence rates of subthreshold anxiety and/or depression were 25.7 and 13.1%, respectively. The impact of threshold anxiety and mood disorders on work performance was considerably higher than the impact of subthreshold symptoms. At the time of the interview, 6.7% of the patients received mood and/or anxiety disorder diagnoses by their PCPs. The measure of agreement between the diagnoses generated by the DIS and the ones given by the PCPs was low. The presence of an acute or chronic physical illness made it more difficult for the PCPs to recognize a psychiatric disorder. Conversely, patients' psychological complaints significantly improved the recognition of anxiety and/or mood disorders. The use of the Beck Depression Inventory (BDI) brief version would help the patients to reveal their psychological symptoms, and the physicians to recognize an underlying psychiatric disorder.

Lifetime patterns of depressive symptoms in the community and among primary care attenders: an application of grade of membership analysis.

The objective of this study was to describe empirical and natural lifetime patterns of depressive and anxiety symptoms reported by community respondents and primary care attenders. The Grade of Membership model was used to analyze data collected from 716 subjects between 18 and 64 years of age with a lifetime diagnosis of DIS/DSM-III-R Major Depressive Episode. Symptoms of depression, mania, and anxiety (GAD, panic attack, and phobias) were processed. Six prototype categories (pure types) provided the best description of the structure of symptoms included in the analysis. Type I: bipolar depression with marked suicidal behaviour, comorbidity and early onset. Type II: non-melancholic-somatisation depression with late onset. Type III: non-melancholic, non-severe bipolar depression with male preponderance. Type IV: depression secondary to anxiety with marked female preponderance. Type V: melancholic depression with suicide ideation. Type VI: melancholic depression with panic attacks and female preponderance. The results support the heterogeneity of the longitudinal symptom pattern of depression and the existence of two time-trend types of comorbid anxiety disorders.

The role of symptoms in the recognition of mental health disorders in primary care.

This study investigates the role of patients' complaints and symptoms in the diagnostic process of mood and anxiety disorders in general practice. In 12 primary care practices, 1,211 patients were diagnosed with the aid of the National Institute of Mental Health Diagnostic Interview Schedule, then the diagnoses were compared with those established by the general practitioners. A low rate of concordance was found between these diagnoses. The absence of somatic illnesses and the presence of psychological complaints were the most important factors in the recognition of a mental illness by the general practitioners. The concordance between the general practitioners and the DIS diagnoses was higher if the patients had neither an acute nor a chronic somatic illness.

Cost-outcome of anxiety treatment intervention in primary care in Hungary.

AIM OF THE STUDY: The purpose of this paper is to estimate the changes in health utilization and indirect costs of anxiety and affective disorders in primary care patients after initiation of mental health treatment. METHOD: This study was conducted in 12 general practices for the primary care of adult populations in Budapest, Hungary. Among 2,000 eligible patients aged 18 to 64 years, 1,815 gave written informed consent to participate in the study. The Hungarian version of the Diagnostic Interview Schedule (DIS) for anxiety and mood disorders was used to generate psychiatric diagnoses. For all patients, health care utilization data for the previous 12 months was collected including number of visits, specialist consultations, days spent in hospital, sick days in the last year and prescribed medication. Among the first 1,000 attenders, 151 patients were given DIS/DSM-III-R diagnoses of current anxiety and/or mood disorder or uncomplicated bereavement. Fifty-one patients who agreed to psychiatric treatment were assigned to the treatment group. After the first 1,000 participants, 75 patients were given DIS diagnoses and were considered as controls. In the treatment group, five psychiatrists administered treatment on an outpatient basis for one year. Patients in the control group received as-usual treatment from their primary care physicians. After one year, health care utilization data for the study period was collected. For the purposes of this study, the direct costs considered were limited to health care expenses and the indirect costs were limited to lost workdays. Statistical significance was calculated using a paired-samples T-test procedure comparing the means of two variables for a simple group. RESULTS: In the treatment group, the total cost of prescription drugs increased sharply due to psychiatric drug treatment, thus increasing the direct overall costs of care. In this same group the cost of non-psychiatric drugs showed a 37% decrease, suggesting that a reduction in general medical treatment partially offset the costs of anxiety and depression treatment. The number of hospital days showed marked decrease in the treatment group and a slight, insignificant increase in the control group. Absenteeism fell sharply in the treatment group (-56%) and in the group of patients who received psychiatric treatment elsewhere (-62%). In the control group, there was a large upturn (+182%) in the number of days spent on sick leave. DISCUSSION: Among primary care patients diagnosed with anxiety or affective disorders, psychiatric treatment led to higher direct costs, but this was offset by a decline in indirect costs due to reduced absenteeism compared with ordinary primary care. LIMITATIONS: Patients were not assigned randomly to the different groups because of ethical concerns. There were also significant differences in the baseline characteristics of the groups. Differences in the severity of illness and reasons not attributable to treatment effects may play a role in the change in the rate of service use. IMPLICATIONS FOR HEALTH POLICY: Limiting anxiety patients access to psychiatric treatment causes an increase in absenteeism, thus resulting in higher indirect costs.

El problema del reconocimiento de la psiquiatria como una disciplina independientes en Hungria / The problem of the recognition of psychiatry as an independent dicipline in Hungary

Los autores analizan el desarrollo histórico de la psiquiatría húngaraa. Hasta mediados del siglo pasado los pacientes eran llevaddos a Austria para su tratamiento. En 1850 se inició la construcción de los hospsitales para enfermos mentales. El presupuesto de estos centros fue muy raquítico y el personal era muy reducido. Fueron concebidos inicialmente como sitios de confinamiento. Paralelamente a la incuria de los asilos, se empezó a desarrollar desde finales del XIX sobre todo en la primera decena de nuestro siglo, un enfoque neuropsiquiátrico apoyado originalmente en Kraepelin, que condujo con el tiempo a un reduccionismo neurohistológico a ultranza, mismo que prosiguió inalterable a pesar de los camvios que se fueron dando en otras partes del mundo. Así una gran resistencia a la aceptación de las corrientes psicoanalíticas a pesar de la gran importancia de algunos psicoanlaistas húngaros que realizaron su obra en el extranjero (P.ej.. Alexander, Radó, Bálint, etc). Esta situación condujo a la preminencia de la neurología en detrimento de todos los posibles enfoques psicológicos, lo que dio por resultado el que los servicios psiquiátricos fueran dirigidos por neurólogos. Por otra parte, los jóvenes médicos interesados en la psiquiatría debían seguir una "doble formación" de neurólogos y psiquiatras, pues la primera especialidad se encuentra todavía relacionada más que la segunda a un buen status y a la posibilidad de obtener mejores condiciones para el ejercicio y la investigación. De esta manera, la psiquiatría ha debido modernizarse en los ultimos años, tratando de conquistar su autonomía y su independencia frente a la neurología que la ha sojuzgado en Hungría, al no querer intentar comprender otras explicaciones que no sean las del determinismo materialista...