[Adherence to therapy in multiple sclerosis and schizophrenia]. / Therapieadhärenz bei Multipler Sklerose und Schizophrenie.

The extent, to which a patients behavior corresponds with agreed recommendations from a health care provider is described as "adherence". Although the concept of adherence is more and more addressed in the context of clinical studies, yet the relevant factors for adherence are hardly systematically examined in neurological and psychiatric diseases. In addition to various different published definitions of adherence, the sample periods constantly differ between publications, thus contributing to inconsistent data on adherence rates, e. g. in specific diseases. Taking the wide range of published data into account, it seems reasonable to assume an averaged adherence rate of 50 percent for patients suffering from schizophrenia and roughly 50 - 60 percent for multiple sclerosis (MS) patients. Approaches for improvements comprise psychoeducational programs and antipsychotic depot formulations in the therapy of schizophrenia. In the therapy of MS, MS nurse services have been established. In the therapy of schizophrenia, there exists limited positive evidence for the effectiveness of psychoeducational measures and depot formulations on adherence, but approaches for improving medication adherence are accessible only to a part of schizophrenic patients. The usefulness of MS nurse services and other measures for coping mechanisms in MS patients is acknowledged, but further research is preferable in order to optimize adherence supporting activities in this clinical field. In summary, adherence rates in both diseases are comparably low emphasizing a further need for the establishment and scientific evaluation of measures to improve adherence in MS and schizophrenia.

Acquired thrombotic thrombocytopenic purpura as the presenting symptom of systemic lupus erythematosus. Successful treatment with plasma exchange and immunosuppression--report of two cases.

Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening syndrome characterized by platelet aggregation causing occlusive microangiopathy. It has been described as a complication in systemic lupus erythematosus (SLE). Recent research indicated that genetic or autoantibody-induced deficiency of the metalloprotease ADAMTS13 plays a key role in the pathogenesis of TTP. Here we report two uncommon cases of TTP as the first presenting symptom of SLE. Both patients were treated with combined plasma exchange and immunosuppressive therapy, and recovered completely. Although TTP and SLE have several clinical findings in common, and both disorders may coexist more frequently than we currently assume, features of one disease should not mislead to reject the alternative disorder.

A simple switching strategy for inadequately treated patients with schizophrenia to olanzapine: changes in psychopathology and subjective well-being.

INTRODUCTION: The aim of the study was to assess the feasibility of abruptly switching inadequately treated psychotic outpatients from another oral antipsychotic to olanzapine and to evaluate subjective well-being under olanzapine. METHODS: Previous medication was switched to olanzapine 10 mg/day and continued for 4 weeks (5-20 mg/day). Successful switch was predefined as no change or any improvement on the Clinical Global Impression-Improvement (CGI-I) scale after one week. A successful switch rate of > or = 70 % was considered a positive study outcome. Well-being was evaluated using the Subjective Well-being under Neuroleptics (SWN) scale. RESULTS: 198 patients (100 %) were switched to olanzapine. In 177 patients (89 %), CGI-I was unchanged (29 %) or improved (60 %) after one week of olanzapine treatment, indicating a positive study outcome (p < 0.001). SWN total score significantly improved from 127.9 (+/- 32.5) at baseline to 139.2 (+/- 31.5) at week 1, continuing to 149.3 (+/- 30.3) at week 4 (LOCF). DISCUSSION: The findings suggest that an abrupt switch from another antipsychotic to olanzapine 10 mg/day can be performed successfully in psychotic patients, while rapidly improving subjective well-being.

Multilead quantitative electroencephalogram profile and cognitive evoked potentials (P300) in healthy subjects after a single dose of olanzapine.

RATIONALE: Olanzapine is an atypical antipsychotic drug with a more favourable safety profile than typical antipsychotics with a hitherto unknown topographic quantitative electroencephalogram (QEEG) profile. OBJECTIVES: We investigated electrical brain activity (QEEG and cognitive event related potentials, ERPs) in healthy subjects who received olanzapine. METHODS: Vigilance-controlled, 19-channel EEG and ERP in an auditory odd-ball paradigm were recorded before and 3 h, 6 h and 9 h after administration of either a single dose of placebo or olanzapine (2.5 mg and 5 mg) in ten healthy subjects. QEEG was analysed by spectral analysis and evaluated in nine frequency bands. For the P300 component in the odd-ball ERP, the amplitude and latency was analysed. Statistical effects were tested using a repeated-measurement analysis of variance. RESULTS: For the interaction between time and treatment, significant effects were observed for theta, alpha-2, beta-2 and beta-4 frequency bands. The amplitude of the activity in the theta band increased most significantly 6 h after the 5-mg administration of olanzapine. A pronounced decrease of the alpha-2 activity especially 9 h after 5 mg olanzapine administration could be observed. In most beta frequency bands, and most significantly in the beta-4 band, a dose-dependent decrease of the activity beginning 6 h after drug administration was demonstrated. Topographic effects could be observed for the beta-2 band (occipital decrease) and a tendency for the alpha-2 band (frontal increase and occipital decrease), both indicating a frontal shift of brain electrical activity. There were no significant changes in P300 amplitude or latency after drug administration. CONCLUSION: QEEG alterations after olanzapine administration were similar to EEG effects gained by other atypical antipsychotic drugs, such as clozapine. The increase of theta activity is comparable to the frequency distribution observed for thymoleptics or antipsychotics for which treatment-emergent somnolence is commonly observed, whereas the decrease of beta activity observed after olanzapine administration is not characteristic for these drugs. There were no clear signs for an increased cerebral excitability after a single-dose administration of 2.5 mg and 5 mg olanzapine in healthy controls.

Analysis of the QTc interval during olanzapine treatment of patients with schizophrenia and related psychosis.

BACKGROUND: There may be a temporal association between some antipsychotics and prolongation of the heart-rate-corrected QT interval (QTc) representing a delay in ventricular repolarization. QTc prolongation significantly exceeding normal intra-individual and interindividual variation may increase the risk of ventricular tachydysrhythmias, especially torsade de pointes, and therefore, sudden cardiac death. METHOD: Electrocardiogram recordings obtained as part of the safety assessment of olanzapine in 4 controlled, randomized clinical trials (N = 2,700) were analyzed. These analyses were conducted to characterize any change in QTc temporally associated with olanzapine, compared with placebo, haloperidol, and risperidone, in acutely psychotic patients (DSM-III-R and DSM-IV) and to characterize variability and temporal course of the QTc in this patient population. Changes from baseline to minimum and maximum QTc were tested for significance, and baseline to acute-phase endpoint change in mean QTc was tested for significance within treatments and for differences between olanzapine and comparators. The possibility of a linear relationship between dose of olanzapine and mean change in QTc, as well as incidence of treatment-emergent prolongation of QTc (change from < 430 msec at baseline to > or =430 msec at endpoint), was tested. RESULTS: The incidence of maximum QTc > or = 450 msec during treatment was approximately equal to the incidence of QTc > or =450 msec at baseline. CONCLUSION: Results of these analyses suggest that olanzapine, as therapeutically administered to patients with schizophrenia and related psychoses, does not contribute to QTc prolongation resulting in potentially fatal ventricular arrhythmias.

Cardiac safety parameters of olanzapine: comparison with other atypical and typical antipsychotics.

Alterations of electrocardiogram results and cases of sudden cardiac death have been reported since the beginning of neuroleptic treatment. In particular, a temporal association exists between some antipsychotics and prolongation of the heart rate-corrected QT interval (QTc), an event that may increase the risk for developing a potentially fatal ventricular tachycardia arrhythmia known as torsades de pointes if it significantly exceeds normal intraindividual and interindividual variation. Although the incidence of serious adverse cardiac events in response to antipsychotic medications is relatively low, any possibility for the occurrence of cardiotoxicity warrants continued study. The present article reviews important differences among antipsychotic drugs in the potential for, and occurrence of, serious adverse cardiac outcomes and suggests that olanzapine, as therapeutically administered to patients with schizophrenia and related psychoses, does not contribute significantly to a QTc prolongation that could result in potentially fatal ventricular arrhythmias.

Efficacy and safety findings from naturalistic fluoxetine drug treatment in adolescent and young adult patients.

This article reports on the efficacy and safety of the selective serotonin reuptake inhibitor, fluoxetine, in 213 patients (ages 11-23 years) treated by psychiatrists/neurologists (PN) or general practitioners/internists (GPI). Data were derived from naturalistic drug utilization observation (DUO) studies with fluoxetine (n = 18,759 patients). Data collection--at the start and the end of the observation period (< or =6 weeks)--included patient characteristics, diagnoses, medication, co-medication, efficacy, and adverse events (AEs). Nonparametric statistics and descriptive p values (two-tailed) were used. Analyses revealed various differences between PN (n = 56) and GPI (n = 157) samples as to patient and treatment characteristics (p < 0.001-0.08). Based on both Clinical Global Impression (CGI; all p < 0.001) and self-assessment (total n = 47; Zung SDS, all p < or = 0.003), both PN and GPI patients showed improvements in their symptomatology over time, including suicidality (all p < 0.001; there were no group differences). Overall AE rates were higher in PN patients (p < 0.01; 17.9% vs. 4.5%); the frequency and type of AEs in both subgroups were typical for fluoxetine and the total DUO samples. In fact, AE rates were lower compared to controlled trials. Findings suggest that PN patients were more severely ill at observation start and suffered a more complicated treatment course. However, clinical efficacy showed highly significant improvements in both subgroups; AE rates were low in both--although higher in PN patients. Thus, results support a positive benefit/risk ratio of fluoxetine use for this young patient population.

Reduced phosphodiesters and high-energy phosphates in the frontal lobe of schizophrenic patients: a (31)P chemical shift spectroscopic-imaging study.

BACKGROUND: (31)Phosphorous magnetic resonance spectroscopy has been widely used to evaluate schizophrenic patients in comparison to control subjects, because it allows the investigation of both phospholipid and energy metabolism in vivo; however, the results achieved so far are inconsistent. Chemical shift imaging (CSI) has the advantage that instead of only one or a few preselected voxels the tissue of a whole brain slice can be examined. The aim of the present investigation was to determine whether the results of previous studies of our group, showing that phosphodiesters (PDE) are decreased in the frontal lobe of schizophrenic patients as compared to control subjects, might be confirmed in an independent unmedicated patient sample using the CSI technique. METHODS: A carefully selected new cohort including 11 neuroleptic-free schizophrenic patients and 11 age- and gender-matched healthy control subjects was recruited. CSI was applied and an innovative analysis method for CSI data based on a general linear model was used. RESULTS: PDE, phosphocreatine, and adenosine triphosphate (ATP) were found to be significantly decreased in the frontal lobe of patients with schizophrenia. CONCLUSIONS: Because PDE was decreased in schizophrenic patients, the membrane phospholipid hypothesis of schizophrenia could not be corroborated. Further results indicate decreased ATP production in the frontal lobe of patients with schizophrenia.

The effect of hypericum extract on cardiac conduction as seen in the electrocardiogram compared to that of imipramine.

The electrocardiographic effects of high-dose hypericum extract were compared to the effects of imipramine hydrochloride on ECG recordings in a randomized, double-blind, multicenter treatment study of 209 patients suffering from depression. ECGs were recorded before and after a six-week treatment period with either hypericum extract or imipramine. At the end of the study ECGs of 84 patients treated with hypericum extract and 76 patients treated with imipramine were suitable for an analysis of conduction intervals and pathological findings. In the first ECG analysis comparing high dose hypericum extract with imipramine, a prolongation of the conduction intervals PR, QRS and QTc was found for imipramine. In contrast, a small acceleration of conduction was seen for the high-dose hypericum extract. The comparison of ECGs at the beginning and after six weeks of treatment showed a significant increase in first degree AV-blocks and abnormalities of repolarization under imipramine but a significant reduction of such pathological findings under treatment with hypericum extract. It should be emphasized that this favorable feature of safe cardiac activity was achieved with 1800 mg of hypericum extract. The reduction in pathological ECG features after treatment with hypericum extract may have resulted mainly from the change of medication, probably tricyclics, to hypericum extract. Our results indicate that for the treatment of patients with a pre-existing conductive dysfunction or elderly patients, high-dose hypericum extract is safer with regard to cardiac function than tricyclic antidepressants.