Ladislav Hosák

Antiepileptic drugs in schizophrenia: a review

The first choice group of psychotropic agents in schizophrenia is neuroleptics. However, this treatment is not effective in all patients and with every symptom. We summarize papers published on the role of antiepileptic drugs in treatment-resistant schizophrenia. We have searched the computer database system MEDLINE for relevant articles including reviews, reports of drug studies and case histories. Antiepileptic drugs can change symptoms of schizophrenia by their action on GABA-ergic neurotransmission or via anti-glutamatergic mechanisms. High doses of adjunctive benzodiazepines reduce positive symptoms, anxiety, and agitation. Carbamazepine is effective in affective symptoms of schizophrenia and influences violent behavior in psychotic patients. Its anti-kindling action may represent a promising treatment strategy for some patients with chronic course of schizophrenia. Valproate treatment leads to a decrease in positive symptoms as well as hostility. Lamotrigine is expected to influence the positive, negative, affective, and cognitive symptoms of schizophrenia. New antiepileptics (e.g., gabapentin, oxcarbazepine, topiramate, vigabatrin) present a promise as potential adjuncts to neuroleptic treatment in resistant symptoms of schizophrenia.

Markers of thrombogenesis are activated in unmedicated patients with acute psychosis: a matched case control study.

BackgroundAntipsychotic treatment has been repeatedly found to be associated with an increased risk for venous thromboembolism in schizophrenia. The extent to which the propensity for venous thromboembolism is linked to antipsychotic medication alone or psychosis itself is unclear. The objective of this study was to determine whether markers of thrombogenesis are increased in psychotic patients who have not yet been treated with antipsychotic medication.MethodsWe investigated the plasma levels of markers indicating activation of coagulation (D-dimers and Factor VIII) and platelets (soluble P-selectin, sP-selectin) in an antipsychotic-naive group of fourteen men and eleven women with acute psychosis (age 29.1 ± 8.3 years, body mass index 23.6 ± 4.7), and twenty-five healthy volunteers were matched for age, gender and body mass index.ResultsD-dimers (median 0.38 versus 0.19 mg/l, mean 1.12 ± 2.38 versus 0.28 ± 0.3 mg/l; P = 0.003) and sP-selectin (median 204.1 versus 112.4 ng/ml, mean 209.9 ± 124 versus 124.1 ± 32; P = 0.0005) plasma levels were significantly increased in the group of patients with acute psychosis as compared with healthy volunteers. We found a trend (median 148% versus 110%, mean 160 ± 72.5 versus 123 ± 62.5; P = 0.062) of increased plasma levels of factor VIII in psychotic patients as compared with healthy volunteers.ConclusionsThe results suggest that at least a part of venous thromboembolic events in patients with acute psychosis may be induced by pathogenic mechanisms related to psychosis rather than by antipsychotic treatment. Finding an exact cause for venous thromboembolism in psychotic patients is necessary for its effective treatment and prevention.

Assessment of risk of venous thromboembolism and its possible prevention in psychiatric patients.

Aims:  The aim of the present study was to compile a specific algorithm of prevention of venous thromboembolism in hospitalized psychiatric patients because this specific issue has not been addressed sufficiently in the literature.

Consensus paper of the WFSBP Task Force on Genetics: genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Abstract Major depressive disorder (MDD) is a heritable disease with a heavy personal and socio-economic burden. Antidepressants of different classes are prescribed to treat MDD, but reliable and reproducible markers of efficacy are not available for clinical use. Further complicating treatment, the diagnosis of MDD is not guided by objective criteria, resulting in the risk of under- or overtreatment. A number of markers of MDD and antidepressant response have been investigated at the genetic, epigenetic, gene expression and protein levels. Polymorphisms in genes involved in antidepressant metabolism (cytochrome P450 isoenzymes), antidepressant transport (ABCB1), glucocorticoid signalling (FKBP5) and serotonin neurotransmission (SLC6A4 and HTR2A) were among those included in the first pharmacogenetic assays that have been tested for clinical applicability. The results of these investigations were encouraging when examining patient-outcome improvement. Furthermore, a nine-serum biomarker panel (including BDNF, cortisol and soluble TNF-α receptor type II) showed good sensitivity and specificity in differentiating between MDD and healthy controls. These first diagnostic and response-predictive tests for MDD provided a source of optimism for future clinical applications. However, such findings should be considered very carefully because their benefit/cost ratio and clinical indications were not clearly demonstrated. Future tests may include combinations of different types of biomarkers and be specific for MDD subtypes or pathological dimensions.

Four cases of venous thromboembolism associated with olanzapine

Aims:  Psychiatric disorders and treatment with conventional antipsychotic medications have been associated with venous thromboembolism, but only a few data on recent antipsychotics such as olanzapine are available.

Genome‑Wide Association Studies in Schizophrenia, and Potential Etiological and Functional Implications of Their Results

BACKGROUND Despite the fact that the genetic basis of schizophrenia has been intensively studied for more than two decades, our contemporary knowledge in this field is rather fractional, and a substantial part of it is still missing. The aim of this review article is to sum up the data coming from genome-wide association genetic studies in schizophrenia, and indicate prospective directions of further scientific endeavour. METHODS We searched the National Human Genome Research Institutes Catalog of genome-wide association studies for schizophrenia to identify all papers related to this topic. In consequence, we looked up the possible relevancy of these findings for etiology and pathogenesis of schizophrenia using the computer gene and PubMed databases. RESULTS Eighteen genome-wide association studies in schizophrenia have been published till now, referring to fifty-seven genes supposedly involved into schizophrenias etiopathogenesis. Most of these genes are related to neurodevelopment, neuroendocrinology, and immunology. CONCLUSIONS It is reasonable to predict that complex studies of sufficiently large samples, involving detection of copy number variants and assessment of endophenotypes, will produce definitive discoveries of genetic risk factors for schizophrenia in the future.

Antipsychotic drugs as a risk factor for venous thromboembolism

Objective. We assessed whether antipsychotic drugs represent a risk factor for venous thromboembolism by comparing the prevalence of antipsychotic drugs use in a population of patients with venous thromboembolism versus a group of individuals treated for hypertension. Methods. We identified 266 patients (141 women) diagnosed as having venous thromboembolism at the average age of 43.1±11 years who had been hospitalized in the University Hospital in Hradec Králové from 1 January 1996 to 31 December 2004. Two hundred and seventy-four patients (140 women) with arterial hypertension, with an average age of 48.3±8.8 years, represented the control population. Results. Use of antipsychotic drugs was moderately more frequent in the group of patients with venous thromboembolism as compared with the control group subjects (4.89 vs. 1.82%; odds ratio 2.76; 95% confidence interval=1.01–7.55). Discussion. We discuss the possible mechanisms of venous thromboembolism induced by antipsychotic agents – hypoactivity, blood status, obesity, abnormal coagulation, autoimmune mechanisms, and hyperhomocysteinemia. Conclusion. Our results indicate the possibility of an increased risk for venous thromboembolism in patients using antipsychotic drugs. It is necessary to seriously consider this possible adverse effect owing to its potentially fatal consequences.

Genetics of schizophrenia: A consensus paper of the WFSBP task force on genetics

Abstract Objectives: Schizophrenia is a severe psychiatric disease affecting about 1% of the general population. The relative contribution of genetic factors has been estimated to be up to 80%. The mode of inheritance is complex, non-Mendelian, and in most cases involving the combined action of large numbers of genes. Methods: This review summarises recent efforts to identify genetic variants associated with schizophrenia detected, e.g., through genome-wide association studies, studies on copy-number variants or next-generation sequencing. Results: A large, new body of evidence on genetics of schizophrenia has accumulated over recent years. Many new robustly associated genetic loci have been detected. Furthermore, there is consensus that at least a dozen microdeletions and microduplications contribute to the disease. Genetic overlap between schizophrenia, other psychiatric disorders, and neurodevelopmental syndromes raised new questions regarding the current classification of psychiatric and neurodevelopmental diseases. Conclusions: Future studies will address especially the functional characterisation of genetic variants. This will hopefully open the doors to our understanding of the pathophysiology of schizophrenia and other related diseases. Complementary, integrated systems biology approaches to genomics, transcriptomics, proteomics and metabolomics may also play crucial roles in enabling a precision medicine approach to the treatment of individual patients.

Costs and outcomes of risperidone treatment in schizophrenia in the Czech Republic

The increasing cost of pharmaceuticals in the Czech Republic has led to restrictions on the prescription of more expensive atypical antipsychotics. The aim of the study was to compare the costs and outcomes of using risperidone versus classical neuroleptics in treatment of schizophrenia in order to see if there was any cost advantage in restricting use of more recent antipsychotics. Sixty-seven patients (39 women) with a mean age of 34.6 years (S.D. = 9.74) suffering from schizophrenia or schizoaffective disorder were treated with risperidone while 67 patients (39 women) with the same diagnoses with a mean age of 35.7 years (S.D. = 9.91) received standard neuroleptics. Yearly direct medical costs and outcomes (indicated by the average Global Assessment of Functioning score) were assessed retrospectively in an open, intent-to-treat study by abstracting psychiatric outpatient charts. The outcomes were not significantly different between the treatment groups while the risperidone treatment was significantly more expensive than the therapy with standard neuroleptics. This result which appears to be inconsistent with the literature was caused by the cheap labor force in the Czech Republic. The difference between the followed treatments in the direct costs will probably become insignificant in the future when the countrys economy will be more developed.

Comorbidity of parkinsonism and schizophrenia in a patient treated with clozapine.

Clozapine is the least likely anti-psychotic to induce extrapyramidal symptoms (EPS). We present a surprising case of a woman schizophrenic patient treated with clozapine suffering from EPS. Single photon emission computed tomography (SPECT) revealed a low density of presynaptic dopamine transporters in our patients brain. A comorbid diagnosis of Parkinsons disease in schizophrenia was confirmed in this way. This helped us to find a proper therapeutic strategy for our patient.