Long-term Treatment Of Schizophrenia Research Articles

P.3.d.025 Safety and tolerability of cariprazine in long-term treatment of schizophrenia: integrated summary of safety data

The continuing increase in multidrug-resistant organisms (MDROs) worldwide has created new challenges in treating complicated intra-abdominal infections (cIAIs). A number of novel antimicrobial agents have been developed against resistant pathogens. To target extended-spectrum β-lactamase (ESBL)-producing pathogens, novel β-lactam antibiotics, such as ceftolozane/tazobactam, ceftazidime/avibactam, aztreonam/avibactam, imipenem/relebactam and S-649266, are antimicrobial alternatives for cIAIs. Two new drugs, eravacycline and plazomicin, have activity against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae, carbapenem-resistant Acinetobacter baumannii and ESBL-producers. New lipoglycopeptides and oxazolidinones provide feasible options against resistant Gram-positive pathogens. These novel antimicrobials may play a role in improving the clinical outcomes of cIAIs caused by MDROs.

Development of novel risperidone implants using blends of polycaprolactones and in vitro in vivo correlation studies.

The objective of this study was to develop a novel implant containing risperidone intended for long-term treatment in Schizophrenia utilizing in vitro in vivo correlation (IVIVC) studies. Different implants (F1-F8) containing an antipsychotic drug, risperidone, were prepared using a hot melt extrusion technique by taking polycaprolactones of different molecular weights (Mwt. 15000, 45000, 80000) either alone or as their blends, and PLGA (75:25). The implants contained 40% of the drug. After fabrication, the implants were characterized for various in vitro properties such as drug release and physical strength. Prior to conducting drug release studies, optimum drug release method was developed based on IVIVC studies. An optimized formulation based on drug release and physical strength at the end of fabrication was selected from the various implants fabricated. The bioactivity, reversibility, and IVIVC of optimized formulation were determined using pharmacokinetic studies in rats. Short-term stability studies were conducted with optimized formulation. Drug release depended on polymer molecular weight. Implant fabricated using 50:50 polycaprolactone 45,000 and polycaprolactone 80,000 was considered optimized implant. Optimized formulation selected released the drug for 3-months in vitro and was physically rigid. The optimized implant was able to release the drug in vivo for a period of 3 months, the implants are reversible throughout the delivery interval and, a 100% IVIVC was achieved with optimized implant, suggesting the development of 3-month drug-releasing implant for risperidone. The optimized implant was stable for 6 months at room temperature (25°C) and 45°C. A novel implant for risperidone was successfully prepared and evaluated.

Review of depot aripiprazole for schizophrenia

Improving outcomes in schizophrenia generally requires an improvement in medication adherence. One of the most effective interventions to improve adherence is the use of depot formulations of antipsychotic medications. A new depot aripiprazole formulation for the treatment of schizophrenia will be available soon. A review of all publically available information on depot aripiprazole as of November 2012 was performed. One peer-reviewed study on depot aripiprazole is published, and the remainder of the data were presented at international scientific meetings. Depot aripiprazole appears to be both safe and effective in the long-term treatment of schizophrenia.

Does long-term treatment of schizophrenia with antipsychotic medications facilitate recovery?

Antipsychotic medications are viewed as cornerstones for both the short-term and long-term treatment of schizophrenia. However, evidence on long-term (10 or more years) efficacy of antipsychotics is mixed. Double-blind discontinuation studies indicate significantly more relapses in unmedicated schizophrenia patients in the first 6-10 months, but also present some potentially paradoxical features. These issues are discussed.

1056 – Comparative effectiveness of long-term treatment with atypical antipsychotics in patients with schizophrenia

Introduction Long-term head-to-head studies comparing atypical antipsychotics are important for clinical decision making. Objectives To evaluate long-term treatment of schizophrenia with lurasidone (LUR) vs. quetiapine XR (QXR; Study 234), or risperidone (RIS; Study 237). Aims To assess efficacy and safety of lurasidone relative to other antipsychotics. Methods In study 234(efficacy and safety), subjects received 12 months double-blind, flexible-dose lurasidone(40-160 mg/day) or QXR(200-800 mg/day) after completing a 6 week, randomized, double-blind, placebo-controlled trial with LUR or QXR. In Study 237 (safety) clinically stable adult outpatients received 12-months double-blind treatment with flexible-dose LUR 40-120 mg/day or RIS 2-6 mg/day. Results Study 234: continued treatment of LUR responders (n=139) reduced relapse risk by 27.2% vs. continued QXR treatment of QXR responders (n=79). Hospitalization risk was 56.7% lower with LUR vs. QXR. More LUR subjects achieved sustained remission vs. QXR (61.9% vs. 46.3%; p=0.043; 12 months, LOCF), and lower all-cause discontinuation (48% vs 61%). Triglycerides were reduced with LUR; total and LDL cholesterol were unchanged or reduced. Median prolactin change was +0.6 for LUR vs. -0.7 ng/mL for QXR. Study 237: clinically significant weight gain was observed with LUR 13%) vs. RIS (19%) with median change in prolactin 0.4 vs. 14.8 ng/mL, respectively. Comparable efficacy was observed for LUR and RIS (change from baseline in PANSS total score:-4.7 vs. -6.5, and CGI-Severity score:-0.4 vs. -0.4, respectively). Conclusion The results of these two 12-month trials suggest that lurasidone is safe and well-tolerated with efficacy comparable to quetiapine XR and risperidone for long-term treatment of schizophrenia.

Sertindole in the long-term treatment of schizophrenia

This study assessed the safety and tolerability of sertindole in the long-term treatment of schizophrenia. An open-label, noncomparative, flexible-dose study was carried out in 11 European countries. Upon completion of an 8-week, haloperidol-referenced randomized clinical trial with sertindole, patients were offered sertindole maintenance treatment up to 18 months. In total, 294 patients were enrolled, of whom 237 (81%) had received sertindole and 57 (19%) had received haloperidol in the lead-in trial. The modal dose during the maintenance period was 16 mg/day. Patients showed therapeutic improvement indicated by significant decreases in the Positive And Negative Syndrome Scale and Clinical Global Impression 'severity-of-illness' scores. An adverse event was the primary reason for withdrawal in 13% of patients. The most common adverse events were fatigue and weight gain, both with incidences of 14%. The incidence of extrapyramidal symptoms was 18%, and 11% of the patients required anticholinergic medication. No statistically significant changes were observed in laboratory values or vital signs, but the mean serum prolactin levels decreased. The mean change in weight from baseline to the last assessment was 2.7 kg. The largest weight increase was observed in patients who were underweight at baseline. Long-term treatment with sertindole was safe and well tolerated, and patients showed clinical improvement beyond acute treatment.

The long-term treatment of schizophrenia

The long-term treatment of schizophrenia is one of the most challenging tasks for practicing physicians. The most pronounced difficulty arises from the deficient compliance due to the lack of insight. Thus the treatment of schizophrenia requires a multimodal approach, which always includes psychosocial interventions beside the pharmacological treatment. The antipsychotic medication means the cornerstone in the pharmacological treatment of schizophrenia within which an increasing role of the long-acting second-generation injections can be detected. The outcome of schizophrenia can be modified by adequately organized management strategies, which in turn can lead to better quality of life and social functioning. If patients are provided with timely initiated effective medication and rehabilitation, then enduring remission can be a realistically achievable goal for the patients.

P-1223 - Schizophrenia: switching from any oral antypsychotics to RLAI, a good solution to avoid relapses

Introduction The long term treatment of schizophrenia must fulfill some medical and functional needs, like: good tolerability for a long time administration, maintaining and improving the patient's psychiatric condition obtained previously and keeping at good levels overall patient's functionality. Objectives Most atypical antipsychotics are effective in the acute phase of schizophrenia, but on long term, the compliance of the patient could get worse due to big amount of tablets, side effects, stigma, diminished ability to think or concentrate, sedation, increase of BMI or prolactin. Aims To improve patients' compliance by switching from oral treatment to RLAI (Risperidone Long Acting Injection) and keep them away from relapses. Methods We evaluated 2 patients: first, 26 years, stabilized with risperidone tablets, 8 mg/day; second, 29 years, treated with amisulpride 800 mg/day, both having previously relapses after refusing to take their tablets. We switched them on a treatment with RLAI 50 mg/i.m., twice a month. Evaluations were made weekly during the 6 weeks of stabilization period and a follow-up for a period of 6 months. The well-being of the patient was evaluated by using the following scales: PANSS, CGI-S, CGI-I, the patients' satisfaction with PSMQ questionnaire and activity with WPAI-GH. Results 1) There was none relapse for both patients. 2) We did not use any corrective co-medication. 3) The patients' satisfaction was greater and the functionality was better, due to a good compliance and fewer side-effects. Conclusions Switching from another antipsychotic to RLAI is a good solution to improve the patients compliance, functionality and quality of life overall.

Efficacy, tolerability and safety of paliperidone extended-release in the treatment of schizophrenia and schizoaffective disorder

The paper represents a systematic review on the efficacy, tolerability and safety of paliperidone, an antipsychotic drug recently approved in Italy for the treatment of schizophrenia and of schizoaffective disorder. A comprehensive PubMed search using the term "paliperidone" was performed from January 1980 to February 2011. Papers reporting data on efficacy in the treatment of schizophrenia and of schizoaffective disorder were included, also if published as abstracts and all retrieved articles were manually searched for other references of interest. Paliperidone was found to be effective in short and long-term treatment of schizophrenia, as well as in the treatment of schizoaffective disorder. For both disorders, paliperidone showed to be effective in improving psychotic and affective symptoms. In the studies analyzed it was well tolerated and the most frequent reported adverse events were mild extrapyramidal symptoms and an increase in serum prolactin levels. Paliperidone has been shown to be an effective and safe medication for the treatment of schizophrenia and schizoaffective disorder. Further controlled clinical trials are needed to confirm this clinical profile in the long-term treatment, as well as for specific conditions such as schizophrenic patients with medical comorbidities.

Pain, affect and psychotic illness

Dear colleagues, In order to cope with the increasing amount of interesting papers and due to the fact that Prof. Gattaz (Brazil) and Prof. Deakin (UK) discontinued to be co-editors based on their enormous work load, Hans-Juergen Moller and myself decided to renew and enlarge the editorial board. We are happy that Prof. Takeda (Japan), Prof. Heckers (USA), Prof. McGuire (England), Prof. Leboyer (France), Prof. Arango (Spain), Prof. Maier (Germany) and Prof. Rupprecht (Germany) have accepted our invitation to join the Editorial Board. We will soon decide how we will distribute the scientific fields to the individual members of the Editorial Board in order to improve our review process to maintain and improve the impact of our journal in the field. The current issue of the European Archives focuses on psychotic disorders. De Hert et al. [1] examined the effects of sertindole and risperidone on metabolic parameters in the short- and long-term treatment of schizophrenia. Segarra et al. [2] connect cognitive performance with smoking in first-episode psychosis. They discuss whether smoking in itself is a self-medication approach in order to improve symptoms like dyscognition. Park et al. [3] take up the discussion of olfactory identification, which is in the literature for schizophrenia for sometime but examining the specificity of this funding. Transcranial magnetic stimulation in the treatment of depression has received much attention from clinicians but recently less support in the literature. The paper by Langguth et al. [4] gives a good account of the usefulness of this method in the treatment of depression under naturalistic conditions. Disturbed pain modulation in psychiatric disorders has been underestimated for long time. Especially in somatoform disorders, this is changing recently. The paper by Klug et al. [5] focuses on the issue of dysfunctional pain modulation in somatoform pain disorder patients. Affective disorders are closely connected to the functioning of the immune system. Along these lines, Puustinen et al. [6] examines the association between psychological distress and C-reactive protein levels in the blood. Predicting psychiatric disorders in the offspring is currently discussed intensively. Steinlechner et al. [7] examines this issue from the other side by asking the question whether “Restless legs syndrome” is a possible predictor of psychiatric disorders in parents of children with ADHD. Predicting outcome of severe alcohol-related problems is the basis of a 20-year prospective epidemiological community study by Fichter et al. [8]. These are important data as the majority of our patients will suffer from psychiatric comorbidities for a substantial proportion of their life time. We hope that you will like the mix of papers relating to main topics in our field and enjoy reading this issue of the European Archives.

The GiSAS study: Rationale and design of a pragmatic randomized controlled trial on aripiprazole, olanzapine and haloperidol in the long-term treatment of schizophrenia

Given the controversy about the comparative efficacy of first- compared with second-generation antipsychotics in the treatment of schizophrenia, more large-scale evidence is needed to guide clinicians in their prescriptions. Most randomized controlled trials (RCTs) were conducted in centers of excellence on highly selected samples, poorly representative of real-world patients, and often suffered conflicts of interest as they were sponsored by drug companies. The primary aim of the present study is to compare the effectiveness of haloperidol, olanzapine and aripiprazole in a representative sample of schizophrenia patients. The GiSAS trial is an open-label, independent, pragmatic RCT in Italian community-based public psychiatric services. At least 260 patients meeting the DSM-IV criteria for schizophrenia will be randomly allocated to one of the study drugs and followed up for one year. A two-year observational phase will follow. The primary outcome for tolerability will be the onset of metabolic syndrome. The primary endpoint for effectiveness will be discontinuation of antipsychotic monotherapy. Secondary measures include global functioning, time to discontinuation due to side-effects, change of lipid profile, extrapyramidal symptoms and other adverse effects. In the last four years, the GiSAS study group has been working to implement this multicenter RCT. The trial mechanism is now fully functional and working. As of end of February 2011, 260 subjects were randomized by 54 study investigators in 33 out of 43 participating centers.

Transitioning From Acute to Long-Term Treatment in Schizophrenia

The ultimate goal of acute treatment for schizophrenia is the resolution of symptoms. Unfortunately, when selecting medications and treatment strategies, many clinicians rely on clinical intuition and informal interviews without also using measurement-based rating scales. This activity discusses methods for improving response to acute pharmacotherapy, the necessity of medication adherence to prevent relapse in the maintenance phase, and the importance of using measurement-based care during all phases of treatment for schizophrenia.

Chronic Treatment With Aripiprazole Prevents Development of Dopamine Supersensitivity and Potentially Supersensitivity Psychosis

Background: Long-term treatment of schizophrenia with antipsychotics is crucial for relapse prevention, but a prolonged blockade of D2 dopamine receptors may lead to the development of supersensitivity psychosis. We investigated the chronic effects of aripiprazole (ARI) on dopamine sensitivity. Methods: We administered ARI (1.5 mg/kg/d), haloperidol (HAL; 0.75 mg/kg/d), or vehicle (VEH) via minipump for 14 days to drug-naive rats or to rats pretreated with HAL (0.75 mg/kg/d) or VEH via minipump for 14 days. On the seventh day following treatment cessation, we examined the effects of the treatment conditions on the locomotor response to methamphetamine and on striatal D2 receptor density (N = 4-10/condition/experiment). Results: Chronic treatment with HAL led to significant increases in locomotor response and D2 receptor density, compared with the effects of chronic treatment with either VEH or ARI; there were no significant differences in either locomotor response or D2 density between the VEH- and ARI-treated groups. We also investigated the effects of chronic treatment with HAL, ARI, or VEH preceded by HAL or VEH treatment on locomotor response and D2 density. ANOVA analysis indicated that the rank ordering of groups for both locomotor response and D2 density was HAL-HAL > HAL-VEH > HAL-ARI > VEH-VEH. Conclusions: Chronic treatment with ARI prevents development of dopamine supersensitivity and potentially supersensitivity psychosis, suggesting that by reducing excessive sensitivity to dopamine and by stabilizing sensitivity for an extended period of time, ARI may be helpful for some patients with treatment-resistant schizophrenia.

CS06-04 - Short and long-term treatment outcomes in schizophrenia

Schizophrenia is a chronic disorder with a high risk of poor outcome in terms of symptoms and social functioning and possibly also progressive brain alterations. The relapse rate is high and each relapse can induce further aggravations, both in psychosocial as well as in neurobiological terms. Thus, acute and long-term treatment with the highest degree of effectiveness should be provided to the patients in acute and long-term treatment.Neuroleptic medication is the most important part of the treatment regimen for schizophrenic patients. The efficacy of neuroleptics in the acute and long-term treatment of schizophrenia is very well proven and the effect size is comparatively high. The second-generation antipsychotics (SGAs) have advantages over the neuroleptics of the first-generation (FGAs), and high expectations have therefore been put into them for the treatment of schizophrenia. Their better extrapyramidal-motor tolerability and efficacy in treating negative, depressive and cognitive symptoms, in addition to positive symptoms, supposedly result in a more favourable influencing of the overall course of the disease and in a higher quality of life for the patients, thus improving their acceptance by patients and leading to increased compliance. Differences in the pharmacological profile can be identified among others by receptor imaging approaches.

Olanzapine pamoate for the treatment of schizophrenia

Introduction: Nonadherence is still a major problem in the long-term treatment of schizophrenia. Long-acting injectable or depot atypical antipsychotics are associated with better maintenance. Olanzapine pamoate, available since 2010, is the second depot atypical antipsychotic.Areas covered: This review covers data on the efficacy and tolerability/safety of olanzapine pamoate, the long-acting formulation of the atypical antipsychotic olanzapine. Administered as a pamoate salt, it has an elimination half-life of 30 days, allowing a 2- or 4-week injection interval. Antipsychotic efficacy was documented in an 8-week trial in 404 acutely ill schizophrenia patients with maintenance therapy in a 24-week trial in 1065 chronic patients. The side-effect profile is comparable to that of oral olanzapine. The most relevant adverse event is the post-injection delirium/sedation syndrome, occurring at a rate of 0.07% of injections or 1.4% of patients. It requires administration by qualified personnel in settings where a post-injection observation period for 3 h by medical personnel is available.Expert opinion: Olanzapine pamoate is an efficacious formulation, particularly for patients with a history of good response to oral olanzapine and doubtful adherence. Psychiatrists should reconsider their negative attitudes toward long-acting or depot antipsychotics and should offer this administration to the majority of patients, not only to a negatively selected population.

Predictors of switching antipsychotic medications in the treatment of schizophrenia

BackgroundTo identify patient characteristics and early changes in patients' clinical status that best predict subsequent switching of antipsychotic agents in the long-term treatment of schizophrenia.MethodsThis post-hoc analysis used data from a one-year randomized, open-label, multisite study of antipsychotics in the treatment of schizophrenia. The study protocol permitted switching of antipsychotics when clinically warranted after the first eight weeks. Baseline patient characteristics were assessed using standard psychiatric measures and reviews of medical records. The prediction model included baseline sociodemographics, comorbid psychiatric and non-psychiatric conditions, body weight, clinical and functional variables, as well as change scores on standard efficacy and tolerability measures during the first two weeks of treatment. Cox proportional hazards modeling was used to identify the best predictors of switching from the initially assigned antipsychotic medication.ResultsAbout one-third of patients (29.5%, 191/648) switched antipsychotics before the end of the one-year study. There were six variables identified as the best predictors of switching: lack of antipsychotic use in the prior year, pre-existing depression, female gender, lack of substance use disorder, worsening of akathisia (as measured by the Barnes Akathisia Scale), and worsening of symptoms of depression/anxiety (subscale score on the Positive and Negative Syndrome Scale) during the first two weeks of antipsychotic therapy.ConclusionsSwitching antipsychotics appears to be prevalent in the naturalistic treatment of schizophrenia and can be predicted by a small and distinct set of variables. Interestingly, worsening of anxiety and depressive symptoms and of akathisia following two weeks of treatment were among the more robust predictors of subsequent switching of antipsychotics.

Metabolic parameters in the short- and long-term treatment of schizophrenia with sertindole or risperidone

The presence of the metabolic syndrome is an important risk factor for cardiovascular disease and diabetes. The short- and long-term metabolic safety of sertindole was compared to that of risperidone in a subset of patients enrolled in the sertindole cohort prospective (SCoP) study, an open randomized study. In 261 randomized patients, there were moderate increases in mean weight, BMI, and waist circumference during treatment with either sertindole or risperidone; after 12 weeks, the increase in weight was 1.3 and 1.1 kg, respectively, and after 36 weeks, it was 2.2 and 2.0 kg, respectively. From baseline to last assessment (up to 60 weeks), weight gains of 1.8 and 1.7 kg for sertindole and risperidone, respectively, were observed. Similar proportions of patients (sertindole: 17% versus risperidone: 16%) had weight increases ≥7% from baseline to last assessment. The mean changes from baseline in triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, plasma glucose and blood pressure were small and not clinically relevant in both treatment groups. No patient in either of the groups developed type 2 diabetes during the study. At last assessment, the prevalence of metabolic syndrome (International Diabetes Federation) was 17% in the sertindole group and 26% in the risperidone group and the incidence of metabolic syndrome was 7% in the sertindole group and 10% in the risperidone group. Treatment with either sertindole or risperidone did not appear to be associated with an increased comparative risk of developing metabolic syndrome. In general, the metabolic effects of sertindole and risperidone were similar.

The need for efficient long-term neuroleptic treatment in schizophrenic patients and the place of long acting injectable antipsychotics

Schizophrenia is a chronic disorder with a high risk of poor outcome in terms of symptoms and social functioning and possibly also progressive brain alterations. The relapse rate is high and each relapse can induce further aggravations. Thus, long-term treatment with the highest degree of effectiveness should be provided to the patients. Amongst others, the suitable drug for the individual patient has to be selected as well as the high risk of non-compliance to be carefully considered. All the available evidence from randomised controlled studies indicates that antipsychotic medications substantially reduce the risk of relapse. The lowest dose should be chosen at which preferably no side effects occur, the risk of relapse seems to be optimally reduced and, if symptoms are still present, suppression of these is optimised. Side effects have to be assessed and, if necessary, pharmacotherapy has to be adjusted. Despite several methodological design issues, second-generation antipsychotics have proven superior efficacy in preventing relapse to FGAs. Available studies of the specific agents supply evidence for periods of up to 2 years. Due to the decreased risk of EPS, especially tardive dyskinesia and the superior efficacy in improving negative, cognitive and depressive symptoms, second-generation antipsychotics should be preferred in long-term treatment. Given all the known problems in compliance and discontinuation, which were underlined in recent years by the CATIE and the EUFEST study, depot preparations should be considered for optimum effectiveness in preventing relapse. Altogether, randomised, control-group studies to determine the long-term advantages of depot preparations of atypical neuroleptics compared to depots of typical neuroleptics are still lacking. However, the huge database for long acting injectable risperidone is so convincing in terms of efficacy, tolerability and effectiveness that its special place in the long-term treatment of schizophrenia becomes obvious. The target strategy in long-term treatment of schizophrenia should be a combination of long-term antipsychotic treatment and psycho- and sociotherapeutic procedures, so that the relapse rate is further reduced and the course of disease can be further improved.

Drug attitude as predictor for effectiveness in first-episode schizophrenia: Results of an open randomized trial (EUFEST)

Effectiveness has become more and more important as a comprehensive outcome measure for (long-term) treatment in schizophrenia. Early predictors to identify patients at a high risk for not succeeding the initiated treatment would be very useful. Discontinuation of the initiated treatment was used as criterion for effectiveness and patients' drug attitude was shown to be predictive for non-adherence or discontinuation of long-term treatment in schizophrenia. Accordingly, the predictive validity of the Drug Attitude Inventory (DAI) for effectiveness should be evaluated. Based on a sub-sample of patients from the EUFEST study for whom DAI assessments were available significant predictors for effectiveness as measured by discontinuation of initiated treatment were identified based on a logistic and a Cox-regression analysis. A Receiver-Operating Characteristic- (ROC-) analysis was conducted for the DAI, prognostic / diagnostic parameters (sensitivity, specificity) were calculated and a cut-off value suggested. In a sample of 228 first-episode patients, the DAI score was the most powerful predictor for effectiveness (p<0.001) besides two other significant predictors (PANSS-positive score and sexual side effects). The ROC-analysis revealed an area under the curve of 0.64 (p<0.001). The suggested cut-off point of about 20 yielded a sensitivity of 70-75% and a specificity of 40-45%. Study results indicate that the Drug Attitude Inventory, filled in by patients early in treatment seems to be a valid predictor for effectiveness as measured by discontinuation of the initiated treatment. DAI scores could also serve as an (differential) indicator for the need of enhanced treatment monitoring. These findings have to be validated in other (first-episode) samples.

P.3.c.057 Double-blind, placebo-controlled trial of asenapine in prevention of relapse after long-term treatment of schizophrenia

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by a hypercoagulable state associated with acute hemolysis. Eculizumab is used to reduce the intensity of intravascular hemolysis in PNH patients.The hemostatic status of three patients with PNH was assessed during eculizumab treatment by D-dimer assay and the global assays: thromboelastography (TEG), thrombin generation test (TGТ), and thrombodynamics (TD).In the state of hemolytic crisis before the therapy D-dimer concentration was increased in two patients accompanied by hypercoagulation changes in TEG parameter angle (α). TD parameter the clot growth velocity (V) revealed hypercoagulability while TGT parameter ETP was within the normal range in all patients.The lactate dehydrogenase (LDH) activity decreased during the 8 months of eculizumab therapy. The physical health was improved, the frequency of hemolytic crisis decreased. Patients periodically exhibited hypercoagulable state: the mean values α = 38 ± 11° (with normal range 20–40°), ETP = 1311 ± 442 nM·min (with normal range 800–1560 nM·min), V = 31 ± 4 μm/min (with normal range 20–29 μm/min). During the eculizumab therapy two patients had the repeated clinical manifestation of acute hemolytic crisis, the parameters of the global tests were increased compared to the previous measurement.The global hemostasis tests TEG, TGT and TD revealed hypercoagulability in patients with PNH during eculizumab therapy.