Valentinas Maciulis

Treatment of acute schizophrenia with paliperidone ER: predictors for treatment response and benzodiazepine use

The Paliperidone ER Treatment in Acute Intervention (PERTAIN) study was designed to explore treatment response, tolerability, and safety of flexible doses of paliperidone ER in patients with schizophrenia admitted for an acute exacerbation. This paper addresses a secondary analysis of PERTAIN data designed to explore predictors for treatment response, flexible dosing, and concomitant benzodiazepine use. This prospective, multicenter, phase 3b, open-label, single-arm, 6-week study used flexible doses of paliperidone ER (3 to 12mg once daily) to treat patients hospitalized for an acute exacerbation of schizophrenia, reflecting more closely daily clinical practice. Predictive models were evaluated for paliperidone ER flexible dosing, treatment response, and concomitant treatment with benzodiazepines as distinct independent variables. For the analysis of explanatory variables, a stepwise logistic regression was used, taking into account patient age, gender, body mass index, diagnosis and duration of schizophrenia, number of prior hospitalizations, psychotic symptoms (PANSS), disease severity (CGI-S), and patient functioning (PSP) at baseline. Early response (defined as response within 2weeks of treatment initiation) was also used as a predictor. Clinical response (defined as ≥30% decrease in PANSS total score and ≥1 point decrease in CGI-S from baseline to endpoint) was predicted by early clinical response (p<0.001) and there was a trend for the diagnosis of paranoid schizophrenia vs. other types of schizophrenia to predict clinical response (p=0.0525). High response (defined as ≥50% decrease in PANSS total score and ≥2 points decrease in CGI-S from baseline to endpoint) was predicted by early high response, higher baseline CGI-S, or female gender. More severely ill patients with a higher baseline CGI-S were twice likely to be treated concomitantly with a benzodiazepine.

Closed eyes condition increases auditory brain responses in schizophrenia.

The 40-Hz auditory steady-state responses (ASSRs) of 14 medicated schizophrenic patients were recorded in eyes-open and eyes-closed conditions as previously done in healthy volunteers. Patients show significantly increased precision of the evoked response with eyes closed, and a significant increase of broad-band noise activity when eyes are open.

40 Hz auditory steady-state response in schizophrenia: Sensitivity to stimulation type (clicks versus flutter amplitude-modulated tones)

Auditory steady-state response (ASSR) at 40Hz has been proposed as a potential biomarker for schizophrenia. The ASSR studies in patients have used click stimulation or amplitude-modulated tones. However, the sensitivity of 40Hz ASSRs to different stimulation types in the same group of patients has not been previously evaluated. Two stimulation types for ASSRs were tested in this study: (1) 40Hz clicks and (2) flutter-amplitude modulated tones. The mean phase-locking index, evoked amplitude and event-related spectral perturbation values were compared between schizophrenia patients (n=26) and healthy controls (n=20). Both stimulation types resulted in the observation of impaired phase-locking and power measures of late (200-500ms) 40Hz ASSR in patients compared to healthy controls. The early-latency (0-100ms) 40Hz ASSR part was diminished in the schizophrenia group in response to clicks only. The late-latency 40Hz ASSR parameters obtained through different stimulation types correlated in healthy subjects but not in patients. We conclude that flutter amplitude-modulated tone stimulation, due to its potential to reveal late-latency entrainment deficits, is suitable for use in clinical populations. Careful consideration of experimental stimulation settings can contribute to the interpretation of ASSR deficits and utilization as a potential biomarker.

Efficacy and Tolerability of Olanzapine in Patients with Schizophrenia in Lithuania: A 13-Week, Multicenter, Open-Label, Nonrandomized Study

BACKGROUND The atypical antipsychotic olanzapine has been approved for the treatment of schizophrenia in Europe since 1996 but has been used primarily as a second-line treatment to the less expensive typical agents. However, similar to other atypical antipsychotic drugs, olanzapine has a lower risk of inducing extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, and sexual dysfunction compared with the typical antipsychotic drugs. OBJECTIVE The aim of this study was to determine whether patients with schizophrenia who have a poor response to their present antipsychotic therapy would show improvement when switched to olanzapine. METHODS This 13-week, multicenter, open-label, nonrandomized trial was conducted at 5 centers in Lithuania. Patients were started on oral olanzapine 10-mg tablets once daily, which could be adjusted by 5 mg/d in the dosing range of 5 to 20 mg/d. The primary efficacy measure was the total score on the Brief Psychiatric Rating Scale (BPRS), which was extracted from the Positive and Negative Syndrome Scale (PANSS). Efficacy response rate was defined a priori as the percentage of patients achieving ≥40% improvement in the BPRS total score. Secondary assessments included the PANSS total and BPRS and PANSS subscales and scores on the Clinical Global Impression-Severity of Illness (CGI-S), the CGI-Global Improvement (CGI-I), and the Patient Global Impression-Improvement (PGI-I) tests. Tolerability was primarily measured by assessing the incidence of treatment-emergent adverse events (AEs) according to the Udvalg fuer Kliniske Undersogelser (UKU) Side Effect Rating Scale and laboratory analyses. RESULTS Twenty-four patients (13 men [54.2%]; mean [SD] age, 32.4 [8.1] years) entered the study. Twenty-three (95.8%) of the 24 patients completed the study. The mean (SD) daily dosage of olanzapine was 11.40 (2.18) mg/d. The total mean (SD) BPRS score improved significantly from 37.8 (7.9) to 19.5 (13.7) (P < 0.001). The response rate was 58.3% (14/24 patients). The mean positive and negative BPRS scores and the mean total and subscale PANSS scores all improved significantly from baseline (P < 0.001). The mean (SD) CGI-S score improved significantly from 4.8 (0.8) at baseline to 3.5 (1.1) at end point (P < 0.001). Twenty-two patients (91.7%) showed improvement on the CGM scale. Similar improvement was found on the PGM scale. Treatment-emergent AEs occurred in 7 patients (29.2%). Improvement was found on 31 of the 48 UKU scale items; no change was shown on 15 items; and slight worsening was shown on 2 items. No clinical abnormalities were detected during the study. CONCLUSION In this study of Lithuanian patients with schizophrenia, significant improvement was shown in all efficacy measures. In addition, olanzapine was well tolerated in these patients.

1088 – ECT and information processing in patients with treatment-resistant psychiatric disorders assessed by event-related potential P300

Introduction The study of non-memory cognitive functions after ECT has been relatively neglected. Event-related potentials (ERP) are thought to reflect some cognitive processes. ERP P300 is a sensitive indicator of disturbances of attentional and working memory processes. Objectives Aim of this study was to examine the effect of course of ECT on auditory ERP P300. Methods P300 potential was recorded in 22 patients. 12 patients had schizophrenia spectrum disorders and 10 patients had various mood disorders. Mean age of patients was 40±13 years (from 22 to 72 years). ERPs were recorded before the first ECT procedure and after the last ECT. Recordings were made at Fz, Cz and Pz electrode sites. Peak-to-peak (N2-P3) amplitude and latency of P300 wave were analyzed. Correlation between P300 parameters, clinical symptoms (measured using PANSS, MADRS, HAM-D scales) and parameters of ECT procedure - delivered energy, seizure energy index (SEI) and duration of seizure - was evaluated. Results After ECT clinical symptoms have improved. There was also a statistically significant increase in P300 amplitude. Increase was greater in the 20-39 years old patient group. Decrease in P300 latency was insignificant. Correlation between P300 latency and SEI, and between P300 amplitude and delivered energy was more reliable in the mood disorders group. According to HAM-D the improvement of depression symptoms correlates with the decreased latency and increased amplitude of the P300 potential. Conclusions ECT may improve information processing in patients with treatment-resistant schizophrenia spectrum disorders and mood disorders as assessed by event-related potential P300.

Evaluation of The Quality of Delivered Services, Specialists’ Performance and Environmental Factors at Republican Vilnius Psychiatric Hospital

Respublikinės Vilniaus psichiatrijos ligoninės (RVPL) specialistai, atsižvelgdami į siuolaikinio mokslo ir praktikos reikalavimus, vykdo įsipareigojimus pacientams, siekdami nuolat gerinti teikiamų paslaugų kokybe bei didinti pasitikėjimą pacia institucija. Norėdami būti tikri, kad jų veikla atitinka pacientų poreikius ir lūkescius, kad sie linke sugrįžti, kai tokios pagalbos ar paslaugų jiems prireiks, RVPL darbuotojai pabandė patikrinti, ar užtikrinamas efektyvus ir saugus medicinos priežiūros paslaugų teikimas, atlikdami tyrimą „Respublikinėje Vilniaus psichiatrijos ligoninėje teikiamų paslaugų kokybės, specialistų darbo bei aplinkos faktorių vertinimas“. Savo nuomone isreiskė tiek ligoninės darbuotojai, tiek pacientai, vertindami pagrindinius paslaugų kokybe atspindincius kriterijus. Tai paslaugų prieinamumas, savalaikiskumas ir veiksmingumas, ligoninės personalo bendravimas su pacientais, dėmesingumas serganciajam ir jį lankantiems artimiesiems, tarpusavio pasitikėjimas ir pagarba bei saugi, jauki aplinka, orientacija į paciento reabilitaciją ir integraciją bendruomenėje. Tyrimas vyko 2009 – 2010 m. Tyrimo tikslas: istirti RVPL teikiamų paslaugų kokybės, specialistų veiklos bei aplinkos pritaikymo ir psichologinio klimato vertinimą. Straipsnyje pateikti tyrimo rezultatai, is kurių paaiskėjo, kad neretai skiriasi ligoninės darbuotojų ir pacientų teikiamų paslaugų kokybės, specialistų ir aplinkos faktorių vertinimas. Paslaugų kokybe geriau įvertino specialistai, o psichologine atmosfera ir supancia aplinka labiau patenkinti pacientai. doi:10.5200/sm-hs.2012.001

Ect Efficacy in the Treatment of Schizophrenia and Schizoaffective Disorder

Nors elektros impulsų terapija (EIT) yra taikoma nuo 1938 m., bet islieka reiksminga ir siuolaikinėje psichiatrijos praktikoje gydant visą eile psichikos sutrikimų. Sizofrenija buvo viena is anksciausiai nustatytų EIT indikacijų. Sio darbo tikslas- įvertinti EIT veiksmingumą gydant sizofreniją ir sizoafektinį sutrikimą. Istirta 60-ties ligonių, gydytų EIT Respublikinėje Vilniaus psichiatrijos ligoninėje (RVPL) 2006 m., medicininė dokumentacija. Įvertintas EIT veiksmingumas realioje kasdieninėje klinikinėje praktikoje. Pagrindinis tyrimo metodas – klinikinis- psichopatologinis, greta jo naudotos vertinimo skalės: klinikinio globalaus įspūdžio sunkumo (KGĮS) ir klinikinio globalaus įspūdžio pagerėjimo (KGĮP). EIT procedūra buvo atliekama Thymatron DGx aparatu pagal ligoninėje nustatytą sios procedūros reglamentą. Pacientų vidutinė ligos trukmė -15,30 ± 9,9 metų, jie vidutiniskai patyrė 7,4 ± 6,8 ligos atkrycius, buvo gydyti įvairiais tipiniais ir atipiniais antipsichoziniais vaistais bei jų deriniais. Tiriamieji buvo rezistentiski gydymui, sugrupuoti į 4 grupes pagal psichopatologijoje vyraujancią simptomatiką: a) haliucinacinis kliedesinis, b) depresinis kliedesinis, c) katatonijos sindromai: atitinkamai 25,15,12 ligonių ir d) sizoafektinis sutrikimas- 8 ligoniai. Vertinant keturias psichopatologijos grupes nustatytas gydymo EIT veiksmingumas, labai didelis ir didelis pagerėjimas gautas gydant katatoniją ( 41,6 % ir 58,3%), didelis pagerėjimas- sizoafektinį sutrikimą (75%) ,didelis pagerėjimas-depresinį kliedesinį sindromą (60%) ir didelis pagerėjimas - haliucinacinį kliedesinį sindromą (48%). Mūsų tyrimas parodė, kad EIT kartu su psichotropiniais vaistais yra veiksmingas ir saugus gydymo metodas rezistentiskai sizofrenijai ir sizoafektiniam sutrikimui gydyti. EIT veiksminga po pagrindinio kurso taikant testine ir palaikomąją terapiją ypac ilgai sergantiems ligoniams. Darbe aptarti duomenys leis gydytojams, įvertinus psichopatologijos ypatumus, pasirinkti tinkamus psichotropinius vaistus ir EIT derinį. doi:10.5200/sm-hs.2012.009

Effect of Electroconvulsive Therapy of Schizophrenia Spectrum Disorders and Affective Disorders on the Auditory Event-Related Potential P300

Auditory event-related potential (ERP) P300 is neurophysiological method of study of human cognitive functions, such as attention and working memory. Electroconvulsive therapy (ECT) is effective method of treatment of different, mainly affective, treatment-resistant psychiatric disorders. However the mechanisms of action of ECT are not clear and sometimes there are negative effects on the memory. The influence of ECT on P300 potential is poorly studied. The aim of this work was to evaluate the effect of ECT on the auditory ERP P300. 38 patients (21 female and 17 male) were studied. Average age was 44.5±13.5 years. Patients were divided into 2 groups according to diagnosis. First group consisted of patients with schizophrenia spectrum disorders (SSD), while the patients with affective disorders were included into the second group. 2 age-matched groups of healthy controls were also formed. ERPs were recorded two times – at the baseline and after the last procedure of ECT course at 3 electrode sites (Fz, Cz and Pz). The medication of patients has not changed during the course of ECT. Clinical symptoms were evaluated using PANSS scale in the case of SSD and HAMD and MADRS scales in the case of affective disorders. 4 parameters of P300 were measured: latency of N2, latency and amplitude of P300 and recognition time of target stimuli. Results have shown that the parameters of P300 potential of patients from both groups were abnormal in comparison with P300 of persons of control groups. The clinical symptoms of schizophrenia and depression have significantly improved after the course of ECT. ECT had positive effect on the P300 potential in the group of SSD – its amplitude has increased at all three sites of recording. In the case of affective disorders the positive changes of P300 potential were less marked. Article in Lithuanian doi:10.5200/sm-hs.2012.013

PTMS8 Transcranial magnetic stimulation effect on depression clinical symptoms and event-related potential P300

delivered at rest and during a sustained voluntary contraction of the target muscle. Results: Changes in the resting motor threshold (RMT), motor evoked potential (MEP) amplitudes and cortical silent period (CSP) duration were measured and compared in patients and healthy controls. Two of the 22 patients were re-tested after surgical removal of the parathyroid adenoma when serum calcium had normalized. In a subgroup of healthy subjects, changes in the rTMS parameters were tested before and after acute hypercalcemia. No significant between groups difference was found in the RMT values and MEP amplitude and CSP duration. During the course of 5 Hz-rTMS trains MEP size increased significantly less in hypercalcemia patients, than in healthy subjects, whereas the CSP duration lengthened to a similar extent in both groups. In the two patients studied after parathyroid adenomectomy, rTMS elicited a normal MEP amplitude facilitation. Conclusions: Our findings indicate that acute hypercalcemia significantly decreased the MEP amplitude facilitation possibly related to Ca2+dependent changes in synaptic plasticity.

P03-132 The effect of quetiapine on auditory P300 response in patients with schizoaffective disorder: Preliminary study

Abnormalities in attention, memory and information processing are considered to be the primary deficits in schizophrenia. Event-related potential (ERP) P300 could reflect deficits in auditory information processing related to active attention in schizophrenia patients. Atypical antipsychotics tend to ameliorate cognitive deficits, however their effects on neural aspects of cognitive dysfunction have not been consistent. Aim To investigate the effects of quetiapine on auditory information processing by using auditory P300. Methods We examined 7 patients with schizoaffective disorder, depressive type and 7 age- and sex-matched healthy controls. ERPs were elicited during active auditory “oddball” paradigm. P300 was recorded before and after two weeks of treatment with quetiapine (468.7±143 mg/day). Results Baseline P300 latencies were significantly delayed in patients compared with controls. Quetiapine did not change P300 amplitudes. However, it normalized P300 latency. These results suggest that already after two weeks of treatment, quetiapine could have a beneficial effect on the active attention reflected in P300 in patients with schizoaffective disorder. Previous studies with antipsychotic drugs such as olanzapine and risperidone failed to show changes in P300 after this treatment interval. Conclusion Quetiapine may be faster than other neuroleptics in ameliorating attentional dysfunction in patients with schizoaffective disorder. However, studies with a larger sample size must be conducted in order to confirm or reject the results of the current study.