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Purpose: While the pivotal role of pharmacotherapy in psychiatry is universal, significant regional differences exist in drug use patterns. Herewith we compare the use of ATC psychotropic drugs (N05, psycholeptics and N06A, antidepressants) in 2010-2015 in the three Baltic Countries with reference to the Nordic Countries.Methods: Data were obtained from the national authorities on medicines as expressed in DDD per 1000 inhabitants per day. A semi-structured questionnaire was used for expert statements on the rationale of current use of medicines.Results: During the observation period the use of antipsychotics, anxiolytics, hypnotics and sedatives, and antidepressants steadily increased, while the growth in use of anxiolytics stagnated in the more recent years. Antipsychotic use was the largest in Lithuania and the lowest in Estonia. The use on anxiolytics in Lithuania was more than twice of that in Estonia and Latvia. Conversely, the use of hypnotics and sedatives was about three times higher in Estonia than in Latvia or Lithuania. Antidepressant use was dominated by the selective serotonin reuptake inhibitors in all three countries, but overall was much lower in Latvia as compared to Lithuania and Estonia. As compared to the Nordic Countries in 2015, antidepressants are used at much lower level throughout Baltics, probably reflecting underdiagnostics of depression and anxiety disorders.Conclusion: While the health-care expenditures in Estonia, Latvia and Lithuania are largely similar, as is the cultural and recent political background of these EU member countries, the extent and the pattern of psychotropic drug use is remarkably variable.

Objective Relapse and acute exacerbation are common in schizophrenia and may impact treatment response and outcome. Evidence is conflicting in respect to superiority of long-acting injectable antipsychotic therapies versus oral antipsychotics in relapse prevention. This randomized controlled study assessed the efficacy of paliperidone palmitate versus oral antipsychotics for relapse prevention. Method Eligible patients with a recent diagnosis of schizophrenia (within 1–5 years) were randomized 1:1 to paliperidone palmitate (n = 376) or oral antipsychotic monotherapy (n = 388) and entered a 2-week initial acute oral treatment phase. Patients who met predefined response criteria were eligible to enter the 24-month rater-blinded core treatment phase. Patients were evaluated for relapse, symptoms, functioning, quality of life, treatment satisfaction, and tolerability. Results In the core treatment phase, time to relapse was significantly longer in the paliperidone palmitate (n = 352) compared with the oral antipsychotics arm (n = 363): 85% of patients were relapse-free at 469 versus 249 days ( P = 0.019). Significantly fewer patients receiving paliperidone palmitate met the relapse criteria (52 [14.8%] versus 76 [20.9%, oral antipsychotics]; P = 0.032), representing a 29.4% relative risk reduction. For paliperidone palmitate, a significantly greater improvement in Positive and Negative Syndrome Scale total score on Day 8 ( P = 0.021) and a trend at endpoint ( P = 0.075) were observed. Functioning improvements were comparable between treatment arms. No new safety signals were identified. Conclusion The observed time to relapse superiority of paliperidone palmitate over oral antipsychotics provides further evidence for the value of long-acting injectable antipsychotic therapies in the treatment of schizophrenia, including during the early stages of illness.

Schizophrenia is a serious public health problem and is ranked among the most disabling diseases in the world. The sub-study presented here was part of a larger project to characterize the burden of schizophrenia on healthcare systems and on individuals living with the disease in Central and Eastern Europe (CEE).This sub-study aimed to assess and analyze the impact of schizophrenia on many aspects of the lives of patients and caregivers.Psychiatrists from selected centers in seven Central and Eastern European countries were asked to complete a questionnaire in order to collect information about the disease history, characteristics, treatment protocols and resources used for each randomly selected patient. All data were statistically analyzed and compared between countries.Data from 961 patients with schizophrenia (mean age 40.7 years, 45.1% female) were included in the analysis. The mean number of days spent in hospital per patient per year across all seven countries was 25.3 days. Hospitalization occurred on average once per year, with psychiatrist visits 9.4 times per year. Of the patients in the study, 61% were single, 12% divorced and 22% married or cohabiting. Almost 84% were living with relatives or a partner; only 17% lived alone and, on average, 25% of patients received support from social workers. Relatives provided care for approximately 60% of patients and 4% of them had to stop working in order to do so. Twenty-nine percent of the patients were unemployed, and 56% received a disability pension or were retired, with only 19% in full-time employment or education.Schizophrenia has a significant effect on the lives of patients and caregivers and impacts their social integration.

Metabolic effects are generally more pronounced with second-generation than first-generation antipsychotics. This study was designed to compare long-term metabolic effects and efficacy of paliperidone extended release (ER) with those of oral olanzapine in patients with schizophrenia. In this 6-month, multicenter, prospective, randomized, controlled, open-label, parallel-group study, adults with schizophrenia were treated with paliperidone ER (6-9 mg/d; n = 239) or oral olanzapine (10-15 mg/d; n = 220). The primary outcome was mean change in the ratio of serum triglyceride level to high-density lipoprotein level (TG/HDL), a marker of insulin resistance. Other outcome measures included the Positive and Negative Syndrome Scale scores, measures of lipid and glucose metabolism, and body weight. Significant improvements in psychotic symptoms were observed with both treatments (P < 0.0001). The TG/HDL ratio was significantly higher at end point versus baseline with olanzapine compared with that of paliperidone ER. Mean end point change in TG/HDL ratio was 0.97 ± 2.72 [corrected] for olanzapine (P < 0.0001, reflecting worsening), with no significant change for paliperidone ER (-0.17 ± 2.51). Newly diagnosed impairment in TG and metabolic syndrome was more common with olanzapine (P < 0.05). Insulin resistance, as measured by the homeostasis model assessment of insulin resistance, worsened significantly with olanzapine (P = 0.0003), but not with paliperidone ER. Glucose sensitivity for insulin worsened significantly with olanzapine (P < 0.03), with no significant changes for paliperidone ER. End point increase in body weight was significantly higher with olanzapine than paliperidone ER (3.8 vs 1.2 kg; P = 0.0013). In summary, both paliperidone ER and olanzapine effectively treated schizophrenia; however, undesirable metabolic effects were significantly greater with olanzapine.

This study was aimed to evaluate differences in the effect of microwave exposure on patients with depressive disorder and healthy subjects. Our experiments were carried out on a group of depressive patients (women, 18 subjects) and comparison group of healthy volunteers (women, 18 subjects) exposed during 30 min to 450 MHz microwave radiation modulated at 1,000 Hz frequency. The field power density at the scalp was 0.9 mW/cm2. As a subjective criteria of microwave effect, the Brief Affect Scale (BAS) and Visual Analogue Scale (VAS) before and after each exposure procedure were used. The analysis of EEG was performed and ratio of the EEG beta and theta power was selected as a measure for evaluation of the microwave effect. The BAS and VAS revealed rather improvement in subjective mood score after exposure for majority of depressive subjects (11) and no changes for others (7). The EEG analysis detected differences between calculated parameters for exposed and sham recordings in depression as well as healthy group. Statistically significant changes were introduced by microwave for five patients with depressive disorder and for one healthy subject. The rate of subjects affected by microwave in depression group (28%) was five times higher compared to that rate in healthy group (5.6%).

Diagnosis of depression is still based mainly on evaluation of the intensity of subjective and clinical symptoms by psychiatrists. This study is aimed to give additional objective information about depression analyzing the electroencephalographic (EEG) signal using the method of detrended fluctuation analysis (DFA). DFA is applied to evaluate the presence and persistence of long range correlations in time in EEG signals. EEG recordings were carried out on the groups of depressive and healthy subjects of 18 female volunteers each. The DFA was calculated on EEG signals from P3-Pz channel at a length of 5 minutes. The DFA method revealed statistically significant difference between healthy and depressive subjects. Resting EEG of healthy subjects exhibited persistent long-range correlation in time. In depression the long-range correlation was less persistent and for about half of the depressed subjects (44%) the EEG revealed long-range anti-correlation in time.

This study is aimed to compare the electroence- phalographic (EEG) spectral asymmetry index (SASI) calcu- lated at fixed and individual frequency bands. In addition, the possible age effect on SASI is analyzed. SASI is based on bal- ance between the powers of two special EEG frequency bands selected lower and higher of the EEG spectrum maximum and excluding the central frequency from the calculations.

The nosological entity of acute and transient psychotic disorders (ATPD) as an independent diagnostic category has become a subject of controversial opinions. The present study aimed to follow-up the diagnostic stability of index episode of ATPD and to examine the influence of clinical and socio-demographic factors on the ATPD prognosis.A sample of 153 (60.1% females; mean age 27.8 ± 8.2) first-admitted patients with ATPD was followed over 2 years. The clinical manifestations, global functioning and quality of life were regularly evaluated during follow-up period.At the end of follow-up, the overall stability rate of ATPD, excluding the cases not readmitted until last assessment, reached 34%. The diagnostic transition was observed in 35.9% of the patients, mostly to schizophrenia and schizoaffective disorders. There was a significant deterioration in several clinical and social indicators among the patients who developed schizophrenia, compared with those with stable ATPD, whereas no reliable predictors were found for diagnostic transition to schizophrenia, except younger age, unmarried status and period of the first hospitalization.A sizeable proportion of the patients with initial diagnosis of ATPD is likely to represent early manifestations of schizophrenia-related disorders. In agreement with some previous observations, our study indicates a lack of strong rationale for separating ATPD from other psychotic disorders within the ICD-10 F2 category.

The aim of this study was to find distinctions of the EEG signal in female depression. Experiments were carried out on two groups of 18 female volunteers each: a group of patients with depressive disorder who were not on medication and a group of control subjects. Patients who had Hamilton depression rating scores higher than 14 were selected. Resting EEG was recorded for the duration of 30 min. Spectral asymmetry (SA) of the EEG spectrum was estimated as relative difference in the selected higher and lower EEG frequency band power. Calculated SA values were positive for depressive and negative for healthy subjects (except for 2-3 subjects). The values behaved similarly in all EEG channels and brain hemispheres. Differences in SA between depressive and control groups were significant in all EEG channels. Dependence of SA on EGG signal length appeared not to be identical for depressive and healthy subjects. Our results suggest that SA based on balance between the powers of the higher and the lower EEG frequency bands seems to enable characterization of the EEG in depression.

This study is aimed to compare sensitivity of different electroencephalographic (EEG) indicators for detection of depression. The novel EEG spectral asymmetry index (SASI) was introduced based on balance between the powers of two special EEG frequency bands selected lower and higher of the EEG spectrum maximum and excluding the central frequency from the calculations. The efficiency of the SASI was compared to the traditional EEG inter-hemispheric asymmetry and coherence methods. EEG recordings were carried out on groups of depressive and healthy subjects of 18 female volunteers each. The resting eight-channel EEG was recorded during 30 min. The SASI calculated in an arbitrary EEG channel differentiated clearly between the depressive and healthy group (p < 0.005). Correlation between SASI and Hamilton Depression Rating Scale score was 0.7. The EEG inter-hemispheric asymmetry and coherence revealed some trends, but no significant differences between the groups of healthy controls and patients with depressive disorder.

The aim of this study was to investigate the changes in the EEG coherence produced by major depressive disorder.

The aim of this study was to investigate the changes in the EEG coherence produced by microwave exposure for healthy and depressive persons. The experiments were carried out on two groups of volunteers: a group of healthy subjects and a group of patients with major depressive disorder. Each group consisted of 18 female subjects. During 30 min experiment volunteers were exposed to 450 MHz microwave radiation modulated at 1000 Hz. The field density at the scalp was 1,6 mW/cm2. The coherence values were calculated for FP1-T3 — FP2-T4, T3-P3 — T4-P4 and P3-O1 — P4-O2 channel pairs. The EEG theta (4–8 Hz), alpha (8–13 Hz), beta1 (13–20 Hz) and beta2 (20–40 Hz) frequency bands were selected for analysis. Statistical analysis of calculated parameter for individuals with post-host Bonferroni correction was applied. The experiments demonstrated no significant changes in the EEG coherence between exposed and not exposed conditions for healthy as well as depressive group. However, the results showed significant changes produced by exposure in the EEG coherence for a part of subjects. In the healthy group: 1) an increase occurred in the EEG coherence in theta and alpha rhythms, and the differences were statistically significant over the frontal and temporal regions in theta (3 subjects, 16 %) and alpha (2 subjects, 11 %) rhythms, 2) decrease in alpha (2 subjects, 11%) rhythm was statistically significant over the parietal and occipital regions. In the group of patients with major depressive disorder microwave exposure caused statistically significant changes in the EEG coherence in beta2 rhythm (2 subjects, 11 %) over frontal and temporal regions and in alpha (3 subjects, 16 %) over temporal and parietal regions.

IntroductionRecent metaanalyses have reported conflicting results on the efficacy of long-acting compared to oral antipsychotics in the prevention of relapse in patients with schizophrenia.Methods2-year international randomized active controlled, open-label, rater-blinded study evaluating time to relapse, relapse rates, psychotic symptoms (PANSS) and treatment-emergent adverse events (TEAEs) in recently diagnosed patients with schizophrenia (≥1-5 years) treated with a monotherapy of paliperidone palmitate (PP) compared to investigators’ choice of oral antipsychotics (oAPs), i.e. aripiprazole, olanzapine, quetiapine, paliperidone ER, risperidone or haloperidol.Results715 patients (58.4% male, mean age 32.5±10.4 years, 86.2% paranoid schizophrenia, no significant differences in baseline characteristics) entered the 2-year study period (352 PP, 363 oAPs). Time to relapse was significantly longer with PP compared to oAPs (mean±SE: 616±10.9 vs 603±13.1 days, p=0.019). Relapse rates were significantly lower with PP vs oAPs (14.8% vs 20.9%; p=0.032), reflecting a relative risk reduction of 29.2%. Reduction of psychotic symptoms in PANSS was significantly superior with PP at treatment day 8 (p=0.021) and showed a trend in favor of PP at endpoint (p=0.074). TEAEs reported in ≥5% in any group (PP vs oAPs) were weight increase (15.9% vs 17.4%), headache (11.1% vs 8.5%), insomnia (9.7% vs 8.0%), schizophrenia (8.2% vs 9.6%), nasopharyngitis (7.1% vs 5.0%), injection site pain (6.8% vs 0%), anxiety (5.7% vs 4.4%), tremor (5.1% vs 2.2%) and suicidal ideation (4.5% vs 5.5%).ConclusionIn this randomized active controlled 2-year study PP was significantly delaying time to relapse and reducing relapse rates compared to investigators’ choice of oral APs.

ObjectiveTo compare the longer-term metabolic effects and efficacy of paliperidone ER and olanzapine in patients with schizophrenia.MethodsProspective 6-month randomized study evaluating flexible doses of paliperidone ER and oral olanzapine (OLA). Primary endpoint was the change in triglyceride to high-density lipoprotein (TG:HDL) ratio, a sensitive measure of insulin resistance. Additional endpoints were the Positive and Negative Syndrome Scale (PANSS), body weight, lipids, homoeostasis model of insulin resistance (HOMA-IR) and adverse events (AEs).Results239 patients were randomized to paliperidone ER, 220 to olanzapine. Demographics and baseline characteristics were comparable. Mean doses were 6.9±1.3 mg/day for paliperidone ER and 11.6±2.3 mg/day for olanzapine. The TG:HDL ratio for olanzapine significantly worsened from baseline to endpoint (0.42±1.19;p< 0.0001); it remained unchanged for paliperidone ER (-0.08±1.10;p=0.4718; between-group difference p< 0.0001). PANSS total scores at endpoint significantly improved (olanzapine -16.6±15.0; paliperidone ER -13.5±15.9; both p< 0.0001 vs. baseline); the between-group difference met prespecified non-inferiority criteria. Endpoint weight change was 3.8±5.9kg for olanzapine and 1.2±4.6kg for paliperidone ER (p< 0.0001). Insulin resistance in HOMA-IR did not change with paliperidone ER (p=0.1507) but significantly worsened with olanzapine (p=0.003 vs. baseline). The most frequently reported treatment-emergent AEs (>=5%) were weight increase (OLA 18.2%;Pali ER 9.6%), insomnia (OLA 1.4%;Pali ER 9.6%), somnolence (OLA 9.5%;Pali ER 3.3%) and schizophrenia (OLA 1.8%;Pali ER 5.0%).ConclusionIn this randomized controlled study paliperidone ER was superior to olanzapine with regards to insulin resistance, weight gain, lipid changes and other relevant metabolic endpoints. Efficacy was non-inferior between paliperidone ER and olanzapine.

Aim: To gather and review data describing the epidemiology of schizophrenia and clinical guidelines for schizophrenia therapy in seven Central and Eastern European countries, with a focus on negative symptoms.Methods:A literature search was conducted which included publications from 1995 to 2012 that were indexed in key databases.Results:Reports of mean annual incidence of schizophrenia varied greatly, from 0.04 to 0.58 per 1,000 population. Lifetime prevalence varied from 0.4% to 1.4%. One study reported that at least one negative symptom was present in 57.6% of patients with schizophrenia and in 50–90% of individuals experiencing their first episode of schizophrenia. Primary negative symptoms were observed in 10–30% of patients. Mortality in patients with schizophrenia was greater than in the general population, with a standardized mortality ratio of 2.58–4.30. Reasons for higher risk of mortality in the schizophrenia population included increased suicide risk, effect of schizophrenia on lifestyle and environment, and presence of comorbidities. Clinical guidelines overall supported the use of second-generation antipsychotics in managing negative symptoms of schizophrenia, although improved therapeutic approaches are needed.Conclusion:Schizophrenia is one of the most common mental illnesses and poses a considerable burden on patients and healthcare resources alike. Negative symptoms are present in many patients and there is an unmet need to improve treatment offerings for negative symptoms beyond the use of second-generation antipsychotics and overall patient outcomes.