The safety profile of Polyoxidonium in daily practice: results from postauthorization safety study in Slovakia.

AIM: This study assessed the safety of Polyoxidonium® 6 mg lyophilisate for solution for injection in routine practice with a special focus on signs or symptoms of potential adverse renal effects. MATERIALS & METHODS: A local, multicenter, prospective, open-label, noninterventional, uncontrolled postauthorization safety study was conducted in 15 healthcare centers in Slovakia. Adult patients who received commercially available Polyoxidonium 6 mg lyophilisate for solution for injection as a part of their routine care were observed for one cycle of treatment, consisting of five or ten injections. For safety assessment, adverse events were monitored with a special focus on signs or symptoms of potential adverse renal effects. At the end of the study, investigators and subjects rated the overall tolerance of Polyoxidonium treatment as well as improvement. Data collection was based on the review of medical records and routine examination of subjects. RESULTS: In total, 502 subjects were enrolled and 498 (99.2%) subjects completed the study. 19 (3.8%) subjects experienced a total of 34 adverse events. Only one (0.1%) subject experienced eight adverse drug reactions (ADRs): restlessness, fatigue, feeling hot (n = 2), pyrexia (n = 3) and asthenia. There were no renal ADRs or serious ADRs. At the end of the study, both investigators and subjects very positively rated global tolerability and global improvement. CONCLUSION: Polyoxidonium was well tolerated in the heterogenous population of patients, mostly with chronic recurrent bacterial or viral infections. No renal ADRs were reported in this postauthorization safety study, which was designed with a special focus on identifying potential adverse renal effects.

Comparison of the pharmacokinetic and pharmacodynamic properties of two recombinant granulocyte colony-stimulating factor formulations after single subcutaneous administration to healthy volunteers.

BACKGROUND AND OBJECTIVE: The aim of this randomized, single dose, two-period crossover study with two weeks wash-out period was the demonstration of bioequivalence of two recombinant human granulocyte colony-stimulating factor (rG-CSF) formulations after subcutaneous administration of 300µg comparing their pharmacokinetic (primary endpoints AUC0-24, AUC0-∞ and Cmax) and pharmacodynamic (primary endpoints ANC AUC0-72, ANC AUC0-∞ and ANCmax) profiles in healthy male subjects. MATERIALS AND METHODS: A total of 36 (23.0±6.0 years, 76.6±7.2kg) healthy subjects were recruited. Using a 1:1 randomization ratio, subjects were randomly assigned to one of two possible treatment-sequence groups to receive the single dose of test formulation (Gp-02) and reference product (Neupogen™) concentrations were measured by enzyme-linked immunosorbent assay (ELISA) up to 24h and the Absolute Neutrophil Count (ANC) was determined using hematology analyzer Coulter STKS™ (Beckman Coulter) up to 72h after injection. The geometric mean of primary pharmacokinetic and pharmacodynamic variables were considered bioequivalent if the 90% confidence intervals (CI) would fall in the bioequivalence range of 80%-125%. RESULTS: AUC0-24 (ratio of means 103.4, 90% CI: 95.6-111.9), AUC0-∞ (103.4, 90% CI: 95.7-111.7), Cmax (99.6, 90% CI: 89.0-111.4), ANC AUC0-72 (100.0, 90% CI: 96.6-103.5), ANC AUC0-∞ (100.8, 90% CI: 96.5-105.3), and ANCmax (100.2, 90% CI: 95.4-105.1) were determined. Single doses of test and reference formulations were well tolerated. The incidence of AEs was equally distributed across treatment groups with the most frequent AEs being headache, fever, and back pain. CONCLUSIONS: The study results demonstrated the bioequivalence of Gp-02, a new formulation of filgrastim, and the reference product Neupogen™.

Paracetamol and simvastatin: a potential interaction resulting in hepatotoxicity.

The safety profile of paracetamol and simvastatin is sufficiently well known, although no interactions between these two medicinal products have been described in the scientific literature so far. A 66-year-old female patient who experienced myocardial infarction and underwent coronary artery bypass grafting 9 years ago was taking simvastatin at a daily dose of 10 mg. Liver enzyme tests were carried out regularly, and their results were always normal. Later on, the patient took 6 tablets of fixed combination medicinal product Gripex(TM) (paracetamol, pseudoephedrine, and dextromethorphan) per day due to a fever. The daily dose of paracetamol taken by the patient totaled 1.95 g. The patient developed severe jaundice, nausea, vomiting; blood bilirubin levels increased more than 3 times; alanine transaminase, more than 10 times; and asparagine transaminase, more than 5 times. Paracetamol is metabolized by CYP enzymes (CYP2E1, 1A2, 2A6, 3A4) to a reactive metabolite, N-acetyl-p-benzoquinone-imine (NAPQI). Under conditions of excessive NAPQI formation or reduction in glutathione stores by approximately 70%, NAPQI covalently binds to the cysteinyl sulfhydryl groups of cellular proteins, forming NAPQI-protein adducts. Simvastatin is a substrate of CYP3A4 enzyme. Clinical and pharmacological data, available in the published literature, allow the assumption that simvastatin may induce CYP3A4 and result in increased hepatoxicity of paracetamol.

The prevalence of metabolic risk factors among outpatients with diagnosed nonalcoholic fatty liver disease in Lithuania.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease; there is growing evidence that it is a hepatic manifestation of a metabolic syndrome. This study aimed to assess the prevalence of metabolic risk factors among patients with NAFLD. MATERIAL/METHODS: Outpatients with NAFLD were recruited into the study. Family physicians recorded patients' demographic and anthropometric data, leisure-time physical activity, concomitant diseases, and pharmacological treatment for NAFLD into standardized Case Report Forms. RESULTS: In total, data on 798 patients were analyzed. Most patients were women and they were older than the men (mean age, 60.2 ± 9.6 vs. 54.5 ± 11.4 years; p<0.05). Metabolic risk factors (obesity, arterial hypertension, dyslipidemia) were highly prevalent in the study patients, and these factors were more prevalent among women. There were no differences in the mean Body Mass Index (BMI), in the proportion of men or women with BMI >30 kg/m2 or central obesity in the 2 age groups (≤ 60 years and >60 years). Hypertension and diabetes were more prevalent among older men and women. Dyslipidemia was more common among older women. The level of leisure-time physical activity was lower in women and in older patients. The most frequently prescribed pharmacological agents were cytoprotective agents, lipid-lowering drugs, and antioxidants. CONCLUSIONS: Metabolic risk factors were highly prevalent among patients with NAFLD. Obesity, hypertension, and dyslipidemia were more prevalent among women. The differences in the prevalence of hypertension seemed to be influenced by older age of women.

An open-label multicenter safety, tolerability, and efficacy study of recombinant granulocyte colony-stimulating factor in the prevention of neutropenic complications in breast cancer patients.

UNLABELLED: The primary objective of this open-label, two chemotherapy arm, phase 4 study was to evaluate the safety and efficacy of newly developed recombinant granulocyte colony-stimulating factor (rG-CSF) used to prevent neutropenia-related complications in patients with metastatic breast cancer treated with docetaxel (75 mg/m(2)) and doxorubicin (50 mg/m(2)) or docetaxel (100 mg/m(2)) alone. MATERIAL AND METHODS: A total of 50 patients who were treated with a maximum of 6 cycles of either docetaxel-doxorubicin (36 patients) or docetaxel alone (14 patients) every 21 days were recruited from 3 centers in Lithuania. All the patients received study medication rG-CSF at a dosage of 5 µg/kg per day (Sicor Biotech UAB, Teva Group) from day 2 of each cycle and continued for minimum 5 days or until absolute neutrophil count reached ≥1.5×10(9)/L. RESULTS: A total of 611 adverse events were reported. Most of them were related to myelotoxic chemotherapy. Two patients withdrew due to adverse events (neuropathy and bone pain). One patient died possibly because of pulmonary thromboembolism. The most frequently reported adverse events related to study drug in the docetaxel-doxorubicin and docetaxel groups were leukocytosis (22% and 21%, respectively), bone pain (19% and 21%, respectively), and headache (8% and 14%, respectively). The incidence of grade 4 neutropenia in both the groups was 47% and 29%, respectively, in all cycles and 42% and 21%, respectively, in cycle 1. The incidence of febrile neutropenia was 8% in cycle 1 and 14% across all cycles. The mean duration of febrile neutropenia was 2.1 days (SD, 1.9) in cycle 1 and 2.14 days (SD 2.0) across all cycles in both the treatment groups. CONCLUSION: This study provide data that the study drug rG-CSF has the expected safety and could be an efficacious medication to decrease the risk of febrile neutropenia and related complications of myelosuppressive chemotherapy in patients with metastatic breast cancer.

Rationality of administered gentamicin dose in cerebral coma patients treated in an intensive care unit.

Gentamicin is still widely used in the treatment of patients in an intensive care unit (ICU). The efficacy of aminoglycosides correlates with the peak serum concentration (Cmax), and the toxicity with the minimum serum concentration (Cmin). The aim of this study was to determine Cmax and Cmin in serum of cerebral coma ICU patients when a dosage of gentamicin of 5 mg/kg body weight was administered once daily; to evaluate the rationality of mentioned dose; and to identify factors associated with these concentrations. Material and METHODS. A total of 24 ICU patients suffering from cerebral coma were included into this analysis. A dosage of gentamicin of 5 mg/kg body weight was administered once a day. Gentamicin concentrations were tested twice after the first dose infusion (immediately and 5 hours after 1-hour infusion). Cmax, Cmin, volume of distribution (Vd), and elimination half-life (T1/2) were obtained. RESULTS. The mean Cmax was 17.96 (SD, 4.31) µg/mL (range, 10.30-27.87 µg/mL). The desirable Cmax (≥ 20 µg/mL) was reached only in 6 patients (25%). Cmin was calculated using a special pharmacokinetic program "Kinetica." Cmin of 0.5 µg/mL was not exceeded in any patient. A correlative analysis indicated a significant inverse direct correlation between Cmax and Vd and between Cmax and treatment duration in the ICU. An inverse correlation was observed between Cmin and T1/2, evaluation of coma according to the Glasgow coma scale, and creatinine clearance. CONCLUSIONS. A dosage of 5 mg/kg body weight once a day was not sufficient in cerebral coma ICU patients. This dose was not associated with the nephrotoxic effect of gentamicin (additional risk factors were absent). It is recommended to obtain gentamicin concentration at two time points following administration of the first dose (e.g., immediately after 1-hour infusion and 5 hours later), and using a special pharmacokinetic software, to calculate a necessary dose and interval of administration.

Severe vancomycin-induced anaphylactic reaction.

Vancomycin is widely used against methicillin-resistant Staphylococcus aureus infections, but it is associated with many adverse effects such as nephrotoxicity, ototoxicity, gastrointestinal disturbances, blood disorders, and two types of hypersensitivity reactions - an anaphylactoid reaction known as "red man syndrome" and anaphylaxis. We report a case of a 23-year-old man who developed a vancomycin-induced anaphylactic reaction in the treatment of methicillin-resistant Staphylococcus aureus infection.

Efficacy, tolerability, and preference of mirtazapine orally disintegrating tablets in depressed patients: a 17-week naturalistic study in Lithuania.

Mirtazapine is an established antidepressant with well-documented efficacy demonstrated in controlled clinical trials. However, the gap between the results obtained in controlled clinical trials and everyday clinical practice exists. Therefore, the importance of naturalistic studies in psychiatry is becoming recognized. The aim of present naturalistic study was to acquire data on efficacy, safety, and preference of mirtazapine orally disintegrating tablets during a 17-week treatment of depression. This prospective, open-label, multicenter study in patients with mild to severe depression was conducted at 47 mental health centers of Lithuania by 78 psychiatrists. Patients were initially given 15 mg or 30 mg of mirtazapine orally disintegrating tablets; the maximum allowed dose was 45 mg per day. The primary efficacy measure was the total score on the Hamilton Depression Rating Scale-17 (HAMD-17), the Clinical Global Impression-Severity (CGI-S), and Clinical Global Impression-Improvement (CGI-I) scales. Tolerability was primarily measured by assessing the incidence of treatment-emergent adverse events. Patients were evaluated at baseline, at weeks 1, 5, 9, 13, and 17. A total of 779 patients (595 women [76.4%] with a mean [SD] age of 50.2 [13.65] and 184 men [23.6%] with a mean [SD] age of 52.4 [14.6] years) were enrolled into the study; 687 (88.2%) patients completed the study. The mean (SD) daily dose of mirtazapine orally disintegrating tablets was 29.0 (3.8) mg. The mean total (SD) HAMD-17 score improved significantly from 25.7 (4.6) to 7.3 (4.3) (P<0.005). At each visit, the mean HAMD-17 score was significantly lower than that at the preceding visit. At week 17, remission (HAMD-17 score < or =7) was observed in 436 (56%) patients. The mean (SD) CGI-S score improved significantly from 4.9 (1.0) at baseline to 1.5 (0.6) at endpoint (P<0.001). According to the CGI-I assessments, 621 patients (89.4%) improved and improved very much. The vast majority of patients (80%) preferred the new formulation of mirtazapine - mirtazapine orally disintegrating tablet. Treatment-emergent adverse events occurred in 106 patients (13.6%). The most frequent adverse events were weight gain, sedation, dizziness, and dry mouth. In this study conducted in Lithuania with depressed patients, a significant improvement was shown in all efficacy measures. In addition, mirtazapine orally disintegrating tablet was a well-tolerated and preferable formulation for the treatment of depressed patients.

[Safety and efficacy study of the recombinant granulocyte colony-stimulating factor for prevention of neutropenia and neutropenia-related complications in women with metastatic breast cancer receiving docetaxel/doxorubicin]. / Rekombinacinio granuliocitu kolonijas stimuliuojamojo faktoriaus, vartojamo neutropenijos ir neutropenijos sukeltu komplikaciju profilaktikai serganciosioms metastazavusiu kruties veziu ir gydomoms docetakseliu ir doksorubicinu, saugumo ir veiksmingumo tyrimas.

BACKGROUND: We evaluated efficacy and safety of recombinant granulocyte-colony stimulating factor (rGCSF) used as primary prophylaxis to prevent neutropenia and neutropenia-related complications induced by docetaxel and doxorubicin chemotherapy in patients with metastatic breast cancer. PATIENTS AND METHODS: Three centers in Lithuania enrolled 36 patients who received rGCSF (5 microg/kg/d) on day 2 of each 21-day chemotherapy with docetaxel 75 mg/m(2) and doxorubicin 50 mg/m(2) (AT) starting in the first cycle. Treatment regimen was repeated for up to six cycles. RESULTS: Leukocytosis, bone pain, and headache were the most frequent adverse events, with incidence rates of 22%, 19%, and 8%, respectively. Adverse events were typical for rGCSF in this patient population. Overall incidence rate of febrile neutropenia was 14%. The mean duration of febrile neutropenia episodes across cycles was 2.14 days. Incidence of chemotherapy delay was 2%. There was no reduction in chemotherapy dose due to expected toxicity or side effects. Intravenous antibiotics for the treatment of febrile neutropenia were needed in 19% of cases. Quality-of-life assessment shows a significant improvement in emotional functioning and a significant decrease in pain score. The efficacy profile of rGCSF observed in the present study was comparable with that of other rGCSF products previously described in the published scientific literature. CONCLUSIONS: The primary prophylaxis of neutropenia and its complications by rGCSF was safe and effective for women with metastatic breast cancer who received chemotherapy with docetaxel and doxorubicin.

Characteristics of gender-related circadian arterial blood pressure in healthy adolescents.

SUMMARY OBJECTIVE: To define 24-h characteristics of arterial blood pressure in healthy adolescent girls and boys; to determine gender-related differences of blood pressure, its circadian pattern. MATERIAL AND METHODS: The 24-h blood pressure was monitored hourly in healthy girls (n=22, without no account for the menstrual cycle phase) and boys (n=22). Additionally, blood pressure of adolescent girls (n=15) was examined during different phases of their menstrual cycle (follicular, ovulation, and luteal). Blood pressure was monitored with an auto-cuff automatic outpatient blood pressure monitor. RESULTS: Investigation showed gender-related differences in 24-h blood pressure. Study results revealed the circadian blood pressure rhythm characterized by a period of low values during nighttime and an early morning increase in both adolescent groups. Nocturnal systolic blood pressure was higher (P<0.05) in boys than in girls in all phases of their menstrual cycle. Diurnal systolic blood pressure in boys was higher than in girls in their follicular phase (P<0.05). The day and night blood pressure differed between boys and girls (P<0.05). A dipping blood pressure pattern as a decrease in mean nighttime blood pressure as compared with mean daytime blood pressure was defined: 10.02+/-6.7% in girls (n=22) and 13+/-6.3% in boys (n=22), without gender-related differences (P>0.05). There were no differences in blood pressure dipping among girls' groups in different menstrual cycle phases (P>0.05). Adolescent boys showed a significant positive correlation between their mean diurnal blood pressure and height (P<0.05). CONCLUSION: The study proved gender-related arterial blood pressure differences in healthy adolescents. The results demonstrate the gender-specific circadian blood pressure rhythm pattern in both gender groups.

Analysis of antidepressant prescribing tendencies in Lithuania in 2003-2004.

Depression is one of the leading causes of disability worldwide, affecting 121 million people in whole world. In many developed countries, the number of prescriptions for antidepressants increased steeply during the 1990s. The objective of the present study was to evaluate the antidepressant prescribing patterns in all regions of Lithuania during 2003-2004, to analyze the use within different antidepressant groups, and to examine trends in age- and gender-specific antidepressant use. Antidepressants were classified into three groups according to Anatomic Therapeutic Chemical (ATC) Classification specifying the defined daily doses. The results of our study show an increase in the use of reimbursed antidepressants except tricyclic in 2004 when compared to 2003. Increase in the use of selective serotonin reuptake inhibitors and other nontricyclic antidepressants is probably related to their better tolerability, improved risk-benefit ratio, and less toxicity in overdose. There was no increase in the percentage of consumed selective serotonin reuptake inhibitors in elderly patients when compared with younger ones, despite elderly patients are most likely to benefit from reduced sedation, less antimuscarinic and less cardiac toxicity of selective serotonin reuptake inhibitors. The prevalence of the antidepressant use is the highest among middle-aged people (40-59 years), while the young (under 20) and elderly (older than 70) patients receive mostly selective serotonin reuptake inhibitors. Additional studies should be carried out in order to assess drug-prescribing patterns in accordance with the guidelines of depression treatment in Lithuania considering diagnosis, dosage, and duration of treatment.

[A case of severe hyponatremia in a patient suffering from epilepsy and using oxcarbazepine]. / Sunki hiponatremija, pasireiskusi pacientei, serganciai epilepsija bei vartojanciai okskarbazepina

A 70-year-old patient treated with oxcarbazepine experienced severe hyponatremia. The patient used oxcarbazepine (600 mg twice a day) concomitantly with diuretics (torasemide 10 mg and indapamide 1.25 mg once per day), perindopril, an angiotensin-converting enzyme inhibitor, and amlodipine, a Ca(2+) channel blocker. The patient complained of a nausea, malaise, diplopia, drowsiness, apathy, decreased diuresis (creatinine clearance - 41.51 ml/min), and exacerbation of epileptic seizures. Sodium concentration in the plasma was 113 mmol/l. The patient was hospitalized. It was suggested that a decrease in plasma sodium concentration was caused by oxcarbazepine used together with diuretics for six months. Oxcarbazepine-induced hyponatremia is reported in 22.2-50% of patients, although symptoms are present only in 5.9% of patients. The most common symptoms of central nervous system injury, experienced by patients, are drowsiness, dizziness, decreased cognitive function, coordination impairment, etc. Physicians not always in time pay proper attention to undesirable antiepileptic drug-induced effects, which can be dangerous.

[Nonsteroidal anti-inflammatory agents--choice between disturbances of gastrointestinal tract and cardiovascular toxicity]. / Nesteroidiniai vaistai nuo uzdegimo--pasirinkimas tarp zalingo poveikio virskinimo traktui bei galimo sirdies ir kraujagysliu pazeidimo.

Nonsteroidal anti-inflammatory agents are used more than 100 years. Most of them can cause undesirable effects on gastrointestinal tract: ulceration, bleeding and perforation of stomach and duodenum. Gastrointestinal toxicity is diminished when selective cyclooxygenase-2 inhibitors are used. However, recent clinical trials have showed that the use of cyclooxygenase-2 inhibitors increases the risk of cardiovascular event and cerebrovascular accident. According to the data such risk may be high using also nonselective nonsteroidal anti-inflammatory agents, however, it is lesser. Incidence rates of the cardiovascular events and cerebrovascular accidents increase due to activated thrombotic activity. Nonsteroidal anti-inflammatory agents are very useful in the management of rheumatic diseases and as pain relievers. Choosing appropriate nonsteroidal anti-inflammatory agent it is essential to consider the risk of gastrointestinal as well cardiovascular damage.

[Compliance in psychiatry: results of a survey of depressed patients using orally disintegrating tablet]. / Gydytojo nurodymu laikymosi problema: pacientu, serganciu depresija ir vartojanciu disperguojamaja burnoje tablete, apklausos duomenys.

As many as 60% of the patients do not follow the therapy recommended by their physicians. An important factor that can influence patient's compliance is the physician's opinion about the tolerability and safety of prescribed medication. However, the efforts of both parties, not only physician but also patient, have benefits on the outcome of treatment. Patient's opinion on choosing the form of medication is appropriate way ensuring better compliance. The aim of the survey was to ascertain the opinion of depressed patients towards a new formulation of antidepressant drug, mirtazapine - orally disintegrating tablet Remeron SolTab. The study was approved by Lithuanian State Medicines Control Agency and local Ethics Committee. A total of 453 depressed patients were included in the survey. Most of the patients used a 30-mg dose of Remeron SolTab (n=344, 75.88%). Most of the patients (n=189, 41.81%) had a positive opinion about the taste of medication ("very pleasant"). According to the results of the survey, 281 (61.95%) used Remeron SolTab regularly. However, 129 (28.54%) patients noted that the new drug formulation had no influence on the regularity of use. Statistically significantly more patients (81.86%) noted that they would choose Remeron SolTab compared to the patients who would prefer conventional form of the medication (2.21%). In 184 (40.71%) patients, a significant mood improvement was noted. Most of the patients (n=246, 54.20%) indicated that mood improved. Based on the results of the survey it can be concluded that patient will prefer the drug (or its new formulation) he/she liked and thus will follow physician's instructions and cooperate with physician more closely. A limitation of this study relates to the study design and questionnaire itself, since it was not validated in appropriate way. However, the results of the survey are in line with the results of the similar surveys from other countries and reflect the general tendencies towards antidepressant use.

Trends in the consumption of antidepressant drugs in Lithuania in 2002-2004.

OBJECTIVE: To evaluate trends in the use of antidepressant drugs in Lithuania between 2002 and 2004 and to perform cost-minimization and reference price analysis enabling more rational use of financial resources of national health system. MATERIAL AND METHODS: The data on sales of antidepressant drugs in Lithuanian over a 3-year period (2002-2004) were obtained from IMS Health Inc. database. Data were calculated by defined daily dose (DDD) methodology and expressed in DDDs per 1000 inhabitants per day. DU90% was used as the quality indicator of the drug prescribing. The pharmacoeconomic analysis of antidepressant drugs was performed by cost-minimization and reference price methodology. RESULTS: The consumption of antidepressants in Lithuanian increased by 30.55% over a 3-year period (2002-2004) reaching the value of 10.00 DDDs/1000 inhabitants/day. Since 2002, the proportion of use of selective serotonin reuptake inhibitors has increased by 27.82%, and the use of tricyclic antidepressants has declined by 10.78%, while the use of other (newer) antidepressant drugs expanded almost three times. The expenditures of antidepressant drugs have reached 26 million Lt in 2004, of which 68.15% were costs for selective serotonin reuptake inhibitors. Choosing the second lowest price in different antidepressant drug class, it is estimated the possible savings of 4.34 million Lt lowering the total expenses by 16.5% (1 euro=3.4528 Lt). CONCLUSIONS: The findings suggest that the use of total antidepressant drugs continues to increase because of the increased use of selective serotonin reuptake inhibitors and other (newer) antidepressant drugs. In comparison with the data in other countries, the consumption of antidepressant drugs in Lithuania is low.

[Ibogaine--the substance for treatment of toxicomania. Neurochemical and pharmacological action]. / Ibogaino vartojimas toksikomanijoms gydyti. Neurocheminis ir farmakologinis veikimas.

The review of scientific literature, concerning the indol alkaloid Ibogaine, which is extracted from the bush Tabernanthe Iboga, is presented in this article. Used as a stimulating factor for hundred of years in non-traditional medicine, this alkaloid could be important for modern pharmacology because of potential anti-addictive properties. The mechanism of action of this alkaloid is closely related to different neurotransmitting systems. Studies with animals allow concluding that Ibogaine or medicines based on this alkaloid can be used for treatment of drug dependencies.

[Antipsychotic agents and pharmacotherapy of psychoses]. / Antipsichoziniai vaistai ir psichoziu farmakoterapija.

Antipsychotic drugs have been used clinically for approximately 50 years. Reserpine and chlorpromazine were first drugs found be useful in schizophrenia. The term "antipsychotic" is used to describe a group of drugs that has been used mainly for treating of schizophrenia, but also is effective in some other psychoses and agitated states. The dopamine hypothesis is the most fully developed of several hypothesis and is the basis for rational drug therapy. However, the dopamine hypothesis is far from complete. Typical antipsychotic drugs have a wide spectrum of central nervous system, autonomic and endocrine effects. The most recently introduced antipsychotics are at least as potent in inhibiting 5-HT receptors as they are in inhibiting D receptors. A rational choice of antipsychotic drugs may be based on differences between chemical structures and pharmacological differences. No basis exists for choosing drugs for the use against selected target symptoms, as there is no evidence of specificity in their effects.

[Present-day approach to pharmacological and clinical aspects of novel antidepressants]. / Siuolaikinis poziuris i farmakologines ir klinikines nauju antidepresantu savybes.

Depression is the most common illness that affects a large number of individuals in all countries. Recent evidence suggest that depressive episodes if left untreated may heighten severity of subsequent episodes and may increase need for more health care resources. The first antidepressants, tricyclics and monoamine oxidase inhibitors, became available in the late 1950s. A progressive tightening of requirements by drug licensing authorities has ensured that efficacy evidence is good for most antidepressants that are in use. Contemporary antidepressant classification system is based on the mechanism of action, which is presumed to be responsible for their antidepressant effects. A pharmacodynamic system of classification has advantages because it incorporates the current theories of disease pathophysiology. Understanding the basic aspects of mechanism of action of antidepressants is important for treatment of depressive episode, for development of augmenting strategies and combining antidepressants with other antidepressants or antipsychotics. Antidepressants as a class of psychotropic medication have the broad range of indications. The choice of initial antidepressant legitimately varies considerably among clinicians and countries. Referring to some differences of recommendations for the first line treatment of depressive episode we suppose that the choice of antidepressant medication must be individualized for a particular patient. Novel antidepressants (SSRI, SNRI, NaSSA, NARI, NDRI and other) are safe and better tolerated. Metabolism of novel antidepressants is much improved compared with MAOIs and TCAs. The combination of antidepressants is an important clinical issue. There are the following principles of combining antidepressants: 1. to combine mechanisms of action not just drugs, 2. to combine antidepressants and to promote pharmacological synergy and tolerability, 3. to use important synergies within the serotonin, noradrenaline and even dopamine monoaminergic systems. Adequate treatment of depression including modern treatment approaches has the potential to reduce suffering and disability substantially and minimise the risk of suicide.