RESUMO
AIMS: The aim of this study was to investigate the efficacy and safety of 10 mg vardenafil orodispersible tablet (ODT) vs. placebo in a general population of men with erectile dysfunction (ED). METHODS: This was a double-blind, multicentre, randomised, parallel-group, placebo-controlled study conducted at 35 centres in Australia, Canada, Mexico and the United States. Subjects aged > or =18 years, with ED for at least 6 months, were randomised to receive 12 weeks of on-demand treatment with either 10 mg vardenafil ODT or placebo. Each treatment group was stratified such that approximately half of the subjects were aged > or = 65 years. Primary efficacy variables were the erectile function domain of the International Index of Erectile Function (IIEF-EF) and Sexual Encounter Profile questions 2 (SEP2) and 3 (SEP3). Secondary variables included SEP diary questions 1, 4, 5 and 6, the patient version of the Treatment Satisfaction Scale (TSS) and the Global Assessment Question (GAQ). RESULTS: Of the 473 men enrolled in the study (51.4% aged > or =65 years), 331 were included in the intent-to-treat population (vardenafil ODT, n = 169; placebo, n = 162). Vardenafil ODT therapy was statistically significantly superior to placebo for all primary (i.e. IIEF-EF, SEP2, SEP3) and secondary efficacy variables (p < 0.0001). Treatment-emergent adverse events were mostly mild to moderate in severity, and comparable in both incidence and type with those of the film-coated tablet formulation. CONCLUSIONS: Treatment with 10 mg vardenafil ODT, taken on demand, significantly improved erectile function and was effective and well tolerated in a broad population of men with ED.
Assuntos
Disfunção Erétil/tratamento farmacológico , Imidazóis/administração & dosagem , Inibidores de Fosfodiesterase/administração & dosagem , Piperazinas/administração & dosagem , Administração Oral , Adulto , Idoso , Método Duplo-Cego , Humanos , Imidazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Inibidores de Fosfodiesterase/efeitos adversos , Piperazinas/efeitos adversos , Sulfonas/administração & dosagem , Sulfonas/efeitos adversos , Comprimidos , Resultado do Tratamento , Triazinas/administração & dosagem , Triazinas/efeitos adversos , Dicloridrato de VardenafilaRESUMO
RATIONALE: Flupentixol (FLX) has been used as a neuroleptic for nearly 4 decades. In vitro data show comparable affinity to dopamine D(2), D(1) and 5-HT(2A) receptors and recently, FLX showed to be not inferior to risperidone in schizophrenic patients with predominant negative symptomatology, which was implicated with flupentixol's interaction with 5-HT(2A) and/or D(1) receptors. OBJECTIVES: To assess in vivo receptor occupancy (RO) in patients clinically treated with FLX (n = 13, 5.7 +/- 1.4 mg/day) in comparison with risperidone (RIS, n = 11, 3.6 +/- 1.3 mg/day) and haloperidol (HAL, n = 11, 8.5 +/- 5.5 mg/day). MATERIALS AND METHODS: Each patient underwent two PET scans with 3-N-[(11)C]methylspiperone (target: frontal 5-HT(2A)), [(11)C]SCH23390 (striatal D(1)) or [(11)C]raclopride (striatal D(2)). RO was calculated as the percentage reduction of specific binding in comparison with healthy controls. RESULTS: D(2)-RO under FLX was between 50% and 70%, indicating an ED(50) of about 0.7 ng/ml serum. 5-HT(2A) and D(1)-RO was 20 +/- 10% and 20 +/- 5% (mean, SEM). Under HAL, D(1)-RO was 14 +/- 6% and under RIS not significantly different from zero. CONCLUSIONS: We were able to demonstrate a moderate 5-HT(2A) and D(1) occupancy under clinically relevant doses of flupentixol, albeit lower than expected from in vitro data and clearly below saturation. Therefore, if flupentixol's efficacy on negative symptoms is based on its interaction with 5-HT(2A) and/or D(1) receptors, it should be highly dependent on serum concentration and thus on dosage and metabolism. However, these data suggest that mechanisms other than D(1) or 5-HT(2A) antagonism may contribute to flupentixol's efficacy on negative symptoms.
Assuntos
Antipsicóticos/uso terapêutico , Flupentixol/uso terapêutico , Haloperidol/uso terapêutico , Receptor 5-HT2A de Serotonina/efeitos dos fármacos , Receptores de Dopamina D1/efeitos dos fármacos , Receptores de Dopamina D2/efeitos dos fármacos , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adulto , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/efeitos dos fármacos , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Ensaio Radioligante , Receptor 5-HT2A de Serotonina/fisiologia , Receptores de Dopamina D1/fisiologia , Receptores de Dopamina D2/fisiologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/fisiopatologiaRESUMO
Vascular dementia is a major cause of mental and physical disability in Western countries. Treatment of vascular dementia is currently based on the recognition and control of vascular risk factors, while specific drugs have not been approved yet. The aim of the present multinational, double-blind, placebo-controlled study was to evaluate the safety and efficacy of nimodipine administered for as long as 26 weeks in improving cognition or slowing cognitive deterioration in patients defined as having multi-infarct dementia (DSM-III-R criteria). Two hundred and fifty-nine patients were included (128 nimodipine, 131 placebo), and 251 were available for the intention-to-treat analysis. No significant difference between drug-treated and placebo patients was noted on the Gottfries-Brâne-Steen scale score (primary efficacy criterion), the remaining neuropsychological tests (Zahlen-Verbindungs-Test, Fuld-Object-Memory Evaluation, Word Fluency Test, Digit Span, Mini-Mental State Examination), and the functional scales (index of Activity of Daily Living, Instrumental Activity of Daily Living, Rapid Disability Scale, Clinical Dementia Rating), although the majority of changes were in favor of the active drug group. A lower incidence of cerebrovascular and cardiac events was observed in the nimodipine-treated patients in comparison with the placebo group. This study failed to show a significant effect of nimodipine on cognitive, social or global assessments in patients defined as affected by multi-infarct dementia according to the DSM-III-R criteria. A post-hoc analysis (presented in an accompanying paper) suggests that nimodipine may have a favorable effect in the subgroup of patients defined as affected by subcortical (small vessel) vascular dementia.
Assuntos
Bloqueadores dos Canais de Cálcio/uso terapêutico , Demência por Múltiplos Infartos/tratamento farmacológico , Nimodipina/uso terapêutico , Vasodilatadores/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Bloqueadores dos Canais de Cálcio/efeitos adversos , Cognição/efeitos dos fármacos , Demência por Múltiplos Infartos/psicologia , Dinamarca , Método Duplo-Cego , Feminino , Finlândia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Nimodipina/efeitos adversos , Placebos , Índice de Gravidade de Doença , Suécia , Vasodilatadores/efeitos adversosRESUMO
In Western countries, vascular dementia (VaD) is the most common form of cognitive deterioration after Alzheimer's disease. Therapeutic trials in VaD have so far failed to yield satisfactory results. One explanation of this failure may be the etiological and clinical heterogeneity of the included patients. Patients with subcortical VaD, defined on a clinical and radiological basis, may constitute a more homogeneous group. Thus, we conducted a post-hoc subgroup analysis of the Scandinavian Multi-Infarct Dementia Trial that evaluated the efficacy and safety of oral nimodipine administered for 6 months in 259 patients. The original patients sample was divided on the basis of head CT in those with subcortical VaD (n=92, 45 nimodipine, 47 placebo) and those with multi-infarct dementia (n=167, 83 nimodipine, 84 placebo). While in the total trial population a treatment effect could not be proved, in this subgroup analysis, the subcortical VaD patients treated with nimodipine performed better on the majority of neuropsychological tests and functional scales in comparison with patients on placebo. No trend could be evidenced in the multi-infarct dementia patients. Treatment efficacy was in particular suggested for the Zahlen-Verbindungs-Test, Fuld-Object-Memory Evaluation, Word Fluency, and for the Instrumental Activities of Daily Living scale. The results did not reach statistical significance in this small sample. Our study preliminarily indicates that nimodipine could be effective in patients with small vessel subcortical VaD and supports the rationale for a further controlled and adequately powered trial to test nimodipine in patients with subcortical VaD.
Assuntos
Bloqueadores dos Canais de Cálcio/uso terapêutico , Demência Vascular/tratamento farmacológico , Nimodipina , Vasodilatadores/uso terapêutico , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Bloqueadores dos Canais de Cálcio/efeitos adversos , Demência Vascular/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Nimodipina/efeitos adversos , Tomografia Computadorizada por Raios X , Vasodilatadores/efeitos adversosRESUMO
PURPOSE: Composite mesh prostheses incorporate properties of multiple materials for use in open ventral hernia repair (OVHR). This study examines clinical outcomes in patients who underwent OVHR with a polypropylene/expanded polytetrafluoroethylene (ePTFE) composite graft containing a novel polydioxanone (PDO) absorbable ring to facilitate placement and graft positioning. METHODS: Data were prospectively collected on consecutive patients undergoing OVHR using a synthetic composite mesh. Seven centers enrolled patients during the study period. All patients underwent a standardized surgical procedure consisting of OVHR with sublay intraperitoneal placement of mesh. Mesh fixation was accomplished with peripheral tacks and transfascial sutures. RESULTS: One hundred and nineteen patients underwent OVHR with the composite mesh. Average age was 55.8 years; there were 71 (59.7 %) females and 48 (40.3 %) males with mean BMI of 33.5 ± 7.1 kg/m(2). One hundred and two (85.7 %) patients presented with primary ventral hernias. Mean defect size was 13.6 cm(2), and mean mesh size was 113.6 cm(2). Most patients (67 %) were discharged the day of surgery. Twelve patients (10.1 %) experienced complications in the perioperative time period primarily consisting of seroma (4.2 %) and ileus (1.7 %). Two patients required reoperation and mesh removal in the early postoperative period for infection and herniorrhaphy site pain, respectively. There was a decline in pain and movement limitation scores between baseline and 1-year follow-up. Six-month (n = 109) and twelve-month (n = 99) follow-up revealed no hernia recurrences (95 % CI 0-3 %, and 0-4 %, respectively). CONCLUSIONS: The use of this second-generation composite mesh was associated with no hernia recurrences and a low complication rate after open ventral hernia repair.
Assuntos
Hérnia Ventral/cirurgia , Herniorrafia/instrumentação , Telas Cirúrgicas , Infecção da Ferida Cirúrgica/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Remoção de Dispositivo , Feminino , Herniorrafia/efeitos adversos , Herniorrafia/métodos , Humanos , Íleus/etiologia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Dor Pós-Operatória/etiologia , Vigilância de Produtos Comercializados , Estudos Prospectivos , Qualidade de Vida , Recidiva , Reoperação , Seroma/etiologia , Telas Cirúrgicas/efeitos adversosRESUMO
INTRODUCTION: Earlier studies showed risperidone to be effective in the treatment of aggression and self-injurious behaviour in adults with mental retardation but also having adverse side effects. This study was conducted to evaluate the effects of zuclopenthixol withdrawal. METHODS: After open treatment with zuclopenthixol (n=49) responders were randomly assigned to continue (n=19) or discontinue (n=20) zuclopenthixol treatment during a 12-week double-blind, placebo-controlled period. Effects were measured using the Disability Assessment Schedule (DAS), improvement on the Clinical Global Impression Scale (CGI-I), and the Nurse's Observation Scale for Inpatient Evaluation (NOSIE). RESULTS: Ten patients (20%) discontinued the study due to insufficient therapeutic effect or adverse events in the open period. EFFICACY: The superiority of zuclopenthixol over placebo among all randomized patients was supported not only by primary efficacy measure but also by the comparisons of mean scores of all secondary efficacy measures tested in a step-down-procedure (DAS, p<0.001; CGI-I, p<0.002, NOSIE, p<0.005). SAFETY: In both groups, one patient discontinued (5%) for adverse events. Adverse events were generally mild or moderate in severity. DISCUSSION: Zuclopenthixol proved to be safe and effective to keep a low rate of aggressive behaviour in adults with mental retardation.
Assuntos
Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/tratamento farmacológico , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/psicologia , Clopentixol/efeitos adversos , Clopentixol/uso terapêutico , Deficiência Intelectual/psicologia , Síndrome de Abstinência a Substâncias/psicologia , Adolescente , Adulto , Agressão , Método Duplo-Cego , Feminino , Humanos , Testes de Inteligência , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Adulto JovemRESUMO
We discuss a novel electromagnetic penguin contribution to the transverse helicity amplitudes in B decays to two vector mesons, which is enhanced by two powers of mB/Lambda relative to the standard penguin amplitudes. This leads to unique polarization signatures in penguin-dominated decay modes such as B-->rhoK* similar to polarization effects in the radiative decay B-->K*gamma and offers new opportunities to probe the magnitude and chirality of flavor-changing neutral current couplings to photons.
RESUMO
In an open field study 4184 outpatients were assessed by 508 independent doctors using the Hamilton Anxiety Scale (HAMA). The results of the raw score distributions and item and factor analyses showed that the HAMA is unsuitable for differential diagnosis and, while showing a satisfactory degree of consistency, has relatively poor resolution. Departing from Hamilton's two-factor solution (1959), comparison of various solution models showed that a three-factor solution yields a stable and clinically useful item classification, which is also very similar to Hamilton's three-factor solution (1969).
Assuntos
Transtornos de Ansiedade/diagnóstico , Determinação da Personalidade , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Following experience with several clinical trials, the semantic, logical, and statistical properties of the Clinical Global Impressions Scale (CGI-ECDEU, 1976; CIPS, 1986) were investigated. It was concluded that the CGI in its present version (a) may induce inconsistent rating behavior, (b) contains redundant information, (c) consists of items which exhibit extremely abnormal distribution properties. Furthermore (d), some of these items are inappropriately constructed or (e) cast some doubts on their significance as measurements. It is suggested that item #1 (seriousness of disease) be used at the beginning of a study only, and that item #2 (global improvement) be used sparingly and as single measurement to express the doctor's general impression. There would seem to be no basis for the judgment of a pure drug effect (item #3). The instruction to measure improvement by comparing the patient's present condition to that at admission to the study cannot be recommended. Poor distribution properties and a presumably restricted significance of change ratings suggest that parametric statistics should not be referred to.
Assuntos
Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Humanos , Transtornos Mentais/psicologia , Índice de Gravidade de DoençaRESUMO
Comparative Bioavailability of Eicosapentaenoic Acid and Docosahexaenoic Acid from Triglycerides, Free Fatty Acids and Ethyl Esters in Volunteers. The bioavailability of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from triglycerides, free fatty acids and ethyl esters was investigated in 8 female volunteers in a randomized triple cross-over trial with baseline control. EPA/DHA was administered in capsules in form of triglycerides (1.68/0.72 g), free fatty acids (1.35/1.065 g) and ethyl esters (1.86/1.27 g). The resulting EPA/DHA plasma levels were determined and evaluated. The mean relative bioavailability of EPA/DHA compared to triglycerides was 186/136% from free fatty acids and 40/48% from ethyl esters. Maximal plasma levels were about 50% higher with free fatty acids and about 50% lower with ethyl esters as compared to triglycerides. The tolerability of the free fatty acids was much worse than that of triglycerides and ethyl esters. The main side effect was eructation.
Assuntos
Ácidos Docosa-Hexaenoicos/farmacocinética , Ácido Eicosapentaenoico/farmacocinética , Adulto , Disponibilidade Biológica , Biometria , Ácidos Docosa-Hexaenoicos/efeitos adversos , Ácido Eicosapentaenoico/efeitos adversos , Ésteres/efeitos adversos , Ésteres/farmacocinética , Ácidos Graxos não Esterificados/efeitos adversos , Ácidos Graxos não Esterificados/farmacocinética , Feminino , Humanos , Pessoa de Meia-Idade , Triglicerídeos/efeitos adversos , Triglicerídeos/farmacocinéticaRESUMO
Doctors' prescription and dosing behaviour was investigated using data from 9 clinical trials in 550 patients treated with psychotropics. 7 trials were conducted under double- and 2 under single-blind conditions. In 3 of these trials, oral and i.m. preparations were used demanding a double-dummy design. All patients were evaluated on a weekly or 2-week basis using psychopathological rating scales (i.e. Hamilton Anxiety Scale, Hamilton Depression Scale, Clinical Global Impressions, Simpson and Angus EPS). It was found that (a) oral-medication titration was 3- to 4-fold more broad-ranging than i.m. medication titration, (b) oral placebo was titrated to the same extent as the oral investigational drugs, and (c) the titration schedule did not follow protocol requirements. Moreover, the average doses in all drug and placebo groups were the same. Concomitant medication like sleep inducers was found to be more closely related to doctors' habits than to actual medical need. Independent of trial and investigational drug, 10-33% of all patients received additional sleep inducers.
Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Psicotrópicos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Administração Oral , Amitriptilina/administração & dosagem , Amitriptilina/efeitos adversos , Transtornos de Ansiedade/psicologia , Bemperidol/administração & dosagem , Bemperidol/efeitos adversos , Transtorno Depressivo/psicologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Doxepina/administração & dosagem , Doxepina/efeitos adversos , Esquema de Medicação , Flupentixol/administração & dosagem , Flupentixol/efeitos adversos , Flupentixol/análogos & derivados , Fluspirileno/administração & dosagem , Fluspirileno/efeitos adversos , Haloperidol/administração & dosagem , Haloperidol/efeitos adversos , Humanos , Imipramina/administração & dosagem , Imipramina/efeitos adversos , Injeções Intramusculares , Prometazina/administração & dosagem , Prometazina/efeitos adversos , Psicotrópicos/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Método Simples-CegoRESUMO
Patients with affective disorder insufficiently responding to prophylactic lithium present a major problem to maintenance pharmacotherapy. The present retrospective study tested the efficacy of carbamazepine in 73 such patients. The patients who were switched from lithium to carbamazepine monotherapy had additional benefit, but not those switched to combined lithium plus carbamazepine. This failure to replicate a number of recent pilot studies showing synergistic effects of lithium and carbamazepine may however have been due to a heterogeneity concerning the combined effects of some negative response predictors, although none of these was significant in itself. Nevertheless, synergism cannot be taken as guaranteed. Prospective controlled trials are needed.
Assuntos
Carbamazepina/uso terapêutico , Lítio/uso terapêutico , Transtornos do Humor/prevenção & controle , Adulto , Carbamazepina/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Lítio/administração & dosagem , Masculino , Transtornos do Humor/psicologia , Recidiva , Estudos RetrospectivosRESUMO
This randomised, double-blind study assessed the long-term efficacy and tolerability of vardenafil 10 and 20 mg in men with erectile dysfunction (ED). A total of 566 men who completed an initial 12-month treatment period entered a 12-month extension. In these men, both doses of vardenafil produced improvement in scores for the 'erectile function' Domain of the International Index of Erectile Function, evident from week 4 and maintained through 2 years. Sexual Encounter Profile diary responses indicated that following treatment, penetration was achieved on 92-94% of attempts and erections that lasted long enough for successful intercourse were achieved on 87-89% of attempts. In response to the General Assessment Question, 90-92% of patients reported improved erections with vardenafil. Most treatment-emergent events were mild and transient with no cardiovascular safety concerns. These results support the long-term efficacy, reliability and tolerability of vardenafil 10 and 20 mg in men with ED.
Assuntos
Disfunção Erétil/tratamento farmacológico , Imidazóis/uso terapêutico , Inibidores de Fosfodiesterase/uso terapêutico , Piperazinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Humanos , Imidazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Inibidores de Fosfodiesterase/efeitos adversos , Piperazinas/efeitos adversos , Sulfonas , Resultado do Tratamento , Triazinas , Dicloridrato de VardenafilaRESUMO
Sixty-five inpatients of a psychosomatic hospital in the Federal Republic of Germany with the diagnosis of anxiety neurosis (n = 31) or neurotic depression (n = 34) as defined by the International Classification of Disease (ICD-9), were randomized to a 4-week course of ipsapirone at 7.5 mg t.i.d. or placebo in a prospective, double-blind clinical trial to assess safety, tolerability, and efficacy. This article reports the efficacy results for those patients with the diagnosis of neurotic depression. The primary efficacy variable for patients with neurotic depression was the change from baseline in the Hamilton Rating Scale for Depression (HAM-D) at 4 weeks of treatment. Considering all of the randomized patients with neurotic depression (n = 34, the intent-to-treat population), the mean change from baseline in the HAM-D at Week 4 (observed cases) was -13.13 +/- 6.06 (n = 16) for the ipsapirone group, and -3.19 +/- 5.99 (n = 16) for the placebo group (p less than .001). A parallel analysis of the change from baseline in the Core Depression score of the HAM-D (defined as the sum of items 1, 2, 3, 7, and 8) also showed a significant treatment difference (p less than .01). Results were similar for the intent-to-treat population, last observation carried forward. Safety and tolerability were evaluated for all study patients independent of diagnosis. Treatment-emergent events (n = 65) were reported by 76 percent of patients treated with ipsapirone (n = 33) and by 38 percent of patients treated with placebo (n = 32).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Ansiolíticos/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Pirimidinas/uso terapêutico , Adolescente , Adulto , Transtorno Depressivo/psicologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação PsiquiátricaRESUMO
The neuroendocrine effects (changes in plasma CRF, ACTH and cortisol) of single and multiple (t.d.s. for 2 days) doses of ipsapirone (BAY Q 7821) 5 and 10 mg have been investigated in 6 healthy male volunteers. The study followed a balanced complete block, placebo-controlled and double blind design with two baseline phases (pre and post-treatment). Volunteers were investigated on identical days during 5 successive weeks. The results do not show a specific effect of ipsapirone on the hypothalamic-pituitary-adrenal axis when doses in the range of 5-30 mg per day were given.
Assuntos
Ansiolíticos/farmacologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Pirimidinas/farmacologia , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/efeitos dos fármacos , Adulto , Hormônio Liberador da Corticotropina/sangue , Hormônio Liberador da Corticotropina/efeitos dos fármacos , Humanos , Hidrocortisona/sangue , MasculinoRESUMO
OBJECTIVE: The primary aim of this paper was to compare the effects of flupenthixol and risperidone on subjective quality of life and attitude towards medication in chronic schizophrenic patients with mainly negative symptoms. In a spectrum ranging from its typical end "haloperidol" to its atypical end "clozapine", flupenthixol has typical and atypical characteristics. METHODS: The effects of flupenthixol versus risperidone were investigated in a multicenter, double-blind trial, whereas subjective quality of life was assessed by means of the EuroQuol-Visual Analogue Scale and the patient satisfaction questionnaire. The attitude towards medication was assessed by means of the Drug Attitude Inventory-30 (DAI-30). RESULTS: Mean daily dose of study medication was 6.6 (SD 2.9) mg/day flupenthixol and 3.6 (SD 1.2) mg/day risperidone. Both groups showed a significant improvement regarding subjective quality of life and positive attitude towards medication. Especially the categories "control of their thoughts", concentration and "feeling better in general" ameliorated in both groups. In the flupenthixol group, the "ability to cope with stress", "feel more relaxed" and the "ability to achieve something" improved significantly more than in the risperidone group. CONCLUSIONS: (1) The spectrum of schizophrenia can be treated effectively with different neuroleptic treatments. (2) Flupenthixol especially improves the ability to cope with stress, the ability to achieve something and feeling more relaxed. (3) Subjective quality of life significantly increased with no difference between the groups.
Assuntos
Antipsicóticos/uso terapêutico , Flupentixol/uso terapêutico , Qualidade de Vida , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adolescente , Adulto , Idoso , Atitude Frente a Saúde , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Escalas de Graduação Psiquiátrica , Inquéritos e Questionários , Resultado do TratamentoRESUMO
The absolute and relative bioavailability of chlorprothixene (CAS 113-59-7, Truxal) was studied in eight healthy male volunteers with three different formulations: solution, suspension and coated tablet. An intravenous infusion and an oral aqueous solution served as references. Single doses of 100 mg were administered in a randomized complete-block design with washout periods of two weeks. Serum concentrations of chlorprothixene were assayed using a high-performance liquid chromatographic method with electrochemical detection. After a 1-h infusion period the maximum serum concentration (Cmax) of chlorprothixene was 430 +/- 81 ng/ml (mean +/- S.D.) and subsequently decreased with a terminal elimination half-life (t1/2) of 25.8 +/- 13.6 h. The total serum clearance (Cl) and the apparent volume of distribution at steady state (Vss) were 867 +/- 167 ml/min and 1035 +/- 356 l, respectively. The profiles of the chlorprothixene serum concentration vs. time and the resulting pharmacokinetic parameters were similar for all orally administered formulations. The absolute oral bioavailability of 17% of the solution indicated a marked presystemic metabolism. The bioavailability of chlorprothixene relative to the oral solution was 56.4% with the coated tablet and 67.7% with the suspension. All pharmacokinetic parameters showed wide inter-subject variations, partly attributable to the respective formulation.
Assuntos
Antipsicóticos/farmacocinética , Clorprotixeno/farmacocinética , Administração Oral , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/sangue , Disponibilidade Biológica , Clorprotixeno/administração & dosagem , Clorprotixeno/sangue , Cromatografia Líquida de Alta Pressão , Meia-Vida , Humanos , Infusões Intravenosas , Masculino , Suspensões , Comprimidos com Revestimento EntéricoRESUMO
Vascular dementia (VaD) is a heterogeneous pathology currently regarded as the result of a variety of causes. Different types of VaD can be identified according to different criteria. This heterogeneity might be one of the causes of the controversial results observed, up to now, in clinical trials. Recently, the 10th revision of the International Classification of Diseases (ICD-10) explicitly identified subcortical VaD as a well-defined subgroup. Abnormalities of white matter are clearly detectable with computed tomography or magnetic resonance scans. The clinicoradiological association of dementia, blood hypertension, and other vascular risk factors, extensive white matter lesions, and small subcortical infarcts might be considered as a clinical univocal entity. Following the encouraging results of a preliminary pilot study, the above-mentioned criteria were followed to define a population of patients to be enrolled in a double-blind, parallel-groups, placebo-controlled clinical trial with nimodipine, which has been proposed as a drug that can improve cognitive functions in patients with VaD. The paper discusses the protocol design of this ongoing trial and its main entry criteria, with particular emphasis on the definition of the population to be enrolled. Implication for future trials in subcortical VaD are discussed further.