RESUMO
The hopes for readily implementable precision medicine are high. For many complex disorders, such as bipolar disorder, these hopes critically hinge on tangible successes in pharmacogenetics of treatment response or susceptibility to adverse events. In this article, we review the current state of pharmacogenomics of bipolar disorder including latest results from candidate genes and genome-wide association studies. The majority of studies focus on response to lithium treatment. Although a host of genes has been studied, hardly any replicated findings have emerged so far. Very small samples sizes and heterogeneous phenotype definition may be considered the major impediments to success in this field. Drawing from current experiences and successes in studies on diagnostic psychiatric phenotypes, we suggest several approaches for our way forward.
Assuntos
Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/genética , Farmacogenética/métodos , Antipsicóticos/uso terapêutico , Transtorno Bipolar/diagnóstico , Estudos de Casos e Controles , Humanos , Lítio/uso terapêuticoRESUMO
BACKGROUND: Patients with mental illnesses, especially with schizophrenia, suffer from stigma and discrimination. In addition, the stigma is a barrier to recognising and treating patients with first-episode psychosis; however, a self-rating instrument that assesses the general burden due to stigma experiences is still lacking. MATERIAL AND METHODS: A total of N = 48 patients with first-episode schizophrenia who were participants in the multicenter first-episode (long-term) study within the German Research Network on Schizophrenia, completed a newly developed self-rating questionnaire to assess the burden due to stigma experiences (B-STE). The following variables were analyzed as possible correlates: psychopathology (CGI, PANSS, CDSS and HAM-D), global functioning (GAF), social adjustment (SAS), self-esteem (FSKN), as well as quality of life (LQLP), subjective well-being under neuroleptic treatment (SWN) and anticipated stigma (PDDQ). RESULTS: Of the participants 25 % showed an increased burden due to stigma experiences, which correlated with a lower quality of life, lower subjective well-being under neuroleptic treatment, lower self-esteem and higher anticipated stigma. The results indicate that patients rated higher on the CGI scale who are at the same time better socially adjusted (SAS), are more intensely affected by the burden due to stigma experiences. CONCLUSION: The short self-rating instrument burden due to stigma experiences (B-STE) can help to identify patients who might benefit from therapeutic or educational interventions to support coping with stigma experiences.
Assuntos
Qualidade de Vida/psicologia , Esquizofrenia/epidemiologia , Psicologia do Esquizofrênico , Discriminação Social/psicologia , Discriminação Social/estatística & dados numéricos , Estereotipagem , Adulto , Distribuição por Idade , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Prevalência , Esquizofrenia/diagnóstico , Distribuição por SexoRESUMO
AIMS: The objective of this study was to describe the use of indwelling epidural catheters post-operatively in dogs in a home environment, and to report associated complications. METHODS: Dogs undergoing surgical procedures of the hind limb (n=83) were included in the study and were administered 0.05 or 0.10â mg/kg epidural morphine via an indwelling epidural catheter every 6 hours. Data compiled relating to catheter placement included time of placement, ease of placement and problems encountered, number of attempts of placement, and individual placing the catheter. A client questionnaire was provided to evaluate side effects, complications, pain, and ease of use of the epidural catheter system after discharge from the hospital and catheter removal at home. Side effects were compared between the dogs receiving 0.05 or 0.1â mg/kg epidural morphine. RESULTS: The most common patient complication was abnormal urination patterns (32/82, 39%); specifically dribbling urine where laying, emptying the entire bladder where laying, not urinating for extended periods of time, and taking a longer time to pass urine were reported. There were no significant differences in the number or types of side effects reported in either dosing group. The most common technical issues reported by owners were difficulty getting the needle into the injection port (10/81, 12%) and removing the adhesive covering keeping the epidural catheter system in place (19/78, 24%). There were no reports of inflammation or discharge at the catheter site in any of the dogs. Of the respondents surveyed, 76/79 (97%) found the epidural catheter system easy to use at home in the post-operative period. CONCLUSIONS: Indwelling epidural catheters are a feasible method of administration of post-operative analgesia in the immediate post-operative period in the home environment and were associated with only a few minor complications in this population.
Assuntos
Analgesia Epidural/veterinária , Cateteres de Demora/veterinária , Doenças do Cão/induzido quimicamente , Dor Pós-Operatória/veterinária , Transtornos Urinários/veterinária , Analgesia Epidural/efeitos adversos , Animais , Cateteres de Demora/efeitos adversos , Doenças do Cão/prevenção & controle , Doenças do Cão/cirurgia , Cães , Membro Posterior/cirurgia , Procedimentos Ortopédicos/efeitos adversos , Procedimentos Ortopédicos/veterinária , Dor Pós-Operatória/prevenção & controle , Transtornos Urinários/induzido quimicamenteRESUMO
RATIONALE: There is little clinical data available about seizure rates in psychiatric inpatients, and there are no studies with reference data to the frequencies of antidepressant (AD) use for this important clinical population. OBJECTIVE: This study investigates seizure rates during AD treatment in psychiatric inpatient settings, drawn from the transnational pharmacovigilance programme Arzneimittelsicherheit in der Psychiatrie (AMSP) in relation to the known frequencies of ADs used in the participating clinics. Comparisons are made to former publications and their limitations. RESULTS: Seventy-seven cases were identified with grand mal seizures (GMS) during AD treatment between 1993 and 2008, with a total number of 142,090 inpatients under surveillance treated with ADs in the participating hospitals. The calculated overall rate of reported seizures of patients during AD treatment in this collective is 0.05 % for ADs imputed alone or in combination with other psychotropic drug groups and 0.02 % when only ADs were given and held responsible for GMS. The patients receiving tri- or tetracyclic ADs (TCAs) had a 2-fold risk to develop a seizure as compared to the overall average rate in this sample. In 11 cases, there was only one AD imputed--the majority of these cases (9/11) were TCA. Monotherapy with selective serotonin reuptake inhibitors (SSRI) or dual serotonin and noradrenaline reuptake inhibitors (SNRI) were never imputed alone in this sample. CONCLUSIONS: The results of the study favour the assumption that SSRIs, noradrenergic and specific serotonergic antidepressants (NaSSA) and dual SNRI might be more appropriate than TCAs for the treatment of psychiatric patients with an enhanced seizure risk.
Assuntos
Antidepressivos/efeitos adversos , Epilepsia Tônico-Clônica/epidemiologia , Pacientes Internados , Farmacovigilância , Adolescente , Adulto , Idoso , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Adulto JovemRESUMO
OBJECTIVE: To report the use of an axial pattern flap based on the cranial cutaneous branch of the saphenous artery to close a skin defect left on the medial crus after mast cell tumour removal. CASE REPORT: A seven-year-old, 32.41 kg, neutered male mixed-breed dog had a mast cell tumour incompletely excised from the left medial crus. The resulting 6 cm linear scar was excised with 2 cm wide margins and one fascial plane for deep margins. An axial pattern skin flap incorporating the cranial cutaneous branch of the saphenous artery was used to close the resultant skin defect. RESULTS: The histopathology report documented clean margins and the flap survived completely. A seroma developed postoperatively, however it resolved without treatment. CLINICAL SIGNIFICANCE: An axial pattern skin flap based on the cranial cutaneous branch of the saphenous artery is a viable option for closing medial crus skin defects in the dog.
Assuntos
Doenças do Cão/cirurgia , Mastocitoma/veterinária , Neoplasias Cutâneas/veterinária , Transplante de Pele/veterinária , Retalhos Cirúrgicos/veterinária , Animais , Cães , Masculino , Mastocitoma/cirurgia , Neoplasias Cutâneas/cirurgia , Transplante de Pele/métodosRESUMO
The angularis oris axial pattern flap is based on the blood supply of the angularis oris artery and vein. While the use of this flap for repair of canine facial wounds is well documented, this technique has not been reported in the cat. This case report presents the reconstruction of a large ventral chin and rostral lip wound with the use of this flap. Complete survival of this flap was observed in this patient.
Assuntos
Adenocarcinoma/veterinária , Doenças do Gato/cirurgia , Neoplasias Mandibulares/veterinária , Transplante de Pele/veterinária , Retalhos Cirúrgicos/veterinária , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Animais , Doenças do Gato/patologia , Gatos , Feminino , Neoplasias Mandibulares/patologia , Neoplasias Mandibulares/cirurgia , Transplante de Pele/métodosAssuntos
Inibidores da Monoaminoxidase/intoxicação , Inibidores Seletivos de Recaptação de Serotonina/intoxicação , Síndrome da Serotonina/induzido quimicamente , Suicídio , Tranilcipromina/intoxicação , Tiramina/administração & dosagem , Evolução Fatal , Feminino , Febre/induzido quimicamente , Alimentos , Humanos , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To examine the predictive validity of early improvement in a naturalistic sample of inpatients and to identify the criterion that best defines early improvement. METHODS: Two hundred and forty-seven inpatients who fulfilled ICD-10 criteria for schizophrenia were assessed with the Positive And Negative Syndrome Scale (PANSS) at admission and at biweekly intervals until discharge from hospital. Remission was defined according to the recently proposed consensus criteria, response as a reduction of at least 40% in the PANNS total score from admission to discharge. RESULTS: Receiver operating characteristic (ROC) analyses showed that early improvement (reduction of the PANSS total score within the first 2 weeks of treatment) predicts remission (AUC=0.659) and response (AUC=0.737) at discharge. A 20% reduction in the PANSS total score within the first 2 weeks was the most accurate cut-off for the prediction of remission (total accuracy: 65%; sensitivity: 53%; specificity: 76%), and a 30% reduction the most accurate cut-off for the prediction of response (total accuracy: 76%; sensitivity: 47%; specificity: 90%). CONCLUSION: The findings of clinical drug trials that early improvement is a predictor of subsequent treatment response were replicated in a naturalistic sample. Further studies should examine whether patients without early improvement benefit from an early change of antipsychotic medication.
Assuntos
Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Adolescente , Adulto , Idoso , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Área Sob a Curva , Feminino , Seguimentos , Humanos , Classificação Internacional de Doenças , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Escalas de Graduação Psiquiátrica , Curva ROC , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Tranquilizantes/uso terapêutico , Resultado do TratamentoRESUMO
Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a double-blind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N=39) with defined cognitive deficit (>or=1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40,000 IU rhEPO (N=20) or placebo (N=19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) - perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia.
Assuntos
Transtornos Cognitivos/tratamento farmacológico , Cognição/efeitos dos fármacos , Eritropoetina/administração & dosagem , Esquizofrenia/tratamento farmacológico , Adulto , Doença Crônica , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Crescimento Neural/sangue , Plasticidade Neuronal/efeitos dos fármacos , Efeito Placebo , Proteínas Recombinantes , Subunidade beta da Proteína Ligante de Cálcio S100 , Proteínas S100/sangue , Resultado do TratamentoRESUMO
Higher plasma homocysteine levels have been found in actively drinking alcoholics as well as in early abstinent patients. Furthermore, elevated homocysteine levels are associated with cognitive decline in dementia and in healthy elderly people. The aim of this prospective study was to investigate a possible association between homocysteine serum levels and clinically well known cognitive deficits during alcohol withdrawal. We examined 89 patients (67 men, 22 women) during early withdrawal treatment. Cognitive function was assessed using the c.I.-Test. Patients with cognitive deficits showed significantly higher homocysteine serum levels (Mann-Whitney-U, p=0.004) than patients without cognitive deficits, while the difference in blood alcohol concentration was not significant. Using logistic regression analysis, cognitive deficits were best predicted by high homocysteine serum levels (Wald chi2=4.071, OR=1.043, 95% CI 1.001-1.086, p<0.05), which was confirmed by Receiver Operating Curves (AUC=0.68, 95% CI=0.57-0.79, p=0.004). The present results show first evidence of an association between elevated plasma homocysteine levels in alcoholics and cognition deficits in patients undergoing alcohol withdrawal.
Assuntos
Transtornos do Sistema Nervoso Induzidos por Álcool/sangue , Alcoolismo/metabolismo , Transtornos Cognitivos/sangue , Transtornos Cognitivos/induzido quimicamente , Homocisteína/sangue , Síndrome de Abstinência a Substâncias/sangue , Adulto , Transtornos do Sistema Nervoso Induzidos por Álcool/fisiopatologia , Alcoolismo/sangue , Alcoolismo/fisiopatologia , Biomarcadores/sangue , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Química Encefálica/efeitos dos fármacos , Química Encefálica/fisiologia , Depressores do Sistema Nervoso Central/efeitos adversos , Transtornos Cognitivos/fisiopatologia , Etanol/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Valor Preditivo dos Testes , Síndrome de Abstinência a Substâncias/fisiopatologia , Fatores de Tempo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologiaRESUMO
Assessment of reactive oxygen species (ROS) is highly important in neurodegenerative disorders and neuroleptic treatment. However, conflicting results have been reported, which may arise from methodological difficulties. Obstructive sleep apnea (OSA) syndrome with episodic hypoxia-reoxygenation is proposed as a human model for the investigation of ROS measurements. Despite a broad analytical approach comprising lipid peroxidation and amino acid oxidation products, oxidative DNA damage, and activity of the antioxidant defense, only plasma malondialdehyde (MDA) and urinary o,o'-dityrosine seemed to be appropriate, robust biomarkers of oxidative stress, which are also simple enough for routine clinical use. MDA concentrations correlated with a duration of nocturnal desaturation below 85% (r = 0.77, p<0.0005), and o,o'-dityrosine levels decreased after therapy (p<0.05) as a function of baseline concentrations (r = -0.61, p<0.05). Gender effects in ROS generation also have to be considered. At present, we recommend the application of several oxidative stress measurements at different time points, preferably involving plasma MDA and urinary o,o'-dityrosine.
Assuntos
Estresse Oxidativo/fisiologia , Apneia Obstrutiva do Sono/metabolismo , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Idoso , Antioxidantes/metabolismo , Biomarcadores/sangue , Biomarcadores/urina , Pressão Positiva Contínua nas Vias Aéreas , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Feminino , Dissulfeto de Glutationa/sangue , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Humanos , Masculino , Malondialdeído/sangue , Melatonina/sangue , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio/metabolismo , Apneia Obstrutiva do Sono/terapia , Superóxido Dismutase/sangue , Tirosina/análogos & derivados , Tirosina/urinaRESUMO
The goal of the multicenter drug surveillance project AMSP ("Arzneimittelsicherheit in der Psychiatrie") is the monitoring, assessment and analysis of adverse drug reactions (ADR) of psychopharmalogical drugs. We report about a 23 year-old patient with a depressive episode. He developed severe pseudohallucinations under a treatment with moclobemide. The symptoms occur 6 days after starting the medication and decline within two days after stopping moclobemide. The term "pseudohallucinations" is discussed controversially but still of high interest.
Assuntos
Antidepressivos/efeitos adversos , Alucinações/induzido quimicamente , Moclobemida/efeitos adversos , Inibidores da Monoaminoxidase/efeitos adversos , Adulto , Antidepressivos/uso terapêutico , Transtorno Depressivo/complicações , Transtorno Depressivo/tratamento farmacológico , Alucinações/fisiopatologia , Alucinações/psicologia , Humanos , Masculino , Mianserina/análogos & derivados , Mianserina/uso terapêutico , Mirtazapina , Moclobemida/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Sertralina/uso terapêuticoRESUMO
The goal of the German drug safety program in psychiatry AMSP (Arzneimittelsicherheit in der Psychiatrie) is the assessment of severe or new adverse drug reactions (ADRs). Here we report on 53,042 of 122,562 patients treated with antidepressants who were monitored from 1993 to 2000 in 35 psychiatric hospitals in German-speaking countries. The overall incidence of severe ADRs of antidepressants was 1.4 % of exposed patients; when only ADRs rated as probable or definite were considered, a rate of 0.9 % in patients treated with antidepressants was observed. ADR rates were higher for TCAs (imputed in 1.0 % of patients overall, respectively in 0.6 % of patients when only ADs were imputed) and lower for MAO inhibitors and SSRIs (0.7 % for both, respectively 0.3 % and 0.4 %). Within the TCA group there was a difference among clomipramine (2.1 %, respectively 1.0 %), amitriptyline (1.0 %, respectively 0.6 %), and doxepin or trimipramine (both 0.6 %, respectively 0.3 %). With regard to single SSRI, similar rates were observed for paroxetine (0.8 %, respectively 0.5 %) and for citalopram (0.7 %, respectively 0.4 %). Of the new dual-acting antidepressants, venlafaxine ranged at 0.9 %, (respectively 0.5 %) and mirtazapine at 0.6 % (respectively 0.5 %). In particular, TCAs were associated with known risks, such as toxic delirium, grand mal seizures, and hepatic (i. e., increased liver enzymes), urologic (i. e., urinary retention), allergic (i. e., exanthema), or cardiovascular (i. e., mainly orthostatic collapse) reactions. In SSRI-treated patients (non-delirious) psychic and neurological ADRs were most prominent, followed by gastrointestinal, dermatologic, and endocrinological/electrolyte reactions, with agitation, hyponatremia (probably as part of the SIADH syndrome and associated with severe neurologic or psychiatric symptoms in 64 % of all cases), increased liver enzymes, nausea, and the serotonin syndrome as leading unwanted symptoms. Venlafaxine (in the immediate-release formulation) was associated with adverse CNS and somatic symptoms such as severe agitation, diarrhea, increased liver enzymes, hypertension, and hyponatremia. Mirtazapine was mostly connected with increased liver enzymes, cutaneous edema, and collapse, but with no case of significant hyponatremia. For drugs that potently inhibit serotonin uptake, serum sodium concentration should be controlled when applied in high-dose therapy or in vulnerable patients.
Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Antidepressivos/efeitos adversos , Inibidores da Monoaminoxidase/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Adulto , Distribuição por Idade , Idoso , Depressão/complicações , Depressão/tratamento farmacológico , Depressão/epidemiologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Alemanha , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Vigilância de Produtos Comercializados/métodos , Estudos Prospectivos , Distribuição por SexoRESUMO
Numerous studies compare side effects or adverse drug reactions (ADRs) of the various typical and newer atypical neuroleptics in patients with schizophrenia. However, these studies, as controlled randomized trials, represent an artificial setting of drug administration and do not easily relate to the "real-life" setting of psychiatric treatment. In contrast, the AMSP drug safety program allows the monitoring of ADRs of all types of psychopharmacological agents in the naturalistic setting of routine clinical practice. In the present study, the data on neuroleptics acquired in the AMSP program from 1993 to 2000 are analyzed. In this period, 86,439 patients treated with at least one neuroleptic agent were monitored. In 1.1 % of the patients severe ADRs occurred. In contrast to the results from controlled trials, atypical neuroleptics caused more severe ADRs than did typical neuroleptics. This result was mainly caused by the high number of severe ADRs in patients treated with clozapine and concerned delirium and non-EPS neurological, gastrointestinal, hepatic, dermatological, hematological, and endocrinological ADRs. Atypical neuroleptics were found to be superior in EPS and urological ADRs. Excluding the data on clozapine, we found typical and atypical neuroleptics to be similar in the occurrence of severe ADRs, although the profiles differ between these two groups as well as between the single substances. Our findings provide valuable information on the type and frequency of ADRs in psychiatric practice, thus enabling differential indication of neuroleptics based not only on the efficacy and tolerability data of controlled trials but also on their differential ADR profile occurring in the "real-life" setting of routine clinical treatment.
Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Antipsicóticos/efeitos adversos , Esquizofrenia/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Depressão/tratamento farmacológico , Relação Dose-Resposta a Droga , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Humanos , Pacientes Internados , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Preparações Farmacêuticas , Vigilância de Produtos Comercializados , Estudos Prospectivos , Estudos Retrospectivos , Esquizofrenia/fisiopatologia , Resultado do TratamentoRESUMO
The introduction of new antipsychotics has resulted in the availability of drugs with improved safety and tolerability as well as proven efficacy compared to the older antipsychotics. New compounds might show new or different adverse effects that arise in the post-marketing phase when a greater number of patients are treated. One goal of the drug safety program in psychiatry AMSP ( Arzneimittelsicherheit in der Psychiatrie) is the detection and description of severe, new, or rare adverse drug reactions (ADRs). Between 1993 and 2000, 122,562 patients were monitored in 35 psychiatric institutions, 86,349 patients of which received antipsychotics. Hyperglycemia related to antipsychotics was observed in association with only two compounds so far: clozapine and olanzapine (clozapine 2 cases, olanzapine 7 cases). In 6 of 9 patients, weight gain preceded hyperglycemia. The relative frequency of these adverse drug related events was 0.013 % for clozapine and 0.075 % for olanzapine. The symptomatology included reversible hyperglycemia, worsening of existing diabetes, and new-onset diabetes. Control for glycemic dysregulation should be maintained in clinical practice with these drugs.
Assuntos
Antipsicóticos/efeitos adversos , Diabetes Mellitus Tipo 2/induzido quimicamente , Hiperglicemia/induzido quimicamente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Idoso , Benzodiazepinas/efeitos adversos , Clozapina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina , Avaliação de Resultados em Cuidados de Saúde , Vigilância de Produtos Comercializados/métodos , Estudos Prospectivos , Transtornos Psicóticos/tratamento farmacológico , Estudos Retrospectivos , Fatores de RiscoRESUMO
Within the drug safety program in psychiatry AMSP ( Arzneimittelsicherheit in der Psychiatrie), severe adverse drug reactions (ADRs) are assessed. Currently 35 psychiatric hospitals and departments are participating in detecting severe ADRs. This paper focuses on prolactin-dependent ADRs such as gynecomastia and galactorrhea due to psychotropic medications. Related to the number of patients surveyed (122,562 from 1993 to 2000), these are rare events (0.03 % or 35 cases). Imputed drugs were mostly antipsychotics, but antidepressants were also imputed in single cases. In the group of antipsychotics, relative frequencies of galactorrhea were highest for amisulpride and risperidone and corresponded to the degree of D2 binding. Galactorrhea assessed as "severe" was accompanied by distressing symptoms such as pain, tension, enlargement of breasts, or soaked clothing. The AMSP data contribute to the knowledge on endocrine ADRs by the large number of patients examined and help clinicians select the appropriate drug if their patients have been prone to for these ADRs in the past.
Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Galactorreia/induzido quimicamente , Psicotrópicos/efeitos adversos , Adulto , Feminino , Seguimentos , Galactorreia/epidemiologia , Humanos , Incidência , Masculino , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/fisiopatologia , Pessoa de Meia-Idade , Vigilância de Produtos Comercializados , Prolactina/sangue , Estudos Prospectivos , Fatores de TempoRESUMO
Erythropoietin (EPO) is a candidate compound for neuroprotection in human brain disease capable of combating a spectrum of pathophysiological processes operational during the progression of schizophrenic psychosis. The purpose of the present study was to prepare the ground for its application in a first neuroprotective add-on strategy in schizophrenia, aiming at improvement of cognitive brain function as well as prevention/slowing of degenerative processes. Using rodent studies, primary hippocampal neurons in culture, immunohistochemical analysis of human post-mortem brain tissue and nuclear imaging technology in man, we demonstrate that: (1) peripherally applied recombinant human (rh) EPO penetrates into the brain efficiently both in rat and humans, (2) rhEPO is enriched intracranially in healthy men and more distinctly in schizophrenic patients, (3) EPO receptors are densely expressed in hippocampus and cortex of schizophrenic subjects but distinctly less in controls, (4) rhEPO attenuates the haloperidol-induced neuronal death in vitro, and (4) peripherally administered rhEPO enhances cognitive functioning in mice in the context of an aversion task involving cortical and subcortical pathways presumably affected in schizophrenia. These observations, together with the known safety of rhEPO, render it an interesting compound for neuroprotective add-on strategies in schizophrenia and other human diseases characterized by a progressive decline in cognitive performance.
Assuntos
Eritropoetina/farmacocinética , Fármacos Neuroprotetores/farmacocinética , Esquizofrenia Paranoide/diagnóstico por imagem , Esquizofrenia Paranoide/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antipsicóticos/farmacologia , Morte Celular/efeitos dos fármacos , Células Cultivadas , Cognição/efeitos dos fármacos , Feminino , Haloperidol/farmacologia , Humanos , Radioisótopos de Índio , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neurônios/citologia , Neurônios/efeitos dos fármacos , Ratos , Proteínas Recombinantes , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
OBJECTIVE: The effectiveness of atypical antipsychotic agents in the treatment of acute schizophrenic episodes is still a subject of controversial debate. The objective, therefore, was to investigate the efficacy and tolerability of an initial therapy with the atypical antipsychotic agent risperidone in acutely exacerbated patients under the conditions of clinical practice. A sub-analysis was performed to show if highly agitated and aggressive patients may profit from an initial risperidone therapy as well. MATERIAL AND METHODS: In a still ongoing prospective multicentre observational trial, schizophrenic patients with acute exacerbations treated with risperidone within 24 hours of in-patient admission were observed for six weeks. Patients showing a total score of > or = 15 in the items "excitement", "hostility" and "uncooperativeness" of the Positive and Negative Syndrome Scale (PANSS) were defined as highly agitated patients. Evaluation of efficacy was carried out according to a modified PANSS, the Clinical Global Impression (CGI) and the Brief Psychiatric Rating Scale (BPRS). RESULTS: 1,117 patients were evaluated. An improvement of all parameters was shown in the whole study group (51 % males, age 39.8 + 14.3 years, paranoid schizophrenia in 70.1 % of cases) and in particular in the subgroup of highly agitated patients. In these patients (n = 163), a greater improvement of symptoms was observed. Only in 4,1 % of cases was risperidone discontinued because of side effects. At the end of the observation, the mean dosage was 5.1 mg/day in both groups. More than 50 % of the patients were finally treated with a risperidone monotherapy. CONCLUSION: The initial acute treatment with risperidone proves to be effective and safe even for highly agitated schizophrenic patients under the conditions of clinical practice.
Assuntos
Antipsicóticos/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Doença Aguda , Adulto , Agressão/efeitos dos fármacos , Antipsicóticos/efeitos adversos , Feminino , Humanos , Masculino , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Agitação Psicomotora/tratamento farmacológico , Risperidona/efeitos adversos , Esquizofrenia/complicações , Psicologia do EsquizofrênicoRESUMO
There is evidence that a higher incidence of diverse neurodegenerative diseases is associated with the apolipoprotein E epsilon4 allele (ApoE4). Most recently it has been found that the ApoE4 allele is specifically related to an accelerated hippocampal atrophy in patients with Alzheimer's disease. Therefore, the aim of the present study was to investigate the association between ApoE4 genotypes and brain hippocampal volume reduction in alcoholics by using volumetric high-resolution MR imaging. In the present study, female alcoholics with the ApoE4 genotype were found to have significantly smaller hippocampal volumes than those not carrying an epsilon4 allele (ANOVA, p < 0.05), whereas no differences in hippocampal volume were seen in male alcoholics. Since hippocampal volume reduction is lately discussed to be proportional to brain atrophy, we propose that the alcohol-related brain atrophy in patients suffering from chronic alcoholism, is more pronounced in female carriers of the apoE epsilon4 allele. These findings indicate a genetic disposition for alcohol related brain atrophy in female carrying the ApoE4 genotype, which may also explain why female alcoholics are more susceptible to alcohol-induced brain damage.
Assuntos
Alcoolismo/genética , Alcoolismo/patologia , Apolipoproteínas E/genética , Hipocampo/patologia , Caracteres Sexuais , Adulto , Idoso , Alelos , Análise de Variância , Apolipoproteína E4 , Feminino , Genótipo , Heterozigoto , Hipocampo/efeitos dos fármacos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-IdadeRESUMO
Chronic alcohol consumption can induce brain atrophy, whereby the exact mechanism of brain damage in alcoholics remains unknown. There is evidence that chronic alcoholism is associated with hyperhomocysteinemia. Homocysteine is an excitatory amino acid which markedly enhances the vulnerability of neuronal cells to excitotoxic and oxidative injury in vitro and in vivo. The present volumetric magnetic resonance imaging study included 52 chronic alcoholics and 30 non-drinking healthy controls. Patients were active drinkers and had an established diagnosis of alcohol dependence. We investigated the influence of different variables on the hippocampal volume of patients suffering from chronic alcoholism. We observed that pathological raised levels of plasma homocysteine showed the most significant correlation to hippocampal volume reduction (P<0.001, multiple regression analysis). Raised plasma levels of homocysteine are associated with hippocampal (brain) atrophy in alcoholism.