RESUMO
Aggressive behavior among treatment-resistant schizophrenic patients is a major clinical challenge whose prevalence is underestimated.In our 420-bed psychiatric hospital, some 15% of patients exhibit active psychosis and high rates of verbal/physical aggression necessitating physical restraints. In addition to their condition, these individuals endanger staff and other patients, consume extensive resources, and induce a sense of clinical helplessness.Physicians managing such complex patients face dilemmas regarding choice of treatment, criteria for treatment decisions, treatment goals, and outcome assessments. We address some of these by following the progress of a persistently psychotic severely aggressive treatment-resistant inpatient treated with repeated electroconvulsive therapy (ECT). The motivation for this report was our desire to examine whether there was objective evidence to support our clinically based treatment decisions.To this end, we compiled a retrospective chronological life chart recording ECT administrations and aggression using case note information. Physical restraint was chosen as the outcome measure, as it was accurately documented. Because it was used only after all other means failed, a recorded incident represents an extreme peak of ongoing aggressive behavior.
Assuntos
Agressão , Eletroconvulsoterapia , Esquizofrenia/terapia , Violência , Antipsicóticos/uso terapêutico , Resistência a Medicamentos , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Esquizofrenia/tratamento farmacológico , Resultado do TratamentoRESUMO
Clinical studies have shown that negative symptoms of schizophrenia unresponsive to antipsychotic given alone can improve after augmentation with SSRI antidepressant. Laboratory investigations into the mechanism of this synergism showed that co-administration of SSRI and antipsychotic produces changes in GABA(A) receptor and related systems, which differ from the effects of each drug alone. To examine the clinical relevance of these findings, the current study examined the effects of SSRI augmentation treatment on GABA(A) receptor and related systems in schizophrenia patients. Schizophrenia patients with high levels of negative symptoms unresponsive to antipsychotic treatment received add-on fluvoxamine (100 mg/d). Blood was taken before and 1, 3 and 6 wk after adding fluvoxamine and peripheral mononuclear cells (PMC) isolated. RNA encoding for GABA(A)ß3, 5-HT2A, and 5-HT7 receptors, PKCß2, and brain-derived neurotrophic factor (BDNF) was assayed with real-time RT-PCR. Plasma BDNF protein was assayed using ELISA. Clinical symptoms were assessed with validated rating scales. We found significant increase in mRNA encoding for GABA(A)ß3 and 5-HT2A, 5-HT7 receptors and BDNF and a reduction in PKCß2 mRNA. Plasma BDNF protein concentrations were increased. There were significant correlations among the genes. Clinical symptoms improved significantly. mRNA expression of PKCß2, 5-HT2A and 5-HT7 showed significant associations with clinical symptoms. Combined SSRI+antipsychotic treatment is associated with changes in GABA(A) receptor and in related signalling systems in patients. These changes may be part of the mechanism of clinically effective drug action and may prove to be biomarkers of pharmacological response.