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1.
Int J Neuropsychopharmacol ; 7(4): 471-9, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15154974

RESUMO

An aim in development of new antidepressants (ADs) now includes increasing speed of action. New drugs are tested primarily in outpatients who are less severely depressed than the patients treated in earlier trials of the tricyclic drugs. To determine early efficacy requires measures sensitive to initial changes in components of the illness as well as in the severity of the entire syndrome of depression. This paper describes the development of a brief 'multivantaged' (MV) method for assessing the major behavioural and affective components of depression. The revised Brief MV was significantly reduced from the original to make it more feasible to apply in outpatient studies. In this study we determined the Brief MV's (1) reliability and comparability to the original and (2) its ability to detect the onset of specific behavioural effects in outpatients treated with paroxetine for 6 wk. The latter is compared to the ability of the Hamilton Depression Scale (HAMD) to detect changes in global severity. The constructs derived from the Brief MV were found to be highly similar to those of the original version and as reliable. In depressed patients who responded to paroxetine, the HAMD and MV detected onset of improvement after 7 d of treatment. The Brief MV revealed that the improvement in global severity was due to the drug's action at this time on behaviours such as anxiety and distressed expression, as well as on a severity dimension of anxiety-agitation-somatization. Thus, the Brief MV, in uncovering underlying behavioural actions, represents an important addition to the current unidimensional HAMD approach in drug research.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/psicologia , Adolescente , Adulto , Idoso , Antidepressivos de Segunda Geração/uso terapêutico , Comportamento/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paroxetina/uso terapêutico , Escalas de Graduação Psiquiátrica , Reprodutibilidade dos Testes , Análise de Sobrevida , Fatores de Tempo
2.
Am J Psychiatry ; 159(5): 728-37, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-11986125

RESUMO

OBJECTIVE: Administration of placebo can result in a clinical response indistinguishable from that seen with active antidepressant treatment. Functional brain correlates of this phenomenon have not been fully characterized. METHOD: Changes in brain glucose metabolism were measured by using positron emission tomography in hospitalized men with unipolar depression who were administered placebo as part of an inpatient imaging study of fluoxetine. Common and unique response effects to administration of placebo or fluoxetine were assessed after a 6-week, double-blind trial. RESULTS: Placebo response was associated with regional metabolic increases involving the prefrontal, anterior cingulate, premotor, parietal, posterior insula, and posterior cingulate and metabolic decreases involving the subgenual cingulate, parahippocampus, and thalamus. Regions of change overlapped those seen in responders administered active fluoxetine. Fluoxetine response, however, was associated with additional subcortical and limbic changes in the brainstem, striatum, anterior insula, and hippocampus, sources of efferent input to the response-specific regions identified with both agents. CONCLUSIONS: The common pattern of cortical glucose metabolism increases and limbic-paralimbic metabolism decreases in placebo and fluoxetine responders suggests that facilitation of these changes may be necessary for depression remission, regardless of treatment modality. Clinical improvement in the group receiving placebo as part of an inpatient study is consistent with the well-recognized effect that altering the therapeutic environment may significantly contribute to reducing clinical symptoms. The additional subcortical and limbic metabolism decreases seen uniquely in fluoxetine responders may convey additional advantage in maintaining long-term clinical response and in relapse prevention.


Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Transtorno Depressivo/tratamento farmacológico , Glucose/metabolismo , Efeito Placebo , Encéfalo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Transtorno Depressivo/metabolismo , Método Duplo-Cego , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Humanos , Sistema Límbico/diagnóstico por imagem , Sistema Límbico/efeitos dos fármacos , Sistema Límbico/metabolismo , Masculino , Pessoa de Meia-Idade , Placebos/farmacologia , Placebos/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Tomografia Computadorizada de Emissão
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