A regulatory perspective on psychiatric syndromes in Alzheimer disease.
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Biomedical subjects
Publications and source records attributed to T Laughren.
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This paper discusses the premarketing safety database that the US Food and Drug Administration receives from drug manufacturers. It reviews the kind of data we usually receive, what we do with the data, and how the data affect labeling. In addition, it discusses some of the limitations of that database in ensuring the safe use of medications.
Serum neuroleptic levels, prolactin levels, and clinical state were assessed for 1 year in 29 schizophrenic outpatients whose clinically determined neuroleptic dose had been reduced by 50%. Fifty-five percent of the subjects remained stable. Neuroleptic dose did not differ between relapsed and stable patients. Serum prolactin (PRL) assessed 2 weeks after dose reduction and mean PRL after reduction were significantly lower among relapsers. Serum neuroleptic levels were significantly lower for relapsers in patients on haloperidol. Among relapsers, there were no serum PRL or neuroleptic level differences between stable periods and the relapse episode. Among patients with relatively low neuroleptic bioavailability, relapsers reported lower levels of social activity and had social networks that were less enjoyable, more aversive, and less helpful than those of stable patients.
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Relapse occurs in a substantial proportion of schizophrenic patients treated with neuroleptics. The determinants of relapse have been elusive. In our study, low serum neuroleptic levels identified patients who had a relapse during a six-month period. Neuroleptic levels were measured by radioreceptor assay in 61 schizophrenic men and their clinical status was assessed in the subsequent six months. Ten patients had relapses, four showing a worsening of chronic psychotic symptoms and six showing eruption of psychotic symptoms after a period of remission. These ten patients had significantly lower normalized neuroleptic levels than those whose conditions remained stable. The lowest neuroleptic levels occurred in patients who had relapses after a period of remission. Serum neuroleptic levels in drug-responsive patients appear to be a critical determinant of remission. If these observations are replicated, a rational basis may be provided for prescribing and monitoring neuroleptic treatment and perhaps for preventing relapse.
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