On November 3, 1906, a clinical psychiatrist and neuroanatomist, Alois Alzheimer, reported "A peculiar severe disease process of the cerebral cortex" to the 37th Meeting of South-West German Psychiatrists in Tubingen, He described a 50-year-old woman whom he had followed from her admission for paranoia, progressive sleep and memory disturbance, aggression, and confusion, until her death 5 years later. His report noted distinctive plaques and neurofibrillary tangles in the brain histology. It excited little interest despite an enthusiastic response from Kraepelin, who promptly included "Alzheimer's disease" in the 8th edition of his text Psychiatrie in 1910. Alzheimer published three further cases in 1909 and a "plaque-only" variant in 1911, which reexamination of the original specimens in 1993 showed to be a different stage of the same process, Alzheimer died in 1915, aged 51, soon after gaining the chair of psychiatry in Breslau, and long before his name became a household word.
Recent clinical trials have raised questions over the perceived advantages of second-generation 'atypical' antipsychotics over those from the first generation. An atypical antipsychotic in its original sense is one that lacks extrapyramidal side effects. However, the addition of other clinical features to the original concept of atypicality, such as efficacy against negative and cognitive symptoms, seems to have become a feature of searches for novel antipsychotics in the past two decades. Although this approach has led to some therapeutic advances, we propose that it has also hampered antipsychotic drug research and that reframing the concept of atypicality could have a key role in making genuine breakthroughs in schizophrenia therapy.
The AMSP (Arzneimittelsicherheit in der Psychiatrie) study is a new program for continuous assessment of adverse drug reactions (ADR) in psychiatric inpatients under naturalistic conditions of routine clinical treatment. It is based on the preceding drug surveillance study AMUP (Arzneimittelüberwachung in der Psychiatrie). Currently, 29 hospitals are participating in the study. This paper reports on the methods of the AMSP study and the first findings on the comparative risks of tricyclic antidepressants (TCA) and selective serotonin reuptake inhibitors (SSRI) . Data assessment is restricted to "severe" ADR as defined in the study protocol. Drug use is estimated from reference day data. From 1993 to 1997, 896 cases of severe ADR were observed in 48,564 patients (1.84%). SSRI and the new substances mirtazapine and venlafaxine were increasingly used as antidepressants (AD), but TCA were still the most common AD in 1997 (52.1% of all AD patients). Similar rates of ADR were observed for SSRI and TCA (1.7% and 1.5%, respectively, for all cases, 0.9% and 1.0%, respectively, only for cases rated as probable). However, different types of ADR occurred with the two AD subgroups; whereas toxic delirium and increased liver enzymes were the most frequent ADR related toTCA, nondelirious psychic and neurologic ADR predominated with SSRI. The duration of inpatient treatment was considerably longer in patients who experienced an ADR due to TCA or SSRI than in those who did not. The AMSP study promises to contribute greatly to drug safety by providing the relative frequencies of severe ADR from a large-scale database and by improving our knowledge of ADR.
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