David Fischer-Barnicol

Typical and Atypical Antipsychotics – The Misleading Dichotomy

Objectives: (1) To investigate the risk of extrapyramidal motor side effects (EPS) associated with the prescription of different antipsychotics under naturalistic treatment conditions; (2) to test the rationale of the terms ‘typical’ and ‘atypical’ based on EPS rates. Design: Cross-sectional study in the federal state of Bavaria. Setting: 20 psychiatric hospitals in Bavaria. Participants: 6,061 inpatients, aged 18–65 years, with psychotic disorders. Main Outcome Measures: Co-medication with the anticholinergic biperiden was used as an index of EPS. Odds ratios for EPS and numbers needed to harm [number of patients who would need to be treated to obtain one more case with an adverse outcome (i.e. EPS) as compared with the control treatment (clozapine)] were calculated to obtain risk estimates for 15 different antipsychotics. Results: Groups of ‘typical’ and ‘atypical’ antipsychotics were not homogeneous in their EPS rates, and showed wide variation within each group. Nor did the frequency of EPS allow a clear distinction between the groups. There were 2 reasons for this: first, EPS rates rose continuously over the whole spectrum of drugs under study, and therefore precluded the definition of a cut-off score; second, there was considerable overlap between the 2 groups as EPS rates of various ‘atypicals’ (e.g. amisulpride, risperidone and zotepine) did not differ from some ‘typical’ substances (e.g. fluphenazine), while one ‘typical’ antipsychotic (perazine) even had a lower EPS risk than most ‘atypicals’. Conclusions: The odds of inducing EPS are not distinguishable between ‘typical’ and ‘atypical’ antipsychotics as EPS rates rise on a continuous scale throughout both classes. We propose dropping the categorization of antipsychotics as ‘typical’ and ‘atypical’ and instead using risk estimates like number needed to harm for EPS to help in benefit/risk considerations for antipsychotic treatment.

Memantine: a therapeutic approach in treating Alzheimer's and vascular dementia.

Memantine has been clinically used in the treatment of organic disorders in Germany for over ten years and has now been approved in Europe and also in the US for moderate to severe Alzheimers disease. The rationale for this indication is strongly related to the physiological and pathological role of glutamate in neurotransmission. Glutamate is an agonist of NMDA, kainate and AMPA (ionotropic) receptors, where its influence on NMDA receptors plays an important role with regard to neuronal plasticity effecting memory and learning. Excessive levels of glutamate result in neurotoxicity, in part by overactivation of NMDA receptors. Memantine acts as an uncompetitive antagonist of NMDA receptors and therefore compensates for this overactivation. Furthermore, memantine is a neuroprotective agent in various animal models based on both neurodegenerative and vascular processes, as it ameliorates cognitive and memory deficits. Memantine was effective and safe in several clinical studies, particularly in Alzheimers disease. The compound is completely absorbed after oral intake and undergoes little metabolism. Having a low probability for drug-drug interactions, memantine, in principle, is suited for elderly patients exposed to multiple therapeutic therapies.