Typical and atypical antipsychotics--the misleading dichotomy. Results from the Working Group 'Drugs in Psychiatry' (AGATE).

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.

Studies of the brain specificity of S100B and neuron-specific enolase (NSE) in blood serum of acute care patients.

Laboratory monitoring with damage markers of brain and of non-nervous tissues in blood serum of 401 acute care patients showed increased contents of neuron-specific enolase (NSE) and S100B besides raised levels of markers of heart, skeletal muscle, bile duct, liver, prostate, kidney, salivary gland damage or of inflammatory stress to varying frequencies. Correlation between raised NSE and S100B contents ascertained brain damage. Correlation between raised NSE and troponin I (cTnI) values indicated brain damage induced by heart failure (probably caused by hypoxia and anemia); this was assessed with correlations between NSE and other heart markers, e.g. creatine kinase (CK) isoenzymes, alpha-hydroxybutyrate dehydrogenase. S100B did not show such correlations: data indicated S100B release from non-nervous tissues having high S100B content, e.g. fat, cartilage, skin. S100B release might be triggered by inflammatory stress and tissue damage. This was further supported by low NSE/S100B concentration ratios in serum compared to cerebrospinal fluid (CSF) of patients with comatose state, convulsive status, or intracerebral hemorrhage. Our data revealed CSF to be the relevant sample to monitor brain damage with NSE and S100B, whereas in serum raised S100B levels together with normal NSE levels indicated release from non-nervous tissues of acute care patients pointing out multi-organ dysfunction.

New and old diagnostic markers of meningitis in cerebrospinal fluid (CSF).

Five new markers (tumor necrosis factor TNF-alpha, interleukin IL-1 beta, IL-6, IL-8, lipopolysaccharide binding protein (LBP)) and 11 old classical markers were evaluated in 180 cerebrospinal fluid (CSF) and serum pairs to discriminate acute bacterial meningitis (BM) on admission from aseptic (viral) meningitis (AM), bacterial meningitis treated with antibiotics (TM) from AM, and AM from multiple sclerosis (MS). Statistical tests were computed which classified correctly > or =90% of the patients with BM, TM, AM at a sum minimum of false positive plus false negative results, and which reached additionally > or =90% sensitivity and specificity. To discriminate BM from AM, CSF IL-6 test > or =500 ng/l and CSF IL-1 beta test > or =8 ng/l besides CSF lactate test > or =3.5mM/l and CSF granulocyte test > or =150 M/l were revealed. CSF lactate test > or =3.2 mmol/l discriminated TM from AM. CSF leukocyte test > or =35 M/l discriminated AM from MS. Tests with the new markers were more laborious, expensive, and time consuming compared to CSF lactate test. Test candidates, detecting > or =80% of patients with > or =80% sensitivity and specificity, were evaluated with CSF TNF-alpha, IL-8 and LBP, serum IL-6, CSF leukocytes, lymphocytes and monocytes, Qglucose, CSF total protein, albumin, and Qalbumin. All tests should be reviewed in context of clinical findings to diagnose BM reliably.

Approach to discriminate subgroups in multiple sclerosis with cerebrospinal fluid (CSF) basic inflammation indices and TNF-alpha, IL-1beta, IL-6, IL-8.

Lumbar CSF and serum pairs of untreated multiple sclerosis patients (MS; n=47) were analyzed on admission. On average, higher CSF leukocyte (lymphocyte and monocyte) counts, IgG index, CSF IgG contents, but not of TNF-alpha, IL-1beta, IL-6, IL-8 in CSF and serum, were revealed in all MS or patients with long disease course (LO-MS) compared with controls. In primary progressive MS (PP-MS) cell counts were low, but IgG contents were high, when compared to relapsing-remitting MS (RR-MS). In clinically probable MS (CP-MS) both contents were low, in clinically definite MS (CD-MS) high. Spearman's correlation with the four monokines and the basic indices in CSF revealed activation patterns known for microglia/macrophages in the four MS subgroups, for astrocytes in CP-MS and RR-MS, for CSF lymphocytes in CP-MS and PP-MS, for cells of blood-brain barrier (BBB) in CP-MS, for intrathecal IgG synthesis in PP-MS and for lymphocyte transfer in CD-MS. Correlations between CSF and serum parameters indicated CNS disease processes to be associated with systemic processes of inflammation (acute, chronic) in CD-MS, RR-MS, and PP-MS in different ways. CSF IgG content, IgG index and systemic markers of inflammation correlated with overall disability scores in LO-MS; increasing levels may indicate a bad outcome.