Clinical relevance and treatment possibilities of bipolar rapid cycling

Bipolar rapid cycling (RC) is defined as 4 or more affective episodes within 1 year. It has been postulated that RC is related to a poor response to lithium, to the same extent as mixed episodes or other atypical symptoms of the illness. This article reviews the current status of alternative pharmacological or otherwise supportive therapies of RC. Biological parameters and characteristics of the illness associated with RC like gender prevalence in women, hyperthyroid ism, catecholamine-O-methyltransferase allele, the influence of sleep, different subtypes of bipolar disorder and the risk of antidepressant-induced cycling will be discussed in detail. Copyright (C) 2002 S. Karger AG, Basel

Clozapine as add-on medication in the maintenance treatment of bipolar and schizoaffective disorders - A case series

Atypical neuroleptics are increasingly used in the treatment of bipolar and schizoaffective disorders. Currently, numerous controlled short-term studies are available for clozapine, olanzapine, risperidone or quetiapine, but long-term data are still missing. Three patients (2 with bipolar disorder, 1 with schizoaffective disorder) are described who showed a marked reduction of affective symptomatology after clozapine had been added to mood stabilizer pretreatment. The patients were seen once a month before and after the introduction of clozapine for at least 6 months. Treatment response was evaluated using different rating scales (IDS, YMRS; GAF; CGIBP) and the NIMH Life Chart Methodology. All patients showed a marked improvement after the add-on treatment with clozapine had been initiated. Clozapine was tolerated well with only transient and moderate weight gain and fatigue as only side effects. This case series underlines the safety and efficacy of clozapine as add-on medication in the treatment of bipolar and schizoaffective disorders. Copyright (C) 2002 S. Karger AG, Basel

Is the efficacy of psychopharmacological drugs comparable to the efficacy of general medicine medication?

There is an ongoing debate concerning the risk benefit ratio of psychopharmacologic compounds. With respect to the benefit, recent reports and meta-analyses note only small effect sizes with comparably high placebo response rates in the psychiatric field. These reports together with others lead to a wider, general critique on psychotropic drugs in the scientific community and in the lay press. In a recently published article, Leucht and his colleagues compare the efficacy of psychotropic drugs with the efficacy of common general medicine drugs in different indications according to results from reviewed meta-analyses. The authors conclude that, overall, the psychiatric drugs were generally not less effective than most other medical drugs. This article will highlight some of the results of this systematic review and discuss the limitations and the impact of this important approach on the above mentioned debate

The Stanley Foundation Bipolar Network: Results of the naturalistic follow-up study after 2.5 years of follow-up in the German centres

The Stanley Foundation Bipolar Network (SFBN) is an international, multisite network investigating the characteristics and course of bipolar disorder. Methods (history, ratings and longitudinal follow-up) are standardized and equally applied in all 7 centres. This article describes demographics and illness characteristics of the first 152 German patients enrolled in them SFBN as well as the results of 2.5 years of follow-up. Patients in Germany were usually enrolled after hospitalisation. More than 72% of the study population suffered from bipolar I disorder and 25% from bipolar 11 disorder. The mean +/- SD age of the study participants was 42.08 +/- 13.5 years, and the mean SD age of onset 24.44 +/- 10.9 years. More than 40% of the sample reported a rapid-cycling course in history, and even more a cycle acceleration overtime. 37% attempted suicide at least once. 36% had an additional Axis I disorder, with alcohol abuse being the most common one, followed by anxiety disorders. During the follow-up period, only 27% remained stable, 56% had a recurrence, 12.8% perceived subsyndromal symptoms despite treatment and regular visits. 27% suffered from a rapid-cycling course during the follow-up period. Recurrences were significantly associated with bipolar I disorder, an additional comorbid Axis I disorder, rapid cycling in history, a higher number of mood stabilizers and the long-term use of typical antipsychotics. Rapid cycling during follow-up was only associated with a rapidcycling course in history, a higher number of mood stabilizers and at least one suicide attempt in history. Copyright (c) 2003 S. Karger AG, Basel

Lagrangian Distributions and Connections in Symplectic Geometry

We discuss the interplay between lagrangian distributions and connections in symplectic geometry, beginning with the traditional case of symplectic manifolds and then passing to the more general context of poly- and multisymplectic structures on fiber bundles, which is relevant for the covariant hamiltonian formulation of classical field theory. In particular, we generalize Weinstein's tubular neighborhood theorem for symplectic manifolds carrying a (simple) lagrangian foliation to this situation. In all cases, the Bott connection, or an appropriately extended version thereof, plays a central role.Comment: 42 page

Mirroring everyday clinical practice in clinical trial design: a new concept to improve the external validity of randomized double-blind placebo-controlled trials in the pharmacological treatment of major depression

Background: Randomized, double-blind, placebo-controlled trials constitute the gold standard in clinical research when testing the efficacy of new psychopharmacological interventions in the treatment of major depression. However, the blinded use of placebo has been found to influence clinical trial outcomes and may bias patient selection. Discussion: To improve clinical trial design in major depression so as to reflect clinical practice more closely we propose to present patients with a balanced view of the benefits of study participation irrespective of their assignment to placebo or active treatment. In addition every participant should be given the option to finally receive the active medication. A research agenda is outlined to evaluate the impact of the proposed changes on the efficacy of the drug to be evaluated and on the demographic and clinical characteristics of the enrollment fraction with regard to its representativeness of the eligible population. Summary: We propose a list of measures to be taken to improve the external validity of double-blind, placebocontrolled trials in major depression. The recommended changes to clinical trial design may also be relevant for other psychiatric as well as medical disorders in which expectations regarding treatment outcome may affect the outcome itself

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum