[Telephone coaching for depression]. / Telefoncoaching bei Depression.

BACKGROUND: Depression is associated with a substantial utilization of resources in the German healthcare system. A typical symptom in depression is loss of drive, which possibly contributes to non-adherence and increased costs. OBJECTIVE: The study is based on routine healthcare data and tested the hypothesis that telephone coaching in cases of depression leads to a reduction in total healthcare costs. MATERIAL AND METHODS: Based on approximately 80 covariates and using propensity score matching, a total of 1586 persons who had received telephone coaching for depression and covered by a German statutory health insurance fund were matched to a comparable cohort of patients with depression to whom telephone coaching had not been provided. RESULTS: Within the study period of 12 months (3rd quarter 2012-4th quarter 2013) a positive program effect was observed for the intervention group by a significant reduction of total healthcare costs (2332 € vs. 2626 €, p = 0.0015) resulting in total savings to the statutory health insurance fund of 415,532 €. Investment costs amounted to 256,683.42 € leading to a return on investment of 1.62 € (total savings/total investment). The coaching program was well accepted by patients. CONCLUSION: Telephone coaching for depression was able to significantly reduce total healthcare expenditure and the intervention was well accepted by patients.

Neuropeptide S receptor gene -- converging evidence for a role in panic disorder.

Animal studies have suggested neuropeptide S (NPS) and its receptor (NPSR) to be involved in the pathogenesis of anxiety-related behavior. In this study, a multilevel approach was applied to further elucidate the role of NPS in the etiology of human anxiety. The functional NPSR A/T (Asn¹°7Ile) variant (rs324981) was investigated for association with (1) panic disorder with and without agoraphobia in two large, independent case-control studies, (2) dimensional anxiety traits, (3) autonomic arousal level during a behavioral avoidance test and (4) brain activation correlates of anxiety-related emotional processing in panic disorder. The more active NPSR rs324981 T allele was found to be associated with panic disorder in the female subgroup of patients in both samples as well as in a meta-analytic approach. The T risk allele was further related to elevated anxiety sensitivity, increased heart rate and higher symptom reports during a behavioral avoidance test as well as decreased activity in the dorsolateral prefrontal, lateral orbitofrontal and anterior cingulate cortex during processing of fearful faces in patients with panic disorder. The present results provide converging evidence for a female-dominant role of NPSR gene variation in panic disorder potentially through heightened autonomic arousal and distorted processing of anxiety-relevant emotional stimuli.

[Preoperative anemia in orthopedic surgery: clinical impact, diagnostics and treatment]. / Präoperative Anämie in der Orthopädie: Klinische Relevanz, Diagnostik und Therapie.

In a national audit of elective orthopedic surgery conducted in the US, 30% of patients were found to have hemoglobin (Hgb) levels < 13 g/dl at preadmission testing. Preoperative anemia has been associated with increased mortality and morbidity after surgery, increased allogeneic blood transfusion therapy and increased rates of postoperative infection leading to a longer length of hospital stay. Because of the risks associated with allogeneic blood transfusions according to German law patients have to be offered the option of autologous transfusion if the risk associated with allogeneic blood transfusion is > 10%. However, one of these measures, the autologous blood donation, can exaggerate anemia and can increase the overall transfusion rates (allogeneic and autologous). As autologous procedures (autologous blood donation and cell salvage) are not always appropriate for anemic patients together with an expected shortage of blood and because preoperative anemia is associated with perioperative risks of blood transfusion, a standardized approach for the detection, evaluation and management of anemia in this setting was identified as an unmet medical need. A panel of multidisciplinary physicians was convened by the Society for Blood Management to develop a clinical care pathway for anemia management in elective surgery patients for whom blood transfusion is an option. In these guidelines elective surgery patients should have Hgb level determination at the latest 28 days before the scheduled surgical procedure. The patient target Hgb before elective surgery should be within the normal range (normal female ≥ 120 g/l, normal male ≥ 130 g/l). Laboratory testing should take place to further determine nutritional deficiencies, chronic renal insufficiency and/or chronic inflammatory diseases. Nutritional deficiencies should be treated and erythropoiesis-stimulating agent (ESA) therapy should be used for anemic patients in whom nutritional deficiencies have been ruled out and/or corrected.

[Do individuals with substance use disorders find information for crisis intervention and suicide prevention resources on the Internet?]. / Finden suizidale Suchtkranke Hilfsangebote im Internet?

BACKGROUND AND OBJECTIVE: Suicidality is an important issue for substance-dependent people. The few studies about Internet searches have provided ambiguous results regarding help and support using suicide-related terms. MATERIAL AND METHODS: Five popular search engines and several substance use- and suicide-related German search terms were used; the search results were classified as being pro-suicide, anti-suicide, suicide-neutral, websites not associated with suicide or "page could not be loaded". RESULTS: The majority of identified websites was not associated with suicide at all, whereas websites offering help and support were less frequent. Using suicide-associated search terms (such as "Selbsttötung") almost half of all web pages were help sites. Websites with instructions for committing suicide were very rarely found. CONCLUSIONS: In view of the difficulties for substance abusers to get immediate and adequate information about help and support in a suicidal crisis via the Internet, it is urgently necessary to extend fast available help sites on the Internet.

[Equal access to medical services over the lifespan]. / Versorgungsgerechtigkeit in der Lebensspanne.

Demand for health services is in principle unlimited, in contrast to resources. People covered by public health funds in principle have equal access to treatment according to the highest level of medical evidence available. In order to restrict expenditure the legislator stipulates different instruments. These include reference pricing for generics as well as price capping. The legislator still shies from price fixing which is well established in other states. Instead, office-based physicians are confronted by law with rationing decisions concerning their own services as well as services prescribed where the mentally ill are at special risk of becoming victims of intransparency, as exemplified by the heterogeneity of the prescription of psychotropic drugs. A systematic prioritization approach following internationally available models might open new perspectives.

[Predictors of major mental disorders]. / Prädiktoren psychischer Krankheiten.

Predictors of several major mental disorders include strong genetic linkage that is modified by biological, psychological and social factors. Insight into the biological mechanisms underlying these interactions is growing. Several candidate genes have been identified but their predictive value is still limited for predictions in the single individual. Comorbidities are common, including combinations of different mental disorders and/or combinations of mental and physical disorders. The combination of a mental and physical disorder often indicates a worse outcome for the physical disorder.

[Selective serotonin and noradrenaline reuptake inhibitors: a step forward in the treatment of depression?]. / Medikamentöse Behandlung von Depressionen und Angststörungen. Dem Therapieziel Remission wieder ein Schritt näher.

With the tricyclics, selective serotonin reuptake inhibitors (SSRIs) and other substances, we now have available a range of medications for the treatment of depression and other psychological disorders (e.g. anxiety, panic). Nevertheless, only some of the patients experience a remission of their depressive symptoms. The occurrence of side effects and the only modest level of effectiveness result in inadequate compliance on the part of the patient. With venlafaxine and duloxetine two representatives of the selective serotonin and noradrenaline reuptake inhibitor (SSNRI) class of antidepressants are now available. SSNRIs have a dual effect coupled with high selectivity. The present article the extent to which this particular action mechanism results in an improved clinical efficacy and tolerability profile of the SSNRIs, in particular in comparison with SSRIs.

Erythrocyte acetylcholinesterase in psychiatric disorders and controls.

Acetylcholinesterase (AChE) from erythrocytes was solubilized by Triton X-100. Size and charge heterogeneity of AChE was investigated by polyacrylamide gel electrophoresis (PAGE) and isoelectric focusing (IEF) in polyacrylamide gels in the presence of 0.5% (v/v) Triton X-100. There were no interindividual differences in these parameters in 46 psychiatric patients (schizophrenia, major affective disorder, personality disorder, dependency, dementia) and controls. The specific activity of solubilized AChE did not discriminate between controls and patients or between the diagnostic subgroups.

3H-spiroperidol binding to human peripheral mononuclear cells: methodological aspects.

3H-spiroperidol binding to lymphocytes has been proposed as a vulnerability marker for schizophrenia. However, the biological significance and even existence of this "binding site" are still in controversy. Therefore, the present study reevaluated methodological details using a filtration binding assay. The results indicated that some well-known, but obviously uncontrolled pitfalls might contribute to this controversy [e.g., unspecific filter binding, which increased in the presence of (+)-butaclamol, or a variable amount of contaminating granulocytes). Moreover, due to an atypically shaped saturation curve, different mathematical methods to analyze the data were used and compared. The present data should help us to understand the biological relevance of this marker, as viewed in different laboratories.

Organic schizophrenic syndrome associated with symmetrical basal ganglia sclerosis and XO/XY-mosaic.

Psychopathological alterations associated with symmetrical basal ganglia sclerosis have been well characterized. A preponderance of a so-called organic affective syndrome has been reported (König 1989), but schizophrenic syndromes have also been described, in particular in young patients (Cummings et al 1983). Symmetrical basal ganglia sclerosis may be secondary to ischemia, hypoxia, trauma, intoxications, inflammations, or hyporesp. pseudohypoparathyroidism. Among idiopathic forms sporadic as well as familial ones with dominant and recessive inheritance have been observed (Billard et al 1989).

3H-spiroperidol binding to peripheral mononuclear cells in schizophrenic and healthy subjects.

3H-spiroperidol binding to peripheral blood mononuclear cells was measured in 28 patients, who fulfilled DSM-III-R-criteria for schizophrenia and 17 healthy subjects. There were no significant differences in characteristic binding parameters (Kd, Bmax) between schizophrenic and healthy subjects. Moreover, there was no relation of binding parameters to any of the subtypes of schizophrenia or to the course of illness according to DSM-III-R-criteria. However, some patients exhibited higher Bmax values without having a unique clinical symptomatology according to known diagnostic criteria. Neuroleptic treatment had no consistent effect on binding parameters intraindividually. Kd and Bmax values were not related to age or gender. In conclusion, despite our previously reported improved methodology, we were not able to corroborate the clinical importance of this "peripheral marker" as a tool for diagnosing schizophrenia or for predicting the response to neuroleptic treatment in our sample of schizophrenic patients.

Lack of association between dopamine D1 and D2 receptor genes and bipolar affective disorder.

Fifty-six patients with bipolar affective disorder and 69 healthy control subjects were tested for association of restriction fragment length polymorphism alleles at the dopamine D1 and D2 receptor loci. No significant associations were found; thus, the hypothesis that a single mutant form of either receptor gene is responsible for the phenotype of patients with bipolar affective disorder was not supported.

The adrenergic-cholinergic imbalance hypothesis of depression: a review and a perspective.

The catecholamine deficiency hypothesis of depression was essentially based on the incidental detection of iproniazide and imipramine. However, current findings favor noradrenergic overactivity, at least in the periphery. The incidental observation of acute behavioral inhibition by centrally active cholinomimetics like physostigmine suggested a cholinergic-adrenergic balance involved in the regulation of drive and mood. Indeed, cholinomimetics seem to have acute depressiogenic and antimanic properties and, conversely, anticholinergics some acute euphoriant activity. However, time course and dose-response relationships of drugs influencing mood and drive do not favor simple concepts of too much or too little activity of one or the other transmitter system. Cholinomimetics and psychostimulants show an acute mutual antagonism, the mechanism of which is obscure. In healthy volunteers clonidine and the putative antidepressant brofaromine did not influence the effects of physostigmine. Patients with mood disorders respond supersensitively to a cholinergic challenge in terms of behavior, neuroendocrine regulation and REM sleep induction. Thus, the anticholinergic properties of tricyclics might be relevant to their antidepressant activity. However, adjunctive treatment with the cholinolytic biperiden as compared to placebo did not enhance the antidepressant efficacy of mianserin or viloxazine. This is incompatible with cholinergic overactivity contributing to the depressive state. Physostigmine induces autonomous and endocrine responses reminiscent of stress reactions. Findings in healthy volunteers suggest relationships between the sensitivity to physostigmine and personality traits like irritability and emotional lability and passive stress coping strategies. Thus, the cholinergic supersensitivity in mood disorders might be related to some personality dimension like stress intolerance rather than the depressive state itself.

Can neuroleptics influence the function of the brain hemispheres asymmetrically?

A long-term intracarotid tube was implanted in 32 rats. Intracarotid injection of 4 different neuroleptics (haloperidol, cis- and trans-flupenthixol, clopenthixol and reserpine) elicited a typical posture with abduction of the limbs on one side and and adduction on the other. Only the neuroleptically-active cis-isomers of flupenthixol and clopenthixol provoked this dystonic reaction. The posture spontaneously vanished after 24 hr and could be antagonized with the anticholinergic biperiden. Sham injections of Ringer's solution and isotonic glucose proved to be behaviourally inert. These results indicate an asymmetric distribution of the drugs in this experimental procedure. Their implications concerning drug-induced and spontaneous dystonias as well as psythopathology are discussed.

Demonstration of monoamine oxidase-A and -B in the human brainstem by a histochemical technique.

The distribution of both monoamine oxidase subtypes, monoamine oxidase-A and -B, is demonstrated in brainstems from 16 humans by use of a histochemical technique. The results presented here, focus primarily upon the aminergic areas of the substantia nigra, the locus coeruleus and the raphe nuclei. While dopaminergic neurons of the substantia nigra revealed no staining for monoamine oxidase, noradrenergic neurons of the locus coeruleus stained positively with the monoamine oxidase-A substrate serotonin, and serotonergic neurons of the raphe nuclei were stained by the monoamine oxidase-B substrate beta-phenylethylamine. In addition, data are presented showing that glial cells stain predominantly for monoamine oxidase-B.

Plasma moclobemide and metabolites: lack of correlation with clinical response and biogenic amines.

The concentration of the reversible monoamine oxidase type-A (MAO-A) inhibitor moclobemide (Ro 11-1163) was determined by high pressure liquid chromatography (HPLC) in the plasma of 16 depressives treated with moclobemide. Moreover, the inhibitory potency of organic extracts of the plasma on a standard MAO-A preparation from human placenta was measured spectrophotometrically. The inhibitory potency significantly correlated with the HPLC results. However, it overestimated the concentration of moclobemide by one order of magnitude possibly due to the presence of yet unknown metabolites more active than moclobemide itself. These have already been suggested in view of the higher inhibitory potency of moclobemide ex vivo than in vitro. This new methodological approach might represent a comfortable alternative to HPLC procedures in pharmacokinetic studies on reversible MAO inhibitors. Plasma biogenic amines and their metabolites might be indicative of the biologic activity of moclobemide. Plasma homovanillic acid (HVA) decreased and norepinephrine (NE) increased under moclobemide, although insignificantly. There was no significant correlation between the plasma concentration of moclobemide as estimated by either method and the therapeutic response and the change of plasma HVA and NE.

Exonic variants of the GABA(B) receptor gene and panic disorder.

The enhancement of GABAergic neurotransmission has been closely linked to antipanic drug efficacy. This is the first study to investigate a putative association of exonic sequence variants of the human GABA(B) receptor 1 (GABA(B)R1) gene and susceptibility to panic disorder. Three DNA sequence variants in exons 1a1, 7 and 11 were assessed by polymerase chain reaction-based restriction fragment length polymorphism in a case-control study among patients with panic disorder with and without agoraphobia (DSM III-R criteria) and blood donors. There was no indication of an increased vulnerability to panic disorder or agoraphobia with respect to the allelic variants under study.

Design of clinical trials of antidepressants: should a placebo control arm be included?

There is no doubt that available antidepressants are efficacious and effective. Nevertheless, more effective drugs with improved tolerability are needed. With this need in mind, some protagonists claim that future antidepressants should be proved superior to, or at least as effective as, established antidepressants, making placebo control methodologically dispensable in clinical trials. Moreover, the use of placebo control is criticised as unethical because it might result in effective treatment being withheld. There are, however, a number of methodological reasons why placebo control is indispensable for the proof of efficacy of antidepressants. Comparing investigational antidepressants only with standard antidepressants and not placebo yields ambiguous results that are difficult to interpret, be it in superiority or equivalence testing, and this method of assessment requires larger sample sizes than those required with the use of placebo control. Experimental methodology not adhering to the optimal study design is ethically questionable. Restricting the testing of investigational antidepressants only to superiority over standard antidepressants is an obstacle to therapeutic progress in terms of tolerability and the detection of innovative mechanisms of action from which certain subgroups of future patients might benefit. The use of a methodology that requires larger samples for testing of superiority or equivalence is also ethically questionable. In view of the high placebo response rates in trials of antidepressants, placebo treatment does not mean withholding effective treatment. Accepting the necessity of the clinical evaluation of new, potentially ineffective antidepressants implicitly means accepting placebo control as ethically justified. Three- or multi-arm comparisons including placebo and an active reference represent the optimal study design.

A calcium antagonist for the treatment of depressive episodes: single case reports.

Preclinical studies indicate that a disturbed intracellular calcium ion homeostasis is involved in the pathophysiology of affective disorders. Therefore some calcium antagonists were investigated, especially in the treatment of the manic syndrome. In the present study the calcium antagonist nimodipine was used in 10 out-patients with single or recurrent depressive episodes. As a result the mean HAMD scores changed from 26.5 to 9.9 after the individual nimodipine administration. These single case reports suggest an effective new therapy strategy for the treatment of affective dysregulations and give rise to controlled clinical studies with calcium antagonists.

Isoelectric focusing of monoamine oxidase subtypes as identified by MAO inhibitors.

Monoamine oxidase from various human tissues from several individuals was labeled with [3H]pargyline and solubilized by means of Triton X-100 or Triton X-100 and urea. The specificity of the labeling was assessed using various selective, reversible and irreversible inhibitors as pharmacologic tools in competition experiments. The labeled material was submitted to isoelectric focusing on polyacrylamide gels according to one- and two-dimensional electrophoretic procedures and with fluorographic detection. While the differences in electrophoretic mobility of the two subtypes, MAO-A and MAO-B, could be replicated the subtypes showed identical although heterogeneous charges in isoelectric focusing. This contrasts with recent findings of clear differences in the primary structure of monoamine oxidase subtypes and thus needs further clarification.