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Biomedical subjects

Bruno Müller-Oerlinghausen

Publications and source records attributed to Bruno Müller-Oerlinghausen.

At least 19 recordsLinked to original sources
PubMed2006

Platelet 5-HT2A receptor binding and tryptophan availability in depression are not associated with recent history of suicide attempts but with personality traits characteristic for suicidal behavior.

BACKGROUND: Abnormalities in the serotonergic (5-HT) system have been implicated in the pathogenesis of suicidal behavior. Studies on peripheral serotonergic parameters as a measure for central serotonergic function in suicidal patients appear to be promising, yet failed to show a clear association with suicidality. The objective of this study was to elucidate the role of serotonergic blood parameters in depressed suicidal patients and to examine their usefulness as a potential biological marker for suicidality. A number of personality traits were assessed in order to provide a basis for a psychobiological model of suicidal behavior. METHODS: Depressed patients with a recent suicide attempt (SA; n = 59) were compared to those without history of suicide attempts (NSA; n = 28). 5-HT2A receptor binding in platelets and tryptophan/amino acid ratio in plasma were measured. Acute psychopathology and personality traits as well as characteristics of suicide attempts were assessed. RESULTS: There was no significant difference between SA and NSA in terms of peripheral serotonergic parameters as well as personality traits. However, the whole sample showed associations between certain personality traits and serotonergic platelet parameters. Furthermore, we observed a relation between suicidal ideation, lethality of suicide attempts and peripheral serotonergic markers. LIMITATIONS: The number of cases with data on peripheral markers is relatively low. The potential influence of antidepressant medication previous to study inclusion has to be taken into account. The study focussed on depressed patients only. CONCLUSIONS: Low serotonergic function is involved in the pathogenesis of suicidality, whereas the use of platelet 5-HT2A receptor activity and tryptophan availability as biological markers for suicidality in depressed patients could not be proven an appropriate tool. Alterations in the serotonergic system are associated with trait aggression and other character dimensions.

Adult↗
PubMed2005

Adverse reactions to anticoagulants and to antiplatelet drugs recorded by the German spontaneous reporting system.

According to their code of professional conduct, German physicians are obliged to report suspected cases of adverse drug reactions (ADRs) to the Drug Commission of the German Medical Association (AkdA). On the basis of an agreement between the German Medical Association and the Federal Institute for Drugs and Medical Devices (BfArM) a common pharmacovigilance database within the German spontaneous reporting system was created. A user-friendly application program developed in-house enables the user to conduct searches about reported ADRs covering a wide variety of questions within a short period of time. ADRs caused by anticoagulants and by antiplatelet drugs still belong to the most reported adverse events. The most frequently reported suspected drugs are heparins, followed by ticlopidine, phenprocoumon, acetylsalicylic acid, and clopidogrel. Bleeding complications are the most often described ADR symptoms of any anticoagulation therapy, especially of phenprocoumon and acetylsalicylic acid. Another serious ADR is heparin-induced thrombocytopenia or changes in blood counts (CBC) due to ticlopidine and clopidogrel. During the past few years a reduction in severe reactions, such as cerebral hemorrhage, especially with fatal outcome was detectable because of better clinical management of oral anticoagulant therapy and of adverse events concerning heparin.

Administration, Oral↗
PubMed2005

A multicenter study about Neurobiology of Suicidal Behavior: design, development, and preliminary results.

The subproject 1.5 "Neurobiology of Suicidal Behavior" is a multicenter study assessing peripheral parameters of the serotonergic, noradrenergic, and dopaminergic transmitter systems. Additionally, stress hormones and the lipid system as well as inhibitory and excitatory amino acids will be investigated. The different parameters are collected in cerebral spinal fluid (CSF), blood, and saliva. Patients with a depressive spectrum disorder with and without a suicide attempt (during the last three weeks) and being medication free for two weeks are included in the study. So far, 103 patients and controls have been recruited. The design and development of this project as well as interconnections with the others subprojects are described. Preliminary results about the stress hormone system and suicidality are presented.

Aggression↗
PubMed2005

The impact of lithium long-term medication on suicidal behavior and mortality of bipolar patients.

The article reviews the existing evidence and the concept of the anti-suicidal effect of lithium long-term treatment in bipolar patients. The core studies supporting the concept of a suicide preventive effect of lithium in bipolar patients come from the international research group IGSLI, from Sweden, Italy, and recently also from the U.S. Patients on lithium possess an eight- time lower suicide risk than those off lithium. The anti-suicidal effect is not necessarily coupled to lithium's episode suppressing efficacy. The great number of lives potentially saved by lithium adds to the remarkable benefits of lithium in economical terms. The evidence that lithium can effectively reduce suicide risk has been integrated into modern algorithms in order to select the optimal maintenance therapy for an individual patient.

Algorithms↗
PubMed2005

Long-term combination therapy versus monotherapy with lithium and carbamazepine in 46 bipolar I patients.

BACKGROUND: Despite wide clinical use of mood-stabilizer combinations for long-term treatment of patients with bipolar disorder, research on risks and benefits of this practice is limited. We found 14 small, usually brief, clinical trials of maintenance treatment with lithium plus carbamazepine. These trials suggest added benefit of combination treatment over use of either agent alone but also indicate the need for further studies. METHOD: In a post hoc analysis, we reviewed the course of 46 patients with DSM-IV-diagnosed bipolar I disorder identified as not improving during long-term monotherapy in a mood disorders clinic, comparing days per year hospitalized in 3 consecutive time periods: before prophylactic treatment, during monotherapy with lithium (N = 31) or carbamazepine (N = 15), and during their combined use (N = 46). Secondary outcome measures were rates of hospitalization, time to first recurrence of an affective episode, use of adjunctive treatments, and adverse effects. We compared outcomes with nonparametric bivariate methods and tested predictive factors by multiple regression. RESULTS: Subjects showed significant reductions in hospitalized days per year during combination therapy, averaging a decrease of 55.9% (p = .004). Among secondary outcomes, hospitalizations per year fell by 36.1%, and median time to recurrence nearly doubled during combination therapy. Rates of adverse effects increased 2.5-fold, compared with monotherapy, and use of adjunctive psychotropic agents increased by 21.9%. CONCLUSION: Combining lithium with carbamazepine yielded substantial benefit but more adverse effects.

Adult↗
PubMed2005

[Which evaluations are fundamental for medical training in pharmacotherapy?].

In Germany the medical profession is regulated by the state. The state defines the contents of the medical training within the clear boundaries of scientific medicine, which differs from science or biological medicine. The concepts and practice of many complementary therapeutic or diagnostic methods such as homeopathy do not fit within this state-set frame. Medical students, therefore, must be well acquainted with accepted scientific criteria by which we evaluate the value and validity of various therapeutic approaches. Lecturing pharmacotherapy implies posing questions such as: How do I come to statements which can be falsified? Within which constructs are they valid? Within which social context are they meaningful? Which aspects of reality must stay out of focus in order to reach such statements? This will help students to understand the frequent cognitive dissociations between doctors and patients as to concepts of disease and therapy, and the potential reasons why patients often prefer alternative medicine. Alternative methods can be openly discussed and evaluated on the basis of a critical methodology. For the sake of optimal patient care, "pluralistic" approaches towards setting valid therapeutic rules and standards are no alternative during the periods of basic medical training.

Complementary Therapies↗
PubMed2005

The AGNP-TDM Expert Group Consensus Guidelines: focus on therapeutic monitoring of antidepressants.

Therapeutic drug monitoring (TDM) of psychotropic drugs such as antidepressants has been widely introduced for optimization of pharmacotherapy in psychiatric patients. The interdisciplinary TDM group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) has worked out consensus guidelines with the aim of providing psychiatrists and TDM laboratories with a tool to optimize the use of TDM. Five research-based levels of recommendation were defined with regard to routine monitoring of drug plasma concentrations: (i) strongly recommended; (ii) recommended; (iii) useful; (iv) probably useful; and (v) not recommended. In addition, a list of indications that justify the use of TDM is presented, eg, control of compliance, lack of clinical response or adverse effects at recommended doses, drug interactions, pharmacovigilance programs, presence of a genetic particularity concerning drug metabolism, and children, adolescents, and elderly patients. For some drugs, studies on therapeutic ranges are lacking, but target ranges for clinically relevant plasma concentrations are presented for most drugs, based on pharmacokinetic studies reported in the literature. For many antidepressants, a thorough analysis of the literature on studies dealing with the plasma concentration-clinical effectiveness relationship allowed inclusion of therapeutic ranges of plasma concentrations. In addition, recommendations are made with regard to the combination of pharmacogenetic (phenotyping or genotyping) tests with TDM. Finally, practical instructions are given for the laboratory practitioners and the treating physicians how to use TDM: preparation of TDM, drug analysis, reporting and interpretation of results, and adequate use of information for patient treatment TDM is a complex process that needs optimal interdisciplinary coordination of a procedure implicating patients, treating physicians, clinical pharmacologists, and clinical laboratory specialists. These consensus guidelines should be helpful for optimizing TDM of antidepressants.

Antidepressive Agents↗
PubMed2004

Prophylaxis of schizoaffective disorder with lithium or carbamazepine: outcome after long-term follow-up.

OBJECTIVES: This study was conducted (1) to assess the prophylactic efficacy of lithium and carbamazepine in the maintenance treatment of schizoaffective disorder (SAD) with long-term follow-up, (2) to find predictors of the success or failure of prophylaxis, and (3) to search for differences in outcome between schizoaffective patients diagnosed according to either ICD-10 or DSM-IV. METHODS: Participating patients met the ICD-10 and/or DSM-IV criteria for schizoaffective disorder. Outcome was assessed using the Morbidity Index and time elapsed until the first recurrence during prophylaxis. Predictor variables were age at onset of illness, gender, and family history, as well as the following parameters prior to prophylaxis: time between onset of illness and start of prophylactic treatment (latency), severity of illness (hospitalization rate), number of hospital admissions and polarity of schizoaffective disorder (schizobipolar vs. schizounipolar). The time spent in the hospital per year was used to compare the course of illness before maintenance therapy to the time during maintenance therapy. Co-medication was taken into account. The clinical data during prophylaxis were ascertained prospectively. RESULTS: Forty-nine patients met the ICD-10 criteria for schizoaffective disorder, 34 of whom also met the DSM-IV criteria. All 49 patients underwent prophylactic therapy with either lithium (n=41) or carbamazepine (n=8) for an average of 6.8 years. After initiating prophylaxis, the number of days spent in the hospital declined dramatically from an average of 71 days to 11 days per year. No independent variable proved to be a consistent predictor of the course of treatment. In regard to the subgroup of patients diagnosed according to DSM-IV, no significant differences were observed when this subgroup was compared to the whole sample. LIMITATIONS: As this is a naturalistic study it does not allow for exact quantitative measures of effectiveness. CONCLUSIONS: This study is the first of its kind to investigate the efficacy of maintenance therapy in SAD over such an extended period of time. The results of the study show that lithium and carbamazepine appear to be highly effective in treating patients with schizoaffective disorder. However, it remains unclear how many schizoaffective patients will respond to mood stabilizer treatment and whether predictors of clinical relevance exist. In our sample, differences in the ICD-10 and DSM-IV diagnostic criteria for schizoaffective disorder were not related to significant differences in clinical outcome.

Adult↗
PubMed2003

Platelet-5HT uptake and gastrointestinal symptoms in patients suffering from major depression.

The objective of this study was to determine whether the presence of gastrointestinal symptoms, as defined by item 12 of Hamilton-Rating-Scale for Depression, is related to kinetic characteristics of platelet-5HT uptake in patients with major depression. The clinical picture of depression in patients with severe form of appetite loss with difficulties of eating (item 12 = 2) and weight loss was characterized by the combination of depressed mood with somatic symptoms of anxiety, sleep disturbances, decreased activity and the presence of nausea. The high frequency of relatively low Vmax and Km of 5HT uptake in this group (n = 12), all in the lower range of controls, resulted in significantly lower mean values compared with patients without gastrointestinal symptoms (n = 16; item 12 = 0) or 57 healthy subjects (Vmax = 1.36 +/- 0.27 vs. 2.14 +/- 0.85 vs. 2.05 +/- 0.74 nMol 5HT/10(9)plat.x min; Km = 382 +/- 68 vs. 467 +/- 94 vs. 492 +/- 123 nM respectively). Although our finding needs confirmation, it seems that in the research for serotonergic mechanisms in major depression, it makes sense to look at depressed patients with or without somatic symptoms separately. Based on findings in 5HT transporter knock-out mice (J. Neurosci. 15 (2001) 6348), we assume that the low apparent Vmax of platelet-5HT uptake reflects the low expression of 5HT transporter not only in platelets, but also in the gut mucosa and enteric serotonergic neurons, which probably increases the risk of typical gastrointestinal symptoms such as appetite loss and nausea occurring in some depressed patients.

Adult↗
PubMed2003

High platelet-serotonin uptake activity is associated with a rapid response in depressed patients treated with amitriptyline.

Based on the assumption that there is a biological basis behind the individual differences in the speed with which an antidepressant produces its therapeutic effects, we compared initial serotonin (5HT) uptake characteristics in platelets of rapid (2 weeks), slow (4 weeks) and non-responders in a group of 47 depressed patients who were treated with amitriptyline for at least 4 weeks. A response was defined as a reduction in the Hamilton Depression Rating Scale score of > or =50% from baseline. In 16 rapid responders, a significantly higher mean 5HT uptake efficiency (Vmax/Km) corresponded with a significantly higher 5HT uptake activity at a low, physiological substrate concentration in comparison with the 15 non-responders or the 16 slow responders (33.1+/-7.8 versus 25.5+/-7.7 versus 24.1+/-5.8 pMol [3H]-5HT/10(9) plat. x 5 min, respectively). The findings indicate that pre-treatment 5HT uptake activity contributes to the individual variability in response time to amitriptyline treatment.

Adult↗
PubMed2003

[Pharmacologic management of atrial fibrillation by specialists in internal medicine, cardiologists, and general practitioners (GPs) in Berlin].

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is the most frequent form of arrhythmia with a prevalence of 9%. During the last 15 years, there have been considerable changes of antiarrhythmic treatment. Aim of the present study was to investigate in which way general practitioners (GPs) as well as specialists in internal medicine and cardiologists in private practice are managing treatment of AF in the German capital. METHODS: A random sample of physicians practicing in all parts of Berlin were interviewed in written or oral form about their common attitudes to cardioversion, maintenance treatment, and anticoagulation in patients with AF. RESULTS: A very conservative, restrictive attitude in using internationally recommended antiarrhythmic drugs and anticoagulation was observed. Cardioversion is performed over too long time periods. CONCLUSIONS: The findings indicate uncertainty and lack of quality assurance in the management of AF and underline the necessity to follow the existing international guidelines more carefully.

Anti-Arrhythmia Agents↗
PubMed2003

Lithium augmentation increases post-dexamethasone cortisol in the dexamethasone suppression test in unipolar major depression.

Although considerable evidence exists on the efficacy of lithium as an augmenting agent in refractory depression, the underlying neurobiology of this phenomenon is unknown. In patients with major depression, changes of the hypothalamic-pituitary-adrenocortical (HPA) system have been detected by means of the dexamethasone suppression test (DST), when administered during treatment with tricyclic antidepressants. We investigated whether the DST also reveals alterations of the HPA system during lithium augmentation. We also sought to identify whether response to lithium augmentation can be predicted with the DST. Twenty-five patients with unipolar major depression, who did not respond to an adequate antidepressant monotherapy of at least 4 weeks, were measured for basal (pre-dexamethasone, 0800h) cortisol and ACTH levels and were administered the DST the day before initiation of lithium augmentation treatment. The same neuroendocrine procedures were repeated after 3 to 4 weeks. Criteria of response to lithium augmentation, defined as a reduction of the Hamilton Depression Rating Scale (HDRS17) score by > or =50% and an end point score of 9 or less, were determined by weekly HDRS ratings. The DST revealed a statistically significant increase of the post-dexamethasone cortisol values (P = 0.021) and an increase in the post-dexamethasone ACTH values (P = 0.051) during lithium augmentation as compared to pre-treatment baseline evaluations. The pre-dexamethasone hormone values were unchanged. The number of non-suppressors at baseline was one and increased to three at follow-up. Results of DST did not predict response to lithium augmentation, which occurred in 40% of subjects. Results suggest that lithium augmentation increases HPA system activity, as indicated by the increase of post-dexamethasone cortisol and ACTH levels measured by the DST. This is in contrast to the established decline of HPA system activity during treatment with tricyclic antidepressants.

Adolescent↗
PubMed2003

The antisuicidal and mortality-reducing effect of lithium prophylaxis: consequences for guidelines in clinical psychiatry.

The suicide-related mortality among patients with affective disorders is approximately 30 times higher, and overall mortality 2 to 3 times higher, than suicide-related mortality in the general population. Lithium has demonstrated possibly specific antisuicidal effects apart from its prophylactic efficacy: it significantly reduces the high excess mortality of patients with affective disorders. To date, suicide-prevention effects have not been shown for antidepressant or anticonvulsant long-term treatment. Clozapine appears to reduce the suicide rate in schizophrenia patients. Against this background, guidelines and algorithms for selecting an appropriate prophylactic strategy for affective disorders should consider the presence of suicidality in patient history. Appropriate lithium prophylaxis prevents approximately 250 suicides yearly in Germany, although lithium salts are infrequently prescribed within the National Health Scheme (specifically, to 0.06% of the population). Rational treatment strategies most likely would demand that prescription rates be about 10 times higher.

Algorithms↗
PubMed2003

Effectiveness and outcome predictors of long-term lithium prophylaxis in unipolar major depressive disorder.

OBJECTIVE: To determine the effectiveness of lithium prophylaxis in unipolar major depressive disorder (MDD) and to identify predictors of outcome including comedication. METHODS: In this long-term naturalistic study, clinical data from 55 patients with MDD (DSM-III-R) were collected prospectively in an outpatient clinic specializing in the treatment of affective disorders. OUTCOME MEASURES: Change in hospital admission rate (number and duration) during prophylaxis compared with the period before prophylaxis, Morbidity-Index during prophylaxis and time to first recurrence after initiation of lithium treatment. RESULTS: During an average follow-up period of 6.7 years, a significant decline in the number of days spent in hospital (p<0.001; 52 d/yr less; 95; CI 31-73 d) and a low Morbidity-Index (mean 0.07) was observed. Only in 6 patients did medication have to be changed because of side-effects (n=4) or a lack of efficacy (n=2). None of the independent variables we analyzed proved to be important in predicting the outcome of lithium prophylaxis. Comedication was necessary in 21 patients. The overall outcome of their prophylactic treatment, however, did not differ from the group that did not receive comedication in the symptom-free intervals. CONCLUSIONS: The results of this study, with its long observation period and the inclusion of comedication as a confounding variable, indicate that lithium is a potent prophylactic agent for unipolar MDD in a naturalistic setting. In contrast to the findings of others, age was not associated with the outcome of prophylaxis, and latency did not predict outcome. Contrary to doubts that have been raised in recent years with regard to the effectiveness of lithium in everyday clinical practice, lithium appears to be a safe and potent alternative to antidepressants.

Adult↗
PubMed2002

Suicidality, impulsivity and aggression--is there a link to 5HIAA concentration in the cerebrospinal fluid?

In biological suicide research, low cerebrospinal fluid-5-hydroxyindolacetic acid (CSF-5HIAA) concentrations have been associated with suicidality, aggression and impulsivity. However, it frequently appears that the interpretation of existing study results is flawed. The analysis of various published findings suggests that contaminating factors like impulsivity or depressive symptoms in suicide attempters are often not taken into consideration at the time of suicide. The seemingly 'robust' association of low CSF-5HIAA concentration with 'suicidality' and 'aggression' is in fact rather weak. Reported associations of subgroups of suicidal behavior (e.g. violent suicide attempts) with low CSF-5HIAA concentrations are likely to represent somewhat premature translations of findings from studies that have flaws in methodology. Furthermore, the perception of 'suicidal behavior' as autoaggressive behavior or inwardly directed aggression in the view of the authors may not be useful in biological suicide research. The construct of aggressivity is insufficiently defined, resulting in difficulties to interpret empirical data. Some evidence exists, however, that reduced CSF-5HIAA concentrations might be related to certain depressive symptoms and changes in impulsivity. More carefully designed studies are required to overcome the existing methodological shortcomings.

Aggression↗
PubMed2002

Correlation between serotonin uptake in human blood platelets with the 44-bp polymorphism and the 17-bp variable number of tandem repeat of the serotonin transporter.

Dysfunctions of the central serotonin (5-hydroxytryptamine, 5-HT) system seem to be associated with psychiatric disorders such as schizophrenia or depression. Previous studies suggested that a 44-bp insertion/deletion polymorphism of the 5-HT transporter (5-HTT) promoter region might influence the transcriptional activity of the 5-HTT gene, and the insertion variant resulted in increased 5-HTT expression and 5-HT uptake. Moreover, a 17-bp variable number of tandem repeat (VNTR) polymorphism of the second intron may act as a transcriptional regulator with allele dependent differential enhancer-like properties. Since the 5-HTT of human platelets shares many properties with the transporter of neural tissue, platelets are widely used as a surrogate tissue source, possibly reflecting central 5-HT metabolism. Therefore, we investigated the impact of the 44-bp polymorphism and the 17-bp VNTR for 5-HT uptake in platelets of 50 male subjects. We found no significant effect of the 44-bp polymorphism and of the 17-bp VNTR on maximum rate (Vmax) of 5-HT uptake. However, individuals homozygous for the 5-HTT intron 2 allele with 12 repeats (STin2.12) of the 17-bp VNTR appeared to have lower affinity of 5-HT uptake than individuals heterozygous for the STin2.10/STin2.9 allele. This was also observed for the combined analysis of both polymorphisms. In conclusion, we found no association between the different genotypes of the 44-bp polymorphism and the 17-bp VNTR and maximum rate of 5-HT uptake into platelets.

Adult↗
PubMed2002

Bipolar disorder.

Bipolar, or manic-depressive, disorder is a frequent, severe, mostly recurrent mood disorder associated with great morbidity. The lifetime prevalence of bipolar disorder is 1.3 to 1.6%. The mortality rate of the disease is two to three times higher than that of the general population. About 10-20% of individuals with bipolar disorder take their own life, and nearly one third of patients admit to at least one suicide attempt. The clinical manifestations of the disease are exceptionally diverse. They range from mild hypomania or mild depression to severe forms of mania or depression accompanied by profound psychosis. Bipolar disorder is equally prevalent across sexes, with the exception of rapid cycling, a severe and difficult to treat variant of the disorder, which arises mostly in women. Because of the high risk of recurrence and suicide, long-term prophylactic pharmacological treatment is indicated. Lithium salts are the first choice long-term preventive treatment for bipolar disorder. They also possess well documented antisuicidal effects. Second choice prophylactic treatments are carbamazepine and valproate, although evidence of their effectiveness is weaker.

Anticonvulsants↗