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Biomedical subjects

B Müller-Oerlinghausen

Publications and source records attributed to B Müller-Oerlinghausen.

At least 19 recordsLinked to original sources
PubMed2006

Peripheral serotonergic markers in acutely suicidal patients. 1. Comparison of serotonergic platelet measures between suicidal individuals, nonsuicidal patients with major depression and healthy subjects.

BACKGROUND: A robust association between "suicidality" and deficits of the serotoninergic neurotransmission has been claimed in the past. However, many studies having investigated the relationship between suicidality and peripheral indicators of serotoninergic neurotransmission suffer from considering only one or a very small number of potentially useful serotoninergic parameters, whereas a synoptic multidimensional approach appears to be more appropriate. Furthermore, the psychiatric context within which suicidal behaviour occurs should be considered when interpreting biochemical findings of patients with suicidal ideation and suicide attempts. METHODS: In the present study 5 peripheral serotonergic markers, (platelet 5HT concentration, 5HT uptake activity, 5HT(2A) receptor binding characteristics, MAO-B activity and tryptophan concentration in plasma) were assessed simultaneously. Of the 60 acutely suicidal inpatients (ICD-10: F43.xx, n = 52; F31/32/33, n = 8), 45 were suicide attempters. Data of 28 nonsuicidal patients with major depression (F31, n = 4; F32, n = 14; F33, n = 10) and 123 healthy volunteers represented the control groups. RESULTS: Mean platelet 5HT concentration was significantly lower in suicidal inpatients when compared to nonsuicidal depressed patients, but did not differ from the figure in healthy subjects. Nonsuicidal depressed patients showed significantly higher mean platelet-5HT concentration than healthy controls. Mean V(max) of 5HT uptake in washed platelets, but not in platelet-rich plasma, was significantly higher in suicidal patients than in healthy controls, not, however, when compared to nonsuicidal depressed patients. Mean K(D) for the platelet 5HT(2A) receptor and MAO-B activity were significantly lower in suicidal patients as compared to nonsuicidal depressed patients and healthy controls. The observed differences in peripheral serotonergic markers between groups are partially due to a significant gender effect. A lower MAO-B activity was observed only in suicidal females, while the higher V(max) of 5HT uptake in washed platelets of suicidal patients was due to suicidal males. CONCLUSIONS: In view of conflicting observations made by other authors and the present findings on suicidal patients with adjustment disorder it remains doubtful whether and if so to which extent platelet studies can provide valid information on serotonergic mechanisms related to suicidal behaviour.

Adult↗
PubMed2004

[Effects of slow-stroke massage as complementary treatment of depressed hospitalized patients].

BACKGROUND AND OBJECTIVE: Among methods of complementary treatment of depression, massage plays an important role, at least in the U.S.A. Although there are some pointers to the antidepressive and anxiolytic action of slow-stroke massage in various randoms studies of patient cohorts, there have been no controlled trials of depressed hospitalized patients. PATIENTS AND METHODS: 32 depressed patients (24 women, 8 men; average 48 years - coveringthe entire spectrum of affective disorders listed in the ICD but without comorbidity in axis 2) with a minimum BRMS score of 16,7 - were included in the study. The randomized cross-over trial involved three massage sessions at set times (M) and sessions in two control groups (C) (relaxation and perception) lasting for 60 min 2-3 days apart. Under the control conditions there was no touching. The effects of depression-specific variables (e.g. mood, drive, abnormal cognition, as well as typical progress variables of the slow-stroke massage (bodily awareness, general state of health, etc.) were measured by both the patients' own assessment and that of an independent observer. RESULTS: Under condition of both M and C, comparison of before and after effects, there was not only the primarily postulated mood-enhancing effect, but also some very marked changes in almost all dimension, the mean improvement ratio under M often being stronger than under C. After Bonferroni correction for multiple tests, the statistical significance there remained the stronger effect of M in four dimensions (global tenseness, restlessness, depressed mood, neck/shoulder tension). The intensive effect of M compared with C was confirmed by both female and male patients regarding the answers to various open questions. CONCLUSIONS: Slow-stroke massage is suitable for adjuvant acute treatment of patients with depression. It is very readily accepted also by very ill patients. In relation to the skin as an organ that aids identity, non-hedonic depressed patients are able to recognize the sensory quality of therapeutic touching as a positive stimulus. In view of the latent period of many weeks and the only moderate efficacy of antidepressants, the described complementary method, which does not require physiotherapeutic training, should be more often applied in both a hospital and general practice setting.

Complementary Therapies↗
PubMed2004

Serotonergic platelet markers of suicidal behavior--do they really exist?

BACKGROUND: Abnormal changes in platelets used as peripheral markers of central serotonergic functions are said to be associated with suicidality and depression, but this association has not been supported by consistent findings. AIM: This review based on selected, often quoted publications in this area focuses firstly, on obviously contradictory findings and, secondly, on potential methodological flaws explaining these discrepancies. RESULTS: The platelet 5-HT transporter has been found to have an inconsistent association with suicidality; furthermore, the specificity of imipramine for the 5-HT transporter is most likely low, since the number of platelet impramine binding sites has not been reliably associated with platelet serotonin uptake (Vmax). Significant changes of platelet serotonin content in suicidal individuals, as described in various studies, are most likely due to washout periods that are too short to eliminate the effects of a previous drug intake, or, in violent suicide attempters, due to blood loss and dilution. Similar methodological shortcomings might account for an often-reported elevated number of platelet 5-HT(2) receptor binding sites in suicidal individuals. In many studies, the results have not been sufficiently controlled for drug effects on platelet 5-HT(2) receptors, and associations of platelet 5-HT(2) binding with selective classifications of suicidal behavior are often generalized as further evidence for an association of platelet 5-HT(2) receptors with 'suicidality'. Finally, changes in platelet MAO-B-activity in suicidal patients have not been reproducibly found, and the impact of smoking on MAO-B activity has not been controlled in any studies. CONCLUSIONS: Methodological flaws such as small sample sizes, insufficient matching criteria for controls, use of inadequate ligands in binding experiments, nonconsideration of comorbidity etc. and considerable methodological differences between studies limit their validity and comparability. It does not seem possible, at present, to integrate published findings and concepts into a plausible biological model of suicidality.

Biomarkers↗
PubMed2004

Time experience and time judgment in major depression, mania and healthy subjects. A controlled study of 93 subjects.

OBJECTIVE: Studies on the time sense of depressed patients have revealed inconsistent results. Manic patients have been almost neglected. METHOD: Patients with a major depressive episode (n = 32), or a manic episode (n = 30) (both Diagnostic and Statistical Manual of Mental Disorders-IV, Mini-International Neuropsychiatric Interview-confirmed), and 31 healthy controls were included. The subjective time experience was assessed by a visual analog scale (VAS), the objectively measurable time judgment abilities by the Chronotest, a computer program developed for this study, consisting of time estimation and time production tasks. RESULTS: Controls reported a balanced, manic patients an enhanced, and depressive patients a slowed experience of time flow in the VAS (P < 0.001). In the time judgment tasks, however, both depressed and manic patients showed time overestimation for the longer time spans (P < 0.008). CONCLUSION: This largest study on time sense in manic patients confirmed results of a divergent alteration of time experience in depressive and in manic patients but revealed an uniform time overestimation by both patient groups in time judgment tasks.

Analysis of Variance↗
PubMed2004

Blood dyscrasias induced by psychotropic drugs.

Drugs can cause a variety of blood dyscrasias, e. g., by interfering with hematopoiesis in the bone marrow or damaging mature blood cells by antibodies. Although numerous reports on the risks of adverse hematological effects associated with psychotropic drugs have led to stringent monitoring requirements for some compounds, particularly neuroleptics, it is still difficult to estimate the true prevalence of such risks. Sixteen episodes of thrombocytopenia, 63 of neutropenia, 22 of agranulocytosis, 4 episodes of severe neutro- and thrombocytopenia, and 2 of pancytopenia were documented by the drug safety program in psychiatry AMSP (Arzneimittelsicherheit in der Psychiatrie) in a population of 122,562 patients between 1993 and 2000. All cases were related to the epidemiological data provided for this population and systematically analyzed as regards history of medication, co-medication, and the clinical course. Putative risk rates for the main groups of medications and a number of drugs could be estimated with this database. Most changes in the white blood cell counts, which were rated as probably or definitely drug-induced, were attributed to clozapine (0.18 % of patients exposed), carbamazepine (0.14 %) and perazine (0.09 %). In patients on newer atypical neuroleptics, we documented neutropenia assumed to be probably or definitely drug-related in five patients during treatment with olanzapine and in one case with risperidone. In all five olanzapine-related cases, the drugs were the sole cause of the adverse drug reactions. All surveyed patients who received clozapine showed no difference in age and gender distribution from those who developed hematological changes. Incidences of hematological changes for antidepressants were much lower (about 0.01 %). Although the methodological accuracy of these findings has to be critically discussed these data could be of considerable clinical relevance and should be helpful in making clinical treatment decisions.

Adult↗
PubMed2004

The AGNP-TDM expert group consensus guidelines: therapeutic drug monitoring in psychiatry.

Therapeutic Drug Monitoring (TDM) is a valid tool to optimise pharmacotherapy. It enables the clinician to adjust the dosage of drugs according to the characteristics of the individual patient. In psychiatry, TDM is an established procedure for lithium, some antidepressants and antipsychotics. In spite of its obvious advantages, however, the use of TDM in everyday clinical practice is far from optimal. The interdisciplinary TDM group of the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) has therefore worked out consensus guidelines to assist psychiatrists and laboratories involved in psychotropic drug analysis to optimise the use of TDM of psychotropic drugs. Five research-based levels of recommendation were defined with regard to routine monitoring of plasma concentrations for dose titration of 65 psychoactive drugs: (1) strongly recommended, (2) recommended, (3) useful, (4) probably useful and (5) not recommended. A second approach defined indications to use TDM, e. g. control of compliance, lack of clinical response or adverse effects at recommended doses, drug interactions, pharmacovigilance programs, presence of a genetic particularity concerning the drug metabolism, children, adolescents and elderly patients. Indications for TDM are relevant for all drugs either with or without validated therapeutic ranges. When studies on therapeutic ranges are lacking, target ranges should be plasma concentrations that are normally observed at therapeutic doses of the drug. Therapeutic ranges of plasma concentrations that are considered to be optimal for treatment are proposed for those drugs, for which the evaluation of the literature demonstrated strong evidence. Moreover, situations are defined when pharmacogenetic (phenotyping or genotyping) tests are informative in addition to TDM. Finally, practical instructions are given how to use TDM. They consider preparation of TDM, analytical procedures, reporting and interpretation of results and the use of information for patient treatment. Using the consensus guideline will help to ensure optimal clinical benefit of TDM in psychiatry.

Drug Monitoring↗
PubMed2004

Therapeutic monitoring of psychotropic drugs: an outline of the AGNP-TDM expert group consensus guideline.

TDM of psychotropic drugs is widely used, but there is little consensus regarding its optimal use in the clinical context. This prompted a multidisciplinary group comprised of clinical biochemists, clinical pharmacologists, and psychiatrists of the AGNP (Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie) to provide a consensus guideline. This will allow clinical psychiatrists, practitioners, and laboratory directors involved in psychopharmacotherapy to optimize TDM of antidepressants, antipsychotics, and opioid substituents. Recommendations are also given on the combined use of TDM and pharmacogenetic tests.

Drug Monitoring↗
PubMed2003

How should findings on antisuicidal effects of lithium be integrated into practical treatment decisions?

Beyond its prophylactic efficacy lithium has demonstrated possibly specific antisuicidal effects. Lithium significantly reduces the high excess mortality of patients with affective disorders. Appropriate lithium prophylaxis prevents ca. 250 suicides per year in Germany although lithium salts are prescribed within the National Health Scheme at low frequency (0.06% of the population). Rational treatment strategies most likely would demand for about 10 times higher prescription rates. Guidelines and algorithms for selecting an appropriate prophylactic strategy in affective disorders should take into consideration the suicide risk of an individual patient.

Algorithms↗
PubMed2003

Does prophylaxis-delay in bipolar disorder influence outcome? Results from a long-term study of 147 patients.

OBJECTIVE: This study investigated the impact of latency (the time between illness onset and initiation of prophylactic treatment) on the outcome of prophylaxis in bipolar disorders. METHOD: The effect of prophylaxis delay (latency) on the course of illness was assessed in 147 patients. Dependent variables were: reduction of days spent in the hospital (prior to vs. during prophylaxis), time to first recurrence, and Morbidity-Index during prophylaxis (lithium or carbamazepine). Latency and other independent variables were tested using a multivariate approach. RESULTS: Latency (9.3 years on average) had no significant effect on the subsequent response. Illness severity prior to prophylaxis, however, did predict the relative response. The course of illness during treatment could not be predicted by any one factor. CONCLUSION: The delay in initiating prophylaxis appears to have no influence on prophylaxis outcome. Instead, those whose illness was more severe were treated earlier and these patients subsequently showed a relatively greater response. If severity is not controlled for as part of the analysis, latency may be mistaken as an important predictor for response.

Adult↗
PubMed2003

Predictors of therapeutic effects in amitriptyline treatment--1. Plasma drug levels.

OBJECTIVE: To analyze the spectrum of relationships between clinical effects of amitriptyline (At) treatment after 2 and 4 weeks (wks) and plasma levels of At, nortriptyline (Nt), At+Nt, demethylation rate of At, treatment modalities, age, and gender. METHODS: Patients with major depression (ICD 10: F31-F33) and a HAMD-21 total score of 15-41 received At on a dosage schedule chosen by the doctor for at least 4 wks. Plasma drug levels were assessed at baseline and at wks 2 and 4. RESULTS: Of the 58 patients enrolled in the study, 47 (15males, 32 females) were eligible for statistical analysis. An early response by wk 2 (decrease in HAMD-21 score of at least 50 % from baseline) was observed in 34.0 % of patients, and after 4 wks, the response rate was 63.8 % (males 86.6 %, females 53.1 %). There was a low, negative, and significant correlation between percent reduction in HAMD and steady state At concentration only at wk 2 (n = 47 r Sp. = -0.306 p < 0.05). However, the correlation was dependent on the degree of At demethylation and treatment modalities. A ratio of Nt/At >1 was observed in 23 patients; of these, 11 (47.8 %) were non-responders by wk 4. A low rate of demethylation (Nt/At </= 1) in 24 patients was associated with a lower frequency of non-response (6/24 = 25.0 %). In the latter subgroup, the 2-wk At plasma concentration varied between 20 and 240 ng/ml, and all patients with </= 110 ng At /ml were responders by wk 4. On the other hand, in the Nt/At >1 group, the non-responders were distributed in the whole range of observed At plasma concentrations (20-150 ng/ml). Only in patients with Nt/At </= 1 and constant doses from wk 1 to wk 4 (n = 14) was a strong, linear, and negative correlation between percent reduction in HAMD and plasma At, Nt, or At+Nt concentrations found for the 2-wk data (r Sp. = -0.754, -0.716, and -0.732, respectively), but not after 4 wks. CONCLUSIONS: The frequently assumed dependence of clinical effects on plasma drug levels is not a simple function. There most likely exist different patterns of relationships with partially unknown backgrounds. The ratio Nt/At may become a discriminating variable in future studies on the nature of plasma level-therapeutic effect relationship in At treatment of major depression.

Adult↗
PubMed2002

Physicians' knowledge and attitudes regarding the spontaneous reporting system for adverse drug reactions.

The spontaneous reporting system (srs) is the most important early warning system of adverse drug reactions. As there is serious under-reporting we studied the respective knowledge and attitudes of two samples of physicians in Germany. Five hundred randomly sampled physicians and 815 physicians who had actually reported an ADR were included; the response rate to the mail questionnaire was 51.4 and 43.9%, respectively; 61.3% said to have reported at least one case in their life. As many as 75-85% of physicians said never to have sent an ADR report to the governmental or professional reporting systems. Reporting to pharmaceutical companies, on the other hand, has been substantially better. Sixty-eight and two-tenths percent indicated to have suspected an ADR without reporting it. Major reasons for not reporting were: ADR well known (75.6%), too trivial (71.1%), causality uncertain (66.3%). The ADR with the highest probability of being reported were serious unknown adverse reactions of a new drug (81.1%) or an established drug (72.9%) and serious known reactions to a new drug (65.2%). Almost 20% of the physicians admitted to not know the spontaneous reporting system and 30% to not know how to report; 54% would rather report an ADR if therapeutic advice was offered. The results indicate that the traditional ways of advertising the srs and communicating with physicians could be improved. Proactive services and professional marketing of srs are needed to reduce underreporting.

Adult↗
PubMed2002

Concretism in biological suicide research -- are we eating the menu instead of the meal? Some thoughts on present research strategies.

Research into serotonergic parameters associated with suicidal behaviour has resulted in many inconsistent and ambiguous findings. In this mini-review, we have tried to name some examples of methodological and conceptual vagueness and pitfalls in biological suicide research. The existing literature indicates various critical issues considered when interpreting existing data in this area: -- The 'suicidality' construct is not useful in biological suicide research. Autodestructive tendencies mostly occur in suicide completers and are probably not found in many suicide attempters and individuals with suicidal thoughts. No consistent association has been found between suicide intent and injury, suicide intent and suicide risk, choice of suicide method (violent vs. non-violent) and suicide risk, suicidal thoughts or attempted suicide. No close relationship between different degrees and different forms of suicidal behaviour has yet been demonstrated with any degree of consistency. According to many studies, serotonergic markers do not correlate with the various qualities and intensities of suicidal behaviour. -- The association between suicidality and impulsivity or aggression is weak. There probably is a disturbance in impulse and aggression control, but only in a subgroup of'suicidal' patients. -- It might be misleading to use nosological constructs of depression in order to characterize suicidal individuals in biological suicide research. Biological variables might be associated with specific depressive symptoms, but not with some nosological construct or the sum score of a depression rating scale. -- The alleged association between peripheral and central serotonergic parameters is based on assumptions for which there is insufficient proof. Several studies indicate that there is no correlation between changes in central and peripheral serotonergic parameters. The mechanism of changes of peripheral serotonergic parameters is not sufficiently understood.

Aggression↗
PubMed2001

Arguments for the specificity of the antisuicidal effect of lithium.

UNLABELLED: Affective disorders are characterized by first a high recurrence risk, second a 30-50 times increased suicide risk and third a 2- to 3 times increased overall mortality. In contrast to a populistic belief no scientific evidence exists that antidepressant treatment, particularly long-term treatment, could reduce the the risk of suicidal acts in depressive patients with a history of suicide attempts. Data, however, coming from international, systematic, retrospective analyses of well-documented long-term courses of illness in reliably diagnosed patients, and from a large national, prospective long-term trial on the prophylactic efficacy of lithium versus carbamazepine and amitriptyline has accumulated in the last 10-15 years strongly supporting a (possibly specific) antisuicidal effect of lithium. The large collaborative IGSLI study (International Group for the Study of Lithium-treated Patients) covering 5,616 patient years clearly showed that adequate long-term lithium treatment significantly reduces and even normalizes the excess mortality of patients with affective disorders. A metaanalysis on 17,000 patients pooled from 28 studies demonstrated that the rate of suicidal acts is 8.6 fold higher in patients without lithium as compared to those with regular lithium treatment. A post-hoc analysis of a large multicenter, controlled long-term trial found no suicidal acts in 146 patients randomized to lithium compared to 9 suicidal acts in 139 patients randomized to carbamazepine. Reanalysis of the data from the IGSLI study supports the concept of the specificity of lithium, i.e., evidence could be provided that lithium also reduces suicidal behavior in patients who do not benefit from the lithium treatment in terms of episode reduction. CONCLUSION: Lithium has to be considered as a first line mood stabilizer in affective disorders, particularly in patients with a history of suicide attempts. Extreme caution is required when lithium is discontinued or a patient is switched to another mood stabilizer, because such a patient might have been protected against suicidal impulses in spite of an incomplete response as to the number and quality of depressive/manic episodes.

Antimanic Agents↗
PubMed2001

Predictors of response to lithium augmentation in tricyclic antidepressant-resistant depression.

BACKGROUND: The efficacy of lithium augmentation in therapy-resistant depression has been shown in a series of well-designed, placebo-controlled studies. However, little is known about the predictors of a good response to this treatment strategy. METHODS: We retrospectively examined the predictive value of 20 demographic, clinical, biochemical and endocrinological variables using a two-step logistic regression. Seventy-one in-patients with depression refractory to tricyclic antidepressants had received lithium augmentation as part of a standardised treatment protocol. RESULTS: Within 4 weeks 37 patients (52%) responded to lithium augmentation. Five variables with predictive value were found. Responders were more severely depressed according to the Bech-Rafaelsen Melancholia Scale. The duration of their index episode was shorter. Triiodothyronine serum levels were lower and neuroleptic co-medication and co-diagnosis of personality disorder were less frequent. LIMITATIONS: This was an open, retrospective study. CONCLUSIONS: Severity of depression is a predictor of response to lithium augmentation. This result conflicts with recent studies but is similar to results found in studies of other pharmacological antidepressant strategies.

Adult↗
PubMed2001

Serotonin transporter polymorphisms: no association with response to antipsychotic treatment, but associations with the schizoparanoid and residual subtypes of schizophrenia.

The human serotonin transporter gene (5-HTT) demonstrates two polymorphisms with possible functional impact: a 44-bp insertion/deletion polymorphism of the promoter region and a 17-bp variable number of tandem repeat polymorphism (VNTR) in intron 2 (STin2). Such genetic polymorphisms in the serotoninergic system may increase the susceptibility to schizophrenia or may serve as predictors of therapeutic response. We therefore analyzed these polymorphisms as susceptibility factors for schizophrenia by comparison of 684 schizophrenic inpatients with 587 healthy controls. We furthermore compared the therapeutic outcome of schizophrenic patients differentiated by the 5-HTT genotypes. Schizo-affective patients were more frequently homozygous for the 44-bp insertion allele (Odds ratio, OR: 1.6, 95% confidence interval, CI: 1.1--2.3, P < 0.03) than were all other schizophrenic patients and controls. The 17-bp VNTR alleles found were: STin2.7, 9, 10, and 12. Sequence analysis revealed seven different sequence motifs with an invariable arrangement. Patients with schizo-paranoid schizophrenia were more frequently homozygous for the STin2.12 allele than were controls (OR: 1.4, CI: 1.1--1.8, P < 0.007) and all other schizophrenic patients (OR: 1.6, CI: 1.2--2.3). The STin2.9 allele represented a risk factor for the residual subtype of schizophrenia (OR: 6.4, CI: 2.5--16.2, P < 0.001). On the basis of global clinical impressions, as well as measurements with the positive and negative syndrome scale we found no association of the polymorphisms with therapeutic response. In conclusion, the 44-bp polymorphism may be associated with the schizo-affective and the 17-bp VNTR with the residual and schizo-paranoid subtype of schizophrenia, findings which require further biochemical and epidemiological confirmation.

Adolescent↗
PubMed2001

Does lithium exert an independent antisuicidal effect?

AIM OF STUDY: Recent investigations have indicated that adequate lithium treatment lowers the suicide mortality associated with affective illness. One important question is whether the mechanism by which lithium prophylaxis may be effective in prolonging survival can be explained exclusively in terms of successful protection against the recurrence of depressive episodes, or whether one should consider an independent anti-suicidal factor. METHODS: We investigated a group of high-risk patients with recurrent affective disorders (n = 167) who had committed one or more suicide attempts before the start of lithium prophylaxis within a collaborative project by the International Group for the Study of Lithium Treated Patients (IGSLI). According to their recurrence-related response to long-term lithium prophylaxis, patients were classified into three groups: excellent (n = 45), moderate (n = 81) and poor responders (n = 41). Only depressive episodes resulting into hospitalisation were considered. A marked reduction in the number of suicide attempts was observed in the excellent lithium responders. However, we also found that over 80% of moderate responders and nearly 50% of poor responders did not exhibit any further suicidal behaviour during lithium treatment. Furthermore, we could demonstrate a significant reduction of suicide attempts per year as compared to a corresponding pre-lithium period in all three groups (0.10 vs. 0.33, 0.06 vs. 0.27, 0.02 vs. 0.26). There were four suicides in this high-risk group, corresponding to a suicide-related standardised mortality ratio (SMR) of 13.7. This contrasts sharply with an expected suicide SMR of approx. 100 in this population. Suicide risk was not related to the recurrence-preventing effect. CONCLUSION: The reduction in suicide attempts, in both responders and non-responders, indicates that lithium possesses a specific anti-suicidal effect besides its mood-stabilising property.

Adult↗