Bruno Pfuhlmann

University of Wuerzburg | JMU

Abnormal movements are intrinsic to some forms of endogenous psychoses. Spontaneous dyskinesias are observed in drug-naïve first-episode patients and at-risk subjects. However, recent descriptions of spontaneous dyskinesias may actually represent the rediscovery of a more complex phenomenon, ‘parakinesia’ which was described and documented in exten...

Current classification systems use the terms “catatonia” and “psychomotor phenomena” as mere a-theoretical descriptors, forgetting about their theoretical embedment. This was the source of misunderstandings among clinicians and researchers of the European collaboration on movement and sensorimotor/psychomotor functioning in schizophrenia and other...

Objetivo: La Monitorización Terapéutica de Drogas (llamada en inglés TDM: therapeutic drug monitoring) combina la cuantificación de las concentraciones de medicamentos en la sangre, la interpretación farmacológica y las directrices de tratamiento. La TDM introduce una herramienta de medicina de precisión en una época de gran conciencia de la necesi...

While the ICD-DSM paradigm has been a major advance in clinical psychiatry, its usefulness for biological psychiatry is debated. By defining consensus-based disorders rather than empirically driven phenotypes, consensus classifications were not an implementation of the biomedical paradigm. In the field of endogenous psychoses, the Wernicke-Kleist-L...

Erratum zu: Nervenarzt 2018 10.1007/s00115-018-0643-9 Im Originalbeitrag ist Tab. 2 leider fehlerhaft. Für die Substanzen Carbamazepin und Valproat wurde im Originalbeitrag ein Empfehlungsgrad zur Anwendung des therapeutischen Drug-Monitorings (TDM) von 2 (empfohlen) angegeben. …

Lithium is a well established therapeutic agent in the treatment of uni- and bipolar affective disorders. Angiotensin-converting enzyme (ACE) inhibitors are the most frequently used class of drugs in the treatment of cardiovascular diseases. Combination therapy with both may be considered in clinical practice on occurrence of arterial hypertension...

Therapeutisches Drug-Monitoring (TDM) umfasst die Quantifizierung und die Interpretation von Serum- oder Plasmakonzentrationen von Arzneistoffen im Blut, um die Pharmakotherapie zu optimieren. TDM ist ein Werkzeug, mit dem sich die hohe interindividuelle Variabilität der Pharmakokinetik von Patienten identifizieren lässt und es ermöglicht somit ein...

Objectives: Valproic acid and clozapine are drugs commonly used in the treatment of schizophrenic and schizoaffective disorders. Pharmacokinetic interactions of valproic acid with several drugs are well known, yet results concerning the interaction with clozapine are inconsistent. Methods: Steady-state dose-corrected serum concentrations of cloz...

Objectives: Therapeutic drug monitoring (TDM) combines the quantification of drug concentrations in blood, pharmacological interpretation and treatment guidance. TDM introduces a precision medicine tool in times of increasing awareness of the need for personalized treatment. In neurology and psychiatry, TDM can guide pharmacotherapy for patient sub...

Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children a...

Background Genome wide association studies reported two single nucleotide polymorphisms in ANK3 (rs9804190 and rs10994336) as independent genetic risk factors for bipolar disorder. Another SNP in ANK3 (rs10761482) was associated with schizophrenia in a large European sample. Within the debate on common susceptibility genes for schizophrenia and bip...

Pannexins are a group of brain-expressed channel proteins thought to be regulators of schizophrenia-linked pathways including glutamate release, synaptic plasticity and neural stem proliferation. We got evidence for linkage of a catatonic phenotype to the PANX2 locus in a family study. Aim of our study was to evaluate the role of Pannexins in schiz...

Electrocardiographic pathologies are a common problem during antidepressant treatment. The authors investigated the association of serum concentrations of antidepressants and heart rate, QT, and QTc. Polymorphisms of NOS1AP (nitric oxide synthase 1 adaptor protein) rs10494366 and rs12143842 as potential influence factors also were considered. In th...

Objective: The effects of genetic variants in genes encoding the target structures of antidepressants on the therapeutic efficacy of antidepressant drugs have been investigated with unconclusive results. One possible confounding factor in most studies was the fact that drug serum concentrations had not been determined. Methods: Within a clinical...

This study examines the inclusion of preventive factors and new media developments in media recommendations on suicide reporting. Of the 193 member states of the United Nations screened for media recommendations, information was available for 74 countries. Similarities and differences in their contents were analyzed by cluster analysis. Results ind...

Valproic acid and the antidepressants doxepin and venlafaxine are frequently used psychotropic drugs. In the literature, an influence of valproic acid on serum levels of antidepressants has been described, although studies have focused on amitriptyline. The authors assessed their therapeutic drug monitoring (TDM) database for patients receiving a c...

Venlafaxine (VEN) is a widely used antidepressant drug, which is available in both brand-name and generic formulations. Bioequivalence studies indicate some pharmacokinetic variability. However, naturalistic therapeutic drug monitoring studies of different generic formulations are lacking. In 2010, inpatients of the Department of Psychiatry, Psycho...

Objective: To optimize psychiatric consultation service epidemiological information is needed. Methods: We compared data on gender, age and diagnoses of patients in the consultation service to psychiatric inpatients. Results: In psychiatric consultation service patients are older (56.6 vs. 44.9 years, p < 0.05) and males are older than females...

Polypharmacy is widely used in somatic as well as psychiatric pharmacotherapy and is often indispensable due to multimorbidity or insufficient response to treatment with a single drug. However, with an increasing number of simultaneously applied drugs the probability of pharmacodynamic or pharmacokinetic drug-drug interactions is increasing. Such i...

Amitriptyline (AMI) and valproic acid (VPA) are common psychotropic drugs which are frequently used in psychiatry and also administered in neurology or anesthesia in the absence of a psychiatric indication. On the basis of the case of a 73-year-old man with therapy-resistant major depressive episode who experienced anticholinergic delirium after ad...

Atypical antipsychotic agents are a frequently and effectively used treatment in schizophrenia and psychotic disorders. Other than conventional antipsychotics, which mainly exert their pharmacological effect in subcortical dopaminergic systems, atypical antipsychotics additionally affect partly serotonergically innervated structures within prefront...

Background and Objectives: Cycloid psychoses are characterized by polymorphic symptomatology with intraphasic bipolarity, a remitting and recurrent course and favourable prognosis. Perris and Brocicington (P&B) described the first set of operational criteria that were partly incorporated in ICD-10. The present study investigates psychopathological...

Objective: This naturalistic therapeutic drug monitoring (TDM) study aimed to evaluate the relationship between dosage, serum concentration, and clinical outcome in children and adolescents treated with the serotonin reuptake inhibitor sertraline for different indications. Methods: Steady-state trough serum concentrations were analyzed in 90 sub...

22q11 microdeletion is the most common genetic risk factor for psychoses with an assumed prevalence of 1:2000 to 1:4000. Majority of deletions are sporadic encompassing ∼ 3 million base pairs with 40 genes. Up to one third of the subjects with 22q11 deletion syndrome develop psychotic symptoms. It is still on debate whether these patients show a cl...

Therapeutic drug monitoring (TDM) data of antidepressant drugs are often evaluated using homogeneous samples of selected individuals without psychiatric or somatic comorbidity. These data may have limitations in transferability to everyday clinical practice. Hence, studies under naturalistic conditions are important to clarify the full clinical rel...

Background and Objectives: Cycloid psychoses are characterized by polymorphic symptomatology with intraphasic bipolarity, a remitting and recurrent course and favourable prognosis. Perris and Brockington (P&B) described the first set of operational criteria that were partly incorporated in ICD-10. The present study investigates psychopathological p...

As a consequence of individualized antipsychotic pharmacotherapy, many patients need more than a single drug, since they do not respond sufficiently to monotherapy. Other patients suffer from comorbid diseases and therefore require additional drugs from other pharmacological classes. Drug combinations, however, can give rise to pharmacokinetic and/...

Introduction and Aims: Aripiprazole is an atypical antipsychotic used in the treatment of children and adolescents with various psychiatric disorders despite limited data on dosing, efficacy and safety in this patient group. In this observational study, the relationship between dosage, serum concentration and clinical outcomes in children and adole...

The co-morbidity of depressive disorder and chronic kidney failure is remarkably common. However, knowledge about the influence of haemodialysis on the serum concentration of antidepressants is sparse. In this study we examined the influence of haemodialysis on the serum concentrations of the antidepressants amitriptyline (and its active metabolite...

The aim of antidepressant drug treatment is to produce remission without causing adverse effects during the acute phase of the illness and to prevent relapses or recurrences during continuation or maintenance therapy. To achieve these goals, drug choice and dosage must be optimized for each patient individually. Therapeutic drug monitoring (TDM), w...

Introduction: Citalopram (CIT) is a widely used antidepressant which acts by a selective serotonin reuptake inhibition. It is considered to be safer than tricyclic antidepressants at therapeutic levels, but also with respect to intoxications. Recently, ECG-changes in patients with high dosed CIT were described. Methods: We report the case of a 46-y...

In a polydiagnostic study, a systematically recruited collective of 34 women with a first-episode postpartum psychosis was reexamined after a period of 6–26 years (averaging 12.6 years) in order to establish lifetime-diagnoses according to ICD-10 and Leonhard's classification, and to determine course and outcome. According to ICD-10, unipolar depre...

Introduction: Venlafaxine (VEN) is a modern antidepressant which exerts both serotonin and norepinephrine reuptake inhibition. In this study we examined the influence of age, sex, smoking, and co-medication on serum levels of VEN and its metabolite O-desmethylvenlafaxine (ODVEN) in patients treated with VEN under naturalistic conditions. Methods:...

The antidepressant venlafaxine in overdose can lead to serotonin syndrome, seizures, QTc interval prolongation and can increase the risk of cardiac arrhythmias. It has been reported to be more toxic in overdose than other new antidepressants. We report a case of venlafaxine intoxication with a venlafaxine/O-desmethylvenlafaxine serum level of 2861/...

Citalopram (CIT) is a widely used antidepressant which acts by a selective serotonin reuptake inhibition. It is considered to be safer than tricyclic antidepressants at therapeutic levels, but also with respect to intoxications. We report the case of a 46-year-old woman, who ingested in suicidal intention 1400 mg CIT. During the following inpatient...

Conserved and ultra-conserved non-genic sequence elements (CNGs, UCEs) between human and other mammalian genomes seem to constitute a heterogeneous group of functional sequences which likely have important biological function. To determine whether variation in CNGs and UCEs contributes to risk for the schizophrenic subphenotype of periodic catatoni...

Since the second half of the nineteenth century, disorders of psychomotor behaviour have been described as part of psychotic states. In this respect, the descriptions of catatonia by Kahlbaum and of the motility symptom complex by Wernicke form the historic start of the catatonia concept. In both the German and French psychiatric traditions, psycho...

Body weight may affect pharmacokinetic parameters in various ways and may therefore have a significant impact on the serum concentration of a drug at a given dose. Although patients with major depressive disorder frequently show an elevated body mass index, studies investigating the relation between body weight and serum concentration of antidepres...

Introduction: Venlafaxine (VEN) is a modern antidepressant which exerts both serotonin and norepinephrine reuptake inhibition. In this study we examined the influence of sex, age and smoking on serum concentrations of VEN, its metabolite O-desmethylvenlafaxine (ODVEN) and the sum of both (SUM) in patients treated with VEN under naturalistic conditi...

Introduction: Body weight may affect pharmacokinetic parameters in various ways and may therefore have a significant impact on the serum concentration of a drug at a given dose. Although patients with major depressive disorder frequently show an elevated body mass index (BMI), studies investigating the relation between body weight and serum concent...

Therapeutic drug monitoring (TDM), i. e., the quantification of serum or plasma concentrations of medications for dose optimization, has proven a valuable tool for the patient-matched psychopharmacotherapy. Uncertain drug adherence, suboptimal tolerability, non-response at therapeutic doses, or pharmacokinetic drug-drug interactions are typical sit...

Die Abgrenzung der zykloiden Psychosen hat ihre ideengeschichtliche Basis im Problem der „atypischen Psychosen“, das die Frage nach der Klassifikation derjenigen Krankheitsbilder umfaßt, die innerhalb der Kraepelinschen Dichotomie endogener Psychosen weder der Dementia praecox noch dem manisch depressiven Irresein zugeordnet werden können. Die klin...

Genome wide association studies reported two single nucleotide polymorphisms in ANK3 (rs9804190 and rs10994336) as independent genetic risk factors for bipolar disorder. Another SNP in ANK3 (rs10761482) was associated with schizophrenia in a large European sample. Within the debate on common susceptibility genes for schizophrenia and bipolar disord...

One of the neurobiological core features of schizophrenic illnesses is a hypo-functionality of the frontal cortex ("cerebral hypofrontality"). The two major classes of antipsychotic medication differ regarding their impact on frontal lobe function and metabolism, with a presumably more positive effect of "atypical" compared to "typical" agents. To...

In the genome-wide association study (GWAS) on schizophrenia [O'Donovan et al. (2008); Nat Genet 40:1053–1055] a UK-sample of 479 cases with DSM-IV schizophrenia was genotyped in comparison to control subjects with follow up of 12 putative loci in international replication sets of approximately 15,000 cases and controls. In these cohorts and a comb...

Robert Walser (1878–1956) is among the most prominent German-speaking writers born in Switzerland. His early writings are fascinating due to his intensive affectivity and oneiric experiences; his late work impresses through his idiosyncratic use of language and his micrographs. Due to a psychotic disease he stayed in Swiss Mental State Hospitals (W...

Robert Walser (1878-1956) is among the most prominent German-speaking writers born in Switzerland. His early writings are fascinating due to his intensive affectivity and oneiric experiences; his late work impresses through his idiosyncratic use of language and his micrographs. Due to a psychotic disease he stayed in Swiss Mental State Hospitals (W...

A 14-year-old girl with suicidal ideation was presented to the paediatric hospital about 2 h after ingestion of 21 long-acting methylphenidate (MPH) 54-mg tablets (1,134 mg Concerta(®)). At admission signs of sympathomimetic syndrome were observed like agitation, visual hallucinations, slight hypertension, and sinus tachycardia. Treatment included...

The DAOA/G30 (D-amino acid oxidase activator) gene complex at chromosomal region 13q32-33 is one of the most intriguing susceptibility loci for the major psychiatric disorders, although there is no consensus about the specific risk alleles or haplotypes across studies. In a case-control sample of German descent (affective psychosis: n = 248; contro...

The major aim of this multicenter retrospective analysis was to examine the relationship between paliperidone serum concentrations and clinical effects in patients treated with this new antipsychotic drug. Intra-individual variability in trough serum concentrations was also analyzed in patients under treatment with either the paliperidone-extended...

The aim of this prospective naturalistic study was to examine for the first time the relationship between dosage, serum concentration and clinical outcome in children and adolescents with impulsive-aggressive symptoms during risperidone therapy. Steady state trough serum concentrations of risperidone and 9-hydroxyrisperidone (the active moiety) wer...

Several case reports and a recently published study have reported that infections or inflammations can be associated with increased blood levels of clozapine. The aim of this study was to find out whether high serum concentrations of other atypical antipsychotic drugs are associated with elevated levels of C-reactive protein (CRP), a well establish...

The aim of this study was to relate drug concentrations in serum and clinical effects in patients treated with the new antidepressant duloxetine. Data were obtained from a newly established therapeutic drug monitoring (TDM) survey. Duloxetine was measured using HPLC with UV detection and clinical effects by the clinical global impressions (CGI) sca...

An isocratic liquid chromatographic method with column switching and ultraviolet detection is described for quantitative analyses of amitriptyline, aripiprazole, clomipramine, clozapine, desipramine, duloxetine, fluoxetine, imipramine, nortriptyline, reboxetine, sertraline and trimipramine and metabolites in human serum. The method was validated fo...

Venlafaxine is a widely used modern antidepressant drug which exerts both serotonin and norepinephrine reuptake inhibition. Therapeutic drug monitoring (TDM) is estimated as a useful and recommendable tool to control the influence of pharmacokinetic factors in the treatment with venlafaxine. In this study we aimed to evaluate the influence of vario...

Duloxetine is a dual acting antidepressant (selective serotonin and norepinephrine reuptake inhibitor). Existing data suggest that the advisable therapeutic serum level of duloxetine ranges between 20 and 80 ng/mL. In a naturalistic setting we determined duloxetine serum levels within a steady state in a sample of depressive inpatients by high perf...

The phenomenon of folie à deux has been a topical issue in psychiatry for more than a century. Mainly, genetic and psychodynamic factors are discussed controversially in terms of their relevance to the etiology of folie à deux. In this paper, effort is taken to reconceive the topic applying the criteria of a differentiated psychopathological classi...

Therapeutic drug monitoring (TDM) of psychopharmaceuticals is the practical therapeutic application of pharmacokinetic principles in pharmacopsychiatry. The prescription information (summary of product characteristics, SPC) is provided by pharmaceutical companies according to requirements of regulatory authorities and determines the framework of cl...

Therapeutic Drag Monitoring (TDM) is a tool to optimise antidepressant pharmacotherapy improving efficacy and avoiding side effects. The Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP)-TDM group has worked out consensus guidelines to make progress in the use of TDM which in spite of its obvious advantages, is far fro...

Typical and atypical antipsychotics are thought to exert their effects on different neurotransmitter pathways with specific action of atypical compounds on the prefrontal cortex, but studies directly investigating the effect of those drugs on neurophysiological measures of prefrontal brain function are sparse. We therefore investigated the influenc...

Data about therapeutic drug monitoring (TDM) of psychotropic medications are often obtained from samples of highly selected individuals, who may not be representative for the average psychiatric patient. These data therefore may have limitations with regard to their transferability to everyday clinical practice. Therefore studies under naturalistic...

The dopamine hypothesis of schizophrenia proposes an inherited or acquired presynaptic hyperactivity of dopaminergic neurons. The human dopamine transporter gene (hSLC6A3; hDAT) represents one major mechanism for the termination of dopaminergic neurotransmission. This study examines the degree of genetic association of the 5'-untranslated region (5...

Whereas a growing body of evidence suggests that cycloid psychoses have to be separated from schizophrenic psychoses, their relations to bipolar affective disorder are less clear. In a controlled family study, we recruited 46 patients with cycloid psychosis (CP), 33 with manic-depressive illness (MDI), and 27 controls. Three hundred fifty-six of 38...

Background Whereas a growing body of evidence suggests that cycloid psychoses have to be separated from schizophrenic psychoses, their relations to bipolar affective disorder are less clear. Patients and methods In a controlled family study, we recruited 46 patients with cycloid psychosis (CP), 33 with manic-depressive illness (MDI), and 27 control...

In the recent years, elevated homocysteine plasma levels have been reported to represent a risk factor not only for atherosclerosis, but also to be associated with dementia, depression and-in a gender-specific manner-schizophrenia. Here, we explored a possible association between homocysteinemia and psychiatric disorders. Fasting homocysteine, vita...

Hintergrund Zykloide Psychosen (ZP) stellen klinisch sowohl von schizophrenen als auch von affektiven Psychosen abgrenzbare Erkrankungen dar. Bislang fehlen jedoch methodisch befriedigende Daten zur nosologischen Abgrenzbarkeit gegenüber der manisch-depressiven Erkrankung (MDE), weswegen wir hierzu eine kontrollierte Familienstudie durchführten. Pa...

Therapeutic drug monitoring (TDM) has until now become a routine procedure for many psychopharmacotherapeutical interventions. Its aim is to optimize drug treatment in the sense of a maximization of the therapeutic effect and a minimization of the toxicity risk. However, data about TDM in psychotropic medications are often obtained from study sampl...