Der Psychiatrie Research Articles

Severe parkinsonism under treatment with antipsychotic drugs.

The aim of the study was to assess rates of severe parkinsonism related to different antipsychotic drugs (APDs) using data from an observational pharmacovigilance programme in German-speaking countries-Arzneimittelsicherheit in der Psychiatrie (AMSP). Data on APD utilization and reports of severe APD-induced parkinsonism were collected in 99 psychiatric hospitals in Austria, Germany and Switzerland during the period 2001-2016. Of 340,099 patients under surveillance, 245,958 patients were treated with APDs for the main indications of schizophrenic disorders, depression, mania and organic mental disorders. A total of 200 events of severe APD-induced parkinsonism were identified (0.08%). First-generation low-potency APDs were significantly less often implicated (0.02%) than second-generation APDs (0.07%) and first-generation high-potency APDs (0.16%). Among the second-generation APDs, amisulpride and risperidone ranked highest. The phenothiazines were associated with significantly lower rates of severe parkinsonism (0.02%) than those of the butyrophenones (0.11%) and thioxanthenes (0.12%). In 71 cases (35.5%), more than 1 drug was considered responsible for the induction of severe parkinsonism. In 44 patients (22.0%), the symptoms were extremely severe, leading to complete immobility and/or massive complications such as pneumonia and severe injuries due to falls. Higher age (> 60years) was associated with significantly higher rates of severe parkinsonism, as were the diagnoses of schizophrenic disorder or mania. The large number of patients included in the present survey allows for the comparison of severe parkinsonism rates related to different APD classes and single APDs. The first-generation low-potency APDs had significantly reduced risk of severe parkinsonism compared not only to high potency but also to second-generation APDs.

Update on structured pain assessment for the documentation of diagnosis-independent symptoms and signs associated with pain.

Concerning the diagnosis and therapy of pain syndromes, standardized descriptions similar to those used in the examination of psychopathological findings via the system produced by the AMDP ("Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie", i. e., the working group establishing standardized methodology and documentation within psychiatry) are still lacking. Therefore, the authors of this article have founded aworking group to establish standardized methodology and documentation for symptoms and signs associated with pain, although not at adiagnosis-specific level, in order to promote standardization in the documentation of pain and rating of the symptoms associated with agiven set of medical results. This article presents asystem for documenting the symptoms and signs associated with pain globally and independently of the diagnosis (Structured Pain Assessment System) with nomenclature that is inspired by the AMDP system. The objective of this working group is to develop documentation for auniform multidimensional pain assessment (with defined terminology) that serves as acomparable and unified standard in the field.

Neuroleptic malignant syndrome: evaluation of drug safety data from the AMSP program during 1993-2015.

Neuroleptic malignant syndrome (NMS) is a rare, but severe adverse drug reaction of drugs with anti-dopaminergic properties. The main symptoms are fever and rigor. In addition, other symptoms such as creatine kinase elevation, alteration of consciousness and various neurological symptoms may occur. A total of 52 NMS cases have been documented in the drug safety program 'Arzneimittelsicherheit in der Psychiatrie' from 1993 to 2015. We calculated incidences and analyzed imputed substances and additional risk factors to study the impact of changing therapy regimes. The overall incidence was 0.16‰. High-potency first-generation antipsychotics (FGAs) had the highest incidences, e.g. flupentixol with 0.61‰. Second-generation antipsychotics (SGAs) had lower incidences. Low-potency FGAs had very low incidences, comparable to SGAs, but in contrast to SGAs, had not been imputed alone in any case of NMS. Preexisting organic pathologies of the central nervous system, lithium treatment, infection/exsiccosis and the withdrawal of medication with anticholinergic properties or alcohol were found to be additional risk factors. With the increasing use of SGAs, one should always be aware of the risk of NMS. Better suited diagnostic criteria for 'atypical NMS' would lead to a better understanding and, therefore, to improved treatment possibilities.

Seizure rates under treatment with antipsychotic drugs: Data from the AMSP project

Objectives: The study aimed to assess seizure rates related to different antipsychotic drugs (APDs) in a clinical setting using data from the drug safety programme Arzneimittelsicherheit in der Psychiatrie (AMSP).Methods: Psychotropic drug use data and reports of APD-related seizures were collected in 89 psychiatric hospitals in Austria, Germany and Switzerland from 1993 to 2015.Results: Of 475,096 patients under surveillance, 320,383 patients were treated with APDs for the main indications of schizophrenic disorders, mood disorders and organic disorders. A total of 144 APD-related tonic clonic seizures were identified (0.04%). The butyrophenones ranked slightly lower (0.03%) compared to the phenothiazines, thioxanthenes and second-generation APDs (0.05% each). No significant differences were observed when comparing first- and second-generation APDs. Clozapine was related to the highest seizure rate (0.18%). In 107 cases (74.3%), more than one drug was considered responsible for seizure induction. With the exception of clozapine, seizures imputed to a single APD were in the clear minority. Seizure rates under the combinations of APDs with tricyclic antidepressants or lithium, as well as under triple combinations of APDs, were increased approximately two-fold. Young age (≤30 years), the male gender, and diagnosis of schizophrenic disorder were associated with significantly higher seizure rates (P < 0.05).Conclusions: Closely reflecting daily clinical practice, the present results provide supplementary information regarding APD therapy for patients not only at risk for seizures but also seizure-unaffected psychiatric inpatients.

Severe hair loss associated with psychotropic drugs in psychiatric inpatients—Data from an observational pharmacovigilance program in German-speaking countries

BackgroundThe study aimed to investigate severe hair loss related to psychotropic drugs (PDs) by using data from the drug safety programme Arzneimittelsicherheit in der Psychiatrie (AMSP). MethodsData on PD utilization and reports of severe PD-related hair loss were collected in 83 psychiatric hospitals in Austria, Germany and Switzerland during the period 1993–2013. ResultsOut of 432,215 patients under surveillance, 404,009 patients were treated with PDs for the main indications of depression, schizophrenic disorder, neurosis, mania, and organic psychosis. Severe hair loss related to PD treatment was reported in 43 cases (0.01%). The rates of hair loss under antipsychotic drugs were slightly lower than the mean rates of all PDs and antidepressant drugs. Valproic acid was related to the highest risk. In 6 of the 43 cases, hair loss was imputed to multiple drugs, with 4 cases imputed to double drug combinations and 2 cases to triple combinations. Rates of severe hair loss under valproic acid (VPA) and lithium salts were distinctly lower as compared with the overall rates reported in literature. Severe hair loss under PD treatment was reported significantly more often in female patients than in male patients (p < 0.01). ConclusionThe rate of severe PD-related hair loss was very low in the present survey. The large number of patients included in this multicentre study allows for assessment and comparison of hair loss rates related to different PDs and groups of PDs and provides new and supplementary information on PD-related hair loss.

Suicidal Ideation and Suicidal Behavior as Rare Adverse Events of Antidepressant Medication: Current Report from the AMSP Multicenter Drug Safety Surveillance Project.

BackgroundSuicidal ideations, suicide attempts, and fatal suicides are rare adverse drug reactions to antidepressant drugs, but they essentially are clinically relevant. Drawing on a larger dataset of the European drug surveillance program, the present naturalistic study updates a previous contribution (Stübner et al., 2010).MethodsFirst an analysis of the comprehensive data collected in 81 psychiatric hospitals from 1993 to 2014 by the European drug surveillance program Arzneimittelsicherheit in der Psychiatrie was made. All documented single cases of suicidal ideations or behavior judged as adverse drug reactions to antidepressant drugs were carefully assessed as to their clinical features and drug prescriptions.ResultsAmong 219,635 adult hospitalized patients taking antidepressant drugs under surveillance, 83 cases of suicidal adverse drug reactions occurred (0.04%): 44 cases of suicidal ideation, 34 attempted suicides, and 5 committed suicides were documented. Restlessness was present in 42 patients, ego-dystonic intrusive suicidal thoughts or urges in 39 patients, impulsiveness in 22 patients, and psychosis in 7 patients. Almost all adverse drug reactions occurred shortly after beginning antidepressant drug medication or increasing the dosage. Selective serotonin reuptake inhibitors caused a higher incidence of suicidal ideation and suicidal behavior as adverse drug reactions than noradrenergic and specific serotonergic antidepressants or tricyclic antidepressants, as did monotherapy consisting of one antidepressant drug, compared to combination treatments.ConclusionsThe study supports the view that antidepressant drug-triggered suicidal ideation and suicidal behavior (primarily with selective serotonin reuptake inhibitors) are rare. Special clinical features (restlessness, ego-dystonic thoughts or urges, impulsiveness) may be considered as possible warning signs. A combination therapy might be preferable to antidepressant drug monotherapy when beginning treatment.

Use and safety of antiepileptic drugs in psychiatric inpatients-data from the AMSP study.

The psychiatric utilization patterns and risks of antiepileptic drugs (AEDs) were assessed by using data from the drug safety programme Arzneimittelsicherheit in der Psychiatrie over the time period 1993-2013. In a total of 432,215 patients, the main indications for AED use were acute mania, schizoaffective disorder, and schizophrenic and organic psychoses. Valproic acid (VPA) was the most common substance across all of those groups, reaching administration rates of up to 50% since 2005, at which time carbamazepine (CBZ) administration consistently dropped below a rate of 10%. Lamotrigine (LTG) and pregabalin (PGB) increased in relevance after 2005 and 2010, respectively (with administration rates of up to 9%), whereas oxcarbazepine (OXC) was least prevalent (<3%). The mean rates of severe adverse drug reactions (ADRs) ranged from 6 cases per 1000 patients treated (VPA) to 19/1000 (OXC) and were significantly lower with treatment with VPA compared to OXC and CBZ. Hyponatremia was the leading ADR during treatment with OXC; severe allergic skin reactions were most often observed during treatment with CBZ and LTG, and severe oedema was most common during treatment with PGB. Severe hyponatremia induced by OXC was observed significantly more often in female patients than in male patients.

Venous thromboembolism during treatment with antipsychotics: Results of a drug surveillance programme

Objectives: Venous thromboembolism (VTE) can be a life-threatening medical condition that may lead to leg swelling, respiratory distress and death.Methods: The AMSP (Arzneimittelsicherheit in der Psychiatrie) is a continuous multicentre drug surveillance programme that assesses severe adverse drug reactions during treatment of psychiatric inpatients. We report on a total of 264,422 inpatients who were treated with antipsychotics (APs) and monitored from 1993 to 2011 in 99 psychiatric hospitals.Results: During this period VTE events were reported for 89 inpatients, corresponding to an occurrence rate of 34 cases per 100,000 inpatient admissions treated with APs or 43 cases per 10,000 person-years. The occurrence of VTE was greatest in patients over the age of 65 years of age with mood disorders. The chemical class of butyrophenones (48/100,000) followed by atypical APs (36/100,000) showed the highest occurrence rate for VTE compared to thioxanthenes (23/100,000), which were less associated with VTE. If imputed alone, pipamperone (61/100,000) and risperidone (55/100,000) were most frequently associated with VTE. In general, there was no difference in occurrence rate of VTE between high- and low-potency APs.Conclusions: These results suggest that clinicians should consider AP drug exposure as a potential risk factor for VTE for patients older than 65 years. Additionally, the diagnosis of an affective disorder seems to increase the risk for VTE.

Drug-Induced Liver Injury during Antidepressant Treatment: Results of AMSP, a Drug Surveillance Program.

Background:Drug-induced liver injury is a common cause of liver damage and the most frequent reason for withdrawal of a drug in the United States. The symptoms of drug-induced liver damage are extremely diverse, with some patients remaining asymptomatic.Methods:This observational study is based on data of Arzneimittelsicherheit in der Psychiatrie, a multicenter drug surveillance program in German-speaking countries (Austria, Germany, and Switzerland) recording severe drug reactions in psychiatric inpatients. Of 184234 psychiatric inpatients treated with antidepressants between 1993 and 2011 in 80 psychiatric hospitals, 149 cases of drug-induced liver injury (0.08%) were reported.Results:The study revealed that incidence rates of drug-induced liver injury were highest during treatment with mianserine (0.36%), agomelatine (0.33%), and clomipramine (0.23%). The lowest probability of drug-induced liver injury occurred during treatment with selective serotonin reuptake inhibitors ([0.03%), especially escitalopram [0.01%], citalopram [0.02%], and fluoxetine [0.02%]). The most common clinical symptoms were nausea, fatigue, loss of appetite, and abdominal pain. In contrast to previous findings, the dosage at the timepoint when DILI occurred was higher in 7 of 9 substances than the median overall dosage. Regarding liver enzymes, duloxetine and clomipramine were associated with increased glutamat-pyruvat-transaminase and glutamat-oxalat-transaminase values, while mirtazapine hardly increased enzyme values. By contrast, duloxetine performed best in terms of gamma-glutamyl-transferase values, and trimipramine, clomipramine, and venlafaxine performed worst.Conclusions:Our findings suggest that selective serotonin reuptake inhibitors are less likely than the other antidepressants, examined in this study, to precipitate drug-induced liver injury, especially in patients with preknown liver dysfunction.

Psychopharmacological treatment of 1650 in-patients with acute mania-data from the AMSP study

BackgroundSeveral studies have analyzed prescription patterns for bipolar disorder, but few have for acute mania. Treatment strategies in this complex domain change over time and do not always follow evidence-based guidelines. MethodsPrescription data of in-patients suffering from acute mania in the time period from 2005 to 2012 were obtained from the database of the Drug Safety Program in Psychiatry (Institut für Arzneimittelsicherheit in der Psychiatrie; AMSP). Data were collected on two index dates per year. Changes over time were analyzed comparing the time periods 2005/06 and 2011/12. ResultsAmong 1650 patients (mean ±SD; age: 48.9±14.91 years; 53.1% females) 54.1% received anticonvulsants, 74.5% second-generation antipsychotics (SGAs), 17.8% first-generation antipsychotics (FGAs), 29.1% lithium, 44.1% benzodiazepines and 14.5% antidepressants. Prescription of SGAs increased from 70% to 79% (p=0.005), while prescription of FGAs and anticonvulsants decreased from 19% to 13% (p<0.05) and 59% to 46% (p<0.001), respectively. Only 30% of patients received monotherapy with one mood stabilizer. We observed an impact of gender, age and psychotic symptoms on treatment strategy. 36.8% of the women≤40 years received valproate. LimitationsFollow-up data are missing and no differentiation between acute and maintenance treatments could be made due to the cross-sectional design. Additionally, our findings do not necessarily translate to outpatients or to other countries. ConclusionsCombination therapies represent standard clinical practice. Though many results reflect clinical necessity, the high number of antidepressant prescriptions or valproate use in women of child-bearing age should be judged critically. Further prospective studies should focus on real-world prescription practice in acute mania to evaluate efficacy and safety of common practice.This paper is dedicated to Prof. Dr. Hanns Hippius on the occasion of his 90th birthday.

Cardiovascular adverse reactions during antidepressant treatment: a drug surveillance report of German-speaking countries between 1993 and 2010.

Background:Antidepressants (ADs) are known to have the potential to cause various cardiovascular adverse drug reactions (ADRs). The tricyclic antidepressants (TCAs) were first revealed to be a possible source of cardiovascular ADRs. In recent years, newer classes of ADs were also suggested to have a higher risk of cardiovascular adverse effects. In particular, the selective serotonin reuptake inhibitors (SSRIs) were suspected to have the potential to induce QTc interval prolongation, and therefore increase the risk of ventricular arrhythmia. This descriptive study is based on the continuous pharmacovigilance program of German-speaking countries (Austria, Germany, and Switzerland), the Arzneimittelsicherheit in der Psychiatrie (AMSP), which assesses severe ADRs occurring in clinical routine situations.Methods:Of 169 278 psychiatric inpatients treated with ADs between 1993 and 2010, 198 cases of cardiovascular ADRs (0.12%) were analyzed.Results:Our study showed that the incidence rates of cardiovascular ADRs were highest during treatment with monoamine oxidase inhibitors (0.27%), TCAs (0.15%), and serotonin noradrenaline reuptake inhibitors (0.14%); the risk of occurring during treatment with SSRIs (0.08%) was significantly lower. The noradrenergic and specific serotonergic AD mirtazapine (0.07%) had a significantly lower risk of cardiovascular ADRs than all other ADs. Severe hypotension was the most frequent ADR, followed by hypertension, arrhythmia, and in some rare cases heart failure.Conclusions:Despite certain limitations due to the AMSP study design, our observations on cardiovascular ADRs can contribute to a better knowledge of the cardiovascular risk profiles of antidepressants in the clinical routine setting. However, prospective studies are needed to verify our findings.

Is it time to awaken Sleeping Beauty? European psychiatry has been sleeping since 1980

The Diagnostic and Statistical Manual of Mental Disorders (DSM-III), published in 1980, has led to a dead end, the DSM-V. Following the allegory of Sleeping Beauty, the DSM-III put European psychiatry to sleep; it now must wake up to create a 21st century psychiatric language for descriptive psychopathology and psychiatric nosology.Four topics are reviewed. First, the review of descriptive psychopathology focuses on: (a) Chaslin's and Jaspers’ books, and (b) Schneider's transmittal of Jaspers’ ideas and involvement with Kraepelin in incorporating neuroscience into psychiatric nosology.Second, US psychiatry's historic steps include: (a) the pseudoscience of psychoanalysis, (b) the low level of pre-DSM-III diagnostic expertise, (c) the neo-Kraepelinian revolution which led to DSM-III, (d) the failure to improve diagnostic skills, and (e) the reprise of Kraepelin's marketing (“neuroscience will save psychiatry”).Third, the DSM-III devastated European psychiatry by destroying: (a) the national textbooks which increased consistency but eliminated creative European thinking; and (b) the Arbeitsgemenschaft fur Methodic und Dokumentation in der Psychiatrie, the most reasonable attempt to reach diagnostic agreement: start with symptoms/signs (first level) rather than disorders (second level).Fourth, Berrios elaborated upon Jaspers, who described psychiatry as a hybrid science and heterogeneous. Berrios affirmed that psychiatric symptoms/signs are hybrid. Some symptoms are in the “semantic space” and cannot be “explained” by neuroscience.

Early Recognition of High Risk of Bipolar Disorder and Psychosis: An Overview of the ZInEP "Early Recognition" Study.

Early detection of persons with first signs of emerging psychosis is regarded as a promising strategy to reduce the burden of the disease. In recent years, there has been increasing interest in early detection of psychosis and bipolar disorders, with a clear need for sufficient sample sizes in prospective research. The underlying brain network disturbances in individuals at risk or with a prodrome are complex and yet not well known. This paper provides the rationale and design of a prospective longitudinal study focused on at-risk states of psychosis and bipolar disorder. The study is carried out within the context of the Zurich Program for Sustainable Development of Mental Health services (Zürcher Impulsprogramm zur Nachhaltigen Entwicklung der Psychiatrie). Persons at risk for psychosis or bipolar disorder between 13 and 35 years of age are examined by using a multi-level-approach (psychopathology, neuropsychology, genetics, electrophysiology, sociophysiology, magnetic resonance imaging, near-infrared spectroscopy). The included adolescents and young adults have four follow-ups at 6, 12, 24, and 36 months. This approach provides data for a better understanding of the relevant mechanisms involved in the onset of psychosis and bipolar disorder, which can serve as targets for future interventions. But for daily clinical practice a practicable “early recognition” approach is required. The results of this study will be useful to identify the strongest predictors and to delineate a prediction model.

The ZInEP Epidemiology Survey: background, design and methods.

This article introduces the design, sampling, field procedures and instruments used in the ZInEP Epidemiology Survey. This survey is one of six ZInEP projects (Zürcher Impulsprogramm zur nachhaltigen Entwicklung der Psychiatrie, i.e. the "Zurich Program for Sustainable Development of Mental Health Services"). It parallels the longitudinal Zurich Study with a sample comparable in age and gender, and with similar methodology, including identical instruments. Thus, it is aimed at assessing the change of prevalence rates of common mental disorders and the use of professional help and psychiatric sevices. Moreover, the current survey widens the spectrum of topics by including sociopsychiatric questionnaires on stigma, stress related biological measures such as load and cortisol levels, electroencephalographic (EEG) and near-infrared spectroscopy (NIRS) examinations with various paradigms, and sociophysiological tests. The structure of the ZInEP Epidemiology Survey entails four subprojects: a short telephone screening using the SCL-27 (n of nearly 10,000), a comprehensive face-to-face interview based on the SPIKE (Structured Psychopathological Interview and Rating of the Social Consequences for Epidemiology: the main instrument of the Zurich Study) with a stratified sample (n = 1500), tests in the Center for Neurophysiology and Sociophysiology (n = 227), and a prospective study with up to three follow-up interviews and further measures (n = 157). In sum, the four subprojects of the ZInEP Epidemiology Survey deliver a large interdisciplinary database.

¿Es hora de despertar a la Bella Durmiente? En 1980, la psiquiatría europea cayó en un profundo sueño

The Diagnostic and Statistical Manual of Mental Disorders (DSM-III), published in 1980, has led to a dead end, the DSM-V. Following the allegory of Sleeping Beauty, the DSM-III put European psychiatry to sleep; it now must wake up to create a 21st century psychiatric language for descriptive psychopathology and psychiatric nosology. Four topics are reviewed. First, the review of descriptive psychopathology focuses on: a) Chaslin's and Jaspers's books, and b) Schneider's transmittal of Jaspers's ideas and involvement with Kraepelin in incorporating neuroscience into psychiatric nosology. Second, US psychiatry's historic steps include: a) the pseudoscience of psychoanalysis, b) the low level of pre-DSM-III diagnostic expertise, c) the neo-Kraepelinian revolution which led to DSM-III, d) the failure to improve diagnostic skills, and e) the reprise of Kraepelin's marketing ("neuroscience will save psychiatry"). Third, the DSM-III devastated European psychiatry by destroying: a) the national textbooks which increased consistency but eliminated creative European thinking; and b) the Arbeitsgemenschaft fur Methodic und Dokumentation in der Psychiatrie, the most reasonable attempt to reach diagnostic agreement: start with symptoms/signs (first level) rather than disorders (second level). Fourth, Berrios elaborated upon Jaspers, who described psychiatry as a hybrid science and heterogeneous. Berrios affirmed that psychiatric symptoms/signs are hybrid. Some symptoms are in the "semantic space" and cannot be "explained" by neuroscience.

Commentary to the articles of M. Stier (Normative preconditions for the assessment of mental disorder) and T. Schramme (On the autonomy of the concept of disease in psychiatry)

Commentary to the articles of M. Stier (Normative preconditions for the assessment of mental disorder) and T. Schramme (On the autonomy of the concept of disease in psychiatry)

Seizures during antidepressant treatment in psychiatric inpatients—results from the transnational pharmacovigilance project “Arzneimittelsicherheit in der Psychiatrie” (AMSP) 1993–2008

There is little clinical data available about seizure rates in psychiatric inpatients, and there are no studies with reference data to the frequencies of antidepressant (AD) use for this important clinical population. This study investigates seizure rates during AD treatment in psychiatric inpatient settings, drawn from the transnational pharmacovigilance programme Arzneimittelsicherheit in der Psychiatrie (AMSP) in relation to the known frequencies of ADs used in the participating clinics. Comparisons are made to former publications and their limitations. Seventy-seven cases were identified with grand mal seizures (GMS) during AD treatment between 1993 and 2008, with a total number of 142,090 inpatients under surveillance treated with ADs in the participating hospitals. The calculated overall rate of reported seizures of patients during AD treatment in this collective is 0.05 % for ADs imputed alone or in combination with other psychotropic drug groups and 0.02 % when only ADs were given and held responsible for GMS. The patients receiving tri- or tetracyclic ADs (TCAs) had a 2-fold risk to develop a seizure as compared to the overall average rate in this sample. In 11 cases, there was only one AD imputed--the majority of these cases (9/11) were TCA. Monotherapy with selective serotonin reuptake inhibitors (SSRI) or dual serotonin and noradrenaline reuptake inhibitors (SNRI) were never imputed alone in this sample. The results of the study favour the assumption that SSRIs, noradrenergic and specific serotonergic antidepressants (NaSSA) and dual SNRI might be more appropriate than TCAs for the treatment of psychiatric patients with an enhanced seizure risk.

Depression with psychotic features is influenced by the polymorphism of the serotonin transporter gene

IntroductionCurrent diagnostic classifications regard psychotic symptoms during depressive episodes as indicators of depression severity. However, growing evidence suggests that depression with psychotic symptoms (MDP) may represent a distinct subtype of depression. In the course of the search for discriminating factors we tested the hypothesis that the serotonin transporter gene (5-HTTLPR) may interact with the manifestation of psychotic symptoms in acute depression. Methods112 inpatients (61 female) with a depressive episode (16 bipolar, 86 unipolar) at admission were genotyped for 5-HTTLPR variants. Psychotic symptoms und general psychopathology were evaluated comprehensively using the Manual of the Association for Methodology and Documentation in Psychiatry (Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie, 1981). For statistical analysis a chi-square test and a logistic regression model was used. Results16 (14.3%) out of 112 patients were currently presenting with psychotic symptoms. The primary finding of our study was the higher prevalence of the s-allele of the 5-HTTLPR within the group of MDP patients (Pearson χ²=7.87; df=2; p<0.03). Secondly, in a logistic regression model, 5-HTTLPR was found to significantly contribute to the diagnosis of MDP (χ²=6.5; df=1; p=0.01). This effect was even more pronounced upon comparing only severely depressed patients with MDP patients. From a psychopathological perspective, MDP patients showed higher AMDP hostility and apathy scores but equal AMDP depression scores. DiscussionThis is the first study to show an influence of 5-HTTLPR on psychotic symptoms in acutely depressed patients. LimitationsThe lack of a control group and the relatively small sample size limits the present study's findings, thus replication in a larger sample is necessary.

Flupentixol use and adverse reactions in comparison with other common first- and second-generation antipsychotics: data from the AMSP study

This study compares the first-generation antipsychotic (FGA) flupentixol to haloperidol and common second-generation antipsychotics (SGAs) as to drug utilization and severe adverse drug reactions (ADRs) in clinical treatment of schizophrenia inpatients using data from the drug safety program Arzneimittelsicherheit in der Psychiatrie (AMSP). AMSP drug utilization and reported ADR data were analyzed. Type and frequency of severe ADRs attributed to flupentixol were compared with haloperidol, clozapine, olanzapine, quetiapine, risperidone and amisulpride in a total of 56,861 schizophrenia inpatients exposed to these drugs. In spite of increasing prescription of SGAs, flupentixol was consistently used in schizophrenic inpatients (about 5%) over time. Reporting rates of severe ADR ranged from 0.38 to 1.20% for the individual antipsychotics (drugs imputed alone); flupentixol ranked lowest. The type of ADR differed considerably; as to severe EPMS, flupentixol (0.27%), such as risperidone (0.28%), held an intermediate position between haloperidol/amisulpride (0.55/0.52%) and olanzapine/quetiapine (<0.1%). The study is a heuristic approach, not a confirmatory test. Flupentixol has a stable place in the treatment of schizophrenia in spite of the introduction of different SGAs. Comparative ADR profiles suggest an intermediate position between FGAs and SGAs for flupentixol in clinical practice.

Hyponatraemia during psychopharmacological treatment: results of a drug surveillance programme

Hyponatraemia (HN) can be a life-threatening medical condition which may lead to severe neurological and psychiatric symptoms. The AMSP (Arzneimittelsicherheit in der Psychiatrie) is a multicentre drug surveillance programme that assesses severe or new adverse drug reactions during psychopharmacological treatment in psychiatric inpatients. We report on a total of 263 864 psychiatric inpatients monitored from 1993 to 2007 in 80 psychiatric hospitals in Germany, Switzerland and Austria. During this period plasma sodium levels below 130 mmol/l (severe HN according to AMSP) were reported in 93 patients (relative frequency 0.04%). On average, the plasma sodium levels of all cases were 119.7 mmol/l (±5.8 s.d.); median 121 mmol/l (range 104-129 mmol/l). Patients who showed no clinical signs (n=65, 70%) had a mean sodium level of 121.3 mmol/l (±5.0 s.d.); median 122 mmol/l (range 114-129 mmol/l). By contrast, patients with clinical symptoms (n=28, 30%) had a mean sodium level of 116.0 mmol/l (±6.0 s.d.); median 117 mmol/l (range 104-125 mmol/l). HN was mainly observed during treatment with selective serotonin reuptake inhibitors (SSRIs) (0.06%), Serotonin noradrenaline reuptake inhibitors (SNRIs) (0.08%), carbamazepine (0.10%) and oxcarbazepine (1.29%); the highest rate was found for oxcarbazepine. Antipsychotics, mirtazapine and tricyclic antidepressants were only rarely involved in HN (0.003-0.005%). Combinations of several drugs known to induce HN significantly increased the risk of HN, e.g. more than 10-fold for SSRI+diuretics+ACE inhibitors (0.37%) vs. SSRI given alone (0.02%). This is clinically relevant because such combinations, e.g. SSRI+diuretics may occur especially in elderly patients, who are in general at higher risk of developing HN.