Kai G. Kahl

Quetiapine addition to serotonin reuptake inhibitors in patients with severe obsessive-compulsive disorder: a double-blind, randomized, placebo-controlled study.

Objective: Although many patients with obsessive-compulsive disorder (OCD) benefit from treatment with serotonin reuptake inhibitors (SRIs), it is estimated that 40% to 60% of them do not respond. The objective of the present study was to evaluate the efficacy of quetiapine added to baseline treatment with SRIs for the treatment of OCD in severely ill adult subjects. Method: Forty patients (21 men, 19 women) with primary OCD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria participated in a 12-week, double-blind, placebo-controlled trial. They were randomly assigned to dosages of quetiapine titrated up to 400 mg/d (n = 20) or to placebo (n = 20) in addition to their SRI treatment. During the continuation phase (weeks 6-12), subjects received different dosages between 400 and 600 mg/d depending on clinical response. At entry, all patients were unresponsive to at least 1 course of at least 12 weeks of treatment with SRIs at defined doses. The total Yale-Brown Obsessive-Compulsive Scale score was the primary efficacy parameter. Results: Intention-to-treat, last-observation-carried-forward analysis demonstrated a mean ± SD decrease in Yale-Brown Obsessive-Compulsive Scale score of 5.2 ± 5.4 in the quetiapine group and 3.9 ± 4.9 in the placebo group. The analysis of treatment effects between the 2 groups showed no significant difference. There were no significant group differences in any of the other self-rating scales or clinician-administered rating scales. Conclusions: In this study, augmentation of SRI treatment with quetiapine in severe OCD had no additional effect.

Characterization of the C5a receptor on guinea pig platelets.

Guinea pig (gp) platelets react to nanomolar doses of the complement-derived anaphylatoxin C5a with a shape change, aggregation and release of biogenic amines and nucleotides from their granules. We have investigated the specific receptor for C5a on gp platelets which mediates these biological effects. Competitive binding studies with 125I-labeled guinea pig C5a (125I-gpC5a) revealed approx. 4000 binding sites/cell with Kd = 6 x 10(-9) M. The more than 60-fold higher biological activity (ATP-release from gp platelets) of gpC5a versus recombinant human C5a (rhuC5a) and the different binding behavior of gpC5a and rhuC5a point to a species restriction in the gp platelet system. Cross-linking of 125I-gpC5a to gp platelets (250 microM DSS) and analysis by SDS-PAGE under reducing conditions resulted in labeling of a single band with a molecular mass of 32 kDa (ligand-receptor complex). Because of these characteristics, the C5a receptor on gp platelets clearly differs from all previously described C5a receptors.

Inhaled Loxapine for Acute Treatment of Agitation in Patients With Borderline Personality Disorder: A Case Series.

To the Editors: A cute agitation is very common in patients with borderline personality disorder (BPD). A novel approach for short-term treatment of acute agitation in schizophrenia and bipolar disorder is loxapine as inhalation (Adasuve; Staccato System), which has been approved in the United States since December 2012 and in the European Union since February 2013. Efficacy may also be expected for states of agitation in other psychiatric diseases such as BPD. Loxapine is a tricyclic antipsychotic with a tmax median of 2 minutes after inhalation and a mean half-life of 6.2 hours. The delivery

Intima-media thickness in women with borderline personality disorder.

Objective: Patients with borderline personality disorder (BPD) may have a higher risk of developing cardiovascular disease caused by altered endocrine, metabolic, and inflammatory parameters. Increased intima-media thickness (IMT) is considered an early marker of atherosclerosis and is associated with most cardiovascular risk factors. Methods: The mean IMT of the common carotid arteries was assessed by B-mode ultrasound in 47 women with BPD and 28 age-matched healthy women. Mean (standard deviation) age for BPD participants was 31.2 (10.4) years and 31.9 (11.0) years for the comparison group. In addition, Adult Treatment Panel III criteria for metabolic syndrome and markers of inflammation were measured. The patients were characterized by applying DSM-IV criteria and obtaining self-reports of adverse childhood experiences. Results: Women with BPD had a significantly higher IMT than healthy women (mean [standard deviation] = 0.41 [0.11] versus 0.34 [0.11] mm, p =.02). In linear regression analysis, IMT was significantly associated with BPD even when adjusting for body mass index (&bgr; = 0.27, p =.04) and physical activity (&bgr; = 0.29, p =.02). Conclusions: The data suggest that women with BPD are at increased risk of developing subsequent cardiovascular disease.ACEs = adverse childhood experiences; BDI = Beck Depression Inventory; BMI = body mass index; BPD = borderline personality disorder; CG = comparison group; IMT = intima-media thickness; MDD = major depressive disorder; SCID = Structured Clinical Interview for DSM-IV

[Inhaled loxapine for emergency treatment of agitated patients with borderline personality disorder : A series of five cases].

Patienten mit Borderline-Persönlichkeitsstörung (BPS) leiden häufig an den Symptomen einer Agitation wie Unruhe, Erregung und inneren Spannungen. Diese können in schwere Autoaggression und selbstverletzendes Verhalten eskalieren, mit dem die Betroffenen versuchen, die für sie unerträgliche innere Anspannung zu lösen. Wenn psychotherapeutische Deeskalationsmethoden versagen, empfehlen nationale und internationale Leitlinien und Konsenserklärungen den Einsatz nichtsedierender, nichtinvasiver Medikamente mit schnellem Wirkungseintritt und einem günstigen Nebenwirkungsprofil [2, 5, 11, 15, 23]. Derzeit zählen Benzodiazepine, orale und injizierbare Antipsychotika zur Standardbehandlung akut agitierter Patienten. Die genannten Therapieoptionen können im Kontext einer BPS Nachteile haben: Neben dem Risiko einer Sedation und Abhängigkeitsentwicklung sind unterderTherapiemitBenzodiazepinenbei bis zu 50%der Patienten paradoxe Reaktionen beschrieben worden [18], zudem wurde unter der Gabe von Alprazolam eine Abnahme der Verhaltenskontrolle bei BPS beobachtet [6]. Orale Antipsychotika haben oft einen verzögerten Wirkungseintritt, während die Gabe intramuskulär injizierter Antipsychotika selbst unter günstigsten Voraussetzungen nicht als „nichtinvasives“ Verfahren aufgefasst werden kann [1, 17]. Zusammengefasst ist die Therapie der akuten Agitation bei BPS arbiträr, es fehlen randomisiert-kontrollierte Studien, und kein Medikament ist für die medikamentöse Therapie der BPS zugelassen. Bei agitierten erwachsenen Patienten mit Schizophrenie oder bipolarer Störung steht dagegen in Deutschland seit Februar 2013 mit inhalativem Loxapin eine neue Behandlungsoption zur Verfügung [8]. Aufgrund der Applikationsart weist inhalatives Loxapin eine schnelle Bioverfügbarkeit und einen raschen Wirkeintritt von < 10 min auf [3, 10]. Eine relevante Nebenwirkung ist symptomatischer Bronchospasmus, der häufiger bei Patienten mit vorbestehendem Asthma bronchiale (53,8 % Bronchospasmus vs. 11,5 % nach Placebogabe) und chronisch-obstruktiver Lungenerkrankung (23,1 % vs. 14,8 % nach Placebogabe) auftritt [7]. Unter Beachtung dieser Nebenwirkungen bei entsprechend vorerkrankten Patienten könnte sich inhalatives Loxapin auch als Notfallmedikation für agitierte Patienten mit BPS eignen, um nachfolgende Selbstverletzungen und damit verbundene Komplikationen zu vermeiden.

Inhalatives Loxapin zur Notfallbehandlung bei agitierten Patienten mit Borderline-Persönlichkeitsstörung

Patienten mit Borderline-Persönlichkeitsstörung (BPS) leiden häufig an den Symptomen einer Agitation wie Unruhe, Erregung und inneren Spannungen. Diese können in schwere Autoaggression und selbstverletzendes Verhalten eskalieren, mit dem die Betroffenen versuchen, die für sie unerträgliche innere Anspannung zu lösen. Wenn psychotherapeutische Deeskalationsmethoden versagen, empfehlen nationale und internationale Leitlinien und Konsenserklärungen den Einsatz nichtsedierender, nichtinvasiver Medikamente mit schnellem Wirkungseintritt und einem günstigen Nebenwirkungsprofil [2, 5, 11, 15, 23]. Derzeit zählen Benzodiazepine, orale und injizierbare Antipsychotika zur Standardbehandlung akut agitierter Patienten. Die genannten Therapieoptionen können im Kontext einer BPS Nachteile haben: Neben dem Risiko einer Sedation und Abhängigkeitsentwicklung sind unterderTherapiemitBenzodiazepinenbei bis zu 50%der Patienten paradoxe Reaktionen beschrieben worden [18], zudem wurde unter der Gabe von Alprazolam eine Abnahme der Verhaltenskontrolle bei BPS beobachtet [6]. Orale Antipsychotika haben oft einen verzögerten Wirkungseintritt, während die Gabe intramuskulär injizierter Antipsychotika selbst unter günstigsten Voraussetzungen nicht als „nichtinvasives“ Verfahren aufgefasst werden kann [1, 17]. Zusammengefasst ist die Therapie der akuten Agitation bei BPS arbiträr, es fehlen randomisiert-kontrollierte Studien, und kein Medikament ist für die medikamentöse Therapie der BPS zugelassen. Bei agitierten erwachsenen Patienten mit Schizophrenie oder bipolarer Störung steht dagegen in Deutschland seit Februar 2013 mit inhalativem Loxapin eine neue Behandlungsoption zur Verfügung [8]. Aufgrund der Applikationsart weist inhalatives Loxapin eine schnelle Bioverfügbarkeit und einen raschen Wirkeintritt von < 10 min auf [3, 10]. Eine relevante Nebenwirkung ist symptomatischer Bronchospasmus, der häufiger bei Patienten mit vorbestehendem Asthma bronchiale (53,8 % Bronchospasmus vs. 11,5 % nach Placebogabe) und chronisch-obstruktiver Lungenerkrankung (23,1 % vs. 14,8 % nach Placebogabe) auftritt [7]. Unter Beachtung dieser Nebenwirkungen bei entsprechend vorerkrankten Patienten könnte sich inhalatives Loxapin auch als Notfallmedikation für agitierte Patienten mit BPS eignen, um nachfolgende Selbstverletzungen und damit verbundene Komplikationen zu vermeiden.

Effects of psychopharmacological treatment with antipsychotic drugs on the vascular system

Psychopharmacological treatment with antipsychotic drugs is an essential part of guideline-based treatment strategies in psychotic disorders, such as schizophrenia, schizoaffective disorders, and delusional disorders. Other mental disorders frequently treated with antipsychotic drugs are bipolar disorders, and major depressive disorder. Furthermore, antipsychotic drugs are often given in emergency and surgical units for the treatment of metabolic or postoperative delirium. Antipsychotic drugs can exert direct and indirect effects on the vascular system, potentially leading to severe complications such as thromboembolism. Therefore, knowledge of vascular side effects of antipsychotic drugs is important for clinicians. This clinical orientated review article covers direct and indirect effects of antipsychotics on the vascular system.

The Use of Antidepressive Agents and Bone Mineral Density in Women: A Meta-Analysis

Antidepressive agents are one of the fastest-growing classes of prescribed drugs. However, the effects of antidepressive agents on bone density are controversial. The aim of this meta-analysis is to evaluate the state of research on the relationship between the use of tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs) and bone mineral density (BMD) in women. The database searched was Pubmed. The meta-analysis included human studies in women fulfilling the following criteria: (i) an assessment of bone mineral density in the lumbar spine, the femoral neck or the total hip; (ii) a comparison of the BMD of depressed individuals using antidepressive agents (SSRIs or TCAs), and a control group that did not use antidepressive agents; (iii) measurement of BMD using dual-energy X-ray absorptiometry (DXA); and (iv) calculations of the mean BMD and standard deviation or standard error. Four studies were identified, which, in total, included 934 women using antidepressive agents and 5767 non-using individuals. The results showed that no significant negative composite weighted mean effect sizes were identified for the comparisons between SSRI users and non-users. Similarly, no significant negative composite weighted mean effect sizes were identified for the comparisons between TCA users and non-users, indicating similar BMD in SSRI or TCA users and non-users. The meta-analysis shows that the association between antidepressant medication and bone mineral density has not been extensively researched. Only four studies fulfilled the inclusion criteria. The global result of the literature review and meta-analysis was that the use of antidepressive agents was not associated with lower or higher BMD. This result applies to both SSRIs and TCAs and to all measurement locations (lumbar spine, femoral neck and total hip).

The New Hamburg-Hannover Agitation Scale in Clinical Samples: Manifestation and Differences of Agitation in Depression, Anxiety, and Borderline Personality Disorder

Background/Aims: Agitation is a burdening phenomenon that occurs in a variety of psychiatric disorders. The aim of this study was to give a first direction for agitation occurrence in depression, anxiety disorder, and borderline personality disorder (BPD) as well as in healthy controls with and without psychiatric record. Methods: Using the Hamburg-Hannover Agitation Scale (H2A), an instrument that allows for the measurement of agitation independently of the presence of a specific disorder, a patient sample (n = 158) and a healthy control group (n = 685) with (n = 94) and without (n = 591) psychiatric record were examined. The data were mainly analysed using ANOVAs and post hoc tests. Results: Patients showed significantly higher H2A agitation levels than healthy controls. Within the clinical sample, BPD patients exhibited the strongest manifestation of agitation, scoring significantly higher than the depression and the anxiety disorder sample, while these two subgroups did not significantly differ from each other. Moreover, healthy subjects with a psychiatric record experienced a significantly stronger agitation than subjects without a psychiatric record. Conclusion: Further studies are needed with larger, more balanced, and differentiated sample sizes including a wider range of clinical pictures. The results demonstrate that agitation occurs and differs in psychiatric patients as well as in healthy controls.

Psychopharmacology in transplantation medicine

Abstract Organ transplantation has become a well‐established treatment option in patients with end‐stage organ diseases. Although quality of life has markedly improved, psychiatric disorders before and after transplantation are more frequent compared to the general population. Psychopharmacological treatment is recommended for almost all mental disorders according to current guidelines, but may pose particular problems in organ transplant patients. Changes in the metabolism and elimination of drugs during organ insufficiency, drug interactions, and overlapping side effects between psychopharmacological and immunosuppressive drugs are challenging problems in clinical management. Furthermore, questions frequently arise concerning the use of psychopharmacological treatment options for sleeping and anxiety disorders. This article reviews psychopharmacology in organ transplant patients, with particular attention to frequent psychiatric disorders observed in the disease course of end‐stage organ diseases. HighlightsPsychiatric disorders before and after transplantation are more frequent compared to the general population.Psychopharmacological treatment pose particular problems in organ transplant patients.The article describes changes in the metabolism and elimination of drugs during organ insufficiency.These data may help clinicians to choose an appropriate psychopharmacological treatment for transplant patients.Further, we describe drug interactions and overlapping side effects between psychopharmacological and immunosuppressive drugs.