Background: It is unclear whether generalized anxiety disorder (GAD) has a specific relationship to pain syndromes, going beyond the established association of pain with anxiety syndromes in general. Methods: Mental disorders were assessed in a community sample (N = 4181; 18–65 years) using the DSM-IV/M-CIDI. Several threshold definitions were used to define GAD and medically unexplained pain. Results: The association between pain and GAD (odds ratio, OR = 5.8 pain symptoms; OR = 16.0 pain disorder) is stronger than the association between pain and other anxiety disorders (OR = 2.4 pain symptoms; OR = 4.0 pain disorder). This association extends to subthreshold level definitions of GAD with some indication for a non-linear dose–response relationship. The GAD-pain link cannot sufficiently be explained by demographic factors, comorbid mental or physical disorders. Conclusions: The association of pain and generalized anxiety is not artifactual. Compared to other anxiety syndromes, it appears to be stronger and more specific suggesting the need to explore clinical and public health implications.

Ziel unserer molekulargenetischen Studien ist es, Gene der genetisch komplexen idiopathisch generalisierten Epilepsien (IGE) im Genom des Menschen zu lokalisieren und die verantwortlichen Genstörungen durch die Mutationsanalyse von positionell und funktionell plausiblen Kandidatengenen zu identifizieren. Unsere Kopplungsanalysen konnten einen IGE-Locus (Locus-Symbol: EJM1) in der chromosomalen Region 6p21.3 bestätigen und die Kandidatengenregion auf ein chromosomales Segment von 10 centiMorgan (cM) eingrenzen. Ein positionell und funktionell plausibles Kandidatengen ist das Gen einer Untereinheit des heterodimeren GABAB Rezeptors (Gen-Symbol: GABA-BR1). Die systematische Mutationsanalyse des GABA-BR1 Gens und eine Assoziationsstudie mit drei Sequenzpolymorphismen in den Exonen 1a1, 7 und 11 ergaben keinen Anhalt für eine Beteiligung des GABA-BR1 Gens bei der Epileptogenese der IGE. Kopplungshinweise in den chromosomalen Regionen 20q13, 8q24 und 15q14 konnten wir in unserem Familienkollektiv nicht bestätigen. Die Mutationsanalyse der Kandidatengene CHRNA4 und KCNQ2 in der Kandidatengenregion 20q13 und von zwei Kalziumkanal-Genen (CACNA1A, CACNB4) ergaben keinen Hinweis auf disponierende Sequenzvarianten bei IGE-Patienten. Unsere systematische Genomanalyse bei 130 Familien mit mehreren IGE-Angehörigen zielte auf die positionelle Eingrenzung von Genstörungen, die an der Disposition eines breiten IGE-Spektrums beteiligt sind. Bei 360 der 694 Familienangehörigen lag ein IGE-Phänotyp vor. Bei 617 Familienangehörigen wurden für die systematische Genomanalyse insgesamt 416 Mikrosatelliten-Polymorphismen mit einem durchschnittlichen Abstand von 10 cM genotypisiert. Die parameter-freien Kopplungsanalysen ergaben einen signifikanten Kopplungsbefund in der chromosomalen Region 3q26 (P = 1,7 x 10-5 bei D3S3725) sowie zwei Kopplungshinweise in den chromosomalen Regionen 2q36.1 (P = 5,4 x 10-4 bei D2S1371) und 14q23 (P = 5,6 x 10-4 bei D14S63). Positionell und funktionell plausible Kandidatengene sind die Gene des Kalium-Kanals KCNA1B und des Chlorid-Kanals CLCN2 in der Region 3q26, das Gen des Chlorid-Bikarbonat Austauschers SLC4A3 in der Region 2q36, und das Gen des Natrium-Kalzium Austauschers SLC8A3 in der Region 14q23. Der molekulargenetische Nachweis von Genmutationen für die IGE wird konkrete Einblicke in die molekularen Mechanismen der Epileptogenese eröffnen und die Voraussetzungen dafür schaffen, rational begründete Therapieansätze zu entwickeln. / The aim of our molecular genetic studies is to map genes of the genetically complex idiopathic generalized epilepsies on the human genome and to identify the causative gene variants by mutation analyses of positional and functional plausible candidate genes. Our linkage studies confirmed an IGE-locus (locus symbol: EJM1) in the chromosomal region 6p21.3 and to refine the candidate region to a chromosomal segment of 10 centiMorgan (cM). A positional and functional candidate gene is the gene encoding a subunit of the heterodimeric GABAB receptor (gene symbol: GABA-BR1). The systematic mutation screening of the GABA-BR1 gene and an association analysis with three sequence polymorphisms in exons 1a1, 7 and 11 provided no evidence that the GABA-BR1 gene confers susceptibility to the epileptogenesis of IGE. We failed to replicate previous linkage findings in the chromosomal regions 20q13, 8q24 and 15q14 in our family sample. Mutation analysis of the candidate genes CHRNA4 and KCNQ2 and two genes encoding calcium channel subunits (CACNA1A, CACNB4) did not detect common susceptibility alleles in IGE patients. Our systematic genome scan was designed to identify susceptibility loci that predispose to a broad spectrum of common IGE syndromes. Our study included 130 families with two or more siblings affected by an IGE. In total, 360 out of 694 family members were affected by an IGE-trait. 617 family members were genotyped for 416 microsatellite polymorphisms with an average distance of 10 cM. Non-parametric linkage analysis provided significant evidence for a novel IGE susceptibility locus on chromosome 3q26 (ZNPL = 4.19 at D3S3725; P = 0.000017) and suggestive evidence for two IGE loci on chromosome 14q23 (ZNPL = 3.28 at D14S63; P = 0.000566), and chromosome 2q36 (ZNPL = 2.98 at D2S1371; P = 0.000535). Positional and functional candidate genes include the potassium channel gene KCNA1B and the chloride channel gene CLCN2 in the region 3q26, the chloride-bicarbonate anion exchanger gene SLC4A3 in the region 2q36, and the sodium-calcium exchanger gene SLC8A3 in the region 14q23. The molecular genetic detection of susceptibility genes for IGE will provide clues to elucidate the complex molecular pathways of epileptogenesis, and, finally, will help to develop rational treatment strategies.

Generalized anxiety disorder (GAD) is associated with painful physical symptoms (PPS). These post hoc analyses of previous trial data assessed PPS and their response to duloxetine treatment in GAD patients. Studies 1 and 2 (n = 840) were 9- to 10-week efficacy trials; study 3 (n = 887) was a relapse prevention trial comprising a 26-week open-label treatment phase and a 26-week double-blind, placebo-controlled treatment continuation phase. Mean baseline visual analog scale scores (VAS, 0–100; n = 1727) ranged from 26 to 37 for overall pain, headache, back pain, shoulder pain, interference with daily activities, and time in pain while awake. In studies 1 and 2, improvement on all VAS scores was greater in duloxetine-treated than in placebo-treated patients (p ≤ 0.01). In study 3, pain symptoms worsened in responders switched to placebo compared with those maintained on duloxetine (p ≤ 0.02). In conclusion, duloxetine was efficacious in the short- and long-term treatment of PPS, which are common in GAD patients.

The objective was to examine duloxetine 60–120mg/day treatment for relapse prevention in adults with generalized anxiety disorder (GAD). Adult patients (N=887; mean age=43.3 years; 61.0% female) with DSM-IV-TR-defined GAD diagnosis were treated with duloxetine for 26 weeks. Patients who completed open-label phase and were treatment responders (≥50% reduction in Hamilton Anxiety Rating Scale total score to ≤11 and “much”/“very much improved” ratings for the last 2 visits of open-label phase) were randomly assigned to receive duloxetine or placebo for a 26-week double-blind continuation phase. Relapse was defined as ≥2-point increase in illness severity ratings or by discontinuation due to lack of efficacy. During the double-blind phase, placebo-treated patients (N=201) relapsed more frequently (41.8%) than duloxetine-treated patients (13.7%, N=204, P≤0.001) and worsened on each outcome measure (P≤0.001, all comparisons). Duloxetine 60–120 mg/day treatment was efficacious and reduced risk of relapse in patients with GAD.

Der Beitrag untersucht auf der Grundlage neuer primärärztlicher Befunde die Versorgungsqualität bei der hinsichtlich Chronizität und Arbeitsausfall schwerwiegendsten Angsterkrankung, der Generalisierten Angststörung. Neben einer knappen Einführung in das Störungsbild werden die an über 20 000 Patienten in 558 Hausarztpraxen gewonnenen Kernbefunde der GAD-P-Studie (Generalisierte Angst und Depression in der Primärärztlichen Versorgung) zusammengefasst und Ansatzpunkte zur Verbesserung der Versorgungsqualität dieses selten adäquat behandelten Störungsbildes diskutiert. Insbesondere wird auf die zentrale Bedeutung einer sichereren diagnostischen Erkennung als Voraussetzung für therapeutische Verbesserungen hingewiesen. In Ergänzung zur Verbesserung bestehender Weiterbildungsangebote wird auf Arzt- und Patientenebene der breitere Einsatz bestehender Screeningverfahren, die Nutzung krankheitsspezifischer Patientenratgeber, sowie eine breitere Öffentlichkeitsarbeit zur Information über dieses bislang vernachlässigte, häufig chronisch verlaufende Krankheitsbild empfohlen. / Based on new empirical findings in a large-scale primary care study, the quality of care for the most chronic and debilitating anxiety problem, generalised anxiety disorder, is examined. Following a brief introduction of this disorder, the core findings of the GAD-P study (generalised anxiety and depression in primary care) with more than 20,000 patients of 558 family doctor practices are summarised and measures to improve the quality of care of patients with generalised anxiety disorder, a disorder which is rarely adequately treated, are discussed. This paper particularly emphasises the standard use of time-efficient diagnostic screening instruments, because improved recognition and diagnosis is the prerequisite for appropriate treatment. Further the role of the media to increase awareness of this disorder as well as patient education materials to improve compliance and to enhance treatment outcome effects are highlighted.

No description available.

Pathologische Sorgen sind ungenau definiert. Für die Behandlungsplanung bleiben wichtige Fragen offen: Welche Merkmale sind für die Unterscheidung zwischen behandlungsbedürftigen und nicht behandlungsbedürftigen Sorgen relevant? Welche Art von Sorgen muss wie behandelt werden? Und: Welche Art von Sorgen gilt es eher zu akzeptieren? Wir machen praxisnahe Vorschläge dafür, wie Sorgen mittels einer einfachen Heuristik auch vom Patienten selbst als «pathologisch» identifiziert werden können. Im Sinne eines therapeutischen Arbeitsmodells ergeben sich differentielle Bearbeitungsstrategien, je nachdem, ob es sich um wichtige oder weniger wichtige, auf lösbare oder unlösbare Probleme bezogene sowie angemessene oder überzogene Sorgen handelt. Das vorgestellte Arbeitsblatt zu den Sorgen soll vor allem die wahrgenommene Kontrolle des Patienten stärken und die Psychoedukation zur Generalisierten Angststörung erleichtern. / Pathological worries have not yet been clearly defined. As a consequence, practically relevant questions remain open: Which characteristics distinguish worries relevant for treatment from those which are not? What kind of worries has to be treated in which way? And: What kind of worries is rather to be accepted? We propose a simple rationale which helps the therapist and the patient to identify pathological worries. According to this working model, different treatment strategies result depending on whether worries are central or not, whether they relate to a problem which can be solved or not, and whether they seem proportionate or exaggerated. The presented worksheet is meant to strengthen the perceived control of the patient and to help facilitate psychoeducation for generalised anxiety disorder. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Background: Worry exposure (WE) is a core element of cognitive-behavioral treatment for generalized anxiety disorder (GAD). Its efficacy as a stand-alone treatment method (without further cognitive-behavioral therapy interventions) has never been tested.We aimed to examine whether WE alone is as efficacious as the empirically supported stand-alone treatment for GAD, applied relaxation (AR). Methods: In a randomized controlled study, 73 outpatients meeting DSM-IV criteria for GAD as primary diagnosis were allocated to either WE or AR or a waiting list control group; in a 2nd randomization procedure the waiting list subjects were reallocated to WE or AR. The treatment was manualized (15 sessions with WE or AR), included 6-month and 1-year follow-ups, as well as last observation carried forward and completer analyses, and was controlled for allegiance effects.The Hamilton Anxiety Rating Scale and the State-Trait Anxiety Scale were used as primary outcome measures. Self-report scales of anxiety, worrying and depression including negative metacognition about worrying and thought suppression served as secondary outcome measures. Results: The dropout rate was moderate. The pre-/posttreatment effects were high for the Hamilton Anxiety Rating Scale (standardized mean difference >1) and for the State-Trait Anxiety Inventory (standardized mean difference >0.87). The proportion of patients reaching high end state functioning was 48% (WE) and 56% (AR). WE and AR did not differ with regard to dropout rate or treatment effects. The treatment effects were stable at 6 month and 1 year follow-up. Conclusion: This is the first study to show that a stand-alone exposure in sensu technique – WE – is efficacious in the treatment of GAD. Both AR and WE seem to represent effective principles of change in GAD. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Der Beitrag untersucht auf der Grundlage neuer primärärztlicher Befunde die Versorgungsqualität bei der hinsichtlich Chronizität und Arbeitsausfall schwerwiegendsten Angsterkrankung, der Generalisierten Angststörung. Neben einer knappen Einführung in das Störungsbild werden die an über 20 000 Patienten in 558 Hausarztpraxen gewonnenen Kernbefunde der GAD-P-Studie (Generalisierte Angst und Depression in der Primärärztlichen Versorgung) zusammengefasst und Ansatzpunkte zur Verbesserung der Versorgungsqualität dieses selten adäquat behandelten Störungsbildes diskutiert. Insbesondere wird auf die zentrale Bedeutung einer sichereren diagnostischen Erkennung als Voraussetzung für therapeutische Verbesserungen hingewiesen. In Ergänzung zur Verbesserung bestehender Weiterbildungsangebote wird auf Arzt- und Patientenebene der breitere Einsatz bestehender Screeningverfahren, die Nutzung krankheitsspezifischer Patientenratgeber, sowie eine breitere Öffentlichkeitsarbeit zur Information über dieses bislang vernachlässigte, häufig chronisch verlaufende Krankheitsbild empfohlen. / Based on new empirical findings in a large-scale primary care study, the quality of care for the most chronic and debilitating anxiety problem, generalised anxiety disorder, is examined. Following a brief introduction of this disorder, the core findings of the GAD-P study (generalised anxiety and depression in primary care) with more than 20,000 patients of 558 family doctor practices are summarised and measures to improve the quality of care of patients with generalised anxiety disorder, a disorder which is rarely adequately treated, are discussed. This paper particularly emphasises the standard use of time-efficient diagnostic screening instruments, because improved recognition and diagnosis is the prerequisite for appropriate treatment. Further the role of the media to increase awareness of this disorder as well as patient education materials to improve compliance and to enhance treatment outcome effects are highlighted.

Background and Objectives: To describe patterns of healthcare utilization among patients with generalized anxiety disorder (GAD) in general practitioner (GP) settings in Germany. Methods: Using a large computerized database with information from GP practices across Germany, we identified all patients, aged > 18 years, with diagnoses of, or prescriptions for, GAD (ICD-10 diagnosis code F41.1) between October 1, 2003 and September 30, 2004 ("GAD patients"). We also constituted an age- and sex-matched comparison group, consisting of randomly selected patients without any GP encounters or prescriptions for anxiety or depression (a common comorbidity in GAD) during the same period. GAD patients were then compared to those in the matched comparison group over the one-year study period. Results: The study sample consisted of 3340 GAD patients and an equal number of matched comparators. Mean age was 53.2 years; 66.3% were women. Over the 12-month study period, GAD patients were more likely than matched comparators to have encounters for various comorbidities, including sleep disorders (odds ratio [OR] = 6.75 [95% CI = 5.31, 8.57]), substance abuse disorders (3.91 [2.89, 5.28]), and digestive system disorders (2.62 [2.36, 2.91]) (all p < 0.01). GAD patients averaged 5.6 more GP encounters (10.5 [SD = 8.8] vs 4.9 [5.7] for comparison group) and 1.4 more specialist referrals (2.3 [2.9] vs 0.9 [1.7]) (both p < 0.01). Only 58.3% of GAD patients received some type of psychotropic medication (i.e., benzodiazepines, antidepressants, and/or sedatives/hypnotics). Conclusions: Patients with GAD in GP practices in Germany have more clinically recognized comorbidities and higher levels of healthcare utilization than patients without anxiety or depression.