Hyponatriämie, definiert als Serum-Natrium < 135 mmol/l, ist ein potentiell lebensbedrohender Zustand und wird häufig bei älteren und psychiatrischen Patienten beobachtet. In den letzten Jahren wurden viele Case reports über SSRI- und SNRI- induzierte Hyponatriämien publiziert. Kardiale Veränderungen, insbesondere eine verlängerte QT-Zeit oder erhöhte Herzfrequenz, werden auch als häufig beobachtete Nebenwirkungen unter Therapie mit Antidepressiva beschrieben. Dies konnte bislang insbesondere während der Einnahme von trizyklischen Antidepressiva beobachtet werden. Oft kann der beobachtete Effekt in Zusammenhang mit der verabreichten Dosis gebracht werden. Bei der SSRI- bzw. SNRI-induzierten Hyponatriämie konnte dies bislang nicht gezeigt werden. In der Literatur lassen sich im Allgemeinen kaum Studien finden, die einen Zusammenhang der Serumkonzentration von SSRI und SNRI auf potentiell auftretende Nebenwirkungen untersucht haben. Ziel der vorliegenden Studie war zu zeigen, ob höhere Serumkonzentrationen von Citalopram, Escitalopram, Sertralin, Venlafaxin oder Duloxetin häufiger zu Hyponatriämien bzw. Verlängerungen der QT-Zeit führen. / Hyponatremia, defined as a serum sodium below 135 mmol/L, is a potentially life-threatening condition and was shown to be more frequent in elderly and psychiatric patients. In the last years numerous case reports on SSRI- and SNRI-induced hyponatremia were published indicating a higher incidence than previously thought. Cardiac side effects, especially QT-interval prolongation, are also reported as a common side effect under therapy with antidepressants in general. While QT-interval prolongation seems to be dose-dependent, SSRI-induced hyponatremia was shown not to correlate with dose. There were hardly studies, who investigate a correlation between plasma levels of SSRI and SNRI and potentially occuring side effects. Aim of this study was to show, if there is a higher incidence of hyponatremia and QT-interval prolongation under increasing plasma levels of Citalopram, Escitalopram, Sertralin, Venlafaxin and Duloxetin.

Fibromyalgi är ett kroniskt smärtsyndrom med prevalens i Sverige och internationellt kring 2 %. Karakteristiskt är långvarig, utbredd och generaliserad smärta, dock förekommer andra psykiska och fysiska symtom som gör syndromets symtombild varierad. Syndromet har i decennier inte accepterats på grund av dess oklara etiologi. Avvikelser har beskrivits i centrala nervsystemet och i periferin hos fibromyalgipatienter. Det finns också teorier om att psykiska mekanismer kan vara involverade. Vad som saknas är kausalsamband mellan fynden som rapporterats. Behandlingen är symtomatisk i form av icke-farmakologiska eller farmakologiska alternativ. Val av intervention avgörs utefter patientens symtombild. I Europa finns idag inget godkänt läkemedel för behandling av fibromyalgi och läkemedelsterapi sker utanför godkänd indikation. I USA har tre läkemedel godkänts för behandling av fibromyalgi och två av dessa är duloxetin och pregabalin. Båda dessa läkemedel inkluderas i en nyligen uppdaterad europeisk rekommendation som ligger till grund för läkemedelsverkets rekommendationer i Sverige. Läkemedelsföretagen bakom duloxetin och pregabalin har år 2008 och 2009 ansökt om godkännande till försäljning av läkemedlen till fibromyalgipatienter i Europa, dock avslogs ansökningarna. Trots avslag fortsätter läkemedelsföretagen driva forskning om dessa läkemedel vid fibromyalgi. Denna litteraturundersöknings syfte var att utvärdera effekt och säkerhet för duloxetin och pregabalin vid symtomatisk behandling av smärta orsakad av fibromyalgi. Utvärderingen inkluderar åtta kliniska studier som publicerats från och med år 2008, fyra studier med duloxetin och fyra med pregabalin. Resultat från litteraturundersökningen visar att varken duloxetin eller pregabalin har någon stor effekt, jämfört med placebo, på fibromyalgins främsta symtom smärta. Placeboeffekten är relativt stor och dossamband saknas för läkemedlen. / Fibromyalgia is a chronic pain syndrome characterized by widespread generalized pain. Patients also experience other both mental and physical symptoms making the syndrome heterogeneous. Co-morbidity examples are somnolence, gastrointestinal problems and psychiatric conditions including depression and anxiety. The prevalence of fibromyalgia in Sweden is 2,0 % of the population and the international prevalence is similar. Of these 2,0 % almost 80 % are women and the average age of the patients is middle-age. For decades fibromyalgia has not been accepted because of its unknown etiology. Abnormalities have been found in both the central nervous system and in the periphery of fibromyalgia patients. There are also theories that a mental mechanism like poor well-being and stress can cause local pain that can spread and develop into widespread pain. Currently a causal relationship behind the clinical findings is missing.   The treatment of fibromyalgia is often symptomatic according to the patient’s symptoms and needs. The treatment can either be non-pharmacological or pharmacological. In Sweden and the rest of Europe there is no drug approved by the European Medicines Agency for the treatment of fibromyalgia. In the United States three drugs are approved by the Food and Drugs Administration, the two antidepressants milnacipran and duloxetine and the anticonvulsant pregabalin. In a recent update by the European League Against Rheumatism (EULAR) both duloxetine and pregabalin are listed as recommended drugs for the treatment of symptoms of fibromyalgia. The Swedish medical agency has in their recommendations for Swedish healthcare followed the update from EULAR. The pharmaceutical companies have applied for authorization to market the drugs in Europe for treatment of fibromyalgia but the Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion to all applications on the grounds that there was poor benefit, due to poor evidence of effect from clinical trials, compared to the side effects of the drugs. Despite this assessment, the companies are supporting new clinical trials. This literature study examined eight clinical trials published from year 2008 and later, conducted to assess the effect and safety of the two drugs duloxetine and pregabalin compared to placebo. The aim of this literature study was to analyze the effect and safety of these drugs for symptomatic treatment of pain caused by fibromyalgia. The aggregated results show that neither duloxetine nor pregabalin had any major effect on pain caused by fibromyalgia, nor on other symptoms. There was a lack of dose response relationship and several parameters also improved with placebo treatment.

Comparing the efficacy of different treatments in psychiatry is difficult for many reasons, even when they are investigated in `head-to-head' studies. A consensus meeting was, therefore, held to produce best practice guidelines for such studies. This article presents the conclusions of this consensus and illustrates it using published data in the field of antidepressant treatment of generalized anxiety disorder.

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.

Comparing the efficacy of different treatments in psychiatry is difficult for many reasons, even when they are investigated in `head-to-head' studies. A consensus meeting was, therefore, held to produce best practice guidelines for such studies. This article presents the conclusions of this consensus and illustrates it using published data in the field of antidepressant treatment of generalized anxiety disorder.

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.