Background: Antidepressants are widely used in the treatment of chronic pain. Applied doses are lower than those needed to unfold an antidepressive effect. While efficacy of antidepressants for chronic pain has been reported in large randomized-controlled trials (RCT), there is inconsistent data on adverse effects and tolerability. We aimed at synthesizing data from RCT to explore adverse effect profiles and tolerability of antidepressants for treatment of chronic pain. Methods: Systematic literature research and meta-analyses were performed regarding side effects and safety of different antidepressants in the treatment of chronic pain according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The National Center for Biotechnology Information library and MEDLINE were searched. Randomized placebo-controlled trials were included in quantitative data synthesis. results: Out of 1,975 screened articles, 33 papers published between 1995 and 2015 were included in our review and 23 studies were included in the meta-analyses. A higher risk for adverse effects compared to placebo was observed in all antidepressants included in our analyses, except nortriptyline. The most prevalent adverse effects were dry mouth, dizziness, nausea, headache, and constipation. Amitriptyline, mirtazapine, desipramine, venlafaxine, fluoxetine, and nortriptyline showed the highest placebo effect-adjusted risk of adverse effects. Risk for withdrawal due to adverse effects was highest in desipramine (risk ratio: 4.09, 95%-confidence interval [1.31; 12.82]) followed by milnacipran, venlafaxine, and duloxetine. The most common adverse effects under treatment with antidepressants were dry mouth, dizziness, nausea, headache, and constipation followed by palpitations, sweating, and drowsiness. However, overall tolerability was high. Each antidepressant showed distinct risk profiles of adverse effects. conclusion: Our synthesized data analysis confirmed overall tolerability of low-dose antidepressants for the treatment of chronic pain and revealed drug specific risk profiles. This encompassing characterization of adverse effect profiles might be useful in defining multimodal treatment regimens for chronic pain which also consider patients’ comorbidities and co-medication.

Irritable bowel syndrome (IBS) is a functional disorder that affects the gastrointestinal tract and especially the large intestine. The pathogenesis of the disease is not fully understood, for that reason there is still no cure and current therapy focuses on symptom relief. The disease manifests itself in the form of abdominal pain, bloating, constipation or diarrhoea. New studies have shown a link between IBS and communication between the central nervous system and the gut. Serotonin and norepinephrine seem to be important for the course of the disease. The purpose of this literature review was to study the efficacy and safety of certain antidepressant preparations belonging to tricyclic antidepressants and selective serotonin reuptake inhibitors in the treatment of IBS. This work focused on the effect of preparations and how tolerable they are with respect to their side effects. Articles presented in this work were found in the PubMed database with the keywords "irritable bowel syndrome", "serotonin reuptake inhibitor", " tricyclic antidepressants ". Amitriptyline 10 mg and imipramine 25 mg provided a statistically significant symptom relief in IBS with diarrhoea (IBS-D) compared to placebo. In addition, tianeptine 12.5 mg 3 times / day, which belongs to the selective serotonin reuptake enhancer (SSRE) group, gave a corresponding symptom relief as amitriptyline 10 mg once / day. The difference between the two was not statistically significant, but the study was open label and non-placebo-controlled, which made it difficult to draw any conclusions. Fluoxetine, which belongs to the selective serotonin reuptake inhibitor (SSRI) group, produced a statistically significant effect compared to placebo in the treatment of constipation IBS (IBS-C). In contrast, paroxetine-CR did not have any statistically significant effect on abdominal pain in IBS-C compared with placebo. However, more patients in the paroxetine group achieved the secondary outcome (clinical global improvement) with scores of 1-2 on the scale Clinical Global Impressions-Improvement (CGI-I). Based on the studies presented in this literature study, it is concluded that a low dose of TCA is an effective and safe treatment for IBS-D while SSRIs are effective and safe in the treatment of IBS-C compared to placebo. / Irritable bowel syndrome (IBS), är funktionella störningar som drabbar gastrointestinalkanalen och framför allt kolon. Patogenesen till sjukdomen är inte helt klarlagd, av den anledningen saknas fortfarande någon botande behandling och dagens terapi fokuserar på symtomlindring. Sjukdomen yttrar sig i form av buksmärta, uppblåsthet, förstoppning eller diarré. Senaste studier har visat en koppling mellan IBS och kommunikation mellan centrala nervsystemet och tarmen. Serotonin och noradrenalin verkar ha betydelse för sjukdomsförlopp. Syftet med detta litteraturarbete var att studera effektivitet och säkerhet för några antidepressiva preparat som tillhör tricykliska antidepressiva och selektiva serotonin återupptagshämmare vid behandling av IBS. Detta arbete fokuserade på effekten av preparaten och hur tolererbara de är med avseende på deras biverkningar. Artiklar som presenteras i detta arbete söktes i databasen Pubmed med sökord ”irritable bowel syndrome”, ”serotonin reuptake inhibitors”, ” tricyclic antidepressants”. Amitriptylin 10mg och imipramin 25mg gav en statistiskt signifikant symtomlindring vid IBS med diarré (IBS-D) jämfört med placebo. Dessutom gav tianeptin 12,5mg 3 gånger/dag, som tillhör läkemedelsgruppen selektiv serotonin återupptagsenhancer (SSRE), en likvärdig symtomlindring som amitriptylin 10mg en gång/dag. Skillnaden mellan de två var inte statistiskt signifikant, däremot var studien openlabel och icke-placebokontrollerad vilket gör det svårt att dra någon slutsats. Fluoxetin, som tillhör läkemedelsgruppen selektiva serotonin återupptagshämmare SSRI, gav en statistiskt signifikant effekt jämfört med placebo vid behandling av IBS med förstoppning (IBS-C). Däremot gav paroxetin-CR ingen statistiskt signifikant effekt på buksmärta vid IBS-C jämfört med placebo, dock uppnådde fler i paroxetingruppen den sekundära utfallsvariabeln (global klinisk förbättring) och fick poäng mellan 1 – 2 på skalan Clinical Global Impressions-Improvement (CGI-I).  Baserat på studierna som presenteras i denna litteraturstudie dras slutsatsen att en låg dos TCA är en effektiv och säker behandling vid IBS-D medan SSRI är effektiva och säkra vid behandling av IBS-C jämfört med placebo.

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.

These British Association for Psychopharmacology guidelines cover the range and aims of treatment for anxiety disorders. They are based explicitly on the available evidence and are presented as recommendations to aid clinical decision making in primary and secondary medical care. They may also serve as a source of information for patients and their carers. The recommendations are presented together with a more detailed review of the available evidence. A consensus meeting involving experts in anxiety disorders reviewed the main subject areas and considered the strength of evidence and its clinical implications. The guidelines were constructed after extensive feedback from participants and interested parties. The strength of supporting evidence for recommendations was rated. The guidelines cover the diagnosis of anxiety disorders and key steps in clinical management, including acute treatment, relapse prevention and approaches for patients who do not respond to first-line treatments.

For more than half a decade, lithium has been successfully used to treat bipolar disorder. Worldwide, it is considered the first-line mood stabilizer. Apart from its proven antimanic and prophylactic effects, considerable evidence also suggests an antisuicidal effect in affective disorders. Lithium is also effectively used to augment antidepressant drugs in the treatment of refractory major depressive episodes and prevent relapses in recurrent unipolar depression. In contrast to many psychiatric drugs, lithium has outlasted various pharmacotherapeutic ‘fashions’, and remains an indispensable element in contemporary psychopharmacology. Nevertheless, data from pharmacogenetic studies of lithium are comparatively sparse, and these studies are generally characterized by small sample sizes and varying definitions of response. Here, we present an international effort to elucidate the genetic underpinnings of lithium response in bipolar disorder. Following an initiative by the International Group for the Study of Lithium-Treated Patients (www.IGSLI.org) and the Unit on the Genetic Basis of Mood and Anxiety Disorders at the National Institute of Mental Health,lithium researchers from around the world have formed the Consortium on Lithium Genetics (www.ConLiGen.org) to establish the largest sample to date for genome-wide studies of lithium response in bipolar disorder, currently comprising more than 1,200 patients characterized for response to lithium treatment. A stringent phenotype definition of response is one of the hallmarks of this collaboration. ConLiGen invites all lithium researchers to join its efforts. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

These British Association for Psychopharmacology guidelines cover the range and aims of treatment for anxiety disorders. They are based explicitly on the available evidence and are presented as recommendations to aid clinical decision making in primary and secondary medical care. They may also serve as a source of information for patients and their carers. The recommendations are presented together with a more detailed review of the available evidence. A consensus meeting involving experts in anxiety disorders reviewed the main subject areas and considered the strength of evidence and its clinical implications. The guidelines were constructed after extensive feedback from participants and interested parties. The strength of supporting evidence for recommendations was rated. The guidelines cover the diagnosis of anxiety disorders and key steps in clinical management, including acute treatment, relapse prevention and approaches for patients who do not respond to first-line treatments.

Serotonin gilt als Hauptangriffsstelle gängiger Antidepressiva bei schweren Depressionen, wie bspw. selektive Serotonin-Wiederaufnahmehemmer (SSRI), und -Enhancer (SSRE). Es bleibt offen, ob SSRI / E ausschließlich über die Manipulation des Serotoninspiegels wirken, oder ob alternative Signalwege daran beteiligt sind. Ansatzpunkte hierfür sind beispielsweise die neurotrophen Signalwege (spez. Brain derived neurotophic factor, BDNF) oder die Hypothalamus-Hypophysen-Nebennieren- (HPA) – Signalwege des Stressachsensystems. Ebenfalls wurde in Nagetiermodellen beobachtet, dass mit der Dysregulation des zentralen Serotoninsystems bei schweren Depressionen, ein Rückgang der Neurogenese im Gyrus dentatus des Hippocampus einhergeht. Ziel dieser Arbeit war, das Zusammenspiel von Serotonin, BDNF, adulter Neurogenese und der Stressachse zu untersuchen. Zentrum der Studien ist ein Mausmodell, mit einer genetischen Depletion des zentralen Serotonin-synthetisierenden Enzyms Tryptophanhydroxylase 2 (sog. Tph2-/- Mäuse). Es wurden die physiologische Reaktionen auf die Behandlung mit gängigen Antidepressiva abhängig von der Abwesenheit von Serotonin untersucht, um mögliche alternative Signalwege aufzeigen zu können. Die bekannte Zunahme der Neurogenese nach SSRI/SSRE-Behandlung wurde in Wildtyptieren beobachtet, während die Therapie in Tph2-/- Mäusen keine direkte kausale Wirkung zeigte. Im Gegensatz dazu waren die BDNF-Spiegel in depressionsrelevanten Hirnregionen in Tph2-/- Mäusen nach SSRI, signifikant verringert. Auch zeigen die Studien eine neurobiologische Relevanz von Serotonin im ZNS, bei den antidepressiven Mechanismen einer Elektrokonvulsiven Krampftherapie. Ebenfalls deuten erhöhte Neurogeneseraten bei lebenslanger Abwesenheit von Serotonin im ZNS, Therapiemethoden-unabhängig, möglicherweise auf eine modulierte Stressreaktion hin. Untersuchungen der Parameter des HPA-Stressachsensystems, wiesen auf einen grundlegend veränderten Stresshormonspiegel in Tph2-/- Mäusen hin. / Serotonin, the "molecule of happiness" is an important target for antidepressants. The mainly prescribed drugs in major depression are selective serotonin re-uptake inhibitors (SSRI); but recently, SSR-enhancer (SSRE) have also attracted clinical attention. However, only a quarter of patients responds to treatment. It needs to be determined, whether SSRI/E act solely via manipulating serotonin levels or whether other pathways are involved, e.g. neurotrophic signaling (brain-derived neurotrophic factor, BDNF) or the hypothalamus-pituitary-adrenal (HPA)-axis. Furthermore, in major depression, dysregulation of central serotonin signaling is accompanied with a decline in hippocampal neurogenesis, as has been observed in rodent models. At the center of this thesis is a mouse model deficient in the central serotonin-synthesizing enzyme, tryptophan hydroxylase 2 (Tph2-/- mice). I have investigated physiological responses to antidepressant treatment in the absence of brain serotonin, and the possible role of alternative pathways. I observed the typical increase in neurogenesis upon SSRI treatment in WT mice, while it had no effect in Tph2-/- mice. In contrast, BDNF levels were significantly decreased in Tph2-/- mice after treatment with no effect in WT control mice. Furthermore, my results show a critical role of brain serotonin in the neurobiological effects of electroconvulsive seizure. Surprisingly, in animals lacking central serotonin, increased neurogenesis was observed independently of the treatment. The gathered data indicated an altered stress response; therefore, parameters of the HPA-axis have been studied, indicating a downregulated HPA system in Tph2-/-animals in baseline state, but showed no difference in treatment or feedback control. This thesis gives insight into the mechanisms of antidepressant action and reveals ideas for novel pathways involved in the process that could be used as targets in therapeutic approaches and further research in major depression.

This revision of the 2005 British Association for Psychopharmacology guidelines for the evidence-based pharmacological treatment of anxiety disorders provides an update on key steps in diagnosis and clinical management, including recognition, acute treatment, longer-term treatment, combination treatment, and further approaches for patients who have not responded to first-line interventions. A consensus meeting involving international experts in anxiety disorders reviewed the main subject areas and considered the strength of supporting evidence and its clinical implications. The guidelines are based on available evidence, were constructed after extensive feedback from participants, and are presented as recommendations to aid clinical decision-making in primary, secondary and tertiary medical care. They may also serve as a source of information for patients, their carers, and medicines management and formulary committees.