BACKGROUND: Somatoform disorders are characterised by chronic, medically unexplained physical symptoms (MUPS). Although different medications are part of treatment routines for people with somatoform disorders in clinics and private practices, there exists no systematic review or meta-analysis on the efficacy and tolerability of these medications. We aimed to synthesise to improve optimal treatment decisions.OBJECTIVES: To assess the effects of pharmacological interventions for somatoform disorders (specifically somatisation disorder, undifferentiated somatoform disorder, somatoform autonomic dysfunction, and pain disorder) in adults.SEARCH METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) (to 17 January 2014). This register includes relevant randomised controlled trials (RCTs) from The Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). To identify ongoing trials, we searched ClinicalTrials.gov, Current Controlled Trials metaRegister, the World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry. For grey literature, we searched ProQuest Dissertation {\&} Theses Database, OpenGrey, and BIOSIS Previews. We handsearched conference proceedings and reference lists of potentially relevant papers and systematic reviews and contacted experts in the field.SELECTION CRITERIA: We selected RCTs or cluster RCTs of pharmacological interventions versus placebo, treatment as usual, another medication, or a combination of different medications for somatoform disorders in adults. We included people fulfilling standardised diagnostic criteria for somatisation disorder, undifferentiated somatoform disorder, somatoform autonomic dysfunction, or somatoform pain disorder.DATA COLLECTION AND ANALYSIS: One review author and one research assistant independently extracted data and assessed risk of bias. Primary outcomes included the severity of MUPS on a continuous measure, and acceptability of treatment.MAIN RESULTS: We included 26 RCTs (33 reports), with 2159 participants, in the review. They examined the efficacy of different types of antidepressants, the combination of an antidepressant and an antipsychotic, antipsychotics alone, or natural products (NPs). The duration of the studies ranged between two and 12 weeks.One meta-analysis of placebo-controlled studies showed no clear evidence of a significant difference between tricyclic antidepressants (TCAs) and placebo for the outcome severity of MUPS (SMD -0.13; 95{\%} CI -0.39 to 0.13; 2 studies, 239 participants; I(2) = 2{\%}; low-quality evidence). For new-generation antidepressants (NGAs), there was very low-quality evidence showing they were effective in reducing the severity of MUPS (SMD -0.91; 95{\%} CI -1.36 to -0.46; 3 studies, 243 participants; I(2) = 63{\%}). For NPs there was low-quality evidence that they were effective in reducing the severity of MUPS (SMD -0.74; 95{\%} CI -0.97 to -0.51; 2 studies, 322 participants; I(2) = 0{\%}).One meta-analysis showed no clear evidence of a difference between TCAs and NGAs for severity of MUPS (SMD -0.16; 95{\%} CI -0.55 to 0.23; 3 studies, 177 participants; I(2) = 42{\%}; low-quality evidence). There was also no difference between NGAs and other NGAs for severity of MUPS (SMD -0.16; 95{\%} CI -0.45 to 0.14; 4 studies, 182 participants; I(2) = 0{\%}).Finally, one meta-analysis comparing selective serotonin reuptake inhibitors (SSRIs) with a combination of SSRIs and antipsychotics showed low-quality evidence in favour of combined treatment for severity of MUPS (SMD 0.77; 95{\%} CI 0.32 to 1.22; 2 studies, 107 participants; I(2) = 23{\%}).Differences regarding the acceptability of the treatment (rate of all-cause drop-outs) were neither found between NGAs and placebo (RR 1.01, 95{\%} CI 0.64 to 1.61; 2 studies, 163 participants; I(2) = 0{\%}; low-quality evidence) or NPs and placebo (RR 0.85, 95{\%} CI 0.40 to 1.78; 3 studies, 506 participants; I(2) = 0{\%}; low-quality evidence); nor between TCAs and other medication (RR 1.48, 95{\%} CI 0.59 to 3.72; 8 studies, 556 participants; I(2) =14{\%}; low-quality evidence); nor between antidepressants and the combination of an antidepressant and an antipsychotic (RR 0.80, 95{\%} CI 0.25 to 2.52; 2 studies, 118 participants; I(2) = 0{\%}; low-quality evidence). Percental attrition rates due to adverse effects were high in all antidepressant treatments (0{\%} to 32{\%}), but low for NPs (0{\%} to 1.7{\%}).The risk of bias was high in many domains across studies. Seventeen trials (65.4{\%}) gave no information about random sequence generation and only two (7.7{\%}) provided information about allocation concealment. Eighteen studies (69.2{\%}) revealed a high or unclear risk in blinding participants and study personnel; 23 studies had high risk of bias relating to blinding assessors. For the comparison NGA versus placebo, there was relatively high imprecision and heterogeneity due to one outlier study. Although we identified 26 studies, each comparison only contained a few studies and small numbers of participants so the results were imprecise.AUTHORS' CONCLUSIONS: The current review found very low-quality evidence for NGAs and low-quality evidence for NPs being effective in treating somatoform symptoms in adults when compared with placebo. There was some evidence that different classes of antidepressants did not differ in efficacy; however, this was limited and of low to very low quality. These results had serious shortcomings such as the high risk of bias, strong heterogeneity in the data, and small sample sizes. Furthermore, the significant effects of antidepressant treatment have to be balanced against the relatively high rates of adverse effects. Adverse effects produced by medication can have amplifying effects on symptom perceptions, particularly in people focusing on somatic symptoms without medical causes. We can only draw conclusions about short-term efficacy of the pharmacological interventions because no trial included follow-up assessments. For each of the comparisons where there were available data on acceptability rates (NGAs versus placebo, NPs versus placebo, TCAs versus other medication, and antidepressants versus a combination of an antidepressant and an antipsychotic), no clear differences between the intervention and comparator were found.Future high-quality research should be carried out to determine the effectiveness of medications other than antidepressants, to compare antidepressants more thoroughly, and to follow-up participants over longer periods (the longest follow up was just 12 weeks). Another idea for future research would be to include other outcomes such as functional impairment or dysfunctional behaviours and cognitions as well as the classical outcomes such as symptom severity, depression, or anxiety.

Pharmacological interventions for somatoform disorders in adults.

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Integrative analysis of 111 reference human epigenomes

Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression

https://www.ecnp.eu/~/media/Files/ecnp/communication/reports/ECNP%20EBC%20Report.pdf

The size and burden of mental disorders and other disorders of the brain in Europe 2010

https://cyberleninka.org/article/n/148766.pdf

Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation

Associazione di reboxetina nella depressione resistente a SSRI

Psychiatry is facing a constant increase of services demands from the population. From one side the improvement of life conditions facilitates the emergence of psychopathology that affects about 50% of the population lifetime 1, from the other psychiatrists often serve as an emergency care in social needs (such as homeless or unemployed) where the psychiatric component is marginal if any. This leads to a demand of care from a very large part of the population with consequences that we will analyze and discuss throughout the editorial. Specifically, in Italy, after more than 30 years of the dramatic change occurred in psychiatry services organization, such aspects impact even more with a generalized unsatisfaction both for patients and staff members, though with some local exceptions 2 3. The 1978 change in the whole body of regulations defining psychiatric activity completely reversed the role of the psychiatrist from a figure mainly devoted to social control (as specified in the 1904 law) to a figure promoting patient autonomy. However both aspects are still present and the psychiatrist faces in the everyday clinical practice this dilemma: benefit of the patient vs. benefit of the social context. Further, the huge demand of care by the population faces a relatively insufficient offer from psychiatric services further impaired by a large heterogeneity in the specific models of care (inpatients vs outpatients, drugs vs. psychosocial treatments and so on) that we will discuss later on 4.

/pdf/perspectives-for-italian-psychiatry-4ebs728nms.pdf

Perspectives for Italian Psychiatry

Because of the high variance in response attributable to genetic variants (more than 40% considering only common variants),the pharmacogenetics of antidepressant drugs has been a great challenge in recent years. Candidate gene studies focus on individual polymorphisms in genes selected from molecular studies, experiments with cell lines, animal models, or data obtained in humans (e.g., postmortem studies, neuroimaging, biomarkers). However, despite the careful process of selection based on biological evidence, these studies do not allow identification of the multiple loci involved in antidepressant response; furthermore, the antidepressant mechanisms of action are still only partially known. For these reasons, the results of candidate studies have often been contradictory and poorly replicated, although they have outlined a few good candidate genes ( SLC6A4 , COMT , IL1B , BDNF , and GNB3 ). In order to overcome the limitations of candidate studies, genome-wide association studies (GWASs) were recently introduced. They allow the genotyping of hundreds of thousands of polymorphisms across the whole genome with no a priori hypothesis. Nethertheless, these studies show some technical limitations and a difficult balancing between type I and type II error. Some of the most interesting GWAS results are on the RORA , CDH17 , EPHB1 , and IL11 genes. Current pharmacogenetic trends point to the convergent use of complementary methodologies: GWAS as a discovery approach, candidate gene studies, and analysis of whole molecular pathways as in-depth analyses.

Pharmacogenetics of Antidepressant Drugs

Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy Received 20 April 2022 Accepted 20 April 2022 Correspondence to Alessandro Serretti, MD, Department of Biomedical and NeuroMotor Sciences, University of Bologna, Viale Carlo Pepoli 5, 40123 Bologna, Italy, Tel: +39 051 6584233; fax: +39 051 521030; e-mail: [email protected] 

Alessandro Serretti

Papers

Associazione di reboxetina nella depressione resistente a SSRI

Perspectives for Italian Psychiatry

Pharmacogenetics of Antidepressant Drugs

Strategies for improving schizophrenia treatment

P.2.c.004 Basic fibroblast growth factor (FGF2) gene polymorphisms could contribute to SSRIs treatment response and tolerability