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

Summary Objectives Alexithymia is frequently associated with major depression and anxiety disorders, and in the literature it is considered as a negative prognostic factor in the treatment of these disorders. Nevertheless, limited evidence is available about the effect of alexithymia on treatment outcome. In this study, we analyze the presence of alexithymia in patients with depressive or anxiety disorders. In addition, we investigate the effects of alexithymia considered as a single factor, and the interaction between alexithymia and socio-demographics and clinical variables (personality traits) as modulators of response to combined treatment. Materials and methods Eighteen outpatients with major depression or anxiety disorders underwent pharmacotherapy and individual psychodynamic psychotherapy. Subjects were assessed using the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A) and the Toronto Alexithymia Scale 20-item (TAS-20) at baseline and after eight weeks of treatment. Personality traits were assessed with the SCID II at baseline. Outcome was the change in scores of HAM-D and HAM-A from baseline to the eight weeks of treatment. Predictor was the TAS score. The statistical relationship between outcome and predictor was analyzed by linear regression. In the regression model, we included stratification factors (socio-demographics and clinical variables) as covariates if they had a significant statistic relationship with the main outcome and their interaction with the main outcome is included. Results After eight weeks of treatment, we observed an improvement of 78% on HAM-D and of 69% on HAM-A, while 55.5% of subjects were not alexithymic, 22.2% were borderline alexithymic and 5.5% were diagnosed as alexithymic. No significant effect resulted from the analysis of alexithymia as a modulator of response to anxiety or depressive symptoms. On the other hand, the combination of alexithymia with “older age” predicted worse outcome by the HAM-D (p = 0.02873). Moreover, we observed a negative correlation between “obsessivecompulsive personality traits” and improvement on HAM-D (p = 0.002314), and a positive correlation between alexithymia and obsessive-compulsive personality traits (p = 0.02629).

/pdf/alessitimia-e-personalita-in-pazienti-con-disturbi-d-ansia-e-4i1puuh2lg.pdf

Alessitimia e personalità in pazienti con disturbi d'ansia e depressione maggiore: influenze sull'outcome di trattamento Alexithymia and personality in patients with anxiety disorders and major depression: effects on treatment outcome

Use of psychiatric emergency services by immigrants in an Italian first aid setting

Association analysis of the tumor necrosis factor gene polymorphisms (TNFA 238 and 302) in the development of schizophrenia: Impact on the antipsychotic treatment response

Alessandro Serretti

Papers

Alessitimia e personalità in pazienti con disturbi d'ansia e depressione maggiore: influenze sull'outcome di trattamento Alexithymia and personality in patients with anxiety disorders and major depression: effects on treatment outcome

Use of psychiatric emergency services by immigrants in an Italian first aid setting

Association analysis of the tumor necrosis factor gene polymorphisms (TNFA 238 and 302) in the development of schizophrenia: Impact on the antipsychotic treatment response

P01-112 Are noradrenergic antidepressants a valuable choice in the treatment of panic disorder? A review and meta analysis

Corrigendum to “DTNBP1 haplotype influences baseline assessment scores of schizophrenic in-patients” [Neurosci. Lett. 440 (2008) 150–154]