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.

Background: There is an urgent need to develop safe and effective treatments for patients with treatment-resistant depression (TRD). Several neurosurgical procedu

/pdf/the-history-and-future-of-ablative-neurosurgery-for-major-4238s90bys.pdf

The History and Future of Ablative Neurosurgery for Major Depressive Disorder

The standard life events methodology for the prediction of psychological symptoms was compared with one focusing on relatively minor events, namely, the hassles and uplifts of everyday life Hassles and Uplifts Scales were constructed and administered once a month for 10 consecutive months to a community sample of middle-aged adults It was found that the Hassles Scale was a better predictor of concurrent and subsequent psychological symptoms than were the life events scores, and that the scale shared most of the variance in symptoms accounted for by life events When the effects of life events scores were removed, hassles and symptoms remained significantly correlated Uplifts were positively related to symptoms for women but not for men Hassles and uplifts were also shown to be related, although only modestly so, to positive and negative affect, thus providing discriminate validation for hassles and uplifts in comparison to measures of emotion It was concluded that the assessment of daily hassles and uplifts may be a better approach to the prediction of adaptational outcomes than the usual life events approach

/pdf/comparison-of-two-modes-of-stress-measurement-daily-hassles-3vdstiyzjs.pdf

Comparison of two modes of stress measurement: Daily hassles and uplifts versus major life events

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.22759

Diagnosis, management, and treatment of hepatitis C: An update

In 2 meta-analyses on gender differences in depression in nationally representative samples, we advance previous work by including studies of depression diagnoses and symptoms to (a) estimate the magnitude of the gender difference in depression across a wide array of nations and ages; (b) use a developmental perspective to elucidate patterns of gender differences across the life span; and (c) incorporate additional theory-driven moderators (e.g., gender equity). For major depression diagnoses and depression symptoms, respectively, we meta-analyzed data from 65 and 95 articles and their corresponding national data sets, representing data from 1,716,195 and 1,922,064 people in over 90 different nations. Overall, odds ratio (OR) = 1.95, 95% confidence interval (CI) [1.88, 2.03], and d = 0.27 [0.26, 0.29]. Age was the strongest predictor of effect size. The gender difference for diagnoses emerged earlier than previously thought, with OR = 2.37 at age 12. For both meta-analyses, the gender difference peaked in adolescence (OR = 3.02 for ages 13-15, and d = 0.47 for age 16) but then declined and remained stable in adulthood. Cross-national analyses indicated that larger gender differences were found in nations with greater gender equity, for major depression, but not depression symptoms. The gender difference in depression represents a health disparity, especially in adolescence, yet the magnitude of the difference indicates that depression in men should not be overlooked. (PsycINFO Database Record

Gender differences in depression in representative national samples: Meta-analyses of diagnoses and symptoms.

Deep brain stimulation of the subcallosal cingulate for treatment-refractory anorexia nervosa: 1 year follow-up of an open-label trial.

There is an urgent need to develop novel and effective treatments for Alzheimer disease (AD). Despite decades of advances in genetics and imaging, we are no further in influencing its inexorable decline to functional dependence and death. Much of the challenge stems from the underlying pathology of AD, which implicates a broad range of neurochemical, cerebrovascular, metabolic, and inflammatory pathways. Our current understanding of AD pathophysiology is centered on the amyloid cascade hypothesis, marked by an accumulation of extracellular amyloid beta (Ab) plaques and intracellular tau neurofibrillary tangles. Ab oligomers can impair action potentiation, trigger synaptic dysfunction and inflammation, and influence axonal degeneration through hyperphosphorylation of microtubular tau. Other histopathologic features include accumulation of neurofibrillary tangles and degeneration of cholinergic neurons in the basal forebrain. Neurofibrillary tangles, composed of the microtubuleassociated protein tau, may be triggered by Ab plaques, and are strongly correlated with neuronal loss and cerebral atrophy. The extent of cholinergic dysfunction is also associated with the degree of cognitive impairment and amyloid plaque load. Accordingly, preventing the buildup of beta amyloid, or facilitating its clearance, has become an important target for AD therapeutics.

Focused ultrasound as a novel strategy for Alzheimer disease therapeutics

https://doi.org/10.1016/s0167-8140(22)04446-2

166: Operation of Incident Learning During the COVID-19 Pandemic: A Single Centre Experience

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The History and Future of Ablative Neurosurgery for Major Depressive Disorder

Deep brain stimulation of the subcallosal cingulate for treatment-refractory anorexia nervosa: 1 year follow-up of an open-label trial.

Focused ultrasound as a novel strategy for Alzheimer disease therapeutics

166: Operation of Incident Learning During the COVID-19 Pandemic: A Single Centre Experience