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.

Importance Primary care clinicians find managing chronic pain challenging. Evidence of long-term efficacy of opioids for chronic pain is limited. Opioid use is associated with serious risks, including opioid use disorder and overdose. Objective To provide recommendations about opioid prescribing for primary care clinicians treating adult patients with chronic pain outside of active cancer treatment, palliative care, and end-of-life care. Process The Centers for Disease Control and Prevention (CDC) updated a 2014 systematic review on effectiveness and risks of opioids and conducted a supplemental review on benefits and harms, values and preferences, and costs. CDC used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to assess evidence type and determine the recommendation category. Evidence Synthesis Evidence consisted of observational studies or randomized clinical trials with notable limitations, characterized as low quality using GRADE methodology. Meta-analysis was not attempted due to the limited number of studies, variability in study designs and clinical heterogeneity, and methodological shortcomings of studies. No study evaluated long-term (≥1 year) benefit of opioids for chronic pain. Opioids were associated with increased risks, including opioid use disorder, overdose, and death, with dose-dependent effects. Recommendations There are 12 recommendations. Of primary importance, nonopioid therapy is preferred for treatment of chronic pain. Opioids should be used only when benefits for pain and function are expected to outweigh risks. Before starting opioids, clinicians should establish treatment goals with patients and consider how opioids will be discontinued if benefits do not outweigh risks. When opioids are used, clinicians should prescribe the lowest effective dosage, carefully reassess benefits and risks when considering increasing dosage to 50 morphine milligram equivalents or more per day, and avoid concurrent opioids and benzodiazepines whenever possible. Clinicians should evaluate benefits and harms of continued opioid therapy with patients every 3 months or more frequently and review prescription drug monitoring program data, when available, for high-risk combinations or dosages. For patients with opioid use disorder, clinicians should offer or arrange evidence-based treatment, such as medication-assisted treatment with buprenorphine or methadone. Conclusions and Relevance The guideline is intended to improve communication about benefits and risks of opioids for chronic pain, improve safety and effectiveness of pain treatment, and reduce risks associated with long-term opioid therapy.

/pdf/cdc-guideline-for-prescribing-opioids-for-chronic-pain-j4r6nt5nmj.pdf

CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016

/pdf/cdc-guideline-for-prescribing-opioids-for-chronic-pain-48d7kdjqlr.pdf

CDC guideline for prescribing opioids for chronic pain

Summary estimates of treatment effect from random effects meta-analysis give only the average effect across all studies. Inclusion of prediction intervals, which estimate the likely effect in an individual setting, could make it easier to apply the results to clinical practice

/pdf/interpretation-of-random-effects-meta-analyses-3wqyseoko4.pdf

Interpretation of random effects meta-analyses.

Importance Many people meditate to reduce psychological stress and stress-related health problems. To counsel people appropriately, clinicians need to know what the evidence says about the health benefits of meditation. Objective To determine the efficacy of meditation programs in improving stress-related outcomes (anxiety, depression, stress/distress, positive mood, mental health–related quality of life, attention, substance use, eating habits, sleep, pain, and weight) in diverse adult clinical populations. Evidence Review We identified randomized clinical trials with active controls for placebo effects through November 2012 from MEDLINE, PsycINFO, EMBASE, PsycArticles, Scopus, CINAHL, AMED, the Cochrane Library, and hand searches. Two independent reviewers screened citations and extracted data. We graded the strength of evidence using 4 domains (risk of bias, precision, directness, and consistency) and determined the magnitude and direction of effect by calculating the relative difference between groups in change from baseline. When possible, we conducted meta-analyses using standardized mean differences to obtain aggregate estimates of effect size with 95% confidence intervals. Findings After reviewing 18 753 citations, we included 47 trials with 3515 participants. Mindfulness meditation programs had moderate evidence of improved anxiety (effect size, 0.38 [95% CI, 0.12-0.64] at 8 weeks and 0.22 [0.02-0.43] at 3-6 months), depression (0.30 [0.00-0.59] at 8 weeks and 0.23 [0.05-0.42] at 3-6 months), and pain (0.33 [0.03- 0.62]) and low evidence of improved stress/distress and mental health–related quality of life. We found low evidence of no effect or insufficient evidence of any effect of meditation programs on positive mood, attention, substance use, eating habits, sleep, and weight. We found no evidence that meditation programs were better than any active treatment (ie, drugs, exercise, and other behavioral therapies). Conclusions and Relevance Clinicians should be aware that meditation programs can result in small to moderate reductions of multiple negative dimensions of psychological stress. Thus, clinicians should be prepared to talk with their patients about the role that a meditation program could have in addressing psychological stress. Stronger study designs are needed to determine the effects of meditation programs in improving the positive dimensions of mental health and stress-related behavior.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/1809754/ioi130131.pdf

Meditation Programs for Psychological Stress and Well-being: A Systematic Review and Meta-analysis

Fibromyalgia syndrome (FMS) is a chronic condition characterized by widespread pain, tender points, fatigue, and sleep disturbance. FMS leads to high disability levels, poor quality of life, and extensive use of medical care. Effective pharmacological treatment options are rare, and treatment effects are often of limited duration. Duloxetine is a new selective serotonin and norepinephrine reuptake inhibitor that is licensed for the treatment of pain in diabetic neuropathy. So far two randomized, placebo-controlled trials have investigated the short-term safety and efficacy of duloxetine 60 mg/day and 120 mg/day in patients suffering from FMS over a period of 12 weeks. Both dosages were superior to placebo in pain relief, and improvement in quality of life and depressive symptoms. The analgesic effect was largely independent of the antidepressant action of duloxetine. The higher dose of 120 mg/day further reduced the tender point count and elevated the tender point pain thresholds. Only mild to moderate adverse effects were reported. Duloxetine 60 mg/day and 120 mg/day has proven to be beneficial in the treatment of FMS symptoms. As true for other antidepressants further studies are needed to assess the long-term efficacy and safety of duloxetine as an additional pharmacological treatment option in FMS.

/pdf/new-treatment-options-for-fibromyalgia-critical-appraisal-of-3nrmgdbuux.pdf

New treatment options for fibromyalgia: critical appraisal of duloxetine.

Introduction Up to 64% of the general population reports experiencing chronic pain, with the hip being one of the most frequent sites. An association has been shown between chronic back pain, obesity and depression. To date, a similar association has not been investigated with chronic hip pain. Methods A total of 2,515 subjects were chosen as a representative cross-section of the German population. Each was provided with a questionnaire that included the Regional Pain Scale, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), Beck Depression Inventory-Primary Care and Winkler social class index. Participant height and weight values were obtained from self-reports. Using logistic regression methodology, we analysed the association between hip pain, obesity and increased depression scores. Results A total of 124 (4.9%) subjects reported chronic hip pain and an additional 39 (1.5%) reported chronic hip pain that was disabling. Hip pain affected 1-5 sites (oligolocular) in 47% of cases, and was widespread (6-19 sites) in 50%. Obesity and increased values on the depression scale were associated with an increased likelihood of chronic hip pain (odds ratio [OR] 2.55 and 8.53, respectively) compared with subjects without pain. Increased values on the depression scale (OR 28.22) increased the likelihood of experiencing disabling chronic hip pain in comparison with pain free individuals. Conclusions Hip pain is rarely the sole site of pain. Obesity and increased values on the depression scale are associated with chronic hip pain. Increased values on the depression scale are associated with disabling chronic hip pain.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/msc.1380

Obesity, depression and hip pain.

Meta-analysis is a statistical procedure that integrates the results of at least two independent studies. The biggest threats to meta-analysis are publication bias due to missing studies with negative results and low-quality evidence due to methodological limitations imposed by included studies. Tools to improve the quality of meta-analysis have been developed by the Cochrane Collaboration and by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Meta-analyses of trials have demonstrated that pain responses in patients with chronic pain, following treatment, are not normally distributed but have a bimodal distribution with the majority of patients having either very little or very good pain relief. The benefit can be detected within 2-4 weeks following drug administration. Further, the efficacy of drug and physical treatments is hampered by high placebo response rates, with modest average benefits with active treatments over placebo in both parallel and crossover design trials.

Meta-analyses of pain studies: What we have learned

A comparison of the clinical features of fibromyalgia syndrome in different settings

Bedenken bezuglich einer Langzeitopioidtherapie (LTOT) bei chronischen nichttumorbedingten Schmerzen (CNCP) bestehen wegen des Risikos der missbrauchlichen Verwendung der verschriebenen Opioide Feststellung der Pravalenz und Pradiktoren der Krankenhausaufenthalte von Personen mit einer Langzeitopioidtherapie wegen nichttumorbedingter Schmerzen und moglicher missbrauchlicher Verwendung von rezeptierten Opioiden in einer reprasentativen Stichprobe gesetzlich Krankenversicherter Retrospektive Querschnittsstudie im Jahr 2014 Anonymisierte Routinedaten von 69 gesetzlichen Krankenversicherungen mit 4028618 Versicherten Univariate logistische Regressionsanalysen, um demografische und medizinische Charakteristika zu identifizieren, die bei gesetzlich Krankenversicherten mit einer LTOT wegen CNCP mit einem Krankenhausaufenthalt und Diagnosen von psychischen und Verhaltensstorungen wegen Alkohol, Opioiden, Tranquilizern und multiplem Substanzgebrauch sowie Vergiftungen durch Betaubungsmittel assoziiert waren Die Pravalenz der LTOT wegen CNCP war 0,8 % 9,9 % dieser Versicherten erhielten eine Hochdosis-LTOT (≥120 mg Morphinaquivalent/Tag) Die 1‑Jahres-Pravalenz von Krankenhausaufenthalten mit Diagnosen von psychischen und Verhaltensstorungen wegen Alkohol, Opioiden, Tranquilizern und multiplem Substanzgebrauch und Vergiftungen durch Betaubungsmittel lag bei 1,75 % der Versicherten mit LTOT Diese Diagnosen waren stark mit der Verschreibung von Tranquilizern (Odds Ratio [OR] 3,63; 95 %-Konfidenzintervall [KI] 3,03; 4,36) und masig mit Diagnosen depressiver Storungen (OR 2,52; 95 %-KI 2,12; 3,00) und leicht mit Diagnosen von somatoformer Schmerzstorung (OR 1,89; 95 %-KI 1,56; 2,28) und Hochdosis-LTOT (OR 1,81; 95 %-KI 1,44; 2,27) assoziiert Die Studie unterstreicht Empfehlungen der Leitlinie LONTS, die gleichzeitige Verschreibung von Opioiden und Tranquilizern zu vermeiden und Patienten mit depressiver und somatoformer Schmerzstorung sorgfaltig auszuwahlen und zu uberwachen

Winfried Häuser

Papers

New treatment options for fibromyalgia: critical appraisal of duloxetine.

Obesity, depression and hip pain.

Meta-analyses of pain studies: What we have learned

A comparison of the clinical features of fibromyalgia syndrome in different settings

Langzeitopioidtherapie von nichttumorbedingten Schmerzen