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

Non-opioid analgesics are widely used for pain relief in palliative medicine. However, there is a lack of evidence-based recommendations addressing the efficacy, tolerability, and safety of non-opioids in this field. A comprehensive systematic review and meta-analysis on current evidence can provide a basis for sound recommendations in clinical practice. A database search for controlled trials on the use of non-opioids in adult palliative patients was performed in Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, and EMBASE from inception to 18 February 2018. Endpoints were pain intensity, opioid-sparing effects, safety, and quality of life. Studies with similar patients, interventions, and outcomes were included in the meta-analyses. Our systematic search was able to only identify studies dealing with cancer pain. Of 5991 retrieved studies, 43 could be included (n = 2925 patients). There was no convincing evidence for satisfactory pain relief by acetaminophen alone or in combination with strong opioids. We found substantial evidence of moderate quality for a satisfactory pain relief in cancer by non-steroidal anti-inflammatory drugs (NSAIDs), flupirtine, and dipyrone compared with placebo or other analgesics. There was no evidence for a superiority of one specific non-opioid. There was moderate quality of evidence for a similar pain reduction by NSAIDs in the usual dosage range compared with up to 15 mg of morphine or opioids of equianalgesic potency. The combination of NSAID and step III opioids showed a beneficial effect, without a decreased tolerability. There is scarce evidence concerning the combination of NSAIDs with weak opioids. There are no randomized-controlled studies on the use of non-opioids in a wide range of end-stage diseases except for cancer. Non-steroidal anti-inflammatory drugs, flupirtine, and dipyrone can be recommended for the treatment of cancer pain either alone or in combination with strong opioids. The use of acetaminophen in the palliative setting cannot be recommended. Studies are not available for long-term use. There is a lack of evidence regarding pain treatment by non-opioids in specific cancer entities.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcsm.12352

Systematic review and meta-analysis on non-opioid analgesics in palliative medicine.

Die planmasige Aktualisierung der S3-Leitlinie zum Fibromyalgiesyndrom (FMS; AWMF-Registernummer 041/004) wurde ab Marz 2011 vorgenommen. Die Leitlinie wurde unter Koordination der Deutschen Interdisziplinaren Vereinigung fur Schmerztherapie (DIVS) von 9 wissenschaftlichen Fachgesellschaften und 2 Patientenselbsthilfeorganisationen entwickelt. Acht Arbeitsgruppen mit insgesamt 50 Mitgliedern wurden ausgewogen in Bezug auf Geschlecht, medizinischen Versorgungsbereich, potenzielle Interessenkonflikte und hierarchische Position im medizinischen bzw. wissenschaftlichen System besetzt. Die Literaturrecherche erfolgte uber die Datenbanken Medline, PsycInfo, Scopus und Cochrane Library (bis Dezember 2010). Die Graduierung der Evidenzstarke erfolgte nach dem Schema des Oxford Center for Evidence Based Medicine. Die Formulierung und Graduierung der Empfehlungen erfolgte in einem mehrstufigen, formalisierten Konsensusverfahren. Wirksamkeit, Risiken, Patientenpraferenzen und Umsetzbarkeit von Therapieverfahren wurden in einer Bilanz zusammengefasst. Die Leitlinie wurde von den Vorstanden der beteiligten Fachgesellschaften begutachtet. Die Leitlinie wurde als Lang-, Kurz-, Kitteltaschen- und Patientenversion veroffentlicht.

Methodological fundamentals of the development of the guideline

Der medizinische Gebrauch von Cannabisprodukten in der Gastroenterologie wird fur chronisch-entzundliche Darmerkrankungen (CED), das Reizdarmsyndrom (RDS) und die chronische Pankreatitis diskutiert. Eine systematische Literatursuche bis Marz 2015 wurde in den Datenbanken Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, www.cannabis-med.org
 und Clinicaltrials.gov durchgefuhrt. Gesucht wurde nach randomisierten, kontrollierten Studien (RCT) mit einer Studiendauer von ≥ 4 Wochen und einer Studienteilnehmerzahl von mindestens n = 10 pro Studienarm mit Medizinalhanf und/oder pharmazeutischen Cannabinoiden bei CED, RDS und chronischer Pankreatitis. Klinische Endpunkte der Analyse waren Wirksamkeit (Schmerz, Ubelkeit, Appetit/Gewicht, Durchfalle, gesundheitsbezogene Lebensqualitat und bei CED Remissionsraten), Vertraglichkeit (Abbruchrate wegen Nebenwirkungen) und Sicherheit (schwerwiegende Nebenwirkungen). Die methodische Qualitat der RCT wurde mit dem Cochrane Risk of Bias Tool evaluiert. Es wurde lediglich eine RCT mit Medizinalhanf bei 21 Morbus-Crohn-Patienten gefunden. Die Studie war zu klein, um einen signifikanten Unterschied in der Remissionsrate nachzuweisen, jedoch ergaben sich Hinweise darauf, dass der Konsum von Medizinalhanf zur Reduktion von Bauchschmerzen und Besserung des Appetits fuhrte. Das methodische Risiko der Studie war hoch. Die Ergebnisse von je einer RCT mit pharmazeutischen Cannabisprodukten bei CED bzw. chronischer Pankreatitis waren noch nicht veroffentlicht. RCTs mit therapeutischer Zielsetzung beim RDS wurden nicht gefunden. Eine cannabisinduzierte akute Pankreatitis wurde in mehreren Fallberichten beschrieben. Cannabinoide eignen sich moglicherweise zur symptomatischen Therapie von Morbus-Crohn-assoziierten Beschwerden wie Schmerz, Ubelkeit und Appetitlosigkeit. Um den potenziellen therapeutischen Nutzen sowie die Risiken von Cannabisprodukten in der Gastroenterologie zu beurteilen, sind jedoch methodisch hochwertige Studien mit ausreichender Patientenzahl und Studiendauer notwendig. Aktuell kann ein individueller Heilversuch mit Tetrahydrocannabinol in der Gastroenterologie nur bei Morbus Crohn zur Symptomlinderung von Schmerzen und Appetitlosigkeit und nur nach Versagen aller etablierten medikamentosen Therapieoptionen sowie nach sorgfaltiger Nutzen-Risiko-Abwagung erwogen werden.

Wirksamkeit, Verträglichkeit und Sicherheit von Cannabinoiden in der Gastroenterologie

The hypothesis that fibromyalgia (FM) should be classified as a somatoform disorder was assessed by reviewing current clinical studies. According to the ICD-10, somatic illness beliefs of the patient, high health care utilization, and frustrating patient-doctor relationships are diagnostic criteria of somatoform disorders. For the diagnosis of a somatoform pain disorder, a temporal association between the manifestation of pain and emotional or psychosocial conflicts and the exclusion of a depressive disorder are additionally required. Empirical studies demonstrate a higher lifetime and current prevalence of psychiatric disorders, childhood adversities, life events, and daily hassles and a higher health care utilization of FM patients. Studies also reveal that most patients believe that both somatic and psychosocial factors have caused their disorder. The patient-doctor relationship is characterized to be disappointing for both. Yet in all studies there were patients who did not fulfill the ICD-10 criteria of a somatoform (pain) disorder. A biopsychosocial model of FM differentiating between biological as well as psychosocial predisposing, triggering, and perpetuating factors in the pathogenesis of FM is presented as an alternative model. Hopefully the biopsychosocial model and the distinction of subgroups will enable more differentiated and tailored psychotherapeutic and pharmacological treatment strategies.

[Fibromyalgia -- a somatoform (pain) disorder?].

Fibromyalgia syndrome (FMS) is a chronic disorder characterized by widespread pain and tenderness, accompanied by disturbed sleep, chronic fatigue and multiple additional functional symptoms FMS continues to pose an unmet need regarding pharmacological treatment and many patients fail to achieve sufficient relief from existing treatments As FMS is considered to be a condition in which pain amplification occurs within the CNS, therapeutic interventions, both pharmacological and otherwise, have revolved around attempts to influence pain processing in the CNS In the current review, we present an update on novel targets in the search for effective treatment of FMS

Winfried Häuser

Papers

Systematic review and meta-analysis on non-opioid analgesics in palliative medicine.

Methodological fundamentals of the development of the guideline

Wirksamkeit, Verträglichkeit und Sicherheit von Cannabinoiden in der Gastroenterologie

[Fibromyalgia -- a somatoform (pain) disorder?].

Fibromyalgia syndrome: novel therapeutic targets.