Availability and approval of cannabis-based medicines for chronic pain management and palliative/supportive care in Europe: A survey of the status in the chapters of the European Pain Federation.

BACKGROUND: There is considerable public and political interest in the use of cannabis products for medical purposes. METHODS: The task force of the European Pain Federation (EFIC) conducted a survey with its national chapters representatives on the status of approval of all types of cannabis-based medicines, the covering of costs and the availability of a position paper of a national medical association on the use of medical cannabis for chronic pain and for symptom control in palliative/supportive care. RESULTS: Thirty-one out of 37 contacted councillors responded. Plant-derived tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray is approved for spasticity in multiple sclerosis refractory to conventional treatment in 21 EFIC chapters. Plant-derived THC (dronabinol) is approved for some palliative care conditions in four EFIC chapters. Synthetic THC analogue (nabilone) is approved for chemotherapy-associated nausea and vomiting refractory to conventional treatment in four EFIC chapters'. Eight EFIC chapters' countries have an exceptional and six chapters an expanded access programme for medical cannabis. German and Israeli pain societies recommend the use of cannabis-based medicines as third-line drug therapies for chronic pain within a multicomponent approach. Conversely, the German medical association and a team of finish experts and officials do not recommend the prescription of medical cannabis due to the lack of high-quality evidence of efficacy and the potential harms. CONCLUSIONS: There are marked differences between the countries represented in EFIC in the approval and availability of cannabis-based products for medical use. EFIC countries are encouraged to collaborate with the European Medicines Agency to publish a common document on cannabis-based medicines. SIGNIFICANCE: There are striking differences between European countries in the availability of plant-derived and synthetic cannabinoids and of medical cannabis for pain management and for symptom control in palliative care and in the covering of costs by health insurance companies or state social security systems.

Efficacy, tolerability and safety of cannabis-based medicines for chronic pain management - An overview of systematic reviews.

Medicinal cannabis has already entered mainstream medicine in some countries. This systematic review (SR) aimed at evaluating the efficacy, acceptability and safety of cannabis-based medicines for chronic pain management. Qualitative systematic review of SRs of randomized controlled trials with cannabis-based medicines for chronic pain management. The Cochrane databases of SRs, Database of Abstracts of Reviews of Effects and PubMed were searched for SR published in the period January 2009 to January 2017. Assessment of the methodological quality of SR was performed by the AMSTAR checklist. Out of 748 papers identified, 10 SRs met the inclusion criteria. The methodological quality was high in four and moderate in six SRs. There were inconsistent findings of four SRs on the efficacy of cannabis-based medicines in neuropathic pain and of one SR for painful spasms in multiple sclerosis. There were consistent results that there was insufficient evidence of any cannabis-based medicine for pain management in patients with rheumatic diseases (three SRs) and in cancer pain (two SRs). Cannabis-based medicines undoubtedly enrich the possibilities of drug treatment of chronic pain conditions. It remains the responsibility of the health care community to continue to pursue rigorous study of cannabis-based medicines to provide evidence that meets the standard of 21st century clinical care. SIGNIFICANCE: We provide an overview of systematic reviews on the efficacy, tolerability and safety of cannabis-based medicines for chronic pain management. There are inconsistent findings of the efficacy of cannabinoids in neuropathic pain and painful spasms in multiple sclerosis. There are inconsistent results on tolerability and safety of cannabis-based medicines for any chronic pain.

Folic acid use by women with epilepsy: Findings of the Epilepsy Birth Control Registry.

PURPOSE: To determine the prevalence and predictors of folic acid (FA) use by women with epilepsy (WWE) at risk of unintended pregnancy. METHODS: These retrospective data come from the Epilepsy Birth Control Registry (EBCR) web-based survey of 1144 WWE in the community, 18-47years, who provided demographic, epilepsy, AED, contraception, pregnancy, healthcare visits and FA data. We report prevalence and predictors of FA use in relation to risk of pregnancy (not at risk, at risk, seeking pregnancy, pregnant), demographics, seizure types and AED and contraception categories. RESULTS: 368 (47.6%) of the 773 WWE at risk of unintended pregnancy in the EBCR took FA supplement. Being at risk was a significant predictor in comparison to WWE not at risk (OR=1.464 [1.103-1.944], p=0.008). In comparison to WWE at risk, FA use trended greater for WWE actively seeking pregnancy (29/47, 61.7% v 368/773, 47.6%; p=0.0605) and was greater for pregnant WWE (17/19, 89.5% v 368/773, 47.6%; p=0.0007). Demographic predictors for WWE at risk were race (p=0.003), education (p=0.012) and income (0.043) with significantly greater FA use by Caucasians than minorities and direct correlations between FA use and levels of education and household income. Seizure type, AED use, category and dosage, polytherapy and contraceptive category were not predictors. A healthcare provider visit during the year prior to the survey was not a predictor. Prevalence of FA use was similar following visits with gynecologists - 51.7%, neurologists - 48.7% and primary care - 48.6%. FA supplementation by prescription was greater for WWE at risk on AED versus no AED (190/355, 53.5% v 3/13, 23.1%; p=0.045). CONCLUSION: Low prevalence of preconception FA use may reflect a need for more education. In addition, further research is needed to provide definitive evidence that FA reduces congenital malformations in the offspring of WWE.

[Physiotherapy, occupational therapy and physical therapy in fibromyalgia syndrome : Updated guidelines 2017 and overview of systematic review articles]. / Physiotherapie, Ergotherapie und physikalische Verfahren beim Fibromyalgiesyndrom : Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten.

BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was scheduled for April 2017. METHODS: The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n =8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A literature search for systematic reviews of randomized, controlled trials on physiotherapy, occupational therapy and physical therapy from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The strength of recommendations was achieved by multiple step formalized procedures to reach a consensus. Efficacy, risks, patient preferences and applicability of available therapies were weighed up against each other. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. RESULTS AND CONCLUSION: Low to moderate intensity endurance and strength training are strongly recommended. Chiropractic, laser therapy, magnetic field therapy, massage and transcranial magnetic stimulation are not recommended.

[Psychotherapy and psychological procedures for fibromyalgia syndrome : Updated guidelines 2017 and overview of systematic review articles]. / Psychotherapie und psychologische Verfahren beim Fibromyalgiesyndrom : Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten.

BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was scheduled for April 2017. METHODS: The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n =8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A systematic search of the literature for systematic reviews of randomized, controlled studies on psychological and psychotherapeutic procedures from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The strength of recommendations was achieved by multiple step formalized procedures to reach a consensus. Efficacy, risks, patient preferences and applicability of available therapies were weighed up against each other. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. RESULTS AND CONCLUSION: Cognitive behavioral therapies received a strong recommendation but biofeedback, guided imagery and hypnosis received a weak recommendation.

[Complementary and alternative procedures for fibromyalgia syndrome : Updated guidelines 2017 and overview of systematic review articles]. / Komplementäre und alternative Verfahren beim Fibromyalgiesyndrom : Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten.

BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was scheduled for April 2017. METHODS: The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n =8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A search of the literature for systematic reviews of randomized controlled trials of complementary and alternative therapies from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The strength of recommendations was formed by multiple step formalized procedures to reach a consensus. Efficacy, risks, patient preferences and applicability of available therapies were weighed up against each other. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. RESULTS AND CONCLUSION: Meditative movement therapies (e.g. qi gong, tai chi and yoga) are strongly recommended. Acupuncture and weight reduction in cases of obesity can be considered.

[Impact of conflicts of interest on guideline recommendations : Empirical study within the second update of the German interdisciplinary S3 guidelines on fibromyalgia syndrome]. / Der Einfluss von Interessenkonflikten auf Leitlinienempfehlungen : Eine empirische Studie zur zweiten Aktualisierung der interdisziplinären S3­Leitlinie zum Fibromyalgiesyndrom.

BACKGROUND: The impact of conflicts of interest (COI) in general and of academic COI in particular on guideline recommendations in pain medicine has not yet been studied. Whether the inclusion of patients and of representatives of all relevant healthcare professions into a guidelines group is protective against a systematic bias of decisions of a guidelines group is currently unknown. METHODS: All members of the guidelines group declared their COI before the consensus conferences by a standard form according to the rules and standards of the Association of the German Medical and Scientific Societies. The acceptance or rejection and the strength of consensus of recommendations of the second update of the interdisciplinary guidelines on fibromyalgia syndrome was analyzed twice by first including and then excluding the votes of the guideline group members with COI related to a recommendation from the results of anonymous voting via an internet platform. RESULTS: A total of 42 persons from different healthcare professions and patients participated in the online voting on recommendations. Of the participants 29% had no COI according to the predefined criteria, 53% met the criteria of academic and 33% the criteria of financial COI. In the case of exclusion of participants with a COI related to a specific recommendation, 2 out of 23 recommendations (homeopathy, tramadol) were not accepted. In all votes, there were more participants without COI than with COI. CONCLUSION: Academic COI were more frequent than financial COI in the second update of the German interdisciplinary guidelines group on fibromyalgia syndrome. The impact of COI on guideline recommendations was low. The inclusion of patients and of all relevant healthcare professionals into a guidelines group is a protective factor against the influence of COI on guideline recommendations.

EULAR revised recommendations for the management of fibromyalgia.

OBJECTIVE: The original European League Against Rheumatism recommendations for managing fibromyalgia assessed evidence up to 2005. The paucity of studies meant that most recommendations were 'expert opinion'. METHODS: A multidisciplinary group from 12 countries assessed evidence with a focus on systematic reviews and meta-analyses concerned with pharmacological/non-pharmacological management for fibromyalgia. A review, in May 2015, identified eligible publications and key outcomes assessed were pain, fatigue, sleep and daily functioning. The Grading of Recommendations Assessment, Development and Evaluation system was used for making recommendations. RESULTS: 2979 titles were identified: from these 275 full papers were selected for review and 107 reviews (and/or meta-analyses) evaluated as eligible. Based on meta-analyses, the only 'strong for' therapy-based recommendation in the guidelines was exercise. Based on expert opinion, a graduated approach, the following four main stages are suggested underpinned by shared decision-making with patients. Initial management should involve patient education and focus on non-pharmacological therapies. In case of non-response, further therapies (all of which were evaluated as 'weak for' based on meta-analyses) should be tailored to the specific needs of the individual and may involve psychological therapies (for mood disorders and unhelpful coping strategies), pharmacotherapy (for severe pain or sleep disturbance) and/or a multimodal rehabilitation programme (for severe disability). CONCLUSIONS: These recommendations are underpinned by high-quality reviews and meta-analyses. The size of effect for most treatments is relatively modest. We propose research priorities clarifying who will benefit from specific interventions, their effect in combination and organisation of healthcare systems to optimise outcome.

Efficacy, acceptability and safety of guided imagery/hypnosis in fibromyalgia - A systematic review and meta-analysis of randomized controlled trials.

This systematic review aimed at evaluating the efficacy, acceptability and safety of guided imagery/hypnosis (GI/H) in fibromyalgia. Cochrane Library, MEDLINE, PsycINFO and SCOPUS were screened through February 2016. Randomized controlled trials (RCTs) comparing GI/H with controls were analysed. Primary outcomes were ≥50% pain relief, ≥20% improvement of health-related quality of life, psychological distress, disability, acceptability and safety at end of therapy and 3-month follow-up. Effects were summarized by a random effects model using risk differences (RD) or standardized mean differences (SMD) with 95% confidence intervals (CI).Seven RCTs with 387 subjects were included into a comparison of GI/H versus controls. There was a clinically relevant benefit of GI/H compared to controls on ≥50% pain relief [RD 0.18 (95% CI 0.02, 0.35)] and psychological distress [SMD -0.40 (95% CI -0.70, -0.11)] at the end of therapy. Acceptability at the end of treatment for GI/H was not significantly different to the control. Two RCTs with 95 subjects were included in the comparison of hypnosis combined with cognitive behavioural therapy (CBT) versus CBT alone. Combined therapy was superior to CBT alone in reducing psychological distress at the end of therapy [SMD -0.50 (95% CI -0.91, -0.09)]. There were no statistically significant differences between combined therapy and CBT alone in other primary outcomes at the end of treatment and follow-up. No study reported on safety. GI/H hold promise in a multicomponent management of fibromyalgia. SIGNIFICANCE: We provide a systematic review with meta-analysis on guided imagery and hypnosis for fibromyalgia. Current analyses endorse the efficacy and tolerability of guided imagery/hypnosis and of the combination of hypnosis with cognitive-behavioural therapy in reducing key symptoms of fibromyalgia.

[Efficacy, tolerability and safety of cannabinoids for chronic neuropathic pain: A systematic review of randomized controlled studies]. / Wirksamkeit, Verträglichkeit und Sicherheit von Cannabinoiden bei neuropathischen Schmerzsyndromen : Eine systematische Übersichtsarbeit von randomisierten, kontrollierten Studien.

BACKGROUND: Recently published systematic reviews came to different conclusions with respect to the efficacy, tolerability and safety of cannabinoids for treatment of chronic neuropathic pain. MATERIAL AND METHODS: A systematic search of the literature was carried out in MEDLINE, the Cochrane central register of controlled trials (CENTRAL) and clinicaltrials.gov up until November 2015. We included double-blind randomized placebo-controlled studies (RCT) of at least 2 weeks duration and with at least 9 patients per treatment arm comparing medicinal cannabis, plant-based or synthetic cannabinoids with placebo or any other active drug treatment in patients with chronic neuropathic pain. Clinical endpoints of the analyses were efficacy (more than 30 % or 50 % reduction of pain, average pain intensity, global improvement and health-related quality of life), tolerability (drop-out rate due to side effects, central nervous system and psychiatric side effects) and safety (severe side effects). Using a random effects model absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables. The methodological quality of RCTs was rated by the Cochrane risk of bias tool. RESULTS: We included 15 RCTs with 1619 participants. Study duration ranged between 2 and 15 weeks. Of the studies 10 used a plant-derived oromucosal spray with tetrahydrocannabinol/cannabidiol, 3 studies used a synthetic cannabinoid (2 with nabilone and 1 with dronabinol) and 2 studies used medicinal cannabis. The 13 studies with parallel or cross-over design yielded the following results with 95 % confidence intervals (CI): cannabinoids were superior to placebo in the reduction of mean pain intensity with SMD - 0.10 (95 % CI - 0.20- - 0.00, p = 0.05, 13 studies with 1565 participants), in the frequency of at least a 30 % reduction in pain with an RD of 0.10 [95 % CI 0.03-0.16, p = 0.004, 9 studies with 1346 participants, number needed to treat for additional benefit (NNTB) 14, 95 % CI 8-45] and in the frequency of a large or very large global improvement with an RD of 0.09 (95 % CI 0.01-0.17, p = 0.009, 7 studies with 1092 participants). There were no statistically significant differences between cannabinoids and placebo in the frequency of at least a 50 % reduction in pain, in improvement of health-related quality of life and in the frequency of serious adverse events. Patients treated with cannabinoids dropped out more frequently due to adverse events with an RD of 0.04 [95 % CI 0.01-0.07, p = 0.009, 11 studies with 1572 participants, number needed to treat for additional harm (NNTH) 19, 95 % CI 13-37], reported central nervous system side effects more frequently with an RD of 0.38 (95 % CI 0.18-0.58, p = 0.0003, 9 studies with 1304 participants, NNTH 3, 95 % CI 2-4) and psychiatric side effects with an RD of 0.11 (95 % CI 0.06-0.16, p < 0.0001, 9 studies with 1304 participants, NNTH 8, 95 % CI 7-12). CONCLUSION: Cannabinoids were marginally superior to placebo in terms of efficacy and inferior in terms of tolerability. Cannabinoids and placebo did not differ in terms of safety during the study period. Short-term and intermediate-term therapy with cannabinoids can be considered in selected patients with chronic neuropathic pain after failure of first-line and second-line therapies.

Efficacy, tolerability, and safety of cannabinoids for chemotherapy-induced nausea and vomiting--a systematic review of systematic reviews.

BACKGROUND: There is growing public and legislative body support for the medical use of cannabis products, for example, for chemotherapy-induced nausea and vomiting (CINV), in Germany. METHODS: A comprehensive literature search until November 2015 was conducted in MEDLINE, DARE and Cochrane libraries for systematic reviews of randomized controlled trials (RCTs) comparing herbal or pharmaceutical cannabinoids (CB) versus placebo or conventional antiemetics for CINV. Outcomes were reduction of CINV for efficacy, drop-out rates due to adverse events for tolerability, and serious adverse events for safety. The methodology quality of the systematic reviews was evaluated by the tool assessment of multiple systematic reviews (AMSTAR). RESULTS: Six systematic reviews of RCTs included the pharmaceutical CBs dronabinol, levonantradol, and nabilone or whole plant extract (e.g., nabiximol) compared with placebo or conventional antiemetics. There was moderate quality evidence on the efficacy of CBs compared to placebo and conventional antiemetics for CINV. There was moderate quality evidence that pharmaceutical CBs were less tolerated and less safe than placebo and conventional antiemetics in CINV. One RCT examining whole plant extract was included into the systematic reviews. No RCT was found comparing CBs with neurokinine-1 receptor antagonists. CONCLUSIONS: With safe and effective antiemetics available, CBs cannot be recommended as first- or second-line therapy for CINV. Some guidelines recommend pharmaceutical CBs as third-line treatment in the management of breakthrough nausea and vomiting. Due to the lack of RCT data and safety concerns, herbal cannabis cannot be recommended for CINV.

Medical use of cannabis products: Lessons to be learned from Israel and Canada.

INTRODUCTION: The German government intends to reduce the barriers for the medical use of cannabis products. A discussion on the indications and contraindications of the medical use of cannabis and on the changes of the regulatory framework has already begun in Germany. It is useful to draw from the experiences of other countries with a more liberal medical use of cannabis. METHODS: The Israeli and Canadian experience is outlined by physicians who have been charged with expertise on the medical use of cannabis by their jurisdiction. RESULTS: In Israel, only the plant-based cannabinoid nabiximol (mixture of tetrahydrocannabinol/cannabidiol) can be prescribed for spasticity/chronic pain in multiple sclerosis and for cancer pain. The costs of nabiximole are reimbursed by some, but not by all health maintenance organizations. The medical use of marijuana is permitted; however, it is strictly regulated by the government. Selected companies are allowed to produce marijuana for medical use, and only certain physicians are licensed to prescribe marijuana as a therapeutic drug for specific indications such as chronic neuropathic, and cancer pain, inflammatory bowel diseases, or posttraumatic stress disorder if conventional treatments have failed. The costs of marijuana are not reimbursed by health insurance companies. In Canada, synthetic cannabinoids and the plant-based (nabiximol) are licensed for neuropathic and cancer pain, HIV-related anorexia and chemotherapy-associate nausea. The costs of these synthetic cannabinoids are covered by health insurance companies. The medical use of marijuana as a treatment option is allowed for individual patients suffering from any medical condition when authorized by a medical practitioner or nurse. Licensed producers are the only source for patients to newly access medical cannabis, although those with previous permission to grow may continue cultivation at the present time. The costs of marijuana are not reimbursed by health insurance companies. There are multiple contraindications for the medical use of cannabis products in both countries. CONCLUSIONS: The use of standardized, synthetic, and plant-based cannabis products should be allowed in Germany for defined medical conditions when high-level evidence of efficacy and safety exists. The costs should be reimbursed by the health insurance companies. Contraindications for the medical use of cannabis should be defined. Growing marijuana by patients for their medical use should not be allowed.

Efficacy, tolerability and safety of cannabinoids in chronic pain associated with rheumatic diseases (fibromyalgia syndrome, back pain, osteoarthritis, rheumatoid arthritis): A systematic review of randomized controlled trials.

BACKGROUND: In the absence of an ideal treatment for chronic pain associated with rheumatic diseases, there is interest in the potential effects of cannabinoid molecules, particularly in the context of global interest in the legalization of herbal cannabis for medicinal use. METHODS: A systematic search until April 2015 was conducted in Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, www.cannabis-med.org and clinicaltrials.gov for randomized controlled trials with a study duration of at least 2 weeks and at least ten patients per treatment arm with herbal cannabis or pharmaceutical cannabinoid products in fibromyalgia syndrome (FMS), osteoarthritis (OA), chronic spinal pain, and rheumatoid arthritis (RA) pain. Outcomes were reduction of pain, sleep problems, fatigue and limitations of quality of life for efficacy, dropout rates due to adverse events for tolerability, and serious adverse events for safety. The methodology quality of the randomized controlled trials (RCTs) was evaluated by the Cochrane Risk of Bias Tool. RESULTS: Two RCTs of 2 and 4 weeks duration respectively with nabilone, including 71 FMS patients, one 4-week trial with nabilone, including 30 spinal pain patients, and one 5-week study with tetrahydrocannbinol/cannabidiol, including 58 RA patients were included. One inclusion criterion was pain refractory to conventional treatment in three studies. No RCT with OA patients was found. The risk of bias was high for three studies. The findings of a superiority of cannabinoids over controls (placebo, amitriptyline) were not consistent. Cannabinoids were generally well tolerated despite some troublesome side effects and safe during the study duration. CONCLUSIONS: Currently, there is insufficient evidence for recommendation for any cannabinoid preparations for symptom management in patients with chronic pain associated with rheumatic diseases.

[Efficacy, tolerability, and safety of cannabinoids in gastroenterology: A systematic review]. / Wirksamkeit, Verträglichkeit und Sicherheit von Cannabinoiden in der Gastroenterologie : Eine systematische Übersichtsarbeit.

BACKGROUND: The medical use of cannabis is discussed in gastroenterology for inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), and chronic pancreatitis. MATERIALS AND METHODS: A systematic literature search until March 2015 was performed in the databases Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, www.cannabis-med.org , and clinicaltrials.gov. Randomized controlled trials (RCT) investigating herbal cannabis and/or pharmaceutical cannabinoids in IBD, IBS, or chronic pancreatitis with a study duration of ≥ 4 weeks and a sample size of at least n = 10 per study arm were identified. Clinical outcomes comprised efficacy (pain, nausea, appetite/weight, diarrhea, health-related quality of life, and remission rates for IBD), tolerability (drop-out rate due to side effects), and safety (severe side effects). Methodology quality of RCTs was evaluated with the Cochrane Risk of Bias Tool. RESULTS: Only one RCT treating 21 patients with Crohn's disease and herbal cannabis was identified. The study revealed no significant differences of remission rate because of low statistical power. However, there was a clear tendency for less abdominal pain and improved appetite with medical cannabis. The methodological risk of the study was high. Furthermore, results of two RCTs investigating synthetic cannabis in IBD and chronic pancreatitis, respectively, have not yet been released. No RCT for IBS was found. Several case reports described cannabis-induced acute pancreatitis. CONCLUSIONS: Cannabis may be useful for symptom relief in Crohn's disease such as pain, nausea, and loss of appetite. However, studies with high methodological quality, sufficient sample size, and study duration are mandatory to determine potential therapeutic effects and risks of cannabis in gastroenterology. Currently, use of tetrahydrocannabinol to alleviate symptoms such as pain and appetite loss in Crohn's disease should only be considered in individual patients after failure of established medical therapies and only after careful risk-benefit assessment.

[Cannabinoids in palliative care: Systematic review and meta-analysis of efficacy, tolerability and safety]. / Cannabinoide in der palliativen Versorgung : Systematische Übersicht und Metaanalyse der Wirksamkeit, Verträglichkeit und Sicherheit.

BACKGROUND: Cannabinoids have multiple medical indications in palliative care, such as relief of pain or nausea or increase of appetite and weight stabilisation. The value of cannabinoids for these indications is not resolved sufficiently for palliative patients. A systematic review with meta-analysis of the efficacy, tolerability and safety on the basis of randomised controlled studies (RCT) or randomised open label or crossover studies has not yet been conducted. MATERIALS AND METHODS: An extensive search for RCTs, randomised open label or crossover studies dealing with the underlying question was performed in the databases of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, PubMed, Scopus and Clinicaltrials.gov up to April 2015. Studies with a duration of ≥ 2 weeks and ≥ 10 participants per treatment group were included into analysis. Using a random effects model, pooled estimates of event rates for categorical data and standardized mean differences (SMD) for continuous variables and risk differences (RD) for dichotomous variables were calculated. RESULTS: Out of initially 108 studies 9, with a total of 1561 participants suffering from advanced or end stage diseases, were included. The median study duration of the cancer research was 8 weeks (16 days-11 weeks), of the HIV research 6 weeks (3-12 weeks) and of the study concentrating on Alzheimer's 2 × 6 weeks. The outcome results for cannabis/cannabinoids vs. placebo in patients with cancer were not significant for the 30 % decrease in pain (RD: 0.07; 95 % confidence interval (CI): - 0.01 to 0.16; p = 0.07), caloric intake (SMD: 0.2; 95 % CI: - 0.66 to 1.06; p = 0.65) or sleep problems (SMD: - 0.09; 95 % CI: - 0.62 to 0.43; p = 0.72). In the treatment of HIV cannabinoids were superior to placebo for the outcome of weight change (SMD: 0.57; 95 % CI: 0.22-0.92; p = 0.001). Change in appetite was significant for the treatment of HIV (SMD: 0.57; 95 % CI: 0.11-1.03; p = 0.02), but not for treatment of cancer (SMD: 0.81; 95 % CI: - 1.14 to 2.75; p = 0.42). Nausea/vomiting (SMD: 0.20; 95 % CI: - 0.03 to 0.44; p = 0.09) and health-related quality of life (HRQoL; SMD: 0.00; 95 % CI: - 0.19 to 0.18; p = 0.98) did not show significant differences in the therapy of the two diseases. For the outcomes of tolerability the results were not significant for occurrence of dizziness (RD: 0.03; 95 % CI: - 0.02 to 0.08; p = 0.23) or psychiatric diseases, such as hallucinations or psychosis (RD: - 0.01; 95 % CI: - 0.04 to 0.03; p = 0.69) in the therapy of cancer. The outcome of psychiatric diseases in the treatment of HIV was significant (RD: 0.05; 95 % CI: 0.00-0.11; p = 0.05). The number of withdrawals due to adverse events, as a marker for tolerability, and the reports of serious adverse events as a measure of safety was not significantly different (RD: 1.20; 95 % CI: 0.85-1.71; p = 0.30 and RD: 1.15; 95 % CI: 0.88-1.49; p = 0.30, respectively). Dronabinol vs. megestrol acetate showed a superiority of megestrol in the therapy of cancer-associated anorexia for the endpoints change of appetite (49 vs. 75 %; p = 0.0001), weight gain (3 vs. 11 %; p = 0.02), HRQoL (p = 0.003) and tolerability (p = 0.03). There was no difference in the safety of the therapies (p = 0.12). In the treatment of HIV-associated wasting syndrome megestrol acetate was better than dronabinol for the endpoint of weight gain (p = 0.0001), whereas tolerability and safety did not differ. In the therapy of Alzheimer's dronabinol was better than placebo in the endpoint of weight gain according to one study (n = 15). A difference between herbal cannabis and synthetic cannabinoids, analysed by one study (n = 62) could not be found. CONCLUSION: Cannabinoids can lead to an increase in appetite in patients with HIV wasting syndrome but the therapy with megestrol acetate is superior to treatment with cannabinoids. The included studies were not of sufficient duration to answer questions concerning the long-term efficacy, tolerability and safety of therapy with cannabis or cannabinoids. Due to the sparse amount of data it is not possible to recommend a favoured use of cannabis or cannabinoids at this point.

[Psychotherapeutic procedures for fibromyalgia syndrome]. / Psychotherapeutische Verfahren beim Fibromyalgiesyndrom.

BACKGROUND: Psychosocial factors play an important role in the predisposition, triggering and course of fibromyalgia syndrome (FMS). Cognitive behavioral therapies are strongly recommended in the current guidelines on the management of FMS in Canada, Germany and Israel. AIMS: Review of techniques, aims and efficacy of psychotherapeutic procedures in FMS. MATERIAL AND METHODS: Narrative review based on a selective search for systematic reviews on the efficacy of psychotherapeutic procedures in FMS. RESULTS: There is robust evidence for the short and long-term efficacy of cognitive behavioral therapies on some key symptoms of FMS, e.g. pain, depression and disability. The quality and quantity of the evidence for the efficacy of other psychotherapeutic procedures (e.g. biofeedback, relaxation therapies, hypnosis/guided imagery and psychodynamic therapy) are insufficient. CONCLUSION: Cognitive behavioral therapies (e.g. acceptance and commitment therapy, cognitive behavioral therapy and operant therapy) should play an important role in a graduated and individually tailored therapy of FMS patients.

[Visceral pain]. / Viszeraler Schmerz.

Chronic visceral pain is an unresolved neurobiological, medical and socioeconomic challenge. Up to 20% of the adult population suffer from chronic visceral pain and abdominal complaints constitute a prevalent symptom also in children and adolescents. Existing treatment approaches are often unsuccessful and patients typically suffer from multiple somatic and psychological symptoms. This complex situation requires integrative treatment approaches. This review summarizes current basic and clinical research on acute and chronic visceral pain with a focus on research groups in Germany. Despite significant clinical and scientific advances, a number of questions remain open calling for more funding to support research to elucidate the complex pathophysiology of chronic visceral pain and to develop and test new treatment approaches. Research support should focus on interdisciplinary concepts and methodology using expertise from multiple disciplines. The field would also benefit from a broader integration of visceral pain into teaching curricula in medicine and psychology and should aim to motivate young clinicians and scientists to strive for a career within this important and highly fascinating area.

[Treatment of non-specific, functional and somatoform bodily complaints]. / Umgang mit Patienten mit nicht-spezifischen, funktionellen und somatoformen Körperbeschwerden.

In primary and secondary medicine "non-specific, functional, and somatoform bodily complaints" are common and often take a chronic course, with the patients' quality of life usually markedly impaired, and give rise to high direct and indirect costs. They are challenging as they can deteriorate in case of inappropriate behavior on the physician's part. Coordinated by both German professional associations of Psychosomatic Medicine a new evidence based guideline was developed, aiming to transfer relevant diagnostic and therapeutic knowledge to all physicians who are in charge of these patients. After establishing a stable therapeutic alliance a symptom- and coping-oriented attitude could be demonstrated to be helpful. A biopsychosocial diagnostic evaluation combines a thorough assessment of bodily complaints and early introduces a sensitive discussion of signs of psychosocial stress, which can be extended carefully in case problems of this type are present. In less severe courses, physical/social activation is recommended and the patient's explanatory disease model should be extended towards a psychological dimension. More severe and complicated courses require a more structured approach consisting of regular appointments (as opposed to ad-hoc appointments whenever the patient feels worse) and an active cooperation of the patient. A coordinated, multimodal management includes additional measures as graded activation, psychotherapy, relaxation training or--if indicated--temporary medication.

[Mental disorders in patients with fibromyalgia syndrome: screening in centres of different medical specialties]. / Psychische Störungen beim Fibromyalgiesyndrom: Screening in Einrichtungen verschiedener Fachrichtungen.

BACKGROUND: Systematic reviews have reported a wide range of prevalence rates for depressive, anxiety and posttraumatic stress disorders (PTSD) in patients with fibromyalgia syndrome (FMS) which have been partially explained by setting differences. No data are currently available on the prevalence of potential mental disorders depending on the medical specialty in Germany. MATERIAL AND METHODS: All consecutive FMS patients of 8 study centres (3 rheumatology/orthopaedic surgery, 3 psychosomatic/pain medicine, 2 physical/integrative medicine) were assessed from February 1 to July 31, 2012 with standardised questionnaires. Patients with FMS diagnosed by a study physician were included. Non-German speaking and mentally retarded patients were excluded. The German version of the Patient Health Questionnaire 4 was used to screen for potential depressive and anxiety disorders. Severe life events were assessed by the trauma list of the Munich Composite International Diagnostic Interview and symptom criteria of PTSD of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) using the Posttraumatic Diagnostic Scale. RESULTS: Of 538 patients, 396 patients (93.9 % women, mean age 52.3 years, mean duration since chronic widespread pain 12.8 years, mean duration since FMS diagnosis 4.5 years) were analysed. In all, 65.7 % of patients met the criteria of a potential depressive disorder, 67.9 % of a potential anxiety disorder and 45.5 % of a potential PTSD. Potential depressive disorders were more frequent in the psychosomatic/pain medicine setting than in the rheumatology setting. CONCLUSION: Potential mental disorders were frequent in FMS patients regardless of the medical specialty. All FMS patients of all types of clinical settings should be screened for mental disorders.

[Are members of fibromyalgia syndrome self-help groups "different"? Demographic and clinical characteristics of members and non-members of fibromyalgia syndrome self-help groups]. / Sind Mitglieder von Fibromyalgiesyndrom-Selbsthilfegruppen "anders"? Demografische und klinische Charakteristika von Mitgliedern und Nicht-Mitgliedern von Fibromyalgiesyndrom-Selbsthilfegruppen.

BACKGROUND: No data were available on demographic and clinical characteristics of members of fibromyalgia syndrome (FMS) self-help groups in Germany. MATERIAL AND METHODS: The study was carried out from November 2010 to April 2011. A set of questionnaires was distributed by the German League Against Rheumatism and the German Fibromyalgia Association to members and to all consecutive FMS patients at nine clinical centres of different levels of care. The set included a self-developed questionnaire on demographic and medical data and on previously and currently used therapies, the patient health questionnaire (PHQ 4) and the fibromyalgia survey questionnaire. RESULTS: Members of FMS self-help groups (N = 1,014) were older and reported a longer duration of chronic widespread pain, less anxiety and depression and a more frequent current use of aerobic exercise, relaxation training and complementary alternative medication than participants not affiliated with FMS self-help groups (N = 630). CONCLUSIONS: Membership in FMS self-help groups was associated with less psychological distress and a more frequent use of active self-management strategies.