Sodium Channels in Human Pain Disorders: Genetics and Pharmacogenomics.

Acute pain is adaptive, but chronic pain is a global challenge. Many chronic pain syndromes are peripheral in origin and reflect hyperactivity of peripheral pain-signaling neurons. Current treatments are ineffective or only partially effective and in some cases can be addictive, underscoring the need for better therapies. Molecular genetic studies have now linked multiple human pain disorders to voltage-gated sodium channels, including disorders characterized by insensitivity or reduced sensitivity to pain and others characterized by exaggerated pain in response to normally innocuous stimuli. Here, we review recent developments that have enhanced our understanding of pathophysiological mechanisms in human pain and advances in targeting sodium channels in peripheral neurons for the treatment of pain using novel and existing sodium channel blockers.

[The interaction of Rhodiola rosea and antidepressants. A case report]. / Das Zusammenwirken von Rhodiola rosea (Eisenwurz) und Antidepressiva.

OBJECTIVE: Rhodiola rosea (Russian Rhodiola/Golden Root) is a high mountain plant from the arctic regions of Europe and Asia which has the active substance phenylpropanoide. It has sedative, anti-depressive, drive-enhancing and stress-modulated properties stimulating the distribution of dopamine and serotonin; in combination with other drugs, an increase of side effects and risk profile has to be expected. METHODS: A case report is presented in order to illustrate the interaction between Rhodiola rosea and antidepressants. RESULTS: We report the case of a 68-year-old female patient with recurrent moderate depressive disorder with somatic syndrome (ICD-10 F33.11) who developed vegetative syndrome, restlessness feeling and trembling since she began to ingest Rhodiola rosea in addition to paroxetine. CONCLUSIONS: Prescribing Rhodiola rosea with paroxetine, pharmacokinetic and -dynamic interactions have to be assumed. The symptoms of the patient can be interpreted as a serotonergic syndrome. Because of its different effects, the plant is widely used. An increase of clinical relevant risks should be considered in the add-on treatments.

Effectiveness of a multimodal treatment program for somatoform pain disorder.

Chronic pain conditions are highly prevalent, with somatoform pain disorder accounting for a large proportion. However, the psychological forms of treatment currently used achieve only small to medium effect sizes. This retrospective study investigated the effectiveness of a 5-week multimodal pain program for patients with somatoform pain disorder. The diagnosis of somatoform pain disorder was confirmed by a specialist for anesthesiology and pain management and a specialist for psychosomatic medicine. Therapy outcome was evaluated with a Numeric Rating Scale (NRS), the Pain Disability Index (PDI), and the Pain Perception Scale. Within the study sample (n = 100), all parameters showed a significant and clinically relevant improvement at the end of therapy (P values < 0.001). The highest effect sizes (d) were found for reduction in average pain rating (NRS: d = 1.00) and the affective items of the Pain Perception Scale (SES-A: d = 0.07). The lowest effect sizes were found for improvement of pain-related disabilities (PDI: d = 0.42) and sensory items of the Pain Perception Scale (SES-S: d = 0.50). Despite high chronification of pain condition, with average pain duration of greater than 8 years, the multimodal treatment program showed medium to large effect sizes on the outcome of patients with somatoform pain disorder. Compared with previous data with small to moderate effect sizes, a multimodal program seems to be more effective than other interventions to address somatoform pain disorder.

[Drug therapy of fibromyalgia syndrome. Systematic review, meta-analysis and guideline]. / Medikamentöse Therapie des Fibromyalgiesyndroms. Systematische Übersicht und Metaanalyse.

BACKGROUND: The scheduled update to the German S3 guidelines on fibromyalgia syndrome (FMS) by the Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF; registration number 041/004) was planned starting in March 2011. MATERIALS AND METHODS: The development of the guidelines was coordinated by the German Interdisciplinary Association for Pain Therapy ("Deutsche Interdisziplinären Vereinigung für Schmerztherapie", DIVS), 9 scientific medical societies and 2 patient self-help organizations. Eight working groups with a total of 50 members were evenly balanced in terms of gender, medical field, potential conflicts of interest and hierarchical position in the medical and scientific fields. Literature searches were performed using the Medline, PsycInfo, Scopus and Cochrane Library databases (until December 2010). The grading of the strength of the evidence followed the scheme of the Oxford Centre for Evidence-Based Medicine. The recommendations were based on level of evidence, efficacy (meta-analysis of the outcomes pain, sleep, fatigue and health-related quality of life), acceptability (total dropout rate), risks (adverse events) and applicability of treatment modalities in the German health care system. The formulation and grading of recommendations was accomplished using a multi-step, formal consensus process. The guidelines were reviewed by the boards of the participating scientific medical societies. RESULTS AND CONCLUSION: Amitriptyline and-in case of comorbid depressive disorder or generalized anxiety disorder-duloxetine are recommended. Off-label use of duloxetine and pregabalin can be considered in case of no comorbid mental disorder. Strong opioids are not recommended. The English full-text version of this article is available at SpringerLink (under "Supplemental").

Phase II trial on the effects of Silexan in patients with neurasthenia, post-traumatic stress disorder or somatization disorder.

Silexan, a novel lavender oil preparation for oral use, has been authorized in Germany for the treatment of states of restlessness during anxious mood. An open-label, exploratory trial was performed to assess the potential of the medicinal product in the treatment of restlessness caused by anxiety as related to several disorders. Outcome measures included the Symptom Checklist-90-Revised (SCL-90-R), von Zerssen's Depression Scale (D-S), the 36-item Short Form Health Survey Questionnaire (SF-36), and a sleep diary. 50 male and female patients with neurasthenia (ICD-10 F48.0), post-traumatic stress disorder (PSD; F43.1), or somatization disorder (F45.0, F45.1) were included to receive 1 × 80 mg/day Silexan over 6 weeks; 47 could be analyzed for efficacy as full analysis set. At baseline, patients suffered from restlessness (96%), depressed mood (98%), sleep disturbances (92%), or anxiety (72%). Of those, resp. 62%, resp. 57%, resp.51%, resp. 62% showed improvements during treatment (p < 0.001). For all patients, mean D-S score decreased by 32.7% and SCL-90-R Global Severity Index by 36.4% as compared to baseline, (p < 0.001), while the SF-36 Mental Health Score increased by 48.2% (p < 0.001). Waking-up frequency (p = 0.002), Waking-up duration (p < 0.001) and morning tiredness (p = 0.005) were reduced, while efficiency of sleep (p = 0.018) and mood (p = 0.03) improved. Patients suffering from neurasthenia or PSD showed comparable improvements with most outcomes. The results in this trial justify to further investigate Silexan in disorders with accompanying restlessness caused by sub-threshold anxiety. Adverse reactions, predominantly gastrointestinal complaints, were judged as mild or moderate.

A suspected case of somatoform disorder successfully treated with an herbal medicine.

OBJECTIVE: Subjective physical symptoms, irrespective of whether they are psychosomatic or not, do not always show obvious or reasonable signs in examinations, which often makes the differential diagnosis between somatoform disorders and actual physical disease difficult for psychiatrists. In addition, psychiatrists have few clues as to how to treat diverse "medically unexplained" symptoms. This difficulty has highlighted the need for alternative treatments for somatoform disorders. SUBJECT: A 16-year-old high school baseball player was suffering from coxalgia and was unable to walk without crutches over 6 months. No painkiller was effective, the orthopedist found no remarkable signs in any examinations, and the patient was psychiatrically diagnosed with undifferentiated somatoform disorder. However, conventional therapies such as psychotherapy and selective serotonin reuptake inhibitors were ineffective. INTERVENTIONS AND OUTCOME: The therapeutic strategy was reevaluated from the perspective of Kampo diagnostics and keishikajutsubuto, a traditional Japanese herbal (Kampo) medicine, was chosen to be prescribed, which had a remarkable effect. His leg function improved within 2 weeks, and his pain and need for crutches disappeared in 6 weeks. CONCLUSIONS: Keishikajutsubuto has a different pain-relieving effect from conventional therapies. Kampo medicine thus provides an alternative approach for treating medically unexplained symptoms without strictly distinguishing between physically existing illness and psychologically caused somatoform disorders. Although details regarding the therapeutic mechanisms of Kampo medicine remain unclear and further studies are needed to increase its usefulness in clinical practice, Kampo medicine should be considered as an alternative treatment, especially for somatoform disorders.

[Prevalence of psychiatric disorders in French general practice using the patient health questionnaire: comparison with GP case-recognition and psychotropic medication prescription]. / Prévalence des troubles psychiatriques en médecine générale selon le patient health questionnaire: adéquation avec la détection par le médecin et le traitement prescrit.

INTRODUCTION: Psychiatric disorders, mainly depression and anxiety, are frequently encountered in primary care and are a major cause of distress and disability. Nearly half of cases go unnoticed and among those that are recognised, many do not receive adequate treatment. In France, there is limited research concerning the prevalence, detection and management of these conditions in primary care. OBJECTIVES: To estimate the prevalence of psychiatric disorders, overall and for the main psychiatric diagnostic categories, encountered in primary care; to describe general practitioners' (GPs') case identification rate; to examine psychotropic medication prescription according to diagnosis, in a regionally representative sample of GP attenders. METHODS: GP practicing standard general practice in an urban area of the city of Montpellier and a nearby semi-rural region were recruited to participate. The response rate was 32.8% (n=41). Five additional GP almost exclusively offering homeopathy and acupuncture were recruited nonrandomly for convenience purposes. In each GP surgery, consecutive patients entering the waiting room were invited by a research assistant to participate until 25 patients per GP were recruited. Each participant completed self-report questionnaires in the waiting time, including the patient health questionnaire (PHQ), which yields provisional DSM-IV diagnoses. The GP completed a brief questionnaire during the consultation, giving his/her rating of the severity of any psychiatric disorder present and action taken. RESULTS: The patient response rate was 89.8%. In all, 14.9% of patients reached DSM-IV criteria for major depression or anxiety disorder on the PHQ (9.1% for major depression, 7.5% for panic disorder; 6% for other anxiety disorders). For the subthreshold categories, 7.4% met criteria for other depressive disorders, 11.8% for somatoform disorders and 10.9% for probable alcohol abuse or dependence. 66.3% of patients with DSM-IV diagnoses of major depression or anxiety disorder were identified by the GP as having a psychiatric disorder. The identification rate was 51% for all depressive disorders, anxiety and somatoform disorders. Of patients receiving a prescription for anxiolytic or antidepressant medication on the survey day, 80% were classified as cases of psychiatric disorder by the GP. Only 48.8% met criteria for major depression or anxiety disorder on the PHQ. CONCLUSION: This study highlights the frequency of psychiatric disorders in a regional study of French general practice. Overall, prevalence rates were similar to those found elsewhere, except for probable alcohol abuse and dependence, which was considerably higher than in the USA PHQ validation study. As in other countries, GP identified roughly half of psychiatric cases. Furthermore, half of patients treated by anxiolytic or antidepressant medication did not meet the diagnostic criteria on the survey day for which these medications have mainly shown their efficacy. This confirms the French paradox of one of the highest psychotropic medication consumption rates in Europe despite many cases of depression remaining untreated. The PHQ could be a rapid and acceptable diagnostic aid tool for French general practice but first needs to be validated against the diagnosis of mental health professionals in this setting.

St. John's wort - an overview.

This article aims to summarize the current state of knowledge on St. John's wort (Hypericum perforatum L.) which is one of the oldest and best investigated medicinal herbs. Dried alcoholic extracts are the most important preparations on the market although a variety of other preparations are available. Depressive disorders according to modern diagnostic standards are the best known and most widely investigated indication although the more traditional, broader indication of 'psycho-vegetative disorders, depressive disorders, anxiety and/or nervous agitation', including diagnoses such as somatoform disorders, might more adequately describe what Hypericum extracts are actually used for by many practitioners. The exact mechanisms of action are still unclear, but the available research clearly shows that various bioactive constituents contribute to the clinical effects reported, often in a synergistic manner. Hypericum extracts have consistently shown activity in pharmacological models related to antidepressant effects. Randomized clinical trials show that Hypericum extracts are more effective than placebo and similarly effective as standard antidepressants while having better tolerability in the acute treatment of major depressive episodes. The most important risk associated with Hypericum extracts are interactions with other drugs. Therefore, physicians need to be informed whether their patients take St. John's wort products. If the risk of interactions is adequately taken into account, high quality Hypericum extracts are an effective and safe tool in the hand of qualified health profession-als in primary care.

Fixed herbal drug combination with and without butterbur (Ze 185) for the treatment of patients with somatoform disorders: randomized, placebo-controlled pharmaco-clinical trial.

Herbal drugs are often used in patients with somatoform disorders yet, the available evidence is limited. The aim of the present short-term study was to evaluate in a pharmaco-clinical trial the additional benefit of butterbur in a fixed herbal drug combination (Ze 185 = 4-combination versus 3-combination without butterbur and placebo) in patients with somatoform disorders.For a 2-week treatment in patients with somatization disorder (F45.0) and undifferentiated somatoform disorder (F45.1), 182 patients were randomized for a 3-arm trial (butterbur root, valerian root, passionflower herb, lemon balm leaf versus valerian root, passionflower herb, lemon balm leaf versus placebo). Anxiety (visual analogue scale - VAS) and depression (Beck's Depression Inventory - BDI) served as primary parameters, Clinical Global Impression (CGI) was a secondary parameter.The 4-combination was significantly superior to the 3-combination and placebo (4-combination > 3-combination > placebo) in all the primary and secondary parameters (PP-population). Analysis of the ITT population confirmed these results. As to safety, no serious adverse events occurred. In total 9 non-serious adverse events were documented but the distribution did not differ significantly between the treatment groups.This herbal preparation (Ze185) showed to be an efficacious and safe short-term treatment in patients with somatoform disorders.

Terapias de soporte / Supportive therapy

Uno de los factores que han contribuido de manera decisiva a la mejora de los resultados terapéuticos en los niños con cáncer, ha sido la utilización sistemática de una serie de medidas que han permitido disminuir los efectos tóxicos derivados de la propia terapia. La terapia de soporte engloba todas aquellas medidas dirigidas a la prevención y tratamiento de las complicaciones derivadas de la propia enfermedad o del tratamiento de la misma (AU)

One of the factors that has decisively contributed to the improvement of therapeutic results in children with cancer has been the systematic use of a series of measures that has made it possible to decrease the toxic effects derived form the therapy itself. Supportive therapy includes all those measures aimed at prevention and treatment of the complications cause by the disease itself or from its treatment (AU)

[Lifestyle drugs in medicine]. / Lifestyle-Medikamente in der Medizin.

Lifestyle drugs have become an important new group of medications, which are taken by healthy people to increase the individual well-being and quality of life. Nootropics, psychopharmaceuticals, hormones and "ecodrugs" are today the main groups. The wish for eternal youth, beauty and potency is central, and lifestyle medications are also requested to influence cosmetic findings, which are usually simply a result of the natural aging process. Lifestyle drugs seem to be harmless, but the physician must pay attention to possible abuse, side effects, risks and complications. Additionally, however, lifestyle drugs are also frequently used by patients suffering from emotional disorders such as somatoform disorders. Medicalization of physiological life is then expected to solve psychosocial problems, but without success. The use of lifestyle medications in somatoform disorders is contraindicated and psychotherapy or psychopharmacological treatment come first. With this overview article, we would like to make an update of new lifestyle drugs.

[New developments in hypericum extracts: data on efficacy and interactions]. / Aktuelle Entwicklungen bei Johanniskrautextrakten: Neue Daten zu Wirksamkeit und Interaktionen.

The recent clinical studies on hypericum extract support the present indications for its use in mild to moderate depression and depressive episodes. The effectiveness is superior to placebo and comparable with synthetic antidepressive drugs. The rate of unwanted events is explicitly lower and their severity in general only mild. A further indication for hypericum could be somatoform disorders, but further clinical studies are recommended. The main compound responsible for interactions is presumably hyperforin, but further ingredients could contribute according to the specific composition of the particular extract.

[Phytotherapy in the treatment of functional disorders]. / Phytotherapie bei funktionellen Störungen. So setzen Sie die Kraft der Kraiuter richtig ein.

Although functional cardiac and gastrointestinal disorders are common, standard treatment with chemically defined drugs is not always available. However, Phytotherapy offers a broad spectrum of well-tolerated preparations with either confirmed, or at least - based on the range of constituents - plausible, efficacy. Of importance for the successful outcome of such treatment is that it be oriented to the patient's symptoms. The physician should be in a position to counsel the patient accordingly. In many cases, phytotherapy may well be the treatment of first choice, but wherever there is a need for a change in lifestyle, this should be made clear to the patient.

[Clinical observation on treatment of somatic disorder with combination of Xiaoyao Powder and Wendan Decoction].

OBJECTIVE: To compare the efficacy of Chinese medicine and selective serotonin reuptake inhibitors (SSRI), fluoxetine, on somatic disorder (SD) and to explore the advantage of Chinese medicine. METHODS: Patients with SD screened with Hamilton depression scale (HAMD) were randomly assigned to the fluoxetine group treated with fluoxetine 20 mg once per day administered after breakfast, and the Chinese medicine group with combination of Xiaoyao Decoction (XD) and Wendan Decoction (WD) one dose a day given before supper everyday, the treatment for both groups was lasted for 8 weeks. Clinical general impression (CGI) and symptom checklist 90 (SCL-90) were applied to evaluate the changes in symptoms before and after treatment, and a self-made rating scale was used to evaluate the adverse reaction. RESULTS: CGI score changed significantly in both groups after treatment, showed the average 2-week reduction rate of more than 30% and the average 8-week reduction rate of more than 70%, without significant difference shown between the two groups (P > 0.05). SCL-90 scoring showed the average score of somatic factor was significantly lower in the Chinese medicine group than in the fluoxetine group (P < 0.05) with few adverse reaction, while no significant difference was found in the respective scores of other factors between the two groups (P > 0.05). CONCLUSION: Chinese medicine shows noticeable superiority in treating SD, it has the effect similar to that of new antidepressants.

Effects of Yoku-kan-san on undifferentiated somatoform disorder with tinnitus.

Up to the present, there have been few strategies that are completely effective in treating undifferentiated somatoform disorder with tinnitus. We herein report that Yoku-kan-san (TJ-54), one of Japan's traditional herbal medicines, is an effective treatment for tinnitus in undifferentiated somatoform disorder complicated with headache and insomnia. TJ-54 has been also used as an effective treatment for insomnia and irritability in recent centuries and is considered to have some effects on the excitability of nerves. Further studies are needed to confirm the efficacies of Japanese herbal medicines.

Treatment of somatoform disorders with St. John's wort: a randomized, double-blind and placebo-controlled trial.

OBJECTIVE: To investigate efficacy and safety of St. John's wort (SJW) LI 160 in somatoform disorders. METHODS: In a prospective, randomized, placebo-controlled, and double-blind parallel group study, 184 outpatients with somatization disorder (ICD-10 F45.0), undifferentiated somatoform disorder (F45.1), and somatoform autonomic dysfunction (F45.3), but not major depression, received either 300 mg of SJW extract LI 160 twice daily or matching placebo for 6 weeks. Six outcome measures were evaluated as a combined measure by means of the Wei Lachin test: Somatoform Disorders Screening Instrument--7 days (SOMS-7), somatic subscore of the HAMA, somatic subscore of the SCL-90-R, subscores "improvement" and "efficacy" of the CGI, and the global judgment of efficacy by the patient. RESULTS: In the intention to treat population (N=173), for each of the six primary efficacy measures as well as for the combined test, statistically significant medium to large-sized superiority of SJW treatment over placebo was demonstrated (p <.0001). Of the SJW patients, 45.4% were classified as responders compared with 20.9% with placebo (p =.0006). Tolerability of SJW treatment was equivalent to placebo. CONCLUSIONS: Administration of 600 mg of SJW extract LI 160 daily is effective and safe in the treatment of somatoform disorders, thereby confirming results from a previous study.