[Medical care situation of patients with ankylosing spondylitis and psoriatic arthritis in Germany : Medical care situation of patients with spondyloarthritis (SpA): ankylosing spondylitis (AS) and psoriatic arthritis (PsA) from the perspective of rheumatologists in private practice and hospitals in Germany-Results of the research project "SpA Loop-Life of Outpatients"]. / Versorgungssituation von Patienten mit ankylosierender Spondylitis und Psoriasisarthritis in Deutschland : Versorgungssituation von Patienten mit Spondyloarthritis (SpA): Ankylosierende Spondylitis (AS) und Psoriasisarthritis (PsA) aus der Sicht von niedergelassenen und in Kliniken tätigen Rheumatologen in Deutschland ­ Ergebnisse des Forschungsprojekts "SpA Loop ­ Life of Outpatients".

BACKGROUND: The prevalence of spondyloarthritis (SpA) in Germany is approximately 1-1.4% and includes predominantly axial SpA (axSpA) and predominantly peripheral SpA. Ankylosing spondylitis (AS) belongs to the group of axial SpA but also exhibits peripheral manifestations. Psoriatic arthritis (PsA) can show purely peripheral or also axial manifestations. The total prevalence of SpA in Germany is approximately 1­1.4%, the prevalence of AS is ca. 0.5% and PsA 0.2-1.4%. Patients with AS are mainly treated by internal medical rheumatologists but in many places also basically treated by general practitioners and orthopedists. Patients with PsA are mainly diagnosed and treated by rheumatologists and dermatologists working in private practice or in clinical settings. Besides the control of inflammatory activity and prevention or slowing down of the characteristic disease progression, including irreversible structural changes, the main objectives of patients as well as treating physicians are particularly freedom from pain and a quality of life comparable to non-affected persons. Decisive for successful treatment are an early diagnosis and initiation of adequate therapy as well as regular monitoring of disease activity including treatment adjustment taking the needs of the patient into consideration; however, it is unknown how often this is actually successful in routine daily practice in Germany. OBJECTIVE: The aim of the SpA Loop research project was to display the current medical care situation of patients with AS and PsA treated in private practices and hospitals for rheumatology in Germany focusing on patient/physician profiles as well as the diagnostics and treatment. MATERIAL AND METHODS: The instrument for the survey was a standardized questionnaire with 29 multiple choice and perception questions that was distributed to medical specialists in the field of internal medicine and rheumatology. RESULTS: A high accordance between rheumatologists in private practice and in hospitals was observed with respect to the presentation and perception of the current medical care situation for patients with AS and PsA in Germany. Differences were only occasionally found. CONCLUSION: The results of this research project reflect the current status of the medical care situation of AS and PsA patients in Germany. They provide information on which areas of the medical care situation can selectively be improved as well as on interesting aspects and points of discussion with respect to the patient population treated.

[Hermann Oppenheim. Comments on his life and works]. / Hermann Oppenheim. Anmerkungen zu seinem Leben und Wirken.

The outstanding neurologist Hermann Oppenheim was renowned worldwide during his lifetime and was highly esteemed; however, he was also a contradictory, complex personality and his life was marked by several tragic events. Even for his contemporaries, his life and work was the subject of lively discussions and debates and also some 100 years later, it is an interesting challenge to obtain an insight into the extensive work of this famous man and to understand the reasons for his great successes and failures.

Experimental study of wet granulation in fluidized bed: impact of the binder properties on the granule morphology.

In this work, the effect of the physicochemical properties of aqueous hydroxypropyl-cellulose (HPC) binder solutions and different pharmaceutical excipients (mannitol and anhydrous CaHPO(4)) on the agglomeration kinetics and granule properties were investigated. First, a particle size distribution (PSD) analysis together with a detailed analysis of morphological properties of the excipient particles were performed. Second, the viscosity, density, surface tension and size of the spray droplets of binder solutions with different HPC concentrations were determined and wetting characteristics of the binders on the excipients were measured. Third, several fluid bed wet granulation experiments were conducted for pure excipients and their blends with binder solution of different HPC concentrations in a pilot plant Wurster granulator. The observed granule growth for different binder concentrations was a strong function of the binder concentration and the excipient solubility. For mannitol, a significant "coating" period followed by a slow granule growth was observed for the case with the diluted 5% binder. The "coating" period was significantly shorter for the 10% HPC binder and did not exist for the 15% HPC for which immediate and fast granule growth was observed. For anhydrous CaHPO(4) (trademark A-TAB), no growth was observed for the 10% HPC binder and a long coating period followed by fast granule growth was observed for the 15% HPC. Simple physically based criteria were also evaluated, which employ the morphological properties of excipients (size and surface roughness) together with physical properties of the used binder for prediction of the coating versus agglomeration regime at given flow conditions (collision velocity). As expected, a preferential coalescence and growth of the mannitol granules from the blend of mannitol+A-TAB was observed. Finally, the mechanical and morphological properties of the produced granules were measured and correlated to the HPC concentration of the binder used in the experiments. A clear correlation between the granule porosity (evaluated by X-ray tomography) and the binder concentration was found for the mannitol granules.

The effect of missense mutations in the RhoGAP-homology domain on ocrl1 function.

Lowe syndrome is a rare X-linked disease characterized by congenital cataracts, defects in renal tubule cell function, and mental retardation. Mutations in the OCRL1 gene, which encodes ocrl1, a phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P(2)) 5-phosphatase, are the cause of Lowe syndrome. PtdIns(4,5)P(2), a substrate of ocrl1, is an important signaling molecule within the cell. OCRL1 is ubiquitously expressed and co-localizes with the trans-Golgi network (TGN) and endosomal proteins. The ocrl1 protein contains two recognizable domains, one a conserved Ptd(4,5)P(2) 5-phosphatase domain and the other with homology to Rho GTPase activating proteins (RhoGAPs). The objective of our study was to further characterize the ocrl1 RhoGAP-homology domain by analyzing the effect of two missense mutations in this domain, I751N and A780P, which were previously reported in Lowe syndrome patients. Both mutant proteins were expressed at levels similar to wild-type but their enzyme activity was reduced by 85-90%, indicating that the RhoGAP-homology domain is important for the enzymatic function of ocrl1. Study of a C-terminal region of wild-type ocrl1 containing this domain detected no GAP activity, eliminating the possibility of an effect by mutations in this domain on GTPase activation. Because members of the Arf family of small G-proteins are directly involved in (Ptd(4,5)P(2)) signaling and localize to the TGN like ocrl1, we analyzed by immunoprecipitation the interaction of ocrl1 with Arf1 and Arf6 via its RhoGAP-homology domain. Wild-type ocrl1, but not the I751N mutant protein, co-immunoprecipitated with these two Arf proteins. These results indicate that wild-type ocrl1 and Arf proteins can interact and that this interaction is disrupted by the mutation. It remains unknown whether a disrupted interaction between Arf and ocrl1 plays a role in the Lowe syndrome phenotype.

Physiology and pathophysiology of the 5-HT3 receptor.

The 5-HT3 receptor is a ligand-gated cation channel located in the central and peripheral nervous system; it has also been detected on a variety of other cells. In the periphery, it is found on autonomic neurons and on neurons of the sensory and enteric nervous system. In the CNS, the 5-HT3 receptor has been localized in the area postrema, nucleus tractus solitarii, nucleus vaudatus, nucleus accumbens, amygdala, hippocampus, entorhinal, frontal, cingulate cortex, and in the dorsal horn ganglia. Further extraneuronal locations include among others lymphocytes, monocytes, and foetal tissue. 5-HT3 receptors modulate the release of neurotransmitters and neuropeptides like dopamine, cholecystokinin, acetylcholine, GABA, substance P, and serotonin itself. They have been demonstrated to be involved in sensory transmission, regulation of autonomic functions, integration of the vomiting reflex, pain processing and control of anxiety. While the physiologic functions of the 5-HT3 receptor are discrete and difficult to detect, it plays a key role in certain pathologic situations related to increased serotonin release. Clinical development of 5-HT3 receptor antagonists revealed a remarkable range of activities. 5-HT3 receptor antagonists do not modify any aspect of normal behaviour in animals or induce pronounced changes of physiological functions in healthy subjects. Clinical efficacy was shown for various forms of emesis like chemotherapy-induced, radiotherapy-induced, and postoperative emesis, diarrhoea-predominant irritable bowel syndrome, anxiety, chronic fatigue syndrome, alcohol abuse, and in pain syndromes such as fibromyalgia and migraine. Most recent data also suggest that 5-HT3 receptor antagonists are effective for the treatment of other rheumatic diseases such as rheumatoid arthritis, tendinopathies, periarthropathies, and myofascial pain. Other possible indications under discussion are chronic heart pain and bulimia. Unfortunately, experimental findings do not yet provide a homogenous conception of the significance of 5-HT3 receptors in all investigated fields; in nociception, for example, contradictory observations are still inadequately explained and complicated by bell-shaped dose-response curves. Further elucidation and better understanding of the serotonergic neuronal network remains a task for the next decade.

Spectrum of use and tolerability of 5-HT3 receptor antagonists.

Several 5-HT3 receptor antagonists are available (tropisetron, ondansetron, granisetron, dolasetron, and palonsetron), and further compounds are in clinical development. These substances show only minor differences in the activity profile regarding their affinity for particular receptors. 5-HT3 receptor antagonists are primarily used and found effective in the prevention and treatment of chemotherapy-induced nausea and emesis, and in postoperative nausea and vomiting (PONV). Antagonism of the 5-HT3 receptors in the peripheral and central nervous system is a probable mechanism of action. The substances are suitable as first-line therapy (combined with a corticosteroid) for the prevention of acute nausea and vomiting in patients treated with moderately to severely emetogenic chemotherapeutic agents. This combination is also moderately effective in the prevention of delayed nausea and vomiting. 5-HT3 receptor antagonists are an important constituent in the prevention and treatment of emesis and nausea caused by radiation therapy, especially in patients receiving whole body or upper abdominal treatment. Alosetron was found clinically effective in diarrhoea-predominant irritable bowel syndrome, whereas tropisetron in fibromyalgia and related pain disorders. Further indications for such treatment include anxiety disorders, alcohol dependence, drug withdrawal, and psychosis related to treatment of Parkinson's disease. 5-HT3 receptor antagonists are well tolerated with the most frequently reported adverse effects being headache, constipation, dizziness, tiredness, and gastrointestinal disturbances such as abdominal pain or constipation. Intravenous administration of serotonin induces the Bezold-Jarisch reflex and causes small reversible changes in electrocardiogram (ECG) parameters.

Treatment of fibromyalgia with tropisetron--dose and efficacy correlations.

Previous studies evaluating the efficacy and tolerance of tropisetron for the treatment of fibromyalgia (FM) used the drug either intravenously or orally, and at different dosage levels ranging from 2 mg to 15 mg daily. The shortest treatment was a single dose and the longest treatment period covered 28 days. A significant reduction of the pain intensity was achieved by using tropisetron 5 mg per day. Apart from the fact that treatment periods were different, the efficacy of oral and intravenous administration did not differ significantly. Tropisetron was well tolerated; but in the 15 mg group in one of the studies, the decrease in pain was less than in the placebo group, however, the frequency of constipation and other gastrointestinal symptoms increased. Furthermore, it was hypothesized that due to the impacts of CYP2D6 activities, a daily dose of tropisetron 2 mg may be efficacious in slow metabolizers only. Although tropisetron proved to be efficacious in a group of fibromyalgia patients, the dose-response curves cannot yet be explained in a fully satisfactory manner, which may encourage research focusing on possible subgroups of FM.

The assessment of vegetative and functional symptoms in fibromyalgia patients: the tropisetron experience.

Vegetative and functional symptoms are, besides pain and tenderness of tender points, considered as additional information for the diagnosis of fibromyalgia (FM). In clinical trials, vegetative and functional symptoms have been included for selection of patients (e.g. sleep disturbances) and as secondary outcome parameters. Despite the relevance of these symptoms, no validated method is currently available but symptom lists are ad hoc developed by investigators. In this manuscript, data from a published double blind, randomised study are reanalysed which compared oral therapy over 10 days with 5 mg, 10 mg, and 15 mg to placebo in FM patients. This study applied a list of 17 vegetative and functional symptoms, which had to be scored by the patients by use of a 4-point severity scale (0 = none to 3 = severe). Factor analysis of the baseline data from 195 patients suggested to separate 6 sub-scales: Cardiovascular, gastrointestinal, psychiatric (sleep disturbance), nervous, autonomic system, and general disorders. Sleep disturbances, general symptoms (morning stiffness, fatigue) and autonomic symptoms (cold extremities, hyperhidrosis) were most severe in intensity. Analysis of sensitivity for treatment effects made use of differences between placebo and 5 mg tropisetron in changes between baseline and final assessment of the tropisetron trial. While, on the item level, differences in favour of tropisetron could only be demonstrated for sleep disorders, on the sub-scale level, also favourable effects of tropisetron could be shown for cardiovascular and nervous system complaints and, as a tendency, for general symptoms. On the other side, the sub-scale score of gastrointestinal symptoms worsened under tropisetron whilst it improved under placebo which effect was due to side effects of the active treatment. It is concluded that symptom clusters like sub-scales of a list of vegetative and functional symptoms will be more suitable for diagnostic purposes and evaluation of treatment outcome of clinical trials. Further research is urgently required which addresses the development of a FM-specific scale to assess vegetative and functional symptoms.

Efficacy and tolerability of intravenous tropisetron in the treatment of fibromyalgia.

OBJECTIVE: To determine the efficacy of a serotonin receptor (5-HT(3)) antagonist in the treatment of fibromyalgia (FM) in a prospective, randomized, double-blind, placebo-controlled, multicentre trial. METHODS: Twenty-one female patients (age 21-63 years) with FM according to the American College of Rheumatology classification criteria for FM were assigned randomly to either a placebo group or to receive a daily intravenous bolus injection of 5 mg tropisetron for 5 days. RESULTS: In patients receiving tropisetron, the visual analogue scale (VAS) score for pain decreased by 28.9 compared with a decrease of 6.8 in the placebo group [probability (p)=0.063; effect size: 0.794]. Similar results were obtained using a body diagram pain score as a secondary efficacy parameter: mean pain reduction was 27.2 in the tropisetron group, versus 2.8 in the placebo group (p=0.038; effect size: 0.902). CONCLUSION: 5-HT(3) receptor antagonists provide significant pain relief for a group of FM patients.

Local treatment of tendinopathies: a comparison between tropisetron and depot corticosteroids combined with local anesthetics.

OBJECTIVE: To determine whether local injection of the 5-HT3-receptor antagonist, tropisetron. reduces pain in tendinopathies to the same degree as a local injection of corticosteroids in combination with local anesthetic. METHODS: Forty patients with tendinopathies were enrolled in this randomized, observer-blind study. An injection of either 5 mg tropisetron. or 10 mg dexamethasone combined with 60 mg lidocaine was administered around the affected tendon. The effect was measured with a visual analog pain scale before the injection, after 3 hours and on each of the following 7 days, in patients with good effects also 3 months after the injection. RESULTS: There were no significant differences between the tropisetron and the corticosteroid/anesthetic group in terms of pain at rest or on movement during the study. Both treatments were well tolerated. CONCLUSION: Local injection of tropisetron seems to be as safe and as effective as the combination of corticosteroids and local anesthetics in the treatment of painful tendinopathies.

Pharmacokinetics of therapeutic doses of tropisetron in healthy volunteers.

AIMS: To establish the bioavailability of tropisetron (5 mg) administered orally as capsule compared with 2 mg given intravenously. METHODS: Using a randomized crossover design, 18 healthy volunteers received a single oral dose of tropisetron (5 mg) and an intravenous bolus of tropisetron (2 mg) separated by a wash-out period of 1 week. Plasma concentrations of tropisetron were determined by h.p.l.c. and the pharmacokinetic parameters were estimated. RESULTS: The mean pharmacokinetic parameters for 5 mg tropisetron given orally were Cmax 3.46 ng ml(-1), t(max) 2.6 h, t(1/2) 5.7 h and AUC(0,infinity) 32.9 ng ml(-1) h. After intravenous administration initial plasma concentration was 15.1 ng ml(-1), t(1/2) 5.6 h, AUC(0,infinity) 20.7 ng ml(-1) h, V 678 l and CL 1800 ml min(-1). An inverse correlation was demonstrated between CYP2D6 activity, measured by the sparteine metabolic ratio, and the bioavailability (mean 0.60, range 0.27-0.99) of oral tropisetron. CONCLUSIONS: Tropisetron exhibits a wide range of oral bioavailability at therapeutic doses, which is mainly determined by CYP2D6 activity.

Short-term treatment of primary fibromyalgia with the 5-HT3-receptor antagonist tropisetron. Results of a randomized, double-blind, placebo-controlled multicenter trial in 418 patients.

We investigated the efficacy and tolerability of short-term treatment with tropisetron, a selective, competitive 5-HT3-receptor antagonist in fibromyalgia. The trial was designed as a prospective, multicenter, double-blind, parallel-group, dose-finding study. We randomly assigned 418 patients suffering from primary fibromyalgia to receive either placebo, 5 mg, 10 mg or 15 mg tropisetron once daily for 10 days. Clinical response was measured by changes in pain score, visual analog scale, tender point count and ancillary symptoms. Responders were prospectively defined as patients showing a 35% or higher reduction in pain score. Treatment with 5 mg tropisetron resulted in a significantly higher response rate (39.2%) than placebo (26.2%) (p < 0.05). In the visual analog scale, the group administered 5 mg tropisetron showed a significant improvement (p < 0.05) and the group administered 10 mg tropisetron showed a nonsignificant clinical benefit. The number of painful tender points was significantly reduced (p = 0.002) in the 5 mg tropisetron group. Regarding ancillary symptoms, the 5 mg tropisetron group showed a significant improvement (p < 0.05) in sleep and dizziness. The patients' overall assessment of efficacy was significantly higher for 5 mg (p = 0.016) and 10 mg (p = 0.002) tropisetron than for placebo. The safety and tolerability of tropisetron was good; gastrointestinal tract symptoms were the most frequently reported adverse events. Short-term treatment of fibromyalgia patients with 5 mg tropisetron for 10 days proved to be efficacious and well tolerated. In this study a bell-shaped dose-response curve was seen.

Financial survey. Retirement funding falls again.

Doctors can do more to overcome the lagging pension plan growth reflected in our data.

Fibromyalgia treatment with intravenous tropisetron administration.

A prospective, randomized, placebo-controlled, multicenter, double-blind trial in fibromyalgia patients demonstrated that peroral daily treatment with 5 mg tropisetron for 10 days produced a significant reduction in pain and other symptoms. The aim of the present study was to determine whether intravenous administration of 2 mg tropisetron daily for a limited period of time would produce quicker and more favorable results. In the first cohort 18 fibromyalgia patients received a single intravenous injection of 2 mg tropisetron. In the second cohort 24 fibromyalgia patients were treated with 2 mg intravenous tropisetron daily for 5 days. Pain intensity was measured with the visual analog scale and the pain score. Pain at tender and control points (dolorimeter) as well as 17 ancillary symptoms before and after treatment were evaluated. Pain intensity was followed-up by means of a patient diary until recurrence. Dolorimetry revealed that a single intravenous injection of 2 mg tropisetron significantly reduced pain and enhanced pain threshold. These effects, however, lasted for only a few days. Of 18 patients in the first cohort, only three showed no response to therapy. Of the 24 patients in the second cohort, 23 showed pain reduction when 2 mg tropisetron was administered daily for 5 days. Pain relief lasted for 2 weeks to 2 months in 20 of these patients. Two patients stopped filling in the pain diary. Twelve ancillary symptoms such as sleep disturbances, fatigue, morning stiffness were also significantly improved by the latter treatment. In the global assessment 16 out of 24 patients showed significant improvement and seven showed slight improvement. Only one patient experienced no improvement. Tolerability was good. In conclusion, intravenous injection of 2 mg of the 5-hydroxytryptamine3 receptor antagonist tropisetron once daily for 5 days produced a longer-lasting therapeutic effect on fibromyalgia symptoms than did peroral daily treatment with 5 mg of this drug. The results achieved are currently being evaluated in a randomized, placebo-controlled, double-blind trial.

Effect of tropisetron on circulating catecholamines and other putative biochemical markers in serum of patients with fibromyalgia.

OBJECTIVE: The aim of the study was to assess the influence of the 5HT3-receptor antagonist tropisetron on circulating catecholamines as biochemical markers of the activity of the sympathoadrenal system in fibromyalgia. Moreover, serum concentrations of serotonin, somatomedin C, oxytocin, calcitonin-gene-related-peptide, calcitonin and cholecystokinin were assayed as putative markers in pain-related disorders like primary fibromyalgia. METHODS: In 96 patients, who met the ACR classification criteria for fibromyalgia, and in 20 sex and age matched controls concentrations of dopamine, noradrenaline, adrenaline, serotonin and tropisetron were assayed in serum by HPLC with electrochemical detection. All other transmitters were determined by ELISA. RESULTS: There was with the exception of tropisetron, calcitonin and dopamine, no correlation between doses of tropisetron 5, 10, 15 mg respectively and significant changes in circulating transmitters or other transmitters as putative biochemicals markers in primary fibromyalgia. Regarding the prediction of pain reduction to tropisetron, patients with elevated dopamine and/or reduced plasma 5-HT concentrations tended to show a higher response rate. CONCLUSION: Despite these partly disappointing results another prospective pilot study with selected patients vs. age and sex matched controls, double blind and with comparison of other 5HT3-receptor antagonists e.g. dolasetron and granisetron e.g. after i.v. bolus injection is suggested. Still the data obtained in this preliminary paper provide some evidence regarding the present discussion on subgroups of patients with primary fibromyalgia.

Efficacy and tolerability of tropisetron in primary fibromyalgia--a highly selective and competitive 5-HT3 receptor antagonist. German Fibromyalgia Study Group.

OBJECTIVE: Based on a potential role for serotonin receptors in fibromyalgia, we investigated the efficacy and tolerability of treatment with tropisetron, a highly selective, competitive inhibitor of the 5-HT3 receptor. METHODS: In this prospective, multicenter, double-blind, parallel-group, dose-finding study, 418 patients suffering from primary fibromyalgia (ACR criteria) were randomly assigned to receive either placebo, 5 mg, 10 mg or 15 mg tropisetron once daily, respectively. The duration of treatment was 10 days. The clinical response was measured by changes in pain-score, visual analog scale (VAS), and the number of painful tender-points. RESULTS: Treatment with 5 mg tropisetron resulted in a significantly higher response rate (39.2%) when compared with placebo (26.2%) (p=0.033). The absolute reduction in pain-score was -13.5% for 5 mg tropisetron, -13.0% for 10 mg tropisetron, and -6.3% for placebo (p<0.05). The effects of 15 mg tropisetron were similar to placebo, thus suggesting a bell-shaped dose-response curve. Compared with placebo, treatment with 5 mg tropisetron led to a significant improvement (p<0.05) in VAS, while a clear trend in terms of clinical benefit was seen with 10 mg tropisetron. The number of painful tender-points was also reduced significantly (p=0.002) in the 5 mg tropisetron group. Of interest, during the 12-month follow-up period, pain intensity of responders on 5 mg and 10 mg tropisetron was still markedly below baseline. The treatment was well tolerated, with gastro-intestinal complaints being the most frequently reported side effects, in keeping with the known safety profile for 5-HT3 receptor antagonists. CONCLUSIONS: This study demonstrates the efficacy of short-term treatment with 5 mg tropisetron once daily in primary fibromyalgia. Treatment was well tolerated and prolonged clinical benefits were seen.

Treatment of chronic fatigue syndrome with 5-HT3 receptor antagonists--preliminary results.

OBJECTIVE: The serotonin system presumably is involved in the pathogenesis of chronic fatigue syndrome (CFS). Results from a few studies led to the hypothesis of a "postsynaptic hyperresponsiveness" in CFS. Therefore we intended to evaluate the efficacy of 5-HT3 receptor antagonists in the treatment of CFS. PATIENTS AND METHODS: 2 patient groups (10 patients each; CFS according to the CDC classification criteria) received either oral tropisetron (5 mg once daily) or oral ondansetron (2 x 8 mg daily), open-labelled. Treatment duration was 15 days. Treatment response was evaluated by visual analog scales (VAS) for fatigue and capability. RESULTS: 19 patients finished their respective study. In the tropisetron group 6/9 (VAS fatigue) and 7/9 (VAS capability) patients documented benefit, 8/10 rsp. 8/10 patients in the ondansetron group. The score changes (VAS before and after treatment) in case of response were more pronounced in the tropisetron group. The frequency of concomitant symptoms did not differ significantly in the treatment groups. The overall analysis of both studies showed a remarkable improvement (> or = 35%) of approximately one third of the patients in both VAS. Treatment was well tolerated. CONCLUSION: Our preliminary results encourage to perform placebo-controlled, double-blind studies to further evaluate the efficacy of 5-HT3 receptor antagonists in the treatment of CFS.