Category: Treatment

Classifying medication use in clinical research

Abstract:

BACKGROUND: Medication use data are usually collected in clinical research. Yet no standardized method for categorizing these exists, either for sample description or for the study of medication use as a variable.

OBJECTIVE: The present investigation was designed to develop a simple, empirically based classification scheme for medication use categorization.

METHOD: The authors used factor analysis to reduce the number of possible medication groupings. This permitted a pattern of medication usage to emerge that appeared to characterize specific clinical constellations. To illustrate the technique’s potential, the authors applied this classification system to samples where sleep disorders are prominent: chronic fatigue syndrome and sleep apnea.

RESULTS: The authors’ classification approach resulted in 5 factors that appear to cohere in a logical fashion. These were labeled Cardiovascular or Metabolic Syndrome Medication, Symptom Relief Medication, Psychotropic Medication, Preventative Medication, and Hormonal Medication.

CONCLUSIONS: The findings show that medication profile varies according to clinical sample. The medication profile for participants with sleep apnea reflects known comorbid conditions; the medication profile associated with chronic fatigue syndrome appears to reflect the common perception of this condition as a psychogenic disorder.

 

Source: Rizzo D, Creti L, Bailes S, Baltzan M, Grad R, Amsel R, Fichten CS, Libman E. Classifying medication use in clinical research. J Prim Care Community Health. 2011 Jan 1;2(1):26-32. doi: 10.1177/2150131910385843. Epub 2010 Oct 27. https://www.ncbi.nlm.nih.gov/pubmed/23804659

 

Amisulpride vs. fluoxetine treatment of chronic fatigue syndrome: a pilot study

Abstract:

Different pharmacologic agents have been evaluated in the treatment of Chronic Fatigue Syndrome (CFS), albeit with moderate efficacy. Among the compounds thought to present with potential to be efficacious in CFS patients stands out low-dose amisulpride, a substituted benzamide that has been shown to be an useful treatment for conditions which exhibit some overlap with CFS such as dysthymia and somatoform disorders.

We thus recruited forty non-depressed CFS patients that were randomized to receive either amisulpride 25mg bid, or fluoxetine 20mg uid; all subjects were un-blinded to the treatment regimen. At the time of enrollment in the study and after twelve weeks of treatment, enrolled subjects completed the Krupp Fatigue Severity Scale, the Hospital Anxiety and Depression Scale and a visual analog scale focused on pain and bodily discomfort. Moreover, all subjects were evaluated by a clinician, blinded to the treatment regimen, using the Clinical Global Impression Severity Scale.

Our data revealed a significant improvement both in self-report, and observer-based measures for the amisulpride-treated, but not for the fluoxetine-treated patients. Amisulpride-treated subjects also presented with a significant reduction of somatic complaints, while the amisulpride effect on anxiety and mood levels was not significant. Both drugs were equally well tolerated.

Summing up, we showed a positive symptomatic effect of amisulpride, compared to SSRI treatment, in a group of non-depressed CSF patients on self-report and on observer-based measures of fatigue and somatic complaints. If confirmed by larger, blinded studies, amisulpride thus could represent an effective approach to this difficult-to-treat condition.

Copyright © 2010 Elsevier B.V. and ECNP. All rights reserved.

 

Source: Pardini M, Guida S, Primavera A, Krueger F, Cocito L, Gialloreti LE. Amisulpride vs. fluoxetine treatment of chronic fatigue syndrome: a pilot study. Eur Neuropsychopharmacol. 2011 Mar;21(3):282-6. doi: 10.1016/j.euroneuro.2010.10.008. Epub 2010 Nov 26. https://www.ncbi.nlm.nih.gov/pubmed/21112746

 

TLR3 agonists as immunotherapeutic agents

The interaction of innate and adaptive immune responses is extremely complex and just beginning to be understood in detail. The tendency for biomedical research to establish reproducible models, cell systems and receptor pathways, and then to focus on these systems can sometimes result in opportunity that is not appreciated. The Toll-like receptor (TLR)3 pathway as a therapeutic target falls into this category. There is an immense body of data that has been developed for more than 40 years; all of which is highly relevant to the TLR3 story and yet most of which predates the elucidation of the TLR pathways. A new recognition of TLR3, its unique properties that distinguish it from other TLR pathways, the specificity of relevant and long-available TLR agonists, and new studies of this biology utilizing modern assay methodology suggest that this target may be especially valuable as an adjunct to multiple immunotherapy strategies currently in use or in development.

You can read the rest of this article here: http://www.futuremedicine.com/doi/full/10.2217/imt.10.8 (Full article)

 

Source: Christopher F Nicodemus and Jonathan S Berek. TLR3 agonists as immunotherapeutic agents. Immunotherapy, March 2010 ,Vol. 2, No. 2, Pages 137-140 , DOI 10.2217/imt.10.8 (doi:10.2217/imt.10.8)  http://www.futuremedicine.com/doi/full/10.2217/imt.10.8 (Full article)

Treatment of the narcoleptiform sleep disorder in chronic fatigue syndrome and fibromyalgia with sodium oxybate

Abstract:

This study investigates the response of the underlying sleep disorder associated with Chronic Fatigue Syndrome (CFS) and fibromyalgia (FM) to treatment. We retrospectively reviewed 118 cases clinically consistent with CFS or FM, treated in a neurology practice. Abnormal findings on sleep studies and associated human leukocyte antigen markers, and a clinical pattern suggestive of narcolepsy, are present in a high proportion of patients. When considered appropriate based on the clinical picture and test results, treatment with sodium oxybate was offered to these patients. Sixty percent of patients treated with oxybate experienced significant relief of pain, while 75% experienced significant relief of fatigue. We postulate that the response to oxybate in CFS and FM suggests a disturbance of sleep similar to narcolepsy. These findings support this novel approach to intervention and further research. The inability to distinguish CFS and FM by testing and response to treatment suggests that they may represent variations of the same disorder or may be closely related disorders.

 

Source: Spitzer AR, Broadman M. Treatment of the narcoleptiform sleep disorder in chronic fatigue syndrome and fibromyalgia with sodium oxybate. Pain Pract. 2010 Jan-Feb;10(1):54-9. doi: 10.1111/j.1533-2500.2009.00334.x. https://www.ncbi.nlm.nih.gov/pubmed/20629967

 

Chronic fatigue syndrome: is there a role for non-antidepressant pharmacotherapy?

Abstract:

IMPORTANCE OF THE FIELD: Chronic fatigue syndrome (CFS) is a prevalent but poorly understood condition mainly characterized by debilitating, persistent or recurrent fatigue; increased physical and mental fatigability; cognitive impairment and widespread musculoskeletal pain. Despite intensive treatment research, the role of pharmacotherapy in the illness remains uncertain.

: An updated review is given of pharmacotherapy in CFS, with a focus on non-antidepressant, controlled drug trials performed between 1988 and August 2009.

WHAT THE READER WILL GAIN: Antiviral, immunological and antibiotic therapies, although sometimes associated with symptom amelioration, can be more harmful than beneficial in CFS. Stimulants seem to benefit some CFS patients but their long-term effects is uncertain. Although antidepressants are not curative for the illness, they might be useful for some symptomatic aspects and co-morbid anxiety and depression. There is little or no evidence that CFS patients benefit from other pharmacological agents (e.g., steroids) or from dietary supplements and complementary medicine products. Future research into treatment should take specific subgroups into account and should target immunological aspects of the illness as well as the complex relationships between CFS, stress and depression.

TAKE HOME MESSAGE: Pharmacotherapy can currently not be considered first-line treatment in CFS and should always be used in a context of self-management and rehabilitation.

 

Source: Van Houdenhove B, Pae CU, Luyten P. Chronic fatigue syndrome: is there a role for non-antidepressant pharmacotherapy? Expert Opin Pharmacother. 2010 Feb;11(2):215-23. Doi: 10.1517/14656560903487744. https://www.ncbi.nlm.nih.gov/pubmed/20088743

 

Treatment of chronic fatigue syndrome: findings, principles and strategies

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating condition characterized by serious medically unexplained mental and physical fatigue. The high prevalence and both direct and indirect health costs of CFS patients represent a huge problem for contemporary health care. Moreover, the prognosis of CFS, even when treated, is often poor. In this paper, we first critically review current evidence based treatments of CFS. Second, we discuss the growing insights into the etiopathogenesis of CFS, and the need to translate and integrate these insights into future treatments. In particular, we formulate a pragmatic and empirically testable treatment approach, tailored to the individual needs of patients, which aims at restoring the mental and physical equilibrium of CFS patients by trying to bring about sustained life style changes.

 

Source: Luyten P, Van Houdenhove B, Pae CU, Kempke S, Van Wambeke P. Treatment of chronic fatigue syndrome: findings, principles and strategies. Psychiatry Investig. 2008 Dec;5(4):209-12. doi: 10.4306/pi.2008.5.4.209. Epub 2008 Dec 31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796012/ (Full article)

 

Chronic fatigue syndrome: la bête noire of the Belgian health care system

Abstract:

The World Health Organization acknowledges Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) to be a medical illness. ME/CFS is characterized by disorders in the inflammatory and oxidative and nitrosative stress (IO&NS) pathways. In 2002, the Belgian government started with the development of CFS “Reference Centers”, which implement a “psychosocial” model. The medical practices of these CFS Centers are defined by the Superior Health Council, e.g. treatment should be based upon Cognitive Behavioral Therapy (CBT) and Graded Exercise Therapy (GET); and biological assessments and treatments of ME/CFS should not be employed.

Recently, the Belgian government has evaluated the outcome of the treatments at the CFS Centers. They concluded that a “rehabilitation therapy” with CBT/GET yielded no significant efficacy in the treatment of ME/CFS and that CBT/GET cannot be considered to be curative therapies.

In case reports, we have shown that patients who were “treated” at those CFS centers with CBT/GET in fact suffered from IO&NS disorders, including intracellular inflammation, an increased translocation of gram-negative enterobacteria (leaky gut), autoimmune reactions and damage by O&NS.

Considering the fact that these findings are exemplary for ME/CFS patients and that GET may even be harmful, it means that many patients are maltreated by the Belgian CFS Centers. Notwithstanding the above, the government and the CFS Centers not only continue this unethical and immoral policy, but also reinforce their use of CBT/GET in patients with ME/CFS treated at those Centers.

 

Source: Maes M, Twisk FN. Chronic fatigue syndrome: la bête noire of the Belgian health care system. Neuro Endocrinol Lett. 2009;30(3):300-11. https://www.ncbi.nlm.nih.gov/pubmed/19855351

 

A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS

Abstract:

Benign Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) is a debilitating disease which, despite numerous biological abnormalities has remained highly controversial. Notwithstanding the medical pathogenesis of ME/CFS, the (bio)psychosocial model is adopted by many governmental organizations and medical professionals to legitimize the combination of Cognitive Behavioral Therapy (CBT) and Graded Exercise Therapy (GET) for ME/CFS. Justified by this model CBT and GET aim at eliminating presumed psychogenic and socially induced maintaining factors and reversing deconditioning, respectively.

In this review we invalidate the (bio)psychosocial model for ME/CFS and demonstrate that the success claim for CBT/GET to treat ME/CFS is unjust. CBT/GET is not only hardly more effective than non-interventions or standard medical care, but many patients report that the therapy had affected them adversely, the majority of them even reporting substantial deterioration.

Moreover, this review shows that exertion and thus GET most likely have a negative impact on many ME/CFS patients. Exertion induces post-exertional malaise with a decreased physical performance/aerobic capacity, increased muscoskeletal pain, neurocognitive impairment, “fatigue”, and weakness, and a long lasting “recovery” time.

This can be explained by findings that exertion may amplify pre-existing pathophysiological abnormalities underpinning ME/CFS, such as inflammation, immune dysfunction, oxidative and nitrosative stress, channelopathy, defective stress response mechanisms and a hypoactive hypothalamic-pituitary-adrenal axis.

We conclude that it is unethical to treat patients with ME/CFS with ineffective, non-evidence-based and potentially harmful “rehabilitation therapies”, such as CBT/GET.

 

Source: Twisk FN, Maes M. A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS. Neuro Endocrinol Lett. 2009;30(3):284-99. https://www.ncbi.nlm.nih.gov/pubmed/19855350

 

Use of medications by people with chronic fatigue syndrome and healthy persons: a population-based study of fatiguing illness in Georgia

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a debilitating condition of unknown etiology and no definitive pharmacotherapy. Patients are usually prescribed symptomatic treatment or self-medicate. We evaluated prescription and non-prescription drug use among persons with CFS in Georgia and compared it to that in non-fatigued Well controls and also to chronically Unwell individuals not fully meeting criteria for CFS.

METHODS: A population-based, case-control study. To identify persons with possible CFS-like illness and controls, we conducted a random-digit dialing telephone screening of 19,807 Georgia residents, followed by a detailed telephone interview of 5,630 to identify subjects with CFS-like illness, other chronically Unwell, and Well subjects. All those with CFS-like illness (n = 469), a random sample of chronically Unwell subjects (n = 505), and Well individuals (n = 641) who were age-, sex-, race-, and geographically matched to those with CFS-like illness were invited for a clinical evaluation and 783 participated (48% overall response rate). Clinical evaluation identified 113 persons with CFS, 264 Unwell subjects with insufficient symptoms for CFS (named ISF), and 124 Well controls; the remaining 280 subjects had exclusionary medical or psychiatric conditions, and 2 subjects could not be classified. Subjects were asked to bring all medications taken in the past 2 weeks to the clinic where a research nurse viewed and recorded the name and the dose of each medication.

RESULTS: More than 90% of persons with CFS used at least one drug or supplement within the preceding two weeks. Among users, people with CFS used an average of 5.8 drugs or supplements, compared to 4.1 by ISF and 3.7 by Well controls. Persons with CFS were significantly more likely to use antidepressants, sedatives, muscle relaxants, and anti-acids than either Well controls or the ISF group. In addition, persons with CFS were significantly more likely to use pain-relievers, anti-histamines and cold/sinus medications than were Well controls.

CONCLUSION: Medical care providers of patients with chronic fatigue syndrome should be aware of polypharmacy as a problem in such patients, and the related potential iatrogenic effects and drug interactions.

 

Source: Boneva RS, Lin JM, Maloney EM, Jones JF, Reeves WC. Use of medications by people with chronic fatigue syndrome and healthy persons: a population-based study of fatiguing illness in Georgia. Health Qual Life Outcomes. 2009 Jul 20;7:67. doi: 10.1186/1477-7525-7-67. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731740/ (Full article)

 

Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a disease of unknown aetiology. A patient with CFS had unexpected, marked recovery of CFS symptoms lasting for five months during and after cytotoxic chemotherapy for Hodgkin’s disease. We reasoned that the transient CFS recovery was related to methotrexate treatment, which induces immunomodulation in part through B-cell depletion.

METHODS: In a case series, this patient and two additional CFS patients were B-cell depleted by infusion of the monoclonal anti-CD20 antibody rituximab.

RESULTS: All three had improvement of all CFS symptoms. Patients 1 and 2 had major amelioration from 6 weeks after intervention, patient 3 slight improvement from the same time, but then improved markedly from 26 weeks after intervention. The symptomatic effect lasted until weeks 16, 18 and 44, respectively. At relapse, all were retreated with a single (patient 1) or double rituximab infusion (patients 2 and 3). Again, all three had marked symptom improvement, mimicking their first response. After new symptom recurrence, patients 1 and 2 were given weekly oral methotrexate, patient 1 having effect also from this agent. Patients 1 and 2 were again treated for a third rituximab infusion after new relapse, again with a marked clinical benefit. No unexpected toxicity was seen.

CONCLUSION: These observations suggest that B-lymphocytes are involved in CFS pathogenesis for a subset of patients. Benefit for all CFS symptoms, the delayed symptom relief following B-cell depletion, the kinetics of relapses, and the effect also from methotrexate treatment, provide suggestive evidence that B-cells play a significant role in the ongoing clinical features, and that CFS may be amenable to therapeutic interventions aimed at modifying B-cell number and function. More systematic investigations of this therapeutic strategy, and of its biological basis, are now needed.

 

Source: Fluge Ø, Mella O. Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series. BMC Neurol. 2009 Jul 1;9:28. doi: 10.1186/1471-2377-9-28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711959/ (Full article)