by Sasha Nimmo
Australian scientists looked at 26 studies on drug therapy for chronic fatigue syndrome symptoms and found no recommended pharmaceuticals.
The study looked at the English-language archives of Ovid MEDLINE, EMBASE and PubMed. Just 26 studies were considered suitable for review and only 13 ‘reported statistically significant results’. The scientists only reviewed randomised, placebo-controlled trials.
“…despite some studies reporting significant outcomes, interpreting and applying those results in a different setting or to a different CFS/ME cohort will not necessarily yield the same findings. The results from these studies are limited to their respective cohorts, highlighting the need for trials with clearly defined CFS/ME cohorts using standardised diagnostic criteria.”
A Systematic Review of Drug Therapies for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis was published in Clinical Therapeutics 2016.
The small number of studies and the outcomes highlight the need for standardised criteria and a greater investment in research.
Patient cohorts and definitions
The study identified three criteria: 1988 Holmes criteria for chronic fatigue syndrome (considered outdated by the authors), 2012 International Consensus Criteria for Myalgic Encephalomyelitis, and the 1994 Fukuda criteria for chronic fatigue syndrome (considered ‘too broad’, quoting the US Institute of Medicine’s review.)
The study repeatedly found inconsistency in the studies and stressed the need for well-defined patient cohorts.
“Trials based on more specific criteria such as the International Consensus Criteria are recommended to identify specific subgroups of patients in whom treatments may be beneficial.”
Patient diagnosis is another limiting factor.
“Patients who experience general chronic fatigue but do not meet the other criteria, or experience fatigue as a result of an underlying condition, can be misdiagnosed with CFS/ME. Alternatively, those who may have CFS/ME are often misdiagnosed as having another illness due to lack of recognition.”
The authors of this study recently published a paper showing Australian GPs misdiagnose chronic fatigue syndrome in 38% of cases.
Eleven of the 20 medications identified reported slight to moderate effectiveness according to different outcome measures. (One of the medications, nefazodone, was discontinued in 2004 due to side effects.)
For fatigue, drugs reported to be moderately effective included rintatolimod, acetyl-L-carnitine, and intravenous immunoglobulin.
The study said the rintatolimod study ‘raised ethical considerations’ by investigating exercise tolerance in severely affected patients.
The study described the evaluation of some end points in rituximab results as ‘premature’. (A larger, phase three trial of rituximab is currently underway in Norway and the UK also plans to trial the drug.)
The moclobemide and lisdexamfetamine dimesylate studies were criticised for using outdated criteria and focus on the psychological.
In the moclobemide study, Australian psychiatrist Hickie used outdated Lloyd diagnostic criteria and the Profile Mood States Questionnaire which focuses on “vigor and fatigue to assess depression and general psychological distress, it does not capture the disorder’s underlying immunologic etiology.”
Lloyd, who led an intravenous immunoglobulin study in Australia, is currently undertaking another study of Modafinil.
The appendix of the paper includes an overview of the studies.
The paper says consensus on measuring effectiveness must be reached and universally applied. 34 questionnaires and scales were used to measure the outcomes, plus there are questionnaires and scales developed by the authors of the publications and the interview-style of assessments.
Any trials that considered graded exercise therapy, cognitive behavior therapy, adaptive pacing, or any other nonpharmaceutical treatment plans were excluded.
Although not included in this study, the scientists on the study say graded exercise therapy and cognitive behavioural therapy are not supported by evidence.
“Scientific data from NCNED do not indicate any therapeutic value from these interventions. While harm is difficult to predict we reiterate that we believe these interventions have no scientific merit in ME/CFS and may do harm.”
The study was supported by foundations including the Alison Hunter Foundation and the Queensland state government.