TGI Friday – Plus 1 | our weekly roundup of recently published research articles | 25 March 2016

From Pain, 15 March 2016 (epublished before print).

Combination of pregabalin with duloxetine for fibromyalgia: A randomized controlled trial.

Gilron, Ian MD, MSc(1); Chaparro, Luis E. MD(2); Tu, Dongsheng PhD(3); Holden, Ronald R. PhD(4); Milev, Roumen MD, PhD(5); Towheed, Tanveer MD(6); DuMerton-Shore, Deborah RN(7); Walker, Sarah RN(8).
1) Director of Clinical Pain Research and Professor, Departments of Anesthesiology & Perioperative Medicine and Biomedical & Molecular Sciences, Queen's University
2) Anesthesia Resident, University of Toronto
3) Professor, Departments of Public Health Sciences and Mathematics & Statistics, Queen's University
4) Professor, Department of Psychology, Queen's University
5) Professor and Head, Department of Psychiatry, Queen's University
6) Professor, Department of Medicine (Division of Rheumatology)
7) Research Coordinator, Department of Anesthesiology, Kingston General Hospital
8) Research Nurse, Department of Anesthesiology, Kingston General Hospital.

Abstract

Fibromyalgia is a syndrome characterized by chronic widespread pain and associated with sleep disturbance, depression, fatigue and cognitive dysfunction. Polypharmacy is commonly used but supportive evidence is limited.

Most fibromyalgia trials focus primarily on pain reduction with monotherapy. This trial compares a pregabalin-duloxetine combination to each monotherapy.

Using a randomized, double-blind, four-period crossover design, participants received maximally tolerated doses of placebo, pregabalin, duloxetine and pregabalin-duloxetine combination – for six weeks.

Primary outcome was daily pain (0-10); secondary outcomes included global pain relief, Fibromyalgia Impact Questionnaire (FIQ), SF-36 survey, MOS sleep scale, Beck Depression Inventory (BDI-II), adverse events and other measures.

Of 41 participants randomized, 39 completed >=2 treatments. Daily pain during placebo, pregabalin, duloxetine, and combination was 5.1, 5.0, 4.1 and 3.7, respectively (p<0.05 only for combination versus placebo, and pregabalin).Participants (%) reporting >= moderate global pain relief were 18%, 39%, 42% and 68%, respectively (p<0.05 for combination versus placebo, pregabalin, and duloxetine). FIQ scores were 42.9, 37.4, 36.0 and 29.8, respectively (p<0.05 for combination versus placebo, pregabalin, and duloxetine).SF-36 scores were 50.2, 55.7, 56.0 and 61.2, respectively (p<0.05 for combination versus placebo, pregabalin, and duloxetine).MOS Sleep scores were 48.9, 35.2, 46.1 and 32.1, respectively (p<0.05 only for combination versus placebo, and duloxetine).BDI-II scores were 11.9, 9.9, 10.7 and 8.9, respectively (p<0.05 only for combination versus placebo).Moderate-severe drowsiness was more frequent during combination versus placebo. Combining pregabalin and duloxetine for fibromyalgia improves multiple clinical outcomes versus monotherapy. Continued research should compare this and other combinations to monotherapy for fibromyalgia.SUMMARYThis double-blind randomized controlled trial demonstrates improved outcomes with a pregabalin-duloxetine combination over either single drug for fibromyalgia.

The ME Association's recently appointed research assistant, SOPHIE LOUP, has been working her way through the literature since she joined. Here, she reviews two of the more important papers that she's read

Roberts E, et al. (2016) Mortality of people with chronic fatigue syndrome: a retrospective cohort study in England and Wales from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) Register. The Lancet. (Epub ahead of print). Available at: http://dx.doi.org/10.1016/S0140-6736(15)01223-4.

Lay summary

Please note before reading that the summary and article mention suicide.

This study examines mortality associated with chronic fatigue syndrome in patients in secondary and tertiary care. It uses data from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM), which is a mental health trust that also runs a single secondary and tertiary care national referral service for individuals with suspected chronic fatigue syndrome.

The authors reviewed studies that compared mortality in individuals with chronic fatigue syndrome with that of controls without the illness and found no convincing evidence of increased all-cause mortality or suicide-specific mortality. They argue their study is the largest one conducted on mortality in patients with chronic fatigue syndrome so far, with 2147 individuals.

Participants were included if they had contact with SLaM and received a diagnosis of CFS, meeting either the Fukuda, Oxford or NICE criteria. Over the seven year period for which records were used, 17 deaths were identified. The authors found no significant difference in all-cause mortality or cancer-specific mortality between the participants and the general population in England and Wales, in terms of age and sex. However they found an increase in mortality from suicide among participants. This highlights the need for clinicians to assess suicidality adequately in patients with CFS.

There are limitations to the data including that the sample size remains modest and that the cohort studied was quite young. Furthermore patients might not wish to be referred to mental health services for their chronic fatigue, in which case they would not be part of the sample, although the authors do not expand on this caveat. Finally, two fewer suicide deaths would have meant that the findings could be attributed to chance.

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Nicholson L, et al. (2016) Educational Priorities for Healthcare Providers and Name Suggestions for Chronic Fatigue Syndrome: Including the Patient Voice. Clinical Research 2(1). Available at: https://www.sciforschenonline.org/journals/clinical-research/CLROA-2-112.php

Lay summary

This article analyses the results of a survey conducted in the US in 2014 by the Solve ME/CFS Initiative to inform the Institute of Medicine Committee of patients’ opinions on the name of ME/CFS, as well as what patients believe should be educational priorities for healthcare providers. The articles aims to offer a patient-focused perspective on changing the name of the illness. Researchers external to the survey coded the responses given to two of the questions asked.

Many patients feel that the name of CFS, by focusing on fatigue, gives the impression that the illness is not serious and thus trivialises it. Illness names for misunderstood diseases can stigmatises those affected by them and as such can impede productive relationships between patients and healthcare providers. Therefore, the authors believe patients should be stakeholders in the process of changing the name of ME/CFS.

The vast majority of participants disliked the term CFS. They often cited myalgic encephalomyelitis as a preferred alternative. They offered alternative names, including the original “Catastrophic Multi System Dysfunction”.

Four themes emerged when participants were asked about what they considered the most important issues that healthcare providers should be educated about when it comes to the diagnosis of ME/CFS. These were: attitudes of healthcare providers, symptomatology, research, and implications of inadequate education. The most frequent subtheme was participants wanting providers to acknowledge that ME/CFS is a real/serious illness.

There are limits to the survey and analysis, including, but not limited to, the small sample size and the lack of generalisability of the findings to all ME/CFS sufferers. However, the results echo previous research studies as well as feedback The ME Association has been receiving from patients and carers.