Phase 3 trial of duloxetine/Cymbalta for fibromyalgic pain may show benefit for some patients with ME/CFS | 27 August 2015


The results of a phase 3, Japanese trial of duloxetine/Cymbalta for pain in patients with Fibromyalgia have been published in the journal Arthritis Research and Therapy. Our medical adviser, DR CHARLES SHEPHERD, says that – while the results were not hugely significant – they may point to benefits for some people with ME/CFS.


Duloxetine (trade name = Cymbalta) is a drug that is normally used to treat depression. It is sometimes used for a generalised anxiety disorder and for stress incontinence.

It acts by normalising an imbalance in two brain chemical transmitters – noradrenaline and serotonin – that can occur in depression.

As with other some types of antidepressant medication – low dose amitriptyline, for example – duloxetine has also been shown to help some people with pain, including both fibromyalgic pain and nerve/neuropathic pain.

Neuropathic pain is often described as a more severe type pain that is burning, shooting and stabbing and often keeps people awake at night. Duloxetine has also been used to treat diabetic neuropathy – where nerve damage causes pain in diabetes.

In the case of pain relief, duloxetine may be acting by calming down parts of the central nervous system that are involved in the assessment of messages about pain and reducing the way in which the brain responds to these messages about pain.

Fibromyalgia (FM) is a condition which has a number of overlapping symptoms with ME/CFS and produces tender spots in various specific locations around the body – often on both sides in a symmetrical pattern. Some people with ME/CFS have what can be described as a fibromyalgic pain component and some doctors see no real difference between FM and ME/CFS, which means that there is a considerable degree of diagnostic overlap between FM and ME/CFS.

Consequently, any drug treatment that is safe and effective in FM may also be of value for some people with ME/CFS.

As with all antidepressants, duloxetine has side effects which may make it unacceptable.

Common side effects can include headache, drowsiness, nausea, constipation, dizziness, blurred vision, and dry mouth.

Less common side effects include loss of appetite, flushes, raised blood pressure, feeling anxious, feeling shaky and increased sweating.

As with any antidepressant drug, it should not be discontinued abruptly. There should be a gradual reduction in dose over several weeks to prevent withdrawal symptoms.

A number of clinical trials have assessed the use of duloxetine in FM (but not in ME/CFS) and this new study from Japan adds further support to its use as an option for treating fibromyalgic pain.

The Japanese clinical trial was a randomised, double-blind, placebo-controlled, phase 3 study where one group of FM patients received duloxetine (n =197) and the other group (n=197) received a placebo.

Although the results were not astounding, the trial demonstrated a significant improvement in the change of average pain scores from baseline to week 14 and improvement in overall quality of life.

Duloxetine was generally well tolerated in this trial with somnolence, nausea and constipation being the most common side effects.

So this is a drug treatment option that could be considered for people who have a diagnosis of FM, or in the case of ME/CFS where there is a fibromyalgic or neuropathic component to pain, especially if there is co-existent clinical depression that requires a drug treatment as well.

Dr Charles Shepherd
Hon Medical Adviser, The ME Association.


FROM Arthritis Research and Therapy, 22 AUGUST 2015 (FULL PAPER AVAILABLE TO READ).


A randomized, double-blind, placebo-controlled phase III trial of duloxetine in Japanese fibromyalgia patients

Masato Murakami(1), Kenichi Osada(2), Hiromichi Mizuno(3), Toshimitsu Ochiai(3), Levent Alev(4) and Kusuki Nishioka(5,*).
Corresponding author: kusuki-nishioka@bz04.plala.or.jp
1) Department of Psychosomatic Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kamicho, Itabashi-ku 173-8610, Tokyo, Japan
2) Department of Neuropsychiatry, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8511, Japan
3) Shionogi & Co. Ltd., 12F, Hankyu Terminal Bldg, 1-4 Shibata 1-chome, Kita-ku 530-0012, Osaka, Japan
4) Eli Lilly Japan K.K., Sannomiya Plaza Building, 7-1-5 Isogamidori, Chuo-ku, Kobe 651-0086, Japan
5) Institute of Medical Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku 160-8402, Tokyo, Japan

Abstract

INTRODUCTION

Fibromyalgia is characterised by widespread pain and is often accompanied by accessory symptoms. There are limited treatment options for this condition in Japan. Therefore, we conducted a phase III study to assess the efficacy and safety of duloxetine in Japanese patients with fibromyalgia.

METHODS

This randomised, double-blind, placebo-controlled, parallel-group trial was conducted in Japan. Outpatients who met the American College of Rheumatology 1990 criteria for fibromyalgia and whose Brief Pain Inventory (BPI) average pain score was ≥4 were randomised to duloxetine 60 mg or placebo once daily for 14 weeks. The primary efficacy measure was the change in the BPI average pain score from baseline. Secondary efficacy, quality of life (QoL), and safety outcomes were also evaluated. Mixed-effects model repeated-measures (MMRM) analysis and last observation carried forward (LOCF) analysis of covariance were used to evaluate the primary efficacy measure.

RESULTS

Overall, 393 patients were randomised to receive either duloxetine (n = 196) or placebo (n = 197). The MMRM analysis revealed no significant difference between duloxetine and placebo regarding the change in BPI average pain scores at week 14. Based on LOCF analysis, a statistically significant improvement in the change in BPI average pain scores at week 14 was observed for patients treated with duloxetine compared with placebo. Duloxetine treatment was associated with improved outcomes in nearly all secondary and post hoc analyses. The treatment was generally well tolerated. Somnolence, nausea, and constipation were the most common treatment-emergent adverse events in the duloxetine group. The discontinuation rates due to treatment-emergent adverse events were similar in both groups.

CONCLUSIONS

Although the MMRM analysis did not demonstrate superiority of duloxetine over placebo, duloxetine treatment was associated with improved outcomes in secondary and post hoc analyses of the mean change in the BPI average pain score and most of the secondary outcomes, including analgesia and QoL. Duloxetine treatment was safe and well tolerated. These results suggest that duloxetine treatment could be associated with improvements in pain relief and QoL in Japanese patients with fibromyalgia.

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