Posted by MERM on 1/26/2009, 9:13 am
Cymbalta (Duloxetine) shows efficacy in fibromyalgia with or without concurrent major depression
Cymbalta is a drug that inhibits both norepinephrine and serotinin reuptake. It is currently marketed for depression and has showns a significant improvement in fibromyalgia symtpoms. This effect was independent of whether or not the patient had major depression.
This was a double-blind, placebo-controlled trial involving 207 patients, and it was sponsored by the manufacturer.
I would say the weight of the evidence shows that duloxetine leads to sustained relief of pain, especially in the female subjects, who improved on all pain outcomes," said principal investigator Dr Lesley M Arnold (University of Cincinnati College of Medicine, OH) .
"Are we on the brink of a new era of fibromyalgia syndrome management?" According to Dr. Geoffrey Littlejohn "The future does seem positive in regard to significant improvement in FMS symptoms with these new potential therapies. However, it is wise to continue to reflect on the FMS process and to recognize that social and psychological factors, even everyday life stressors, can dramatically affect FMS neurobiology."
The duloxetine study is part of an effort to improve on results with tricyclic antidepressants, which are widely used in FM in doses lower than those typically used in mood disorders, Arnold et al explain. The tricyclics produce some improvement in FM-related fatigue and in sleep, overall well-being, and pain severity but have less effect on tenderness. These drugs reduce both NE and 5-HT reuptake but also have varied effects on choloinergic and histamine activities and on other mechanisms that modulate pain.
Separating out the effect on reuptake inhibition has not been useful. Targeted inhibition of NE reuptake with venlafaxine (Efexor, Wyeth) and selective inhibition of 5-HT reuptake with fluoxetine (Prozac, Eli & Lilly Co) have both been relatively ineffective in FM The duloxetine study combines both approaches by using a combination reuptake inhibitor to elevate levels of both NE and 5-HT, but without the other effects of the tricyclics.
The multicenter study enrolled 207 subjects meeting the American College of Rheumatology (ACR) criteria for primary fibromyalgia. Patients were randomized to placebo (n=103, including 92 women) or to duloxetine 60 mg bid (n=104, including 92 women). In the placebo group, 42/103 patients had major depressive disorder. In the duloxetine group, 37/104 patients had major depressive disorder.
The double-blind treatment phase continued for 12 weeks and included weekly visits for the first 2 weeks, then visits every 2 weeks.
Significant improvement on most FM symptoms
I would say the weight of the evidence shows that duloxetine leads to sustained relief of pain, especially in the female subjects, who improved on all pain outcomes.
The 2 primary outcome measures were pain severity as measured by the Fibromyalgia Impact Questionnaire (FIQ) pain item and the FIQ total score, reflecting the overall impact of FM. Secondary end points included the FIQ items for fatigue, morning tiredness, and stiffness, and tender point assessment.
Other secondary end points were the Clinical Global Impressions of Severity scale, the Patient Global Impression of Improvement scale, the Brief Pain Inventory (short form), the Beck Depression Inventory, the Beck Anxiety Inventory, the Medical Outcomes Study Short Form 36 (SF-36), the Quality of Life in Depression Scale, and the Sheehan Disability Scale. All of them were assessed on an intention-to-treat analysis.
"The FIQ score was improved at week 12. Only the FIQ pain score was not significantly improved at week 12, although it was improved at week 4. Another pain score, the Brief Pain Inventory, was significantly improved at week 12, as was the SF-36 bodily pain score. Furthermore, the female subjects improved on all pain outcomes (including the FIQ pain score) at week 12," Arnold tells rheumawire.
There was a striking improvement in the FIQ total score for the entire duloxetine group, which became significant at week 4 and continued through week 12 (p=0.027). The group difference in the other primary end point, the FIQ pain score, became significant at week 4 but was not significant at week 12 (p=0.130). Response rates, defined as a <50% decrease in FIQ pain score, were 27.7% for duloxetine vs 16.7% for placebo at week 12 (p=0.06).
Arnold points out that the improvement in tender point measures was particularly important, since previous studies using tricyclic antidepressants found little improvement in tender points.
The duloxetine-treated patients also had significant improvements in general activity, mood, walking ability, normal work, sleep, and enjoyment of life, as measured on the Brief Pain Inventory.
Equally effective in patients without depression
Duloxetine was equally effective in patients with or without major depressive disorder, Arnold notes. "I was not surprised that the improvement in fibromyalgia symptoms with duloxetine was independent of the presence or absence of depression. Duloxetine may have an effect on the descending pain pathways that involve serotonin and norepinephrine that is independent of its effect on mood."
Although the numbers are small, the data also suggest that there may be a sex difference in response to duloxetine for FM. The investigators found that duloxetine-treated women improved significantly more than placebo-treated women on both the primary and secondary end points, while male subjects treated with duloxetine did not have significantly better responses than the placebo-treated men on either primary or secondary efficacy measures.
"I was surprised by the lack of effect in men. I think the power was not great enough to show an effect in men. We need to study a larger group of men before coming to any firm conclusion about duloxetine in the treatment of men with fibromyalgia," Arnold says.internetmedicaldrugnews !M!wellnesstrainresearchteam
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