Summary Research Abstract Fluoxetine use in Fibromyalgia
Yasmine Seidu
Section 8
Question:
Is Fluoxetine effective in the treatment of fibromyalgia?
Search Terms: Fluoxetine and fibromyalgia, fibromyalgia treatments, fluoxetine fibromyalgia
Database/Search Engines Used: PubMed; Science Direct, Online Wiley Library, Google Scholar
Rationale:
Fibromyalgia Syndrome (FMS) is a musculoskeletal disorder characterized by chronic pain and
tenderness lasting longer than three months. It is associated with symptoms of chronic fatigue,
sleep disorders, muscle stiffness, anxiety and depression.1 While the underlying cause of FMS
remains unknown, CNS defects in both the ascending and descending pain pathways is thought
to contribute to pain associated with fibromyalgia.2 Evidence suggests that antidepressants
modulate through both the CNS and PNS.3 Central pain conditions respond best to
neuromodulating agents (i.e. antidepressants). Decreased levels of serotonin has been
recorded in patients with FMS. This suggests that antidepressants, specifically selective
serotonin reuptake inhibitors such as fluoxetine, may provide relief of symptoms associated
with FMS.4
Discussion:
Studies in humans show that fluoxetine does decrease pain transmission associated with FMS.5
While some studies support the use of fluoxetine for decreasing FMS symptoms, other studies
and meta-analysis indicate fluoxetine may not have high quality of evidence.1-5 This presents
conflicting evidence on whether fluoxetine can be effective in the treatment of FMS.
Goldenberg et. al conducted a randomized, double-blind placebo-controlled crossover trial on
the effectiveness of fluoxetine and amitriptyline in treating FMS symptoms. Four treatments
were administered for 6-week periods with a 2-week wash-out period between each treatment.
31 FMS patients were treated with placebo alone, 25 mg amitriptyline at night (PM) with
placebo in the morning (AM), 20 mg fluoxetine in the morning with placebo AM, 20mg
fluoxetine AM and 25mg amitriptyline PM. Fibromyalgia Impact Questionnaire (FIQ), tender
point score, and VAS pain, fatigue, sleep, global well-being, and refreshness upon waking were
measured. There was a statistically significant decrease (n=22) in FIQ (p=0.006), VAS pain
(p=<0.001), global well-being (p=0.02 ), and VAS sleep (p=0.04) compared to the placebo group,
along with a non-significant decrease in tender point, refreshness upon waking, and fatigue
following treatment with fluoxetine.5 These results are questionable with regards to whether
the 2 week wash-out period is long enough to prevent carry-over effects from the amitriptyline
treatment alone and the combination therapy treatment. Although all tablets looked identical,
subject blindness could have been affected by changing treatments. Also, 19 subjects
completed the fluoxetine treatment, but all 31 subjects were included in the data analysis.
Arnold et. al presented a randomized, placebo-controlled, double-blind, flexible-dose study of
fluoxetine in the treatment of women (ages 21-71) with FMS. Over the course of 12 weeks,
subjects received titrated doses of fluoxetine capsules ranging from a starting dose of 20mg to
a maximum dose of 80mg (n=30) and placebo capsules (n=30) with assessments in weeks 2, 4
and 8. There was a statistically significant decrease in the pain scale (p= 0.01), fatigue (p=0.03),
and depression (p=0.02) in subjects treated with fluoxetine (n=19) compared to the placebo
group (n=18). In the intent-to-treat analysis, stiffness also decreased significantly (p=0.07) in
the fluoxetine group (n=25) compared to the placebo group (n=26). There was no significant
decrease in tender point scores. Although this data supports the use of fluoxetine in FMS, 11
subjects from the fluoxetine group withdrew due to adverse effects.6
Population: 61 adult subjects studied receiving fluoxetine therapy. 30 were adult women.
Dosing studied: 20 to 80mg daily fluoxetine, 20mg fluoxetine daily.
Risk/Benefit Considerations:
In all trials reviewed, dropouts were mainly due to intolerable adverse effects such as
headache, insomnia, sedation, and nausea.1-6 A meta-analysis represented by Häuser et. al
reported a relative risk of 1.60 due to either intolerable adverse effects or low efficacy
(symptom relief did not outweigh adverse effects) associated with 7 randomized controlled
trials conducted using SSRIs (two studies each with citalopram and paroxetine and three studies
with fluoxetine).3
All studies and meta-analysis reviewed reported there was no statistically significant difference
in adverse effects in patients who received fluoxetine and other SSRIs to those who received
placebo.1-6 Based on these findings, fluoxetine could offer clinical benefits in the treatment of
FMS with little adverse effects associated with treatment alone.
Response:
The use of fluoxetine in treating FMS is supported with low quality of evidence.4 Goldenberg et.
al study supports the use of fluoxetine in FMS but due to areas of the study that may have
contributed to bias and the quality of evidence is low.1-6 There is a limited number of studies
that evaluate the use of fluoxetine alone compared to many studies evaluating SSRIs in the
treatment of FMS; a meta-analysis does not support the use of SSRIs in the treatment of FMS.4
It would be inappropriate to recommend fluoxetine for FMS treatment.
References:
1. Hadianfard MJ, Hosseinzadeh Parizi M. A randomized clinical trial of fibromyalgia
treatment with acupuncture compared with fluoxetine. Ir an Red Crescent Med J. 2012
Oct 30;14(10):631-40. PubMed
2. The ACPA. Quick Facts on Fibromyalgia. ACPA. [Internet]. 2019 [cited 2019 Oct 30].
Available from:
https://www.theacpa.org/conditions-treatments/conditions-a-z/fibromyalgia/two-takes
-on-fibro/quick-facts-on-fibromyalgia/
3. Häuser W, Wolfe F, Tölle T, Uçeyler N, Sommer C. The role of antidepressants in the
management of fibromyalgia syndrome: a systematic review and meta-analysis. CNS
Drugs. 2012 Apr 1;26(4):297-307. PubMed
4. Walitt B, Urrútia G, Nishishinya MB, Cantrell SE, Häuser W. Selective serotonin reuptake
inhibitors for fibromyalgia syndrome. Cochrane Database Syst Rev. 2015 Jun
5;2015(6).PubMed
5. Goldenberg D, Mayskiy M, Mossey C, Ruthazer R, Schmid C. A randomized, double-blind
crossover trial of fluoxetine and amitriptyline in the treatment of fibromyalgia. Arthritis
Rheum [Internet]. 1996 [cited 2019 Oct 30];39:-. Available from:
https://onlinelibrary.wiley.com/doi/pdf/10.1002/art-. Arnold LM, Hess EV, Hudson JI, Welge JA, Berno SE, Keck PE. A randomized,
placebo-controlled, double-blind, flexible-dose study of fluoxetine in the treatment of
women with fibromyalgia. Am J Med [Internet]. 2002 Feb 15 [cited 2019 Oct 30];112(3).
Available from: https://doi.org/10.1016/S-