Fibromyalgia(FM) – Quetiapine XR (Seroquel) Reduces Pain Similar to Others and Reduces Depression – But Drowsiness High

FM could be considered a neurodegenerate disorder with certain degrees of brain loss and cognitive impairment evident. Some years ago I was at a presentation in which the brain damage evident in Fibromyalgia was bemoaned by speaker. Having dealt with arresting that in bipolar patients with mood stabilizers, , I asked the speaker after if he though about using neuroprotective agents.  He had never thought about it. Quetiapine may help nerve repair. Quetiapine helps pain and depression in a recent study. Could it quell the brain deterioration as well?

Study Design

Arthritis Rheum. 2013 Oct 21.
Quetiapine fumarate extended-release for the treatment of major depression with comorbid fibromyalgia syndrome: A double-blind, randomized, placebo-controlled study.
McIntyre A, Paisley D, Kouassi E, Gendron A.
http://www.ncbi.nlm.nih.gov/pubmed/24150722

• an 8-week, double-blind, randomized controlled trial conducted at a single
  center in Penticton, British Columbia, Canada
• “Quetiapine XR was administered orally once daily in the evening, starting at 50 mg/d for the first 2 days then titrated up to 150 mg/d. After 2 weeks the dose could be doubled to 300 mg/d at the discretion of the investigator.”
• Although I was sceptical that quetiapine could be tolerated in FM subjects, authors reported to me that “Quetiapine XR 300mg is well tolerated by depressed patients”, though they made it clear “[It] Makes no sense to include a patient that can’t tolerate the study medication”. Fortunately, they found 300 mg no better than 150 mg.
• “Subjects taking an antidepressant for their current episode were washed out for >7 days prior to the baseline visit”. Given that these cases had not responded to their antidepressants, this was certainly reasonable. This would be less likely with subjects with some response to antidepressants where an add-on approach would seem more likely.
• 44% were on opioids and 31% on anti-anxiety meds.
• Pain scores dropped from 7.4 to 5.3  versus placebo 7.0 to 6.7

OK – doesn’t look great. but most agents in FM don’t drop pain much more than VAS of 2 over placebo

• Depression scores dropped: – is impressive

Quetiapine in Neuroprectivity

In a recent trial of quetiapine’s neuroprotective effects  in MS they state  “Preclinical studies suggest that quetiapine may exert these effects by stimulating proliferation and maturation of oligodendrocytes, releasing neurotrophic factors, increasing antioxidant defences, scavenging for free radicals, and inhibiting activated microglia, astrocytes, and T lymphocytes”.  Zhornitsky, S. et al. “Quetiapine Fumarate for the Treatment of Multiple Sclerosis: Focus on Myelin Repair.” CNS neuroscience & therapeutics 19, no. 10 (2013): 737-744.  http://www.ncbi.nlm.nih.gov/pubmed/23870612.

Neurodegeneration in FM

Fibromyalgia could be considered a neurodegenerate disorder with one study demonstrating that  in one year, FM subjects could achieve equivalent of 9.5 years of brain aging.
Accelerated Brain Gray Matter Loss in Fibromyalgia Patients: Premature Aging of the Brain?
Anil Kuchinad, Petra Schweinhardt, David A. Seminowicz, Patrick B. Wood, Boris A. Chizh, and M. Catherine Bushnell
The Journal of Neuroscience, 11 April 2007, 27(15): 4004-4007
http://www.jneurosci.org/content/27/15/4004.full.pdf

This is more in FM subjects that are depressed:

Hsu, Michael C., Richard E. Harris, Pia C. Sundgren, Robert C. Welsh, Carlo R. Fernandes, Daniel J. Clauw, and David A. Williams.
“No consistent difference in gray matter volume between individuals with fibromyalgia and age-matched healthy subjects when controlling for affective disorder.”
Pain 143, no. 3 (2009): 262-267.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2719961/pdf/nihms105146.pdf

However, selctive brain losses are usually evident. One of the areas of brain loss, appears to be brain’s  inhibitory pain network, in which connectivity is lost:

Mol Pain. 2012 Apr 26;8:32. doi: 10.1186/1744-8069-8-32.
Patients with fibromyalgia display less functional connectivity in the brain’s pain inhibitory network.
Jensen KB, Loitoile R, Kosek E, Petzke F, Carville S, Fransson P, Marcus H, Williams SC, Choy E, Mainguy Y, Vitton O, Gracely RH, Gollub R, Ingvar M, Kong J.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404927/pdf/1744-8069-8-32.pdf

Depression Rates in FM

Note  –  only a subgroup of FM patients are depressed, though they are more likely to seek help.

In a recent cluster analysis of FM cases,  only 54% had personal/familial psychopatholgy so don’t automatically think depression.

Side Effects: –  38% of cases discontinued treatment – drowsiness and fatigue being a major part of that. Of those that tolerated it, remaining side effects were mild.  Unfortunately, it means the hardy ones get better – go figure… 

Comment – The effect on anti-depressant resistant depressed fibromyalgia cases is impressive albeit in the “hardy ones” that were able to tolerate their side effects (so selection bias). If it indeed does have neuroprotective effects as well, then its function could becomes more essential.  The potentiation of fatigue/drowsiness in subjects already affected so by FM and depression, makes its use more difficult.

The fact that anti-depressant can induce neurogenesis makes their use important in depressed FM subjects as well.

(a recent review)
Hippocampal neurogenesis: a biomarker for depression or antidepressant effects? Methodological considerations and perspectives for future research
Arnaud Tanti, Catherine Belzung
Cell and Tissue Research October 2013, Volume 354, Issue 1, pp 203-219
http://link.springer.com/article/10.1007/s00441-013-1612-z#page-1

A drop of VAS of 2 is what I would expect from gabapentin, lyrica and cymbalta as well ( though in studies where the only discuss “responders” their results are better)