Tackling Pain and Depression in Fibromyalgia: Quetiapine Scores Some Benefits in Clinical Trial
Depression is common in fibromyalgia. In fact, with studies suggesting levels of ‘current depression range from 22-44% and lifetime rates of depression from 60-86%,depression in FM may be very common. This isn’t surprising: the presence of pain in any disorder increases the risk of depression significantly. Being in pain is simply depressing.
This is not simply due to psychological factors. Similar physiological processes may be involved in both pain problems and depression. Both fibromyalgia and mood disorders involve, for instance, alterations in the monamine transmitters serotonin, norepinephrine and dopamine that are involved in pain production. Reduced levels of these transmitters in animal models, for instance, results in increased sensitivity to pain, muscle pain, allodynia and depression.
SNRI’s can, probably by increasing serotonin and norepinephrine levels in the pain inhibiting pathways, halt pain. The activity of these pathways is reduced in FM. People with FM are also more likely to have a polymorphism in a gene that reduces serotonin metabolism (ie. the cells ability to use serotonin). If you have that polymorphism you’re more likely to suffer from psychological distress and pain (ouch).
The monamine pain connection shows that drugs we call ‘antidepressants’ also can have anti-pain properties. Some studies, in fact, have shown FM patients without depression to benefit from them, and, of course there’s the possibility of both depression and pain being reduced. (Some are also now being found to reduce inflammation in the central nervous system. That suggests both depression and pain could be, at least in part, inflammatory disorders.)
An Anti-psychotic, Antidepressant, Anti-pain Drug
Quetiapine is a short-acting atypical antipsychotic that is often used to treat schizophrenia and bi-polar disorder, and in combination with other drugs, depression. So what’s it doing in a fibromyalgia study? Quetiapine may be able to reduce pain by enhancing serotonin and dopamine levels and by reducing sympathetic nervous system functioning.
Somebody is putting some money into FM Quetiapine trials. Quetiapine has been the focus of at least four fibromyalgia studies. An open label study found little effect on pain, but a significant effect on other symptoms. A small 2012 study using low dose quetiapine again found no effect on pain but significant help with sleep and mood. A large (n=120), double-blinded 2013 study found quetiapine significantly reduced pain, improved mood and quality of life. A 2013 study comparing quetiapine with amytriptyline found amytriptyline was superior but the high dropout rate in the quetiapine arm suggested the initial dose may have been set too high.
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. Arthritis Rheumatol. 2014 Feb;66(2):451-61. doi: 10.1002/art.38228.
This was not a happy group of FM patients. Almost half were on opioids. Twenty-five percent were on Lyrica and about a third were on hypnotics. Most were moderately to severely depressed and had a long history of depression. Despite all this drug use, their high baseline FIQ score (76),indicated that pain was severely impacting their functionality.
In general the FM patients responded ‘well’ to quetiapine. Significant improvements were seen in a wide variety of symptoms and signs including t pain, Fibromyalgia Impact scores, mood, stiffness and sleep. The fact that most patients were still improving by the end of the eight week trial suggested it might have been too short to fully capture all the benefits.
Were they well? Not at all; their mean FIQ scores at the end of the trial did drop the group from the severe afflicted range to the moderately afflicted range but they were still quite significantly impacted by FM.
About a quarter of the depressed patients on Quetiapine achieved remission (but check out the 18% who did so on the placebo drug :))
Side effects were common and attrition rates were high with over 30% of the participants (on both arms of the trial) dropping out. Most of the Quetiapine arm dropouts did so because of adverse events; those on the placebo arm did so because they weren’t getting result and because of adverse events.
Seventy percent of trial participants reported increased fatigue, 67% experienced dry mouth, constipation and/or blurred vision and 30% reported dizziness, hypotension or tinnitus. Compare that to 30% of the placebo group reporting increased fatigue and 20% reporting increased dry mouth or constipation, etc.
Quetiapine significantly reduced pain and improved mood and other symptoms in this severely afflicted group of depressed FM patients. The common fatigue side effect suggested many would have to determine whether the tradeoff between reduced pain and still more fatigue was worth it.
Quetiapine may be helpful for some severely afflicted Fibromyalgia patients.
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