Fibromyalgia syndrome is a chronic disease of widespread and debilitating pain 
whose cause is unknown and whose risk factors are poorly understood. It is often 
comorbid with rheumatoid and other pain disorders as well as psychiatric 
disorders such as anxiety and depression. Although they are not officially 
approved for this indication, antiepileptics and antidepressants are often used 
to treat fibromyalgia. The tricyclic antidepressants (TCAs), particularly 
amitriptyline, are among the most common treatment strategies. Because of the 
poor tolerability of the tricyclics, the newer antidepressants have been widely 
tested in fibromyalgia. The selective serotonin reuptake inhibitors (SSRIs) and 
the reversible monoamine oxidase inhibitors do not seem to be particularly 
helpful. The serotonin and norepinephrine reuptake inhibitors (SNRIs), 
duloxetine and milnacipran, on the other hand, have been shown in 
placebo-controlled trials to offer significant relief to patients suffering from 
fibromyalgia. Although no direct comparative studies have been performed, these 
compounds appear to be as effective as the TCAs but much better tolerated. The 
effectiveness of the SNRIs as well as other dual acting antidepressants, such as 
mirtazapine, but not the SSRIs, implies that a dysfunction of both serotonin and 
norepinephrine neurotransmission probably exists in fibromyalgia. The 
effectiveness of antidepressants appears to be independent of their effect on 
comorbid depression.