The Role of "Anticonvulsants" in FM Treatment
The list of epilepsy drugs is extensive and diverse. Pharmacology research has done a seemingly exhaustive search for compounds to treat seizure disorders, targeting many different neurochemical pathways. Recently, (within the last 5-10 years) these drugs have crossed over into treatment for a myriad of other conditions, including bipolar disorder, migraine, insomnia, and neuralgias. A few drugs have been specifically indicated for use in treating fibromyalgia (drugs such as pregabalin, brand name Lyrica, or gabapentin, brand name Neurontin). In theory, many of these drugs could potentially be useful for FM because they all share common mechanisms of action and produce the same end result: they dampen the excitability of the nervous system.
Current theories of the causes of fibromyalgia focus on the hypersensitization of the central nervous system. That is, it’s thought that generalized pain signals are transmitted more frequently than they should be. This is actually similar to what happens in epilepsy: signals to move are transmitted too frequently to the muscles, resulting in seizures. In psychological disorders like bipolar disorder, signals to feel and think are transmitted too frequently. In migraine, specific nerves are signaling pain too frequently.
In all these scenarios, "anticonvulsant" drugs are being used to bring this excess firing down to more normal levels. It turns out that anticonvulsant drugs may be outgrowing their names, because these drugs are now considered to be general central nervous system inhibitors. However, the term "GCNSIs" (which I just made up) seems a little unwieldy. Maybe we could call them "Bob."
That is the gist of how anticonvulsant drugs function. Of course, all drugs come with side effects, like headache and nausea, and these drugs are no exception. As nervous system "dampeners," anticonvulsants often bring along drowsiness and dizziness. Some of these drugs may have more serious side effects, and may present special considerations if you are trying to become or are currently pregnant. If your doctor decides one of the many anticonvulsant drugs may help you, it might take a few tries to find the right one to complement your unique physiology. And as always, consult with and follow the instructions of your doctor, especially when dealing with anticonvulsant drugs.
If you would like to know more biochemical specifics about how anticonvulsants work, read on:
The general reactivity of the nervous system is regulated by a few chemical systems. First of all, neurons fire when their ion (charged atom) balance shifts across a "threshold" of electrical charge. Specifically, neurons "rest" when negatively charged, and "fire" when they cross a certain positive electrical charge.
Neuronal activity can be modified by the presence of excitatory or inhibitory neurotransmitters, which exist in a delicate balance in the nervous system. The ratio of these chemicals determines how likely it is that a given neuron will fire. Two major excitatory neurotransmitters are actually amino acids (the building blocks of proteins), specifically glutamate and aspartate. Two main inhibitory neurotransmitters are glycine, another amino acid, and GABA (gamma aminobutyric acid), a derivative of glutamate. Basically, the excitatory chemicals increase the charge of neurons (more positive=closer to firing), while inhibitory ones make the neurons more negatively charged (less likely to fire).
When neurons "fire," they release other neurotransmitters like serotonin and dopamine. This means that the decrease in serotonin often seen in FM patients could theoretically be a result of altered GABA function, for example, instead of defects in serotonin signaling itself. In this way the excitatory/inhibitory neurotransmitter balance acts as a master regulator of the sensitivity of the nervous system.
Many of the anticonvulsants lead to an increase in GABA signaling, in effect turning the nervous system down a notch by inhibiting firing. Derivatives of the common anticonvulsant valproate (one of the brand names is Depakote) alter levels of GABA in the brain. Tiagabine (Gabitril) and progabide (Gabrene) are also agonists of GABA receptors on neurons, meaning they bind to and activate these receptors. This is also the mechanism of action for benzodiazepines, such as Klonapin, Halcion, and Xanax (although only Klonapin is used as an anticonvulsant; the others are common anti-anxiety medications). The two FM drugs mentioned above, Lyrica and Neurontin, are actually GABA analogs, meaning they look enough like GABA to function the same way in the nervous system.
In contrast, other drugs act on ion channels to alter electrical thresholds of neurons. The carboxamide drugs (like Tegretol and Trileptal) stabilize the inactive, closed state of ion channels on individual neurons to decrease their ability to fire. Topiramate (Topamax), a common migraine drug, is actually structurally related to the sugar fructose, and inhibits neuronal firing by influencing GABA-controlled ion channels and other inhibitory receptors. Lamotrigene (Lamictal), the first drug since lithium FDA approved to treat bipolar disorder, is also a channel blocker, but is chemically unrelated to all other anticonvulsants.
These are only a few of the anticonvulsant medications available. Not all of them have been approved for other uses, and all carry their own set of potentially serious side effects and drug interactions (for example, most of these drugs should not be combined with any of the others). This is not a blanket endorsement of anticonvulsants as the last word in fibromyalgia treatment; it is merely an attempt to explain how this class of medications may help fibromyalgia.
The bottom line: anticonvulsants dull the activity of the nervous system. This is useful in the treatment of many conditions that result from a hyperactive nervous system. It is hoped that one day these drugs may be specifically regarded as "fibromyalgia medication."
