One of the problems with using traditional anti-depressants, especially selective serotonin reuptake inhibitors (SSRI’s) to treat bipolar depression is the potential risk of triggering a switch from depression to mania. Another issue is that traditional anti-depressants may not be effective in treating depression in some patients.

SSRI’s work by inhibiting the reabsorption of the neurotransmitter serotonin, effectively increasing the level of serotonin in the synapses of the brain – the space between the brain cells (neurons). This reduces the symptoms of depression and anxiety in many people.

While insufficient serotonin may be one cause of depression, researchers are exploring another possible cause – dysregulation of glutamate. Glutamate is the most abundant excitatory neurotransmitter in the body. Riluzole (Rilutek), a prescription drug commonly used to treat Lou Gehrig’s disease, amyotrophic lateral sclerosis (ALS), reduces the release of glutamate while increasing its uptake. Some studies have shown that Riluzole is effective in treating acute bipolar depression alone or in combination with other anti-depressants.

Note: Lithium stabilizes the level of glutamate in the brain, and Lamictal (lamotrigine) is a glutamate blocker, which may help explain their antidepressant properties in some patients. However, the effect of glutamate on depression and bipolar depression is not simply a matter of too much or too little – it is a complex set of interactions between glutamate and several types of brain cells. Studies of different parts of the brain have indicated that elevations and low levels of glutamate are both associated with depression.

Perhaps even more important in respect to treating bipolar depression, Riluzole and other medications that target glutamate may have a lower risk of triggering a switch to mania.

Of course, all medications have side effects. Riluzole is no exception. Following are some caveats for Riluzole:

• Possible liver damage, especially in patients already at risk or who drink excessive amounts of alcohol.
• Caffeinated beverages may increase the effect of riluzole.
• Smoking may speed the elimination of riluzole from the body.
• Riluzole must be taken one hour before or two hours after eating, which can make it inconvenient.

Riluzole is not being used in routine clinical practice yet – but in adults with severe, treatment-resistant depression it would be considered a reasonable medication to try. I have not yet used it in my practice, although I do use N-acetyl cysteine – a supplement related to the glutamate systems – for treatment-resistant depression. Look for more and more research and hopefully new treatment options that target glutamate in the near future. For more about N-acetyl cysteine, see my previous post, “Treating Bipolar Depression with an OTC Supplement?”

If you’re a doctor who has prescribed Riluzole or someone who has taken it for depression, please share your experiences and insights.

Photo by FarmStudioField, available under a Creative Commons attribution license.

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    Last reviewed: 10 Mar 2011