Does Gabapentin Have a Dark Side?

Have you heard the recent buzz around gabapentin? Well, you're not alone.The BuzzYou might be surprised to learn that it's not a new drug. Gabapentin was discovered back in the 1970s and gained FDA approval in 1993. Today, prescriptions for this so-called wonder drug are on the rise, with some reports suggesting that gabapentin is among the top five most commonly prescribed medications in the United States, despite the fact that it has only two FDA-approved indications: for neuropathic pain associated with postherpetic neuralgia and as an add-on treatment for partial-onset seizures.Gregory Scott Brown, MDI'm Dr Gregory Scott Brown, a board-certified psychiatrist and a clinical associate professor at the Fertitta College of Medicine at the University of Houston. I write prescriptions for gabapentin all the time and find that it helps some of my patients with conditions such as anxiety and insomnia.Gabapentin is also commonly prescribed for nerve pain, restless leg syndrome, and to help reduce alcohol cravings. For these conditions, gabapentin is used off-label, meaning that it's not FDA-approved but there's enough evidence to suggest that it's generally safe and effective. The majority of my patients tolerate gabapentin well, and they tell me it works great.The EvidenceBut what's going on in the brain? Well, it's complicated. First, gabapentin binds to the alpha-2-delta-1 protein subunit of voltage-gated calcium channels. That blocks the excitatory influx of calcium in the central nervous system. Gabapentin also inhibits the release of the neurotransmitter glutamate.Finally, gabapentin increases cell surface expression of the GABAA receptor. Sound familiar? It's the same receptor that alcohol and benzodiazepines such as alprazolam (Xanax) bind to increase the production of the chemical gamma-aminobutyric acid (GABA) in the brain. Of note, unlike benzodiazepines and alcohol, gabapentin doesn't bind directly to the GABAA receptor but enhances the release of GABA through indirect means.I know that's a mouthful, but I'll translate the science: More GABA in the brain means a calm and relaxed state. Now it's time for the million-dollar question.Does Gabapentin Have a Dark Side? The short answer is, well, it depends. Gabapentin is not without side effects:It can cause fatigue and dizziness and slow down breathing rate (respiratory depression), but the risk appears to be quite low at about 10% in vulnerable patients.It can also cause tinnitus (ringing in the ears).These side effects tend to be more pronounced in people with underlying respiratory problems (such as chronic obstructive pulmonary disease), older adults, or people with underlying kidney disease (as gabapentin is primarily cleared by the kidneys).There's also a risk for gabapentin misuse and abuse, but one study showed that risk to be pretty low at around 1%, although it does tend to be higher in people who are receiving a prescription for gabapentin already, or people with a history of substance abuse, particularly opioids. While you may be aware that alcohol and benzodiazepines can be addictive, you might be surprised to know that it's possible to become physically dependent on gabapentin, too. The risk tends to be higher in those who have been taking gabapentin for a very long time or who are exceeding prescribed recommendations. That being said, gabapentin is thought to be much less addictive than benzodiazepines. My TakeI'm often asked about GABA supplements one can find at local health food stores. While these supplements are easily accessible and marketed to promote sleep and reduce stress, the jury is still out on their safety and effectiveness.My opinion: Gabapentin has its place but only should be taken as prescribed by a doctor.Follow Medscape for more, and I'll see you next time on The Psychiatrist's Take.Gregory Scott Brown, MD, is a board-certified psychiatrist and a clinical associate professor at the University of Houston College of Medicine. Brown is also chair of the American Psychiatric Association’s Council on Communications.