how does gabapentin work

Gabapentin – an anticonvulsant drug – aims to stop or treat epilepsy seizures. It is considered a relatively safe drug, with a low risk of severe side effects and drug interactions. Within the USA and Canada, it is a commonly prescribed drug for a variety of medical disorders. In recent years, gabapentin has been increasingly prescribed by clinicians for both on- and off-label uses. So, how does gabapentin work?

History of gabapentin

Gabapentin was first discovered in Japan in the 1970s. It has a similar structure to gamma-aminobutyric acid (GABA) – a chemical messenger naturally produced by the brain, which functions to decrease activity in the brain. Initially, the focus of the drug was on its ability to relax muscles. With additional research, gabapentin was found to work by having an anticonvulsive effect for those affected by epilepsy. Later, research focused on other uses for gabapentin, including mental disorders, neuropathic pain, and restless leg syndrome. Research continues to test the effectiveness of gabapentin for such disorders.

Approved uses for gabapentin

Depending on the country, the approved uses of gabapentin will differ. For example, the drug is approved to treat restless leg syndrome, partial seizure, and postherpetic neuralgia – which causes long-term nerve pain – in the USA. In Canada, however, it is only approved as an anticonvulsant drug for use by epileptic persons. The United Kingdom has approved gabapentin for treating partial seizures and relieving pain in cases of neuropathic pain – often caused by nerve disease or damage.

Off-label uses for gabapentin

There are many off-label uses of the drug as prescribed by a clinician. For example, alcohol withdrawal symptoms in individuals with alcohol-use disorder may benefit from gabapentin treatment. It is considered to be a relatively safe and easily accessible treatment for alcohol-use disorder. It has the benefit of not requiring dose adjustments in those with impaired liver functioning for which individuals with alcohol-use disorder are at higher risk. Some research indicates it is especially beneficial when used alongside naltrexone – an FDA approved alcohol use disorder treatment. The effectiveness of gabapentin on its own for treating alcohol-use disorder still requires more evidence to establish the extent of its benefit.

Also, clinicians commonly prescribe gabapentin for individuals with bipolar disorder in order to reduce their symptoms of anxiety. It is not often prescribed for primary diagnoses of anxiety disorders or major depressive disorder because there is a lack of clinical evidence of gabapentin being an effective monotherapy for those mental disorders.

Other off-label uses of gabapentin are for the treatment of diabetic neuropathic pain, fibromyalgia, and essential tremors. More clinical research is required to better understand the effects of gabapentin for these off-label uses.

How does gabapentin work?

The drug can be found in a white solid form. Often, prescriptions of gabapentin will be in the form of capsules or tablets, including extended-release tablets, for oral consumption. The dose of gabapentin may differ depending on the form of the drug. In general, doses for capsules can range from 100mg to 400mg, whereas tablets typically range from 600mg to 800mg.  Usually, the maximum dose per day is 1800mg taken in three equal doses. A clinician’s medical advice will likely take into account the unique factors of each patient’s case before determining the appropriate dose of gabapentin.

Its exact mechanism of action is still unknown, however, it is known to easily pass the blood-brain barrier to directly affect the brain. It is thought that gabapentin works by modifying the release of chemical messengers – called neurotransmitters – in the brain, in order to block certain brain signals. Also, it reduces the stimulation of nerve cells, which may produce the anticonvulsive and pain-relieving effects of gabapentin.

How long does it take for gabapentin work?

Gabapentin has an elimination half-life of approximately six hours. The drug may take up to two days to be completely eliminated from the body. Research indicates that patients will typically notice the effects of gabapentin within the first few weeks, however, significant improvement of their condition may take a month of treatment.

Adverse effects associated with gabapentin

Gabapentin is thought to have minor potential side effects. The most common being dizziness, fatigue, drowsiness, nausea, diarrhea, and vomiting. Other possible pain-related side effects can include headaches and back pain. Symptoms of ataxia, a neurological-based movement disorder, including falls and incoordination, may also be potential side effects of the drug, especially at higher doses.

More serious side effects that an individual could experience include depression or suicidality.  However, these effects are less commonly experienced by gabapentin users. Some research suggests that clinicians should screen patients for depression and suicidality before prescribing gabapentin and monitor for any concerning behaviour changes during the course of the medication.

Drug interactions are considered a low risk for gabapentin. One study reported that there is a possibility for drug interactions, specifically with other antiepileptic drugs or caffeine. It has been suggested that pharmacists can help ensure that patients are not taking drugs that have the potential to interact with gabapentin.

In terms of contraindications, some studies indicate gabapentin may not be suitable for use in patients with myasthenia gravis – a neuromuscular disorder – or myoclonus issues, which refers to sudden muscle spasms. Also, the US FDA has reported that individuals with reduced lung function may experience serious breathing difficulties when using gabapentin. For this reason, respiratory risk factors may be a contraindication for taking gabapentin. Individuals with impaired kidney functioning may require adjusted dosing and monitoring throughout treatment because gabapentin is primarily excreted through the renal path, which involves the kidneys.

Misuse of gabapentin

Currently, gabapentin is not considered a controlled substance – a drug which has a high potential for abuse or addiction – in the USA and Canada. Despite this, recent studies have indicated that gabapentin abuse is increasing, which may impact individuals’ health. For example, one study based in Kentucky, USA found that gabapentin had been misused for non-medical purposes in their studied population. A common reason for gabapentin misuse as found in studies is to strengthen the effect of methadone – an opioid addiction treatment – in order to get high or to lessen their opioid withdrawal symptoms. Research shows that concurrent prescribed opioid and gabapentin use can increase the risk of death compared to taking opioids alone.

Always consult your healthcare provider before taking any medications or supplements.

References:

Lennox, R., & Mangin, D. (2019). Gabapentin misuse. Canadian Medical Association Journal, 191(2), E47. https://doi.org/10.1503/cmaj.180599

Narain, T., & Adcock, L. (2018). Gabapentin for adults with neuropathic pain: A review of the clinical effectiveness. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK531934/

Rentsch, C. T., Morford, K. L., Fiellin, D. A., Bryant, K. J., Justice, A. C., & Tate, J. P. (2020). Safety of Gabapentin Prescribed for Any Indication in a Large Clinical Cohort of 571,718 US Veterans with and without Alcohol Use Disorder. Alcoholism, Clinical and Experimental Research44(9), 1807–1815. https://doi.org/10.1111/acer.14408

Quintero, G. C. (2017). Review about gabapentin misuse, interactions, contraindications and side effects. Journal of Experimental Pharmacology9, 13–21. https://doi.org/10.2147/JEP.S124391

U.S. Food and Drug Administration. (2019). FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR). Retrieved from https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-breathing-problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin

Yasaei, R., Katta, S., & Saadabadi, A. (2020). Gabapentin. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK493228/

Image by Arek Socha from Pixabay 

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