Gabapentin (Neurontin) is a “novel anticonvulsant” and is FDA indicated for partial seizures and post-herpetic neuralgia. But the drug has long been heavily marketed to psychiatrists to treat a range of conditions from bipolar disorder to anxiety to alcohol withdrawal. It’s often seen as a “non-addictive” ­off-label drug useful for treating anxiety and insomnia in patients who have substance use disorders.

Unfortunately, we now know that gabapentin can, in fact, become a drug of abuse for some users. It turns out that its typical side effects of dizziness and sedation can be exploited by those who want to use the drug to feel high. People who misuse gabapentin will often say that they feel euphoric, high, or zoned out. Because of this, it has become a popular drug of abuse in prisons, where there is a high rate of diversion. In 2016, the Federal Bureau of Prisons’ Health Services Division removed gabapentin as a formulary agent, and added strict non-formulary criteria to mitigate abuse (see: https://www.bop.gov/resources/pdfs/formulary.pdf). Also, some states have shifted gabapentin to a DEA Schedule V drug, the same category as cough syrups with codeine and pregabalin (Lyrica®).

So where does this leave us? Should we continue to prescribe gabapentin? If so, for whom? And when should we be extra cautious?

The main concern: gabapentin and opioids
While some patients abuse gabapentin alone, this is pretty rare; one study found that only 2% of 44,148 patients using gabapentin alone met criteria for sustained overuse (Peckham et al, Pharmacotherapy, in press). But 11.7% of patients who combined gabapentin with opioids met those same substance abuse criteria. The theory is that gabapentin potentiates the opioid high, making it appealing for those wanting to augment opioid effects.

It’s these patients—the ones combining gabapentin with opioids—who have a greater danger of overdose. One study found a 60% increase in the odds of opioid-related deaths in patients co-prescribed opioids with gabapentin—at least when the doses exceed 900 mg daily (Gomes T, PLoS Med 2017;14(10):e1002396).

The bottom line is that you should try to avoid prescribing gabapentin to patients who have current or past opioid use disorder. And if you feel you must prescribe it in these patients, be aware that doses higher than 900 mg daily carry an extra risk for overdose and should be used only with caution.

If you need to get patients off of gabapentin, be aware that there is a recognized gabapentin withdrawal syndrome. It’s similar to benzodiazepine withdrawal and includes symptoms of disorientation, anxiety, insomnia, palpitations, diaphoresis, and abdominal cramping. Some of these patients may need inpatient detox.

When and how to prescribe gabapentin
There are three off-label situations in which gabapentin is often prescribed in psychiatry: anxiety disorders, insomnia, and alcohol use disorder (AUD). Of course, if you are seeing patients with any of these problems in addition to a neuropathic pain issue, gabapentin is particularly appealing, since it can serve as a “twofer.”

When prescribing gabapentin for anxiety, start with 300 mg at bedtime for one week, then 300 mg twice daily for one week, and then 300 mg 3 times daily thereafter. The 300 mg TID dose is generally when patients are likely to notice a beneficial effect, such as decreased anxiety, though the target dose is 1,200 mg daily (or 400 mg TID) for maximum benefit. If need be, you can increase the dose to 3,600 mg daily, which is the FDA-recommended maximum. With anxiety taking many forms, gabapentin is best used for social anxiety, panic disorder, PTSD, and OCD. While it may be used alone for social anxiety and panic disorder, it is often prescribed in addition to an antidepressant for PTSD and OCD (Berlin RK et al, Prim Care Companion CNS Disord 2015;17(5). doi:10.4088).

For insomnia, gabapentin can be started at 300 mg at bedtime, with weekly titrations of 300 mg and a target dose of 900 mg at bedtime. The key to treating insomnia with gabapentin is to ensure all dosing takes place at bedtime. Remember to tell patients that gabapentin works to improve their overall sleep quality; it does not necessarily put them to sleep or make them fall asleep faster. Therefore, it is best used for patients who have trouble staying asleep rather than falling asleep (Schroeck JL et al, Clin Ther 2016;38(11):2340–2372).

In the case of AUD, gabapentin can be used alone or as an adjunct to medications such as naltrexone, acamprosate, or disulfiram (Soyka M and Müller CA, Expert Opin Pharmacother 2017;18(12):1187–1199). Gabapentin can be started and adjusted just like you would for anxiety, but the target dose for AUD is higher at 1,800 mg daily in 3 divided doses (or 600 mg TID). Tell patients that they may start to experience less intense alcohol cravings around 900 mg, with even greater reductions in cravings as the dose is increased.

Patients should be informed that the most common side effects are dizziness and sedation, and that they are likely to notice these during the second week when the first daytime dose is added. Usually the side effects will subside within 3–7 days, but if they don’t, shift all doses to bedtime and/or reduce the total dose as needed to re-establish tolerability. From there, make more conservative dose increases in 100 mg increments weekly.

CATR Verdict: In patients with substance use disorders, avoid prescribing gabapentin to patients with active or recent opioid use disorder. However, gabapentin is often helpful as an adjunctive agent in the treatment of AUD, and for anxiety and insomnia in patients who might overuse addictive drugs like benzodiazepines.