Off-Label Usages of Gabapentin

Gabapentin is frequently prescribed off-label for a variety of conditions outside its primary approvals for epilepsy and nerve pain. Gabapentin (Neurontin) is not a medication that would make the FDA proud. Less than 1% of its outpatient use is for an FDA indication, and a good portion of the off-label use takes place in psychiatry. These trends sparked a backlash in the 2000s, when Pfizer paid a $1.3 billion fine for misleading marketing practices. Recent reports of misuse of gabapentin and its GABAergic cousin, pregabalin (Lyrica), have added to those concerns. In this article, we’ll look at where gabapentin fits in psychiatric practice.

Here is a list of some of the common off-label uses:

  1. Anxiety Disorders: Gabapentin is sometimes used to manage generalized anxiety disorder (GAD) and social anxiety, especially in patients who don’t respond well to traditional anti-anxiety medications.
  2. Bipolar Disorder: While not a first-line treatment, gabapentin may be used as an adjunct to stabilize mood in patients with bipolar disorder, particularly those who have difficulty tolerating other mood stabilizers. Long ago, there was a consensus in psychiatry that all anticonvulsants had antimanic effects. In 2000, gabapentin became the first anticonvulsant to challenge that idea, with a negative trial in bipolar mania that was followed by similar disappointments from topiramate and oxcarbazepine (Pande AC et al, Bipolar Disord 2000;2(3 Pt 2):249–255). Gabapentin is not reliable on its own in bipolar disorder, but two placebo-controlled trials suggest it may have a role as adjunctive therapy. It augmented lithium in acute mania and had mild preventive effects over a year when added to various mood stabilizers. As encouraging as these results are, both came from small trials with a total n of 85 (Astaneh AN and Rezaei O, Int J Psychiatry Med 2012;43(3):261–271; Vieta E et al, J Clin Psychiatry 2006;67(3):473–477). In practice, gabapentin is best reserved for treating bipolar disorder in patients with comorbidities like anxiety and alcohol or cannabis use disorders.
  3. Insomnia: Due to its sedative effects, gabapentin is occasionally prescribed to help with sleep disorders, especially for those who struggle with sleep due to chronic pain or anxiety.
  4. Alcohol Dependence and Withdrawal: Gabapentin is used to help reduce cravings and manage withdrawal symptoms in patients with alcohol use disorder, as it can help alleviate anxiety, tremors, and insomnia associated with withdrawal.
  5. Migraine Prevention: Gabapentin is sometimes used off-label to prevent migraines, especially in cases where traditional migraine medications are ineffective or not tolerated.
  6. Hot Flashes: Particularly for postmenopausal women or breast cancer patients, gabapentin can be prescribed to help reduce the frequency and intensity of hot flashes.
  7. Restless Legs Syndrome (RLS): Gabapentin can help alleviate symptoms of RLS, a condition that causes uncomfortable sensations and an urge to move the legs.Gabapentin has only three FDA indications: partial seizures, post-herpetic neuralgia, and restless legs syndrome (RLS). Although used widely in pain disorders, it only has clear benefits in post-herpetic neuralgia and diabetic peripheral neuropathy, and is not considered effective for low back pain, sciatica, spinal stenosis, or migraines (Mathieson S et al, BMJ 2020;369:m1315). Gabapentin’s RLS approval is reserved for gabapentin enacarbil (Horizant), a prodrug that delays absorption by attaching the medication to an enacarbil molecule.
  8. Pruritus (Chronic Itching): Gabapentin has shown effectiveness in managing severe itching related to conditions like kidney disease, liver disease, or certain types of neuropathy.
  9. Chronic Cough: Some cases of refractory chronic cough, where traditional treatments are ineffective, have responded to gabapentin.
  10. Multiple Sclerosis (MS)-Related Symptoms: Gabapentin can help alleviate nerve pain, spasticity, and certain types of tremors associated with MS.
  11. Temporomandibular Joint (TMJ) Disorders: In cases of chronic TMJ-related pain, gabapentin may be used to reduce discomfort.
  12. Post-Traumatic Stress Disorder (PTSD): It is sometimes prescribed to help manage PTSD symptoms, particularly anxiety, sleep disturbances, and hyperarousal.
  13. Vulvodynia: Gabapentin can help reduce pain in patients with vulvodynia, a chronic pain condition affecting the vulvar region.
  14. Phantom Limb Pain: After amputation, some patients experience pain in the “phantom” limb, and gabapentin may be used to help relieve these sensations.
  15. Chronic Pelvic Pain: Gabapentin is sometimes prescribed to help manage chronic pelvic pain, especially when associated with nerve involvement.
  16. Trigeminal Neuralgia: Although more commonly used for postherpetic neuralgia, gabapentin can also help with trigeminal neuralgia, a painful nerve condition affecting the face.
  17. Addiction Treatment:  Despite concerns about gabapentin misuse, the medication does have a role in alcohol and cannabis use disorders. Patients who take it for alcohol use disorders report fewer days of heavy drinking, with an effect size in the medium range (0.4) from seven randomized controlled trials (Ahmed S et al, Prim Care Companion CNS Disord 2019;21(4):19r02465). Gabapentin also improves sleep quality during recovery from alcohol use. The dose range was 300–3600 mg/day, with most settling in around 900 mg/day. Gabapentin may also be useful for alcohol withdrawal, but with a caveat. Although it was generally effective in controlled trials that compared it with benzodiazepines and phenobarbital, there were a few seizures during the gabapentin taper—not enough to raise statistical alarms, but enough to give us pause. It does improve cravings, anxiety, and sleep during withdrawal, so it may still have a role as an adjunct to more established methods like a benzodiazepine taper, or its use should be confined to patients with less severe dependence. A typical schedule starts at 1200–2400 mg/day in three or four divided doses, tapers to 600 mg/day over four to seven days, then drops in increments of 300 mg or smaller every few days until reaching zero (Leung JG et al, Ann Pharmacother 2015;49(8):897–906). Alternatively, it may be continued long term to prevent relapse, a use that is endorsed by the APA guidelines on alcohol use disorders.
  18. Akathisia, sleep, and hot flashes :Treatments for RLS often reduce akathisia, and gabapentin has promising results for this antipsychotic side effect, as evidenced in open-label trials at doses of 300–3600 mg/day. Gabapentin is often used as a hypnotic, and this is supported by small controlled and open-label trials where it improved sleep duration and quality (eg, increased slow-wave sleep) at 200–900 mg/day (Furey SA et al, J Clin Sleep Med 2014;10(10):1101–1109). In practice, this means gabapentin may not help your patients fall asleep faster, but it can deepen their sleep and reduce nocturnal awakenings. Women with post-menopausal vasomotor symptoms are good candidates for this hypnotic use, as gabapentin reduced hot flashes in several controlled trials (Saadati N et al, Glob J Health Sci 2013;5(6):126–130).

These off-label uses are based on clinical observations, smaller studies, or anecdotal evidence, so efficacy may vary. Always consult with a healthcare provider for guidance on using gabapentin for any off-label purpose.

The Dosages of Off-Label Usages of Gabapentin